CDH1 encodes E-cadherin (epithelial cadherin), the prototypical type-I classical cadherin and the principal calcium-dependent cell-cell adhesion molecule of epithelia. This single-pass transmembrane glycoprotein has five extracellular cadherin (EC) repeats that bind calcium and mediate homophilic trans-adhesion with E-cadherin on neighbouring cells, while its cytoplasmic tail nucleates the cadherin-catenin complex by binding p120-catenin, beta-catenin and gamma-catenin/plakoglobin; alpha-catenin in turn couples this complex to the cortical actin cytoskeleton. Through these interactions E-cadherin builds and maintains adherens junctions, establishes epithelial apicobasal polarity and tissue integrity, and facilitates early desmosome assembly. E-cadherin is a potent invasion and tumour suppressor: loss of function promotes epithelial-to-mesenchymal transition and is causative in hereditary diffuse gastric cancer and lobular breast carcinoma. E-cadherin is additionally exploited as a host cell-surface receptor by Listeria monocytogenes internalin A.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0000902
cell morphogenesis
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: IBA projection from the PANTHER classical cadherin family tree (PTHR24027, subfamily SF319 Cadherin-1) via GO_REF:0000033. E-cadherin contributes to epithelial cell morphogenesis because cadherin-mediated adhesion shapes epithelial cells and is required to establish and maintain epithelial architecture. However, cell morphogenesis is a broad downstream outcome of the core adhesion and junction-organizing activity rather than a distinct core function. The precise core CDH1 processes (calcium-dependent homophilic cell-cell adhesion, cadherin-mediated adhesion, adherens junction organization) are captured by other rows in this file.
Reason: Real but general developmental/cellular outcome downstream of the core adhesion function; the precise core processes (GO:0044331 cell-cell adhesion mediated by cadherin, GO:0034332 adherens junction organization) are ACCEPTed elsewhere in this batch. Mechanical IBA-PANTHER batch (batch 2 of #348).
|
|
GO:0016477
cell migration
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: IBA projection from the PANTHER cadherin family tree (PTHR24027) via GO_REF:0000033. E-cadherin participates in cell migration processes — it is retained at junctions during collective epithelial migration such as wound healing, and conversely its loss drives the epithelial-mesenchymal transition that licenses single-cell motility and invasion. The bare cell migration term carries no directionality, whereas the best-established directional CDH1 role is suppression of single-cell migration/invasion, separately captured by the IMP GO:0030336 (negative regulation of cell migration) row in this file (PMID:16882694). The generic involved_in cell-migration inference is therefore a real but non-core, context-dependent association.
Reason: Generic non-directional migration term; the core CDH1 activity is cell-cell adhesion rather than migration per se, and the directional regulatory role (suppression of migration/invasion) is captured by GO:0030336 elsewhere in the file. Mechanical IBA-PANTHER batch (batch 2 of #348).
|
|
GO:0007043
cell-cell junction assembly
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA projection from the PANTHER classical cadherin family tree (PTHR24027) via GO_REF:0000033. E-cadherin nucleates assembly of epithelial cell-cell junctions — homophilic trans-engagement of E-cadherin ectodomains initiates cell-cell contact, and the cytoplasmic tail recruits the catenins that build the adherens junction and template subsequent tight-junction and desmosome formation. This is a core, well-established CDH1 function, consistent with the more specific GO:0034332 (adherens junction organization) row.
Reason: Core CDH1 biological process — E-cadherin is the founding adhesion receptor that initiates epithelial cell-cell junction assembly. Mechanical IBA-PANTHER batch (batch 2 of #348).
|
|
GO:0005737
cytoplasm
|
IBA
GO_REF:0000033 |
MARK AS OVER ANNOTATED |
Summary: IBA projection (is_active_in) from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033. E-cadherin is a type-I single-pass transmembrane glycoprotein; its steady-state location is the plasma membrane and adherens junction, with only its ~150-residue C-terminal tail exposed to the cytosol. Annotating the protein as is_active_in the cytoplasm (GO:0005737) is over-broad — it asserts a generic compartment that does not reflect where the protein resides or acts. The accurate localizations (plasma membrane, adherens junction, lateral plasma membrane) are captured by other rows in this file.
Reason: Over-broad CC for a single-pass transmembrane plasma-membrane protein; cytoplasm is not entirely wrong (the cytoplasmic tail faces the cytosol) but does not reflect the protein actual residence or site of action. More precise CC terms (GO:0005886 plasma membrane, GO:0005912 adherens junction, GO:0016328 lateral plasma membrane) are present in the file. Mechanical IBA-PANTHER batch (batch 2 of #348).
|
|
GO:0008013
beta-catenin binding
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA projection from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033. The E-cadherin cytoplasmic catenin-binding domain directly binds beta-catenin (CTNNB1); this interaction links the cadherin to the actin cytoskeleton via alpha-catenin and is the molecular basis of the cadherin-catenin complex. Independently supported within this file by IPI/IDA evidence on this same term (PMID:18593713, Smad7 stabilizes beta-catenin binding to the E-cadherin complex; PMID:17620337) and by Reactome TAS rows describing CDH1-CTNNB1 complex formation.
Reason: Canonical core CDH1 molecular function — direct beta-catenin binding by the cadherin cytoplasmic tail is the defining interaction of the cadherin-catenin complex. Corroborated by IPI (PMID:18593713) and IDA (PMID:17620337) evidence on this exact term elsewhere in the file. Mechanical IBA-PANTHER batch (batch 2 of #348).
Supporting Evidence:
file:human/CDH1/CDH1-deep-research-falcon.md
Experimental/biophysical synthesis emphasizes anchoring through **β‑catenin and α‑catenin**, enabling transmission of actomyosin forces across junctions
PMID:7806582
beta-Catenin is involved in the formation of adherens junctions of mammalian epithelia. It interacts with the cell adhesion molecule E-cadherin
|
|
GO:0044331
cell-cell adhesion mediated by cadherin
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA projection from the PANTHER classical cadherin tree (PTHR24027) via GO_REF:0000033. Cadherin-mediated cell-cell adhesion is the defining function of E-cadherin — calcium-dependent homophilic trans-interaction of ectodomains between adjacent epithelial cells. This is the central core CDH1 process. Independently supported in this file by IDA evidence on the same term (PMID:18593713) and by the crystallographic adhesion-architecture reference PMID:21300292.
Reason: Defining core biological process of E-cadherin — homophilic cadherin-mediated cell-cell adhesion. Corroborated by IDA evidence on this exact term (PMID:18593713) elsewhere in the file. Mechanical IBA-PANTHER batch (batch 2 of #348).
Supporting Evidence:
file:human/CDH1/CDH1-deep-research-falcon.md
E‑cadherin is a **calcium-dependent cell–cell adhesion molecule** that organizes epithelial tissue architecture by mediating **homophilic adhesion** and supporting epithelial integrity and polarity
PMID:3498123
E-cadherin is a cell surface glycoprotein responsible for Ca2+-dependent intercellular adhesion between epithelial cells
|
|
GO:0016342
catenin complex
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA projection (part_of) from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033. E-cadherin is the transmembrane core of the cadherin-catenin (catenin) complex; its cytoplasmic tail scaffolds beta-catenin and gamma-catenin and, via alpha-catenin, the actin cytoskeleton. Independently supported in this file by IDA evidence on the same GO:0016342 term (PMID:18593713).
Reason: Core CDH1 cellular component — E-cadherin is the obligate transmembrane component of the catenin complex. Corroborated by IDA evidence on this exact term (PMID:18593713) elsewhere in the file. Mechanical IBA-PANTHER batch (batch 2 of #348).
Supporting Evidence:
file:human/CDH1/CDH1-deep-research-falcon.md
Broader mechanistic synthesis also highlights interaction with **p120‑catenin**, and how changes in E‑cadherin availability can alter β‑catenin and p120‑catenin signaling states
PMID:2349235
the cytoplasmic region of the cell adhesion molecule uvomorulin associates with three proteins named catenin alpha, beta, and gamma
|
|
GO:0045296
cadherin binding
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA projection from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033. E-cadherin engages in cadherin binding through calcium-dependent homophilic trans- and cis-interactions of its ectodomain (the EC1 strand-swap dimer interface), the mechanistic basis of homophilic cell-cell adhesion. Independently supported in this file by HDA evidence on the same term (PMID:25468996, the E-cadherin interactome) and the crystallographic reference PMID:21300292.
Reason: Core CDH1 molecular function — homophilic cadherin-cadherin binding via the ectodomain is the adhesive activity of E-cadherin. Corroborated by HDA evidence on this exact term (PMID:25468996) elsewhere in the file. Mechanical IBA-PANTHER batch (batch 2 of #348).
Supporting Evidence:
file:human/CDH1/CDH1-deep-research-falcon.md
**homophilic trans-binding** is driven primarily by the **EC1 domain** and proceeds through an **X-dimer intermediate** followed by formation of a stable **strand-swapped dimer**, in which a **tryptophan side chain from one EC1 inserts into a hydrophobic pocket** of the opposing EC1
PMID:20190754
Crystal structures of classical cadherins have revealed two dimeric configurations. In the first, N-terminal beta-strands of EC1 domains 'swap' between partner molecules.
|
|
GO:0070097
delta-catenin binding
|
IPI
PMID:15240885 A role for Galpha12/Galpha13 in p120ctn regulation. |
NEW |
Summary: NEW annotation. The juxtamembrane domain (JMD) of E-cadherin's cytoplasmic tail directly binds p120-catenin (CTNND1) at a site distinct from the C-terminal beta-catenin-binding domain. UniProt cites Krakstad et al. 2004 (PMID:15240885) as the primary reference for "INTERACTION WITH CTNND1" (CDH1-uniprot.txt line 300); Fig. 5B coimmunoprecipitates E-cadherin with p120-catenin in L cells in the context of Galpha12 overexpression (with Galpha12 increasing the association), and the Discussion explicitly references the established direct binding of p120ctn to the juxtamembrane region of E-cadherin (the citation context UniProt relies on when listing this paper). The CDH1-CTNND1 interaction is independently documented in UniProt (P12830 SUBUNIT: "Interacts with CTNND1"; binding-site feature "Required for binding CTNND1 and PSEN1") and by four IntAct/UniProt-curated IPI records against CTNND1/O60716 in this file's GOA (PMID:10725230, PMID:19604117, PMID:33961781, PMID:34591612). Mariner et al. 2000 (PMID:10725230) provides supporting JMD-localization context by showing that ARVCF competes with p120 for the same JMD site. Mechanistically, p120-catenin binding masks a dileucine endocytic motif in the JMD and stabilizes E-cadherin at the plasma membrane, controlling cadherin surface levels, turnover, and adhesion strength — a direct molecular function distinct from beta-catenin binding (GO:0008013, a core function here). Term-usage note: GO:0070097 "delta-catenin binding" is the only available granular GO term for catenin-δ subfamily binding; there is no separate "p120-catenin binding" term. The term is used here for CTNND1 (p120/δ1-catenin) following the convention already established across all 39 GO:0005515 over-annotation rows in this file (e.g. line 285: "delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)"), and consistent with the GO definition "Binding to the delta subunit of the catenin complex."
Reason: Direct, well-supported molecular function (p120-catenin binding at the juxtamembrane domain) currently captured only as uninformative generic protein binding; promoting it to GO:0070097 implements the partner-specific replacement flagged across the GO:0005515 CTNND1 IPI rows of this file. Reference set was tightened after PR review: original_reference_id updated to UniProt's primary direct reference PMID:15240885 (was PMID:10725230, an ARVCF competition assay that only indirectly implies p120 binding), and PMID:24424122 (a suppressor-tRNA therapy paper) was dropped from the summary, leaving only the four IPI records that clearly target CTNND1/O60716. Alpha-catenin binding (GO:0045294) is intentionally NOT proposed, because alpha-catenin associates with E-cadherin indirectly via beta-catenin rather than by direct binding to CDH1.
|
|
GO:0034332
adherens junction organization
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA projection from the PANTHER classical cadherin tree (PTHR24027) via GO_REF:0000033. E-cadherin is the founding component that organizes the epithelial adherens junction — clustering of trans-engaged cadherins together with recruitment of the catenin-actin module assembles and maintains the zonula adherens. Independently supported in this file by IMP evidence on the same term (PMID:21724833).
Reason: Core CDH1 biological process — E-cadherin organizes the adherens junction. Corroborated by IMP evidence on this exact term (PMID:21724833) elsewhere in the file. Mechanical IBA-PANTHER batch (batch 2 of #348).
Supporting Evidence:
file:human/CDH1/CDH1-deep-research-falcon.md
E‑cadherin-based adhesions transmit **actomyosin-generated pulling forces** through β‑catenin/α‑catenin anchorage, and junction stability can be limited by cytoskeletal anchorage rather than cadherin–cadherin binding strength
PMID:3498123
blocking the action of E-cadherin by monoclonal antibodies causes dispersion of compact cell colonies
|
|
GO:0005912
adherens junction
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA projection (is_active_in) from the PANTHER classical cadherin tree (PTHR24027) via GO_REF:0000033. The adherens junction (zonula adherens) is the principal site of E-cadherin residence and function in epithelial cells. This is a core CDH1 cellular component, independently supported in this file by multiple IDA rows on the same term (PMID:22294297, PMID:18343367, PMID:27760340, PMID:24046456, PMID:20086044, PMID:16338932).
Reason: Core CDH1 cellular component — the adherens junction is the defining site of E-cadherin localization and activity, corroborated by numerous IDA rows on this exact term in the file. Mechanical IBA-PANTHER batch (batch 2 of #348).
Supporting Evidence:
file:human/CDH1/CDH1-deep-research-falcon.md
In epithelia, E‑cadherin is enriched at the **plasma membrane** and concentrates at **adherens junctions** where it contributes to epithelial sheet cohesion and tissue architecture
PMID:7806582
beta-Catenin is involved in the formation of adherens junctions of mammalian epithelia. It interacts with the cell adhesion molecule E-cadherin
|
|
GO:0007416
synapse assembly
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: IBA projection from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033, originating from the broad ancestral node PTN000616414. Classical cadherins contribute to synapse assembly and stabilization in the nervous system, and E-cadherin has documented roles at neuronal synapses; however, for the canonical epithelial CDH1 this is a tissue-specific, non-core context rather than a defining function. The core CDH1 role is epithelial cell-cell adhesion at adherens junctions.
Reason: Tissue/cell-type-specific neuronal context (synapse assembly) rather than a core epithelial CDH1 function; projected from a broad ancestral PANTHER node. Mechanical IBA-PANTHER batch (batch 2 of #348).
|
|
GO:0016339
calcium-dependent cell-cell adhesion
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA projection from the PANTHER classical cadherin tree (PTHR24027) via GO_REF:0000033. E-cadherin adhesion is strictly calcium-dependent — Ca2+ ions bridge the linker regions between extracellular cadherin (EC) domains, rigidifying the ectodomain into the conformation competent for homophilic trans-binding. GO:0016339 (attachment of one cell to another via adhesion molecules that require calcium) precisely describes the core CDH1 adhesive process. Consistent with the IEA GO:0005509 (calcium ion binding) row in this file.
Reason: Core CDH1 biological process — calcium-dependent homophilic cell-cell adhesion is the defining activity of E-cadherin. Mechanical IBA-PANTHER batch (batch 2 of #348).
Supporting Evidence:
file:human/CDH1/CDH1-deep-research-falcon.md
E‑cadherin is a **calcium-dependent cell–cell adhesion molecule** that organizes epithelial tissue architecture by mediating **homophilic adhesion** and supporting epithelial integrity and polarity
PMID:3498123
E-cadherin is a cell surface glycoprotein responsible for Ca2+-dependent intercellular adhesion between epithelial cells
|
|
GO:0016600
flotillin complex
|
IBA
GO_REF:0000033 |
MARK AS OVER ANNOTATED |
Summary: IBA projection (part_of) from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033, from the broad ancestral node PTN000616414. GO:0016600 (flotillin complex) is defined as a protein complex containing flotillin-1 and flotillin-2 (and possibly associated proteins). E-cadherin is recruited to flotillin-rich membrane microdomains that stabilize cadherins at cell-cell junctions (shown experimentally in PMID:24046456, the separate IDA GO:0016600 row in this file), but it is not a constitutive flotillin subunit. Annotating E-cadherin as part_of the flotillin complex by phylogenetic inference overstates this microdomain association into structural complex membership. (The IDA flotillin row, PMID:24046456, is left PENDING for a later batch.)
Reason: The part_of qualifier overstates a membrane-microdomain association as structural membership of the flotillin-1/-2 complex; E-cadherin is recruited to flotillin microdomains but is not a flotillin-complex subunit. Not entirely wrong (flotillin-microdomain localization is experimentally supported by PMID:24046456) but an over-annotation as an IBA part_of inference. Mechanical IBA-PANTHER batch (batch 2 of #348).
|
|
GO:0043296
apical junction complex
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: IBA projection (is_active_in) from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033, from the broad ancestral node PTN000616414. The apical junction complex (GO:0043296) is the composite apical unit comprising the tight junction, the zonula adherens and desmosomes. E-cadherin is the core of the zonula adherens, one of the three constituents of the apical junction complex, so the annotation is not wrong; however, the precise and core CDH1 cellular component is the adherens junction itself (GO:0005912, ACCEPTed in this batch), and the broader composite grouping is best treated as non-core.
Reason: Accurate but broader-than-precise CC grouping; the precise core localization is GO:0005912 adherens junction. E-cadherin resides specifically in the zonula adherens sub-compartment of the apical junction complex. Mechanical IBA-PANTHER batch (batch 2 of #348).
Supporting Evidence:
PMID:23643492
E-cadherin supports steady-state Rho signaling at the epithelial zonula adherens
|
|
GO:0005509
calcium ion binding
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: IEA from InterPro2GO (GO_REF:0000002): E-cadherin has five extracellular cadherin (EC) domains, each pair bridged by three Ca2+ ions at the domain linker regions. Ca2+ binding rigidifies the extracellular domain into a rod-like conformation required for homophilic trans-dimerisation and cell-cell adhesion. Calcium ion binding is therefore a core molecular activity of CDH1, corroborated by the IBA GO:0016339 (calcium-dependent cell-cell adhesion) ACCEPT in this file.
Reason: Core CDH1 molecular function — Ca2+ binding via the EC-domain linkers is an obligate step in homophilic cadherin adhesion. IEA batch (batch 3 of #348).
Supporting Evidence:
file:human/CDH1/CDH1-deep-research-falcon.md
extracellular portion contains **five cadherin repeats (EC1–EC5)** with **calcium-binding sites**
|
|
GO:0005576
extracellular region
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: IEA from UniProt-GOA (GO_REF:0000044): CDH1 is a type-I single-pass transmembrane glycoprotein with a large N-terminal extracellular segment comprising five EC repeat domains (EC1-EC5). The ectodomain is entirely extracellular and constitutes the adhesion-competent portion of the protein.
Reason: Core CDH1 cellular component — the large EC1-EC5 ectodomain occupies the extracellular region and is the adhesion-active portion of the protein. IEA batch (batch 3 of #348).
|
|
GO:0005737
cytoplasm
|
IEA
GO_REF:0000044 |
MARK AS OVER ANNOTATED |
Summary: IEA from UniProt-GOA (GO_REF:0000044): CDH1 is a type-I single-pass transmembrane glycoprotein whose steady-state localization is the plasma membrane and adherens junction. Only the ~150-residue C-terminal cytoplasmic tail faces the cytosol; the protein does not reside in or act within the cytoplasm as a compartment. More precise CC terms (GO:0005886 plasma membrane, GO:0005912 adherens junction) are accepted elsewhere in this file. Consistent with MARK_AS_OVER_ANNOTATED on the IBA GO:0005737 row.
Reason: Over-broad CC for a single-pass transmembrane plasma-membrane protein; only the cytoplasmic tail faces the cytosol; more precise CC terms (plasma membrane, adherens junction) are accepted elsewhere. IEA batch (batch 3 of #348).
|
|
GO:0005768
endosome
|
IEA
GO_REF:0000044 |
KEEP AS NON CORE |
Summary: IEA from UniProt-GOA (GO_REF:0000044): CDH1/E-cadherin undergoes clathrin-mediated endocytosis and is trafficked through early endosomes during junction remodelling and in response to growth factor signalling. Endosomal localisation is real but is a trafficking/turnover context rather than the site of CDH1 core adhesion and junction-organising function.
Reason: Real but non-core CC — endosomal localisation reflects CDH1 endocytic turnover/recycling rather than core adhesion function; primary sites of CDH1 activity are plasma membrane and adherens junction. IEA batch (batch 3 of #348).
|
|
GO:0005794
Golgi apparatus
|
IEA
GO_REF:0000044 |
KEEP AS NON CORE |
Summary: IEA from UniProt-GOA (GO_REF:0000044): CDH1 is glycosylated and processed in the Golgi apparatus as part of the secretory pathway before reaching the plasma membrane. Golgi localisation is real but represents a transient biosynthetic/processing compartment rather than a site of CDH1 function.
Reason: Real but non-core CC — Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; core localisation and function are at the plasma membrane and adherens junction. IEA batch (batch 3 of #348).
|
|
GO:0005886
plasma membrane
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: IEA from UniProt keyword mapping (GO_REF:0000120): The plasma membrane is the primary site of CDH1/E-cadherin localization and function. E-cadherin concentrates at the lateral/basolateral plasma membrane of epithelial cells, where it mediates homophilic trans-dimerisation and cell-cell adhesion. Consistent with experimental IDA and TAS evidence on the same term elsewhere in this file.
Reason: Core CDH1 cellular component — the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity. IEA batch (batch 3 of #348).
Supporting Evidence:
file:human/CDH1/CDH1-deep-research-falcon.md
In epithelia, E‑cadherin is enriched at the **plasma membrane** and concentrates at **adherens junctions** where it contributes to epithelial sheet cohesion and tissue architecture
|
|
GO:0005912
adherens junction
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: IEA from UniProt-GOA (GO_REF:0000044): The adherens junction is the principal and defining site of CDH1/E-cadherin localization and function in epithelial cells. E-cadherin is the core transmembrane component of the cadherin-catenin complex at the adherens junction. Already ACCEPTed for the IBA annotation (GO_REF:0000033) in this file.
Reason: Core CDH1 cellular component — the adherens junction is the defining site of CDH1 localization and activity; consistent with IBA ACCEPT on this term elsewhere in the file. IEA batch (batch 3 of #348).
|
|
GO:0007155
cell adhesion
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: IEA from InterPro2GO (GO_REF:0000002): Cell adhesion is the defining biological process of CDH1/E-cadherin. E-cadherin mediates calcium-dependent homophilic cell-cell adhesion between epithelial cells and is the founding member of the classical cadherin family.
Reason: Core CDH1 biological process — cell adhesion is the defining function of E-cadherin. IEA batch (batch 3 of #348).
|
|
GO:0007156
homophilic cell-cell adhesion
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: IEA from InterPro2GO (GO_REF:0000002): Homophilic cell-cell adhesion is the specific core mechanism of CDH1 — E-cadherin engages in calcium-dependent homophilic trans-dimerisation with E-cadherin on adjacent cells, forming the molecular basis of epithelial cell-cell adhesion.
Reason: Core CDH1 biological process — homophilic cell-cell adhesion via the ectodomain strand-swap mechanism is the defining activity of E-cadherin. IEA batch (batch 3 of #348).
Supporting Evidence:
file:human/CDH1/CDH1-deep-research-falcon.md
**homophilic trans-binding** is driven primarily by the **EC1 domain** and proceeds through an **X-dimer intermediate** followed by formation of a stable **strand-swapped dimer**, in which a **tryptophan side chain from one EC1 inserts into a hydrophobic pocket** of the opposing EC1
|
|
GO:0016020
membrane
|
IEA
GO_REF:0000002 |
MARK AS OVER ANNOTATED |
Summary: IEA from InterPro2GO (GO_REF:0000002): CDH1 is a single-pass transmembrane glycoprotein and is associated with membranes. However, GO:0016020 membrane is a broad parent term. The precise CC annotations for CDH1 are GO:0005886 plasma membrane (core, ACCEPTed) and GO:0005912 adherens junction. The generic membrane annotation does not add information beyond the more specific terms.
Reason: GO:0016020 membrane is an uninformative broad parent term — CDH1 is a single-pass transmembrane protein but the informative CC terms are GO:0005886 plasma membrane and GO:0005912 adherens junction (both ACCEPTed elsewhere); the generic membrane term adds no annotation value. Consistent with the MARK_AS_OVER_ANNOTATED treatment of the equally generic GO:0005737 cytoplasm rows. Action reconciled with the IDA GO:0016020 row in this file (#348).
|
|
GO:0030054
cell junction
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: IEA from HGNC (GO_REF:0000117): CDH1 localizes to cell junctions. However, GO:0030054 cell junction is a broad parent term; the more specific and informative CC annotation is GO:0005912 adherens junction (ACCEPTed in this file), which is the precise junction type where E-cadherin resides and functions.
Reason: Broad parent CC — CDH1 localises to cell junctions but the precise junction type is the adherens junction (GO:0005912, accepted elsewhere); the broad parent term adds no annotation value. IEA batch (batch 3 of #348).
|
|
GO:0030057
desmosome
|
IEA
GO_REF:0000044 |
KEEP AS NON CORE |
Summary: IEA from UniProt-GOA (GO_REF:0000044, the UniProtKB Subcellular Location keyword-to-GO mapping — not generic cadherin-family domain mapping): CDH1/E-cadherin localizes to desmosomes. UniProt P12830 curates "Cell junction, desmosome" as an experimentally-supported subcellular location (ECO:0000269|PubMed:25208567, PubMed:29999492, PubMed:33596089), and E-cadherin plays a role in the early stages of desmosome cell-cell junction formation by facilitating recruitment of DSG2 and DSP to desmosome plaques (PubMed:29999492). CDH1 is not itself a desmosomal cadherin (those are the desmogleins/desmocollins), but its desmosome localization and early-assembly role are genuine biology, not an over-annotation. This is peripheral to the core E-cadherin function at the adherens junction (GO:0005912, ACCEPTed in this file). Two IDA annotations on this term (PMID:33596089, PMID:29999492) and an IMP on GO:0002159 desmosome assembly (PMID:29999492) are PENDING for review in a later batch and should be reviewed consistently as KEEP_AS_NON_CORE.
Reason: GO_REF:0000044 propagates UniProt's curated, experimentally-supported "Cell junction, desmosome" subcellular location (ECO:0000269|PubMed:25208567/29999492/33596089) — it is not generic domain mapping, and the desmosome localization plus early-desmosome-assembly role are genuine but peripheral to the core adherens-junction function of E-cadherin. Corrects the prior MARK_AS_OVER_ANNOTATED decision after a UniProt fact-check (see issue #348). IEA batch (batch 3 of #348) follow-up.
|
|
GO:0034329
cell junction assembly
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: IEA from HGNC (GO_REF:0000117): CDH1 participates in cell junction assembly — E-cadherin nucleates adherens junction assembly and via the catenin complex templates subsequent tight junction assembly. GO:0034329 cell junction assembly is valid but is a broad parent of GO:0007043 cell-cell junction assembly (already ACCEPTed via IBA in this file).
Reason: Valid but broad parent BP — CDH1 participates in cell junction assembly but the precise term GO:0007043 cell-cell junction assembly is already ACCEPTed via IBA; broad parent adds no annotation value. IEA batch (batch 3 of #348).
|
|
GO:0098609
cell-cell adhesion
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: IEA from InterPro2GO (GO_REF:0000002): Cell-cell adhesion is the core biological process of CDH1/E-cadherin — the protein mediates calcium-dependent homophilic cell-cell adhesion between adjacent epithelial cells. Consistent with GO:0007155 cell adhesion (also ACCEPTed) and GO:0044331 cell-cell adhesion mediated by cadherin (ACCEPTed via IBA in this file).
Reason: Core CDH1 biological process — cell-cell adhesion is the defining function of E-cadherin; consistent with GO:0044331 (IBA ACCEPT) and GO:0007155 (IEA ACCEPT). IEA batch (batch 3 of #348).
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GO:0005515
protein binding
|
IPI
PMID:11401320 FGF-1 and FGF-2 modulate the E-cadherin/catenin system in pa... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:11401320 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:12526809 Structure of internalin, a major invasion protein of Listeri... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:12526809 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:15695390 E-cadherin phosphorylation by protein kinase D1/protein kina... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:15695390 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:16212417 Biosensor-based micro-affinity purification for the proteomi... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:16212417 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:16983094 The von Hippel-Lindau tumor suppressor gene product represse... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:16983094 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:17220478 Proteomics analysis of the interactome of N-myc downstream r... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:17220478 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:17237808 Helicobacter pylori CagA interacts with E-cadherin and dereg... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:17237808 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:17274640 A limited screen for protein interactions reveals new roles ... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:17274640 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:17715295 Thermodynamically reengineering the listerial invasion compl... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:17715295 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:18093941 EPLIN mediates linkage of the cadherin catenin complex to F-... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:18093941 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:18593713 Smad7 stabilizes beta-catenin binding to E-cadherin complex ... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:18593713 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:19016843 Molecular basis of actin reorganization promoted by binding ... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:19016843 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:19604117 CagA associates with c-Met, E-cadherin, and p120-catenin in ... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:19604117 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:19732724 The Tensin-3 protein, including its SH2 domain, is phosphory... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:19732724 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:20802534 Hypoxia and cell cycle regulation of the von Hippel-Lindau t... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:20802534 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:20951947 Pharmacologic inhibition of the anaphase-promoting complex i... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:20951947 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:21685945 Rack1 promotes epithelial cell-cell adhesion by regulating E... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:21685945 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:22056988 Nuclear PKM2 regulates β-catenin transactivation upon EGFR a... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22056988 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:22158051 Tumor suppressor Alpha B-crystallin (CRYAB) associates with ... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22158051 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:22252131 Structure of a novel phosphotyrosine-binding domain in Hakai... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22252131 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:22750944 Centralspindlin and α-catenin regulate Rho signalling at the... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22750944 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:24189400 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:24424122 Rescue of wild-type E-cadherin expression from nonsense-muta... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:24424122 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0005515
protein binding
|
IPI
PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:24658140 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0005515
protein binding
|
IPI
PMID:25241761 Using an in situ proximity ligation assay to systematically ... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:25241761 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0005515
protein binding
|
IPI
PMID:25344754 ASPP2 controls epithelial plasticity and inhibits metastasis... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:25344754 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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|
GO:0005515
protein binding
|
IPI
PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:31980649 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0005515
protein binding
|
IPI
PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:32814053 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0005515
protein binding
|
IPI
PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:33961781 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0005515
protein binding
|
IPI
PMID:34591612 A protein interaction landscape of breast cancer. |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:34591612 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0005515
protein binding
|
IPI
PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:35271311 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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GO:0042802
identical protein binding
|
IPI
PMID:19114658 Resolving cadherin interactions and binding cooperativity at... |
ACCEPT |
Summary: CDH1 homodimerization documented by single-molecule force spectroscopy (Zhang et al. 2009, PNAS). This study directly measured E-cadherin trans-dimerization at the single-molecule level, confirming homophilic binding between CDH1 ectodomains and characterizing binding cooperativity. CDH1 identical protein binding is the molecular basis of homophilic cadherin-mediated cell adhesion.
Reason: CDH1 homodimerization (identical protein binding) is the molecular basis of homophilic cadherin adhesion. This is a well-established, specific, and biologically meaningful annotation — unlike the generic GO:0005515 protein binding rows removed in batch 1. UniProt documents CDH1 as a disulfide-linked homodimer (PubMed:11856755). ACCEPT.
|
|
GO:0042802
identical protein binding
|
IPI
PMID:19646884 Characterizing the initial encounter complex in cadherin adh... |
ACCEPT |
Summary: CDH1 homodimerization detected by IntAct-curated physical interaction experiment (PMID:19646884). CDH1 identical protein binding reflects the well-established homophilic trans-dimerization mechanism that underlies cadherin-mediated cell-cell adhesion. UniProt documents CDH1 as a disulfide-linked homodimer.
Reason: CDH1 homodimerization (identical protein binding) is the molecular basis of homophilic cadherin adhesion. This is a well-established, specific, and biologically meaningful annotation — unlike the generic GO:0005515 protein binding rows removed in batch 1. UniProt documents CDH1 as a disulfide-linked homodimer (PubMed:11856755). ACCEPT.
|
|
GO:0042802
identical protein binding
|
IPI
PMID:21300292 The extracellular architecture of adherens junctions reveale... |
ACCEPT |
Summary: CDH1 homodimerization detected by IntAct-curated physical interaction experiment (PMID:21300292). CDH1 identical protein binding reflects the well-established homophilic trans-dimerization mechanism that underlies cadherin-mediated cell-cell adhesion.
Reason: CDH1 homodimerization (identical protein binding) is the molecular basis of homophilic cadherin adhesion. This is a well-established, specific, and biologically meaningful annotation — unlike the generic GO:0005515 protein binding rows removed in batch 1. UniProt documents CDH1 as a disulfide-linked homodimer (PubMed:11856755). ACCEPT.
|
|
GO:0042802
identical protein binding
|
IPI
PMID:23112161 Ideal, catch, and slip bonds in cadherin adhesion. |
ACCEPT |
Summary: CDH1 homodimerization detected by IntAct-curated physical interaction experiment (PMID:23112161). CDH1 identical protein binding reflects the well-established homophilic trans-dimerization mechanism that underlies cadherin-mediated cell-cell adhesion.
Reason: CDH1 homodimerization (identical protein binding) is the molecular basis of homophilic cadherin adhesion. This is a well-established, specific, and biologically meaningful annotation — unlike the generic GO:0005515 protein binding rows removed in batch 1. UniProt documents CDH1 as a disulfide-linked homodimer (PubMed:11856755). ACCEPT.
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|
GO:0042802
identical protein binding
|
IPI
PMID:24725409 Intestinal brush border assembly driven by protocadherin-bas... |
ACCEPT |
Summary: This GO:0042802 identical-protein-binding annotation derives from an IntAct-curated interaction in Crawley et al. 2014 (PMID:24725409, Cell), a study primarily about PCDH24/MLPCDH protocadherin-based intermicrovillar adhesion driving intestinal brush border assembly. CDH1/E-cadherin is not a subject of that paper — it appears only as a positive control in a bead aggregation assay (Fig. 4B,C), where E-cadherin ectodomain-coated beads formed large aggregates, demonstrating robust homophilic adhesion. The paper explicitly excludes CDH1 from further study because E-cadherin localizes to the basolateral compartment rather than the brush border. The bead-aggregation control nonetheless confirms CDH1 homophilic (identical protein) binding, consistent with the well-established homophilic trans-dimerization mechanism underlying cadherin-mediated cell-cell adhesion.
Reason: CDH1 homodimerization (identical protein binding) is the molecular basis of homophilic cadherin adhesion — a well-established, specific, and biologically meaningful annotation, unlike the generic GO:0005515 protein binding rows removed in batch 1. PMID:24725409 is not a dedicated CDH1 study (E-cadherin serves only as a bead-aggregation positive control there), but that control is genuine supporting data, and CDH1 homophilic binding is independently established by the other GO:0042802 IPI entries — notably the single-molecule force spectroscopy of PMID:19114658 — and by UniProt, which documents CDH1 as a disulfide-linked homodimer (PubMed:11856755). ACCEPT.
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GO:0042802
identical protein binding
|
IPI
PMID:35922511 A physical wiring diagram for the human immune system. |
ACCEPT |
Summary: CDH1 homodimerization detected in a physical wiring screen of the human immune system (Shilts et al. 2022, Nature). CDH1 identical protein binding reflects the well-established homophilic trans-dimerization mechanism that underlies cadherin-mediated cell-cell adhesion; this large-scale screen provides additional proteomics-level support for CDH1 self-interaction.
Reason: CDH1 homodimerization (identical protein binding) is the molecular basis of homophilic cadherin adhesion. This is a well-established, specific, and biologically meaningful annotation — unlike the generic GO:0005515 protein binding rows removed in batch 1. UniProt documents CDH1 as a disulfide-linked homodimer (PubMed:11856755). ACCEPT.
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GO:0007416
synapse assembly
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: IEA from Ensembl (GO_REF:0000107): Synapse assembly is a neural cadherin function attributed to CDH1 by Ensembl electronic propagation from neural cadherin subfamilies. E-cadherin has documented roles at neuronal synapses in neural tissue contexts, but this is a tissue-specific non-core context for canonical epithelial CDH1. Consistent with the IBA annotation on this same term (KEEP_AS_NON_CORE) in this file.
Reason: Tissue/cell-type-specific neuronal context rather than a core epithelial CDH1 function; consistent with IBA KEEP_AS_NON_CORE on this term. IEA batch (batch 3 of #348).
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GO:0008013
beta-catenin binding
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: IEA from UniProt keyword mapping (GO_REF:0000120): Beta-catenin binding by the CDH1 cytoplasmic tail is the canonical molecular mechanism of the cadherin-catenin complex. The E-cadherin cytoplasmic domain directly binds beta-catenin (CTNNB1); this interaction links the cadherin to the actin cytoskeleton via alpha-catenin and is the basis of the adherens junction. Already ACCEPTed for the IBA annotation in this file.
Reason: Core CDH1 molecular function — beta-catenin binding by the cytoplasmic domain is the canonical interaction of the cadherin-catenin complex; consistent with IBA ACCEPT on this term. IEA batch (batch 3 of #348).
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GO:0009410
response to xenobiotic stimulus
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: IEA from Ensembl (GO_REF:0000107): There is no established direct role for CDH1/E-cadherin in responding to xenobiotic stimuli. CDH1 expression may change after toxic/xenobiotic exposure in some organisms as a secondary transcriptional effect, but this does not constitute a direct CDH1 molecular function in xenobiotic sensing or response.
Reason: No direct CDH1 role in xenobiotic response; Ensembl IEA likely propagated from toxicology studies where CDH1 expression changed as a secondary effect; not a core CDH1 function. IEA batch (batch 3 of #348).
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GO:0009636
response to toxic substance
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: IEA from Ensembl (GO_REF:0000107): Response to toxic substance is not a CDH1 core function. CDH1/E-cadherin is a cell-cell adhesion molecule; its expression may change under toxic conditions as a secondary effect but this does not constitute a direct CDH1 molecular function. Co-propagated with GO:0009410 from the same Ensembl ortholog source.
Reason: No direct CDH1 role in toxic-substance response; co-propagated with GO:0009410 from Ensembl; secondary CDH1 expression changes under toxic conditions are not a core CDH1 function. IEA batch (batch 3 of #348).
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GO:0021983
pituitary gland development
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: IEA from Ensembl (GO_REF:0000107): Pituitary gland development is not a core CDH1 function. CDH1/E-cadherin may be expressed in pituitary cells but pituitary gland development is a tissue-specific, context-dependent association rather than a defining function of E-cadherin. Likely propagated from a pituitary-expressing cadherin ortholog annotation.
Reason: Tissue-specific context not representing a core CDH1 function; CDH1 may be expressed in pituitary but pituitary gland development is not a defining E-cadherin activity; Ensembl electronic propagation. IEA batch (batch 3 of #348).
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GO:0030517
negative regulation of axon extension
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: IEA from Ensembl (GO_REF:0000107): Negative regulation of axon extension is a neural cadherin function (N-cadherin/CDH2 and type II cadherins mediate contact-inhibition of axon extension). CDH1/E-cadherin is primarily an epithelial adhesion molecule; this Ensembl IEA annotation was propagated from a neural cadherin subfamily annotation.
Reason: Neural cadherin function attributed to epithelial CDH1 by Ensembl propagation; negative regulation of axon extension is mediated by neural cadherins (CDH2 etc.), not CDH1. IEA batch (batch 3 of #348).
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GO:0031175
neuron projection development
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: IEA from Ensembl (GO_REF:0000107): Neuron projection development is a neural cadherin function. CDH1/E-cadherin is an epithelial cell adhesion molecule; neuron projection development is not a core CDH1 function. Propagated from neural cadherin annotations, analogous to the synapse assembly and axon extension IEA annotations in this batch.
Reason: Neural cadherin function attributed to epithelial CDH1 by Ensembl propagation; neuron projection development is not a core E-cadherin function. IEA batch (batch 3 of #348).
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|
GO:0071503
response to heparin
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: IEA from Ensembl (GO_REF:0000107): Response to heparin is not a CDH1 core function. CDH1/E-cadherin adhesion does not depend on heparin and there is no established CDH1-specific role in heparin sensing or response. This Ensembl IEA annotation likely reflects non-specific propagation from another cadherin family member or indirect experimental observation.
Reason: No established CDH1 role in heparin response; Ensembl electronic propagation from a non-CDH1 cadherin or indirect experimental observation. IEA batch (batch 3 of #348).
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|
GO:0098794
postsynapse
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: IEA from Ensembl (GO_REF:0000107): The postsynapse is a neural compartment at excitatory and inhibitory synapses. CDH1/E-cadherin is not a canonical postsynaptic protein; this GO location is associated with neural cadherins (CDH2) and protocadherins. This Ensembl IEA annotation was propagated from neural cadherin annotations.
Reason: Neural synaptic CC attributed to epithelial CDH1 by Ensembl propagation; CDH1 is not a postsynaptic component; this location is specific to neural/synaptic cadherins. IEA batch (batch 3 of #348).
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GO:0098978
glutamatergic synapse
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: IEA from Ensembl (GO_REF:0000107): The glutamatergic synapse is a specific neural compartment. CDH1/E-cadherin is not a glutamatergic synapse component; this is a neural cadherin function. Propagated from neural cadherin family annotations in the same batch as GO:0098794 postsynapse and GO:0007416 synapse assembly.
Reason: Neural synaptic CC attributed to epithelial CDH1 by Ensembl propagation; CDH1 is not a glutamatergic synapse component. IEA batch (batch 3 of #348).
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|
GO:0099576
regulation of protein catabolic process at postsynapse, modulating synaptic transmission
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: IEA from Ensembl (GO_REF:0000107): Regulation of protein catabolic process at the postsynapse is a highly specific neural synaptic process. CDH1/E-cadherin is not a canonical synaptic protein and does not regulate postsynaptic protein catabolism. This IEA annotation was propagated from neural cadherin annotations.
Reason: Highly specific neural synaptic process attributed to epithelial CDH1 by Ensembl propagation; CDH1 does not regulate postsynaptic protein catabolism. IEA batch (batch 3 of #348).
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|
GO:0140459
response to Gram-positive bacterium
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: IEA from Ensembl (GO_REF:0000107): While CDH1/E-cadherin is the host receptor for Listeria monocytogenes (a Gram-positive bacterium) via the bacterial internalin InlA, this represents pathogen exploitation of a host cell-surface receptor, not a core CDH1 biological function. Annotating CDH1 as responding to Gram-positive bacteria conflates bacterial hijacking of a host receptor with an intrinsic CDH1 function.
Reason: Pathogen exploitation (Listeria InlA uses CDH1 as an invasion receptor) is not a core CDH1 function; annotating CDH1 as responding to Gram-positive bacteria conflates bacterial hijacking with intrinsic receptor function. IEA batch (batch 3 of #348).
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|
GO:1990782
protein tyrosine kinase binding
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: IEA from Ensembl (GO_REF:0000107): CDH1/E-cadherin cytoplasmic domain interactions with protein tyrosine kinases (PTKs) are documented — Src family kinases phosphorylate the CDH1 cytoplasmic tail and regulate E-cadherin adhesion, and receptor tyrosine kinases including EGFR/HER2 interact with CDH1. However, protein tyrosine kinase binding is a regulatory modulation of the core adhesion activity, not a core CDH1 molecular function. IEA evidence from Ensembl provides lower confidence than direct experimental evidence.
Reason: CDH1 cytoplasmic tail interacts with Src/EGFR/HER2 PTKs modulating E-cadherin function, but PTK binding is a regulatory modulation rather than a core CDH1 MF; lower-confidence Ensembl IEA. IEA batch (batch 3 of #348).
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|
GO:0005576
extracellular region
|
IDA
PMID:34742300 Identification of Desmoglein-2 as a novel target of Helicoba... |
ACCEPT |
Summary: IDA from PMID:34742300 (Bernegger et al. 2021): H. pylori HtrA protease cleaves E-cadherin's extracellular ectodomain, directly confirming the extracellular localization of E-cadherin's cadherin repeat domains. The ectodomain's extracellular region is core to E-cadherin's homophilic trans-adhesion mechanism.
|
|
GO:0005886
plasma membrane
|
IDA
PMID:36309486 Desmoglein-2 is important for islet function and β-cell surv... |
ACCEPT |
Summary: IDA from PMID:36309486 (Myo Min KK et al. 2022): E-cadherin plasma membrane localization confirmed in islet/epithelial context. Plasma membrane is the canonical and core localization for functional E-cadherin mediating cell-cell adhesion.
|
|
GO:0030057
desmosome
|
IDA
PMID:33596089 Regulation of intestinal epithelial intercellular adhesion a... |
KEEP AS NON CORE |
Summary: IDA from PMID:33596089 (Raya-Sandino et al. 2021): E-cadherin is detected at desmosomes in intestinal epithelial cells in the context of desmocollin-2 regulation of adhesion. Consistent with the direct evidence in PMID:29999492 that E-cadherin is enriched in nascent desmosomes but diminishes as desmosomes mature; E-cadherin facilitates desmosome assembly but is not a stable resident of mature desmosome structures.
Reason: E-cadherin appears at nascent desmosomal contacts as part of junction initiation (its trans-adhesion recruits desmosomal cadherins), but mature desmosomes are composed primarily of desmoglein/desmocollin — not E-cadherin. Desmosomal localization is a transient non-core CC. Batch 5 of #348.
|
|
GO:0005794
Golgi apparatus
|
IDA
GO_REF:0000052 |
KEEP AS NON CORE |
Summary: IDA from GO_REF:0000052 (UniProtKB keyword-to-GO mapping): E-cadherin transits through the Golgi apparatus during biosynthesis and post-translational N-glycosylation (critical for correct E-cadherin folding and function). Golgi localization is a real but non-core CC reflecting biosynthetic/trafficking transit.
Reason: Golgi localization is part of the E-cadherin biosynthetic pathway, not its core adhesive function site. Core CC is plasma membrane/adherens junction. Batch 5 of #348.
|
|
GO:0005886
plasma membrane
|
IDA
GO_REF:0000052 |
ACCEPT |
Summary: IDA from GO_REF:0000052 (UniProtKB keyword-to-GO mapping): Plasma membrane localization is the canonical site for functional E-cadherin. E-cadherin is a type-I transmembrane protein whose extracellular cadherin domains mediate homophilic trans-adhesion at the plasma membrane — unambiguously core CC.
|
|
GO:0030054
cell junction
|
IDA
GO_REF:0000052 |
KEEP AS NON CORE |
Summary: IDA from GO_REF:0000052 (UniProtKB keyword-to-GO mapping): E-cadherin is the canonical adhesion receptor at cell-cell junctions. GO:0030054 cell junction is the broad parent of GO:0005912 adherens junction; it is a valid CC annotation but the precise core localization is the adherens junction, ACCEPTed elsewhere in this file.
Reason: Broad parent CC — GO:0030054 cell junction is the direct parent of GO:0005912 adherens junction, the precise core CC for E-cadherin (ACCEPTed in this file). A real but non-core annotation: the informative term is the specific adherens junction. Action reconciled with the IEA and TAS GO:0030054 rows in this file (#348).
|
|
GO:0005768
endosome
|
EXP
PMID:15689490 Rab11 in recycling endosomes regulates the sorting and basol... |
KEEP AS NON CORE |
Summary: EXP from PMID:15689490 (Lock and Stow 2005): Rab11-positive recycling endosomes are an intermediate compartment for post-Golgi trafficking and exocytic delivery of E-cadherin to the basolateral plasma membrane. Endosomal localization is real and functionally important for E-cadherin surface delivery, but represents trafficking transit rather than the core functional site.
Reason: E-cadherin transits through recycling endosomes during biosynthetic delivery to the basolateral membrane — a real but non-core CC. Core localization is at the plasma membrane/adherens junction. Batch 5 of #348.
|
|
GO:0005886
plasma membrane
|
EXP
PMID:19403558 The role of N-acetylglucosaminyltransferase III and V in the... |
ACCEPT |
Summary: EXP from PMID:19403558 (Pinho et al. 2009): GnT-III knockdown causes membrane de-localization of E-cadherin leading to cytoplasmic accumulation, confirming that plasma membrane is the normal core localization of E-cadherin. Wild-type E-cadherin is robustly present at the plasma membrane.
|
|
GO:0098631
cell adhesion mediator activity
|
IDA
PMID:11976333 Galpha12 and Galpha13 negatively regulate the adhesive funct... |
ACCEPT |
Summary: IDA from PMID:11976333 (Meigs et al. 2002): Galpha12/13 negatively regulate the adhesive functions of E-cadherin. The cell-adhesion-mediator-activity annotation is directly supported — E-cadherin functions as a cell adhesion mediator, and Galpha12/13 block cadherin-mediated cell adhesion in K562 and breast cancer cells. Cell adhesion mediator activity is core MF for E-cadherin.
|
|
GO:0005765
lysosomal membrane
|
TAS
Reactome:R-HSA-9935547 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9935547): Endocytosed, ubiquitinated CDH1/E-cadherin is sorted to lysosomes for degradation as part of junction turnover and downregulation. Lysosomal localization is real but reflects CDH1 degradative turnover rather than the site of its core adhesion function.
Reason: Real but non-core CC -- lysosomal localization reflects CDH1 degradative turnover; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005765
lysosomal membrane
|
TAS
Reactome:R-HSA-9935552 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9935552): Endocytosed, ubiquitinated CDH1/E-cadherin is sorted to lysosomes for degradation as part of junction turnover and downregulation. Lysosomal localization is real but reflects CDH1 degradative turnover rather than the site of its core adhesion function.
Reason: Real but non-core CC -- lysosomal localization reflects CDH1 degradative turnover; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9934752 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9934752): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9934753 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9934753): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0031901
early endosome membrane
|
TAS
Reactome:R-HSA-9934752 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9934752): CDH1/E-cadherin undergoes clathrin-mediated endocytosis and is trafficked through early endosomes during junction remodelling, recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination). Early endosome localization is real but reflects CDH1 trafficking/turnover rather than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA endosome annotation in this file.
Reason: Real but non-core CC -- early endosome localization reflects CDH1 endocytic trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0031901
early endosome membrane
|
TAS
Reactome:R-HSA-9935552 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9935552): CDH1/E-cadherin undergoes clathrin-mediated endocytosis and is trafficked through early endosomes during junction remodelling, recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination). Early endosome localization is real but reflects CDH1 trafficking/turnover rather than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA endosome annotation in this file.
Reason: Real but non-core CC -- early endosome localization reflects CDH1 endocytic trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9934751 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9934751): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9934755 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9934755): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9766227 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9766227): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9934584 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9934584): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0031901
early endosome membrane
|
TAS
Reactome:R-HSA-9766223 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9766223): CDH1/E-cadherin undergoes clathrin-mediated endocytosis and is trafficked through early endosomes during junction remodelling, recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination). Early endosome localization is real but reflects CDH1 trafficking/turnover rather than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA endosome annotation in this file.
Reason: Real but non-core CC -- early endosome localization reflects CDH1 endocytic trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0031901
early endosome membrane
|
TAS
Reactome:R-HSA-9934584 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9934584): CDH1/E-cadherin undergoes clathrin-mediated endocytosis and is trafficked through early endosomes during junction remodelling, recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination). Early endosome localization is real but reflects CDH1 trafficking/turnover rather than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA endosome annotation in this file.
Reason: Real but non-core CC -- early endosome localization reflects CDH1 endocytic trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9766219 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9766219): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9816278 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9816278): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9817325 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9817325): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9817330 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9817330): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9934294 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9934294): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9934410 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9934410): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9934411 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9934411): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9934486 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9934486): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0000139
Golgi membrane
|
TAS
Reactome:R-HSA-9816275 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9816275): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.
Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0000139
Golgi membrane
|
TAS
Reactome:R-HSA-9816278 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9816278): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.
Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0000139
Golgi membrane
|
TAS
Reactome:R-HSA-9934330 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9934330): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.
Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0000139
Golgi membrane
|
TAS
Reactome:R-HSA-9935209 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9935209): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.
Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005796
Golgi lumen
|
TAS
Reactome:R-HSA-9816275 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9816275): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.
Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0000139
Golgi membrane
|
TAS
Reactome:R-HSA-9816273 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9816273): CDH1/E-cadherin transits and is further processed/glycosylated in the Golgi apparatus en route from the ER to the plasma membrane. Golgi localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function. Consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.
Reason: Real but non-core CC -- the Golgi is a transient biosynthetic/processing compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9816273 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9816273): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9933194 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9933194): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9933380 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9933380): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9816277 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9816277): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9932352 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9932352): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9932913 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9932913): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9932988 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9932988): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9816276 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9816276): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9932344 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9932344): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005788
endoplasmic reticulum lumen
|
TAS
Reactome:R-HSA-9932162 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9932162): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9932162 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9932162): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0002159
desmosome assembly
|
IMP
PMID:29999492 E-cadherin binds to desmoglein to facilitate desmosome assem... |
KEEP AS NON CORE |
Summary: IMP from PMID:29999492 (Shafraz et al. 2018): E-cadherin cis-dimerization site (Leu-175) is required for efficient desmoglein-2 (Dsg2) recruitment and desmosome assembly in keratinocytes. E-cadherin facilitates desmosome assembly by initially recruiting Dsg2 via a direct Ca2+-independent heterophilic interaction, with Ecad levels in desmosomes decreasing as junctions mature.
Reason: E-cadherin's role in desmosome assembly is real but non-core — it facilitates early desmosomal junction initiation as an auxiliary function. E-cadherin's primary role is adherens junction formation and homophilic cadherin-mediated cell-cell adhesion. Batch 5 of #348.
|
|
GO:0030057
desmosome
|
IDA
PMID:29999492 E-cadherin binds to desmoglein to facilitate desmosome assem... |
KEEP AS NON CORE |
Summary: IDA from PMID:29999492 (Shafraz et al. 2018): Super-resolution imaging shows E-cadherin is enriched in nascent desmosomes (1 hr after Ca2+ switch), declining 50% as desmosomes mature by 18 hr. E-cadherin transiently localizes to nascent desmosomal sites where it recruits Dsg2, but is displaced from mature desmosomes.
Reason: Desmosomal localization is transient and non-core for E-cadherin — it functions to nucleate early junction formation but is not a permanent resident of mature desmosomes (desmoglein/desmocollin are the stable components). Core CC is plasma membrane/adherens junction. Batch 5 of #348.
|
|
GO:1903829
positive regulation of protein localization
|
IMP
PMID:29999492 E-cadherin binds to desmoglein to facilitate desmosome assem... |
MARK AS OVER ANNOTATED |
Summary: IMP from PMID:29999492 (Shafraz et al. 2018): E-cadherin promotes Dsg2 localization to intercellular contacts, supporting positive regulation of protein localization. However, GO:1903829 (positive regulation of protein localization) is too general — this specific function is better captured by the co-annotated GO:0002159 (desmosome assembly) from the same paper and same experiment.
Reason: GO:1903829 is an overly broad parent term; the actual function is promotion of desmosomal cadherin (Dsg2) localization to nascent junctions, captured more specifically by GO:0002159 desmosome assembly. Per CLAUDE.md: prefer informative specific terms. Batch 5 of #348.
|
|
GO:0008013
beta-catenin binding
|
IPI
PMID:18593713 Smad7 stabilizes beta-catenin binding to E-cadherin complex ... |
ACCEPT |
Summary: IPI from PMID:18593713 (Tang et al. 2008): Smad7 stabilizes the beta-catenin-E-cadherin complex at the plasma membrane. E-cadherin physically binds beta-catenin through its cytoplasmic tail — this is the canonical CDH1-CTNNB1 armadillo repeat interaction that links E-cadherin to the actin cytoskeleton via alpha-catenin. Beta-catenin binding is core MF for E-cadherin.
|
|
GO:0044331
cell-cell adhesion mediated by cadherin
|
IDA
PMID:18593713 Smad7 stabilizes beta-catenin binding to E-cadherin complex ... |
ACCEPT |
Summary: IDA from PMID:18593713 (Tang et al. 2008): Smad7 promotes cell-cell adhesion by increasing the beta-catenin-E-cadherin complex level at the plasma membrane. Cell-cell adhesion mediated by cadherin is the defining core BP for E-cadherin, confirmed in this study through perturbation of the cadherin complex.
|
|
GO:0005515
protein binding
|
IPI
PMID:22294297 Non-junctional human desmoglein 3 acts as an upstream regula... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22294297 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0005737
cytoplasm
|
IDA
PMID:22294297 Non-junctional human desmoglein 3 acts as an upstream regula... |
MARK AS OVER ANNOTATED |
Summary: IDA from PMID:22294297 (Tsang et al. 2012): The paper studies how non-junctional Dsg3 regulates Src and E-cadherin junction assembly. GO:0005737 (cytoplasm) for E-cadherin is over-annotated — E-cadherin has a cytoplasmic tail engaged at the adherens junction, but annotating the entire cytoplasm as E-cadherin's CC is non-informative and too general. The more informative and specific CC is GO:0005912 (adherens junction), which is also annotated from this paper.
Reason: GO:0005737 cytoplasm is a highly non-specific CC for a transmembrane protein like E-cadherin whose cytoplasmic domain localizes to the adherens junction plaque; the adherens junction annotation from the same study captures the relevant specificity. Batch 5 of #348.
|
|
GO:0005912
adherens junction
|
IDA
PMID:22294297 Non-junctional human desmoglein 3 acts as an upstream regula... |
ACCEPT |
Summary: IDA from PMID:22294297 (Tsang et al. 2012): Non-junctional Dsg3 regulates Src and E-cadherin adherens junction formation. Adherens junction is the core CC for functional E-cadherin — E-cadherin organizes with beta-catenin, alpha-catenin, and p120-catenin at adherens junctions to mediate epithelial cell-cell adhesion.
|
|
GO:0005912
adherens junction
|
IDA
PMID:18343367 P120-catenin is a novel desmoglein 3 interacting partner: id... |
ACCEPT |
Summary: IDA from PMID:18343367: Adherens junction localization of E-cadherin confirmed experimentally. Core CC for E-cadherin — adherens junctions are the primary site of E-cadherin-mediated cell-cell adhesion in epithelial cells.
|
|
GO:0005886
plasma membrane
|
IDA
PMID:20859650 E-cadherin and plakoglobin recruit plakophilin3 to the cell ... |
ACCEPT |
Summary: IDA from PMID:20859650: Plasma membrane localization of E-cadherin confirmed. Core CC — E-cadherin is a type-I transmembrane protein that localizes to the basolateral plasma membrane of epithelial cells where it mediates homophilic adhesion.
|
|
GO:0005912
adherens junction
|
IDA
PMID:27760340 Macrophage Epithelial Reprogramming Underlies Mycobacterial ... |
ACCEPT |
Summary: IDA from PMID:27760340: Adherens junction localization confirmed experimentally. Core CC for E-cadherin.
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9768614 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9768614): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-9768618 |
KEEP AS NON CORE |
Summary: TAS from Reactome (R-HSA-9768618): As a secretory-pathway transmembrane glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated, and folded within the endoplasmic reticulum before transport to the Golgi and plasma membrane. ER localization is real but represents a transient biosynthetic/processing compartment rather than the site of CDH1 core adhesion function.
Reason: Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding compartment for CDH1 maturation; core localization and function are at the plasma membrane and adherens junction. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005515
protein binding
|
IPI
PMID:11790773 Protein binding and functional characterization of plakophil... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:11790773 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0005515
protein binding
|
IPI
PMID:10725230 ARVCF localizes to the nucleus and adherens junction and is ... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:10725230 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0034332
adherens junction organization
|
IMP
PMID:21724833 Identification of PTPN23 as a novel regulator of cell invasi... |
ACCEPT |
Summary: IMP from PMID:21724833 (Lin et al. 2011): PTPN23 knockdown increases E-cadherin internalization and impairs adherens junction integrity, identifying E-cadherin as a key regulator/component of adherens junction organization. E-cadherin is the core structural component whose proper trafficking and membrane retention is essential for adherens junction maintenance.
|
|
GO:0005515
protein binding
|
IPI
PMID:31473225 Sperm Flagellar 1 Binds Actin in Intestinal Epithelial Cells... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:31473225 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0010468
regulation of gene expression
|
IMP
PMID:19403558 The role of N-acetylglucosaminyltransferase III and V in the... |
MARK AS OVER ANNOTATED |
Summary: IMP from PMID:19403558 (Pinho et al. 2009): Wild-type E-cadherin regulates MGAT3 (GnT-III) gene transcription. While E-cadherin can influence downstream gene expression programs (e.g., via beta-catenin sequestration or epithelial differentiation signaling), GO:0010468 (regulation of gene expression) is far too general an annotation for this specific MGAT3-regulatory phenotype. If retained, a more specific term like 'regulation of gene transcription by E-cadherin' would be needed, but no such specific GO term exists; the general parent is non-informative.
Reason: Over-annotated: the specific CDH1 regulatory activity on MGAT3 transcription is a very narrow context-specific function, not a general gene-expression regulatory role of E-cadherin. GO:0010468 is too broad to be informative for curation. Batch 5 of #348.
|
|
GO:0030336
negative regulation of cell migration
|
IMP
PMID:16882694 Regulation of epithelial wound closure and intercellular adh... |
ACCEPT |
Summary: IMP from PMID:16882694: E-cadherin mutant phenotype supports its role as negative regulator of cell migration. E-cadherin is a well-established suppressor of epithelial cell migration and invasion — loss of E-cadherin is a hallmark of EMT and tumor invasion. This is a core BP function of E-cadherin.
Supporting Evidence:
file:human/CDH1/CDH1-deep-research-falcon.md
EMT programs repress E‑cadherin and that such loss contributes to invasion and metastasis
|
|
GO:0045296
cadherin binding
|
HDA
PMID:25468996 E-cadherin interactome complexity and robustness resolved by... |
ACCEPT |
Summary: HDA from PMID:25468996 (Guo et al. 2014): E-cadherin interactome quantitative proteomics using proximity biotinylation (BioID). Cadherin binding is confirmed — E-cadherin mediates homophilic trans-adhesion by binding to E-cadherin on opposing cells (strand-swap dimer) and to other cadherin family members. Cadherin binding is core MF for E-cadherin.
|
|
GO:0042307
positive regulation of protein import into nucleus
|
IDA
PMID:16338932 E-cadherin-dependent transcriptional control of apolipoprote... |
KEEP AS NON CORE |
Summary: IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin-dependent cell-cell adhesion controls nuclear abundance of HNF4alpha in Caco-2 enterocytes, linking E-cadherin engagement to increased nuclear import of this transcription factor. This is an indirect downstream signaling consequence of E-cadherin adhesion, not a direct E-cadherin MF.
Reason: Positive regulation of protein import into nucleus is an indirect consequence of E-cadherin-mediated adhesion signaling (via HNF4alpha redistribution), not a core CDH1 function. E-cadherin's primary role is cell-cell adhesion at adherens junctions. Batch 5 of #348.
|
|
GO:0005886
plasma membrane
|
IDA
PMID:28301459 Blepharocheilodontic syndrome is a CDH1 pathway-related diso... |
ACCEPT |
Summary: IDA from PMID:28301459: Plasma membrane localization of E-cadherin confirmed experimentally. Core CC.
|
|
GO:0030054
cell junction
|
IDA
PMID:28169360 Loss of DLG5 promotes breast cancer malignancy by inhibiting... |
KEEP AS NON CORE |
Summary: IDA from PMID:28169360: Cell junction localization of E-cadherin confirmed experimentally. GO:0030054 cell junction is the broad parent of GO:0005912 adherens junction; the precise core CC is the adherens junction, ACCEPTed elsewhere in this file.
Reason: Broad parent CC — GO:0030054 cell junction is the direct parent of GO:0005912 adherens junction, the precise core CC for E-cadherin (ACCEPTed in this file). A real but non-core annotation: the informative term is the specific adherens junction. Action reconciled with the IEA and TAS GO:0030054 rows in this file (#348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8876948 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-8876948): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8876993 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-8876993): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8877003 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-8877003): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005912
adherens junction
|
IDA
PMID:24046456 Flotillin microdomains stabilize cadherins at cell-cell junc... |
ACCEPT |
Summary: IDA from PMID:24046456 (Guillaume et al. 2013): Flotillins stabilize E-cadherin at cell-cell junctions; flotillin and E-cadherin complexes co-localize at CCJs. Adherens junction is confirmed as core CC for E-cadherin.
|
|
GO:0016600
flotillin complex
|
IDA
PMID:24046456 Flotillin microdomains stabilize cadherins at cell-cell junc... |
MARK AS OVER ANNOTATED |
Summary: IDA from PMID:24046456 (Guillaume et al. 2013): E-cadherin and flotillin 1/2 are 'constitutively associated at the plasma membrane' and co-localize at cell-cell junctions. E-cadherin associates with flotillin-containing lipid raft microdomains at CCJs; flotillins are required for cadherin stabilization at CCJs.
Reason: E-cadherin is recruited to flotillin-1/-2 membrane microdomains that stabilize cadherins at cell-cell junctions (PMID:24046456), but it is not a structural subunit of the flotillin complex. The part_of GO:0016600 qualifier overstates this microdomain association as constitutive complex membership — not entirely wrong but an over-annotation. Action reconciled with the IBA GO:0016600 row in this file (#348).
|
|
GO:0030027
lamellipodium
|
IDA
PMID:24046456 Flotillin microdomains stabilize cadherins at cell-cell junc... |
MARK AS OVER ANNOTATED |
Summary: IDA from PMID:24046456 (Guillaume et al. 2013): The paper describes flotillin 1/2 as new partners of the cadherin complex that stabilize E-cadherin at cell-cell junctions (CCJs). The abstract focuses exclusively on CCJ biology: flotillins co-localize with cadherins at CCJs, are required for cadherin recruitment to CCJs, and mediate cadherin association with GM1-containing plasma membrane microdomains. Lamellipodium (GO:0030027) — an actin-rich protrusion at the leading edge of migrating cells — is mechanistically and spatially distinct from a stable epithelial CCJ. The abstract makes no mention of lamellipodia.
Reason: The paper is entirely about E-cadherin stabilization at CCJs via flotillin microdomains; the abstract contains no evidence for E-cadherin in lamellipodia. CDH1 core CC is the adherens junction/plasma membrane (both ACCEPTed in this file). Lamellipodium is a migrating-cell leading-edge structure mechanistically distinct from the stable epithelial CCJ context studied in this paper. The annotation is not supported by the abstract and is inconsistent with the paper's experimental focus. MARK_AS_OVER_ANNOTATED rather than REMOVE because full text was not accessible, but abstract evidence strongly argues against this localization.
|
|
GO:0030864
cortical actin cytoskeleton
|
IDA
PMID:24046456 Flotillin microdomains stabilize cadherins at cell-cell junc... |
KEEP AS NON CORE |
Summary: IDA from PMID:24046456 (Guillaume et al. 2013): Cadherin and flotillin complexes are associated with F-actin bundles at cell-cell junctions via flotillin microdomains. E-cadherin associates with the cortical actin cytoskeleton through catenin-actin linkages (alpha-catenin links the cadherin-catenin complex to F-actin).
Reason: Cortical actin association is mechanistically real for E-cadherin (via alpha-catenin) but represents the actin-anchoring support for adherens junctions, not a core CDH1 CC. Core CC is the adherens junction/plasma membrane. Batch 5 of #348.
|
|
GO:0050839
cell adhesion molecule binding
|
IPI
PMID:21724833 Identification of PTPN23 as a novel regulator of cell invasi... |
MARK AS OVER ANNOTATED |
Summary: IPI from PMID:21724833 (Lin et al. 2011): E-cadherin identified as a direct substrate of PTPN23, implying physical interaction. GO:0050839 (cell adhesion molecule binding) is too general — E-cadherin's specific binding partners relevant to its adhesion function are more informatively captured by GO:0008013 (beta-catenin binding), GO:0045296 (cadherin binding), and GO:0045295 (gamma-catenin binding) already annotated in this file.
Reason: GO:0050839 cell adhesion molecule binding is uninformative relative to specific partner terms; PTPN23 is a phosphatase, not a canonical cell adhesion molecule. Per CLAUDE.md, prefer specific functional interaction terms over generic binding. Batch 5 of #348.
|
|
GO:0070062
extracellular exosome
|
HDA
PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... |
KEEP AS NON CORE |
Summary: HDA from PMID:23533145 (Principe et al. 2013): E-cadherin identified by shotgun proteomics in exosomes from expressed prostatic secretions. E-cadherin as a type-I transmembrane surface glycoprotein can be shed in membrane vesicles/exosomes; exosomal release of E-cadherin (or its ectodomain fragments) is real but represents a minor non-core aspect of E-cadherin biology.
Reason: Extracellular exosome localization is a non-core CC reflecting passive vesicular shedding or secretion of E-cadherin/ectodomain fragments. Core localization is at the plasma membrane/adherens junction in epithelial cells. HDA evidence from large-scale proteomics. Batch 5 of #348.
|
|
GO:0005515
protein binding
|
IPI
PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:23086448 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0072659
protein localization to plasma membrane
|
IMP
PMID:20859650 E-cadherin and plakoglobin recruit plakophilin3 to the cell ... |
KEEP AS NON CORE |
Summary: IMP from PMID:20859650: Mutant phenotype supports E-cadherin's role in protein localization to plasma membrane — loss of E-cadherin or related perturbation affects surface delivery. E-cadherin localization to the plasma membrane is actively regulated by trafficking machinery (Rab11, ankyrin-G, spectrin), and E-cadherin mutant phenotype informs this process.
Reason: Protein localization to plasma membrane is a real function related to E-cadherin trafficking, but it is non-core — the core BP is cell-cell adhesion and adherens junction organization, not the localization machinery itself. Batch 5 of #348.
|
|
GO:0005576
extracellular region
|
TAS
Reactome:R-HSA-3827958 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-3827958): CDH1/E-cadherin has a large N-terminal ectodomain (EC1-EC5) that occupies the extracellular space, and proteolytic shedding (e.g. by MMP9/KLK7) releases a soluble extracellular ectodomain fragment. Consistent with the extracellular region annotation ACCEPTed on IEA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the EC1-EC5 ectodomain occupies the extracellular region and the shed soluble ectodomain is an extracellular fragment; consistent with extracellular region ACCEPT on IEA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005576
extracellular region
|
TAS
Reactome:R-HSA-4224014 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-4224014): CDH1/E-cadherin has a large N-terminal ectodomain (EC1-EC5) that occupies the extracellular space, and proteolytic shedding (e.g. by MMP9/KLK7) releases a soluble extracellular ectodomain fragment. Consistent with the extracellular region annotation ACCEPTed on IEA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the EC1-EC5 ectodomain occupies the extracellular region and the shed soluble ectodomain is an extracellular fragment; consistent with extracellular region ACCEPT on IEA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-3827958 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-3827958): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-4224014 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-4224014): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-NUL-2534209 |
ACCEPT |
Summary: TAS from Reactome (R-NUL-2534209): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-202939 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-202939): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-265422 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-265422): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-419001 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-419001): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-419002 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-419002): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
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GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-5672304 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-5672304): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
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GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8876497 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-8876497): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
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GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9825774 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9825774): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-9926527 |
ACCEPT |
Summary: TAS from Reactome (R-HSA-9926527): The plasma membrane is the primary steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed on IEA and IDA evidence elsewhere in this file.
Reason: Core CDH1 cellular component -- the lateral/basolateral plasma membrane is the primary site of CDH1 localization and adhesive activity; consistent with plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome TAS localization batch (batch 4 of #348).
|
|
GO:0005515
protein binding
|
IPI
PMID:19038973 Identification of WNT/beta-CATENIN signaling pathway compone... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:19038973 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
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|
GO:0005802
trans-Golgi network
|
IMP
PMID:17620337 Ankyrin-G is a molecular partner of E-cadherin in epithelial... |
KEEP AS NON CORE |
Summary: IMP from PMID:17620337 (Kizhatil et al. 2007): Ankyrin-G and beta-2-spectrin are required for exit of E-cadherin from the trans-Golgi network in a microtubule-dependent pathway. TGN is the staging point for post-Golgi trafficking of newly synthesized E-cadherin to the lateral plasma membrane.
Reason: Trans-Golgi network localization is non-core — reflects biosynthetic trafficking transit of E-cadherin before its delivery to the lateral plasma membrane. Core CC is plasma membrane/adherens junction. Batch 5 of #348.
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|
GO:0008013
beta-catenin binding
|
IDA
PMID:17620337 Ankyrin-G is a molecular partner of E-cadherin in epithelial... |
ACCEPT |
Summary: IDA from PMID:17620337 (Kizhatil et al. 2007): Ankyrin-G binds to the cytoplasmic domain of E-cadherin at a conserved site distinct from beta-catenin; ankyrin-G recruits beta-2-spectrin to E-cadherin-beta-catenin complexes. This study provides independent experimental confirmation that E-cadherin directly binds beta-catenin (IDA from the ankyrin study, co-IP evidence). Beta-catenin binding is core MF for E-cadherin.
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|
GO:0016328
lateral plasma membrane
|
IDA
PMID:17620337 Ankyrin-G is a molecular partner of E-cadherin in epithelial... |
ACCEPT |
Summary: IDA from PMID:17620337 (Kizhatil et al. 2007): 'E-cadherin is a ubiquitous component of lateral membranes in epithelial tissues.' Ankyrin-G and beta-2-spectrin are required for accumulation of E-cadherin at the lateral membrane. Lateral plasma membrane is the core CC of E-cadherin in epithelial cells.
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|
GO:0030506
ankyrin binding
|
IPI
PMID:17620337 Ankyrin-G is a molecular partner of E-cadherin in epithelial... |
ACCEPT |
Summary: IPI from PMID:17620337 (Kizhatil et al. 2007): Ankyrin-G (ANK3) binds to the cytoplasmic domain of E-cadherin at a conserved site distinct from beta-catenin; this ankyrin-G interaction is required for lateral membrane accumulation and exit from the TGN. Ankyrin binding (GO:0030506) is a specific and informative MF — distinct from generic protein binding, ankyrin links E-cadherin to the spectrin/actin cytoskeleton.
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|
GO:0072659
protein localization to plasma membrane
|
IDA
PMID:17620337 Ankyrin-G is a molecular partner of E-cadherin in epithelial... |
KEEP AS NON CORE |
Summary: IDA from PMID:17620337 (Kizhatil et al. 2007): Ankyrin-G and beta-2-spectrin regulate E-cadherin's localization to the lateral plasma membrane; their loss causes mistargeting. E-cadherin localization to plasma membrane is real but this BP annotation captures the trafficking/targeting aspect rather than the core adhesion function.
Reason: Protein localization to plasma membrane is a mechanistic support function for E-cadherin trafficking, not its core BP. Core BP is cell-cell adhesion and adherens junction organization. Non-core context: ankyrin/spectrin-dependent lateral membrane targeting. Batch 5 of #348.
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|
GO:0032794
GTPase activating protein binding
|
IPI
PMID:20116244 Armus is a Rac1 effector that inactivates Rab7 and regulates... |
KEEP AS NON CORE |
Summary: IPI from PMID:20116244 (Frasa et al. 2010): Armus is a TBC/RabGAP protein that integrates Arf6, Rac1, and Rab7 signaling during E-cadherin junction disassembly. E-cadherin co-immunoprecipitates with Armus (a GTPase activating protein for Rab7), suggesting physical association. E-cadherin's association with Armus/RabGAP is part of the junction disassembly/degradation pathway.
Reason: GTPase activating protein binding by E-cadherin reflects its participation in junction disassembly/endocytic degradation pathways, not a core MF. Core function is homophilic adhesion at adherens junctions. Batch 5 of #348.
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|
GO:0009898
cytoplasmic side of plasma membrane
|
IDA
PMID:20189993 GATA3 inhibits breast cancer metastasis through the reversal... |
ACCEPT |
Summary: IDA from PMID:20189993: E-cadherin's cytoplasmic domain localizes to the cytoplasmic side of the plasma membrane where it interacts with beta-catenin, alpha-catenin, and p120-catenin. As a type-I transmembrane protein, E-cadherin's cytoplasmic tail is definitively on the cytoplasmic side of the plasma membrane, making this a correct CC annotation.
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|
GO:0030054
cell junction
|
TAS
PMID:17047063 E-cadherin regulates human Nanos1, which interacts with p120... |
KEEP AS NON CORE |
Summary: TAS from PMID:17047063: CDH1/E-cadherin localizes to cell junctions. GO:0030054 cell junction is a broad parent term; the precise and informative CC annotation is GO:0005912 adherens junction (ACCEPTed in this file), the specific junction type where E-cadherin resides and functions. Consistent with KEEP_AS_NON_CORE on the IEA cell junction annotation in this file.
Reason: Real but non-core CC -- CDH1 localizes to cell junctions but the precise junction type is the adherens junction (GO:0005912, accepted elsewhere); consistent with KEEP_AS_NON_CORE on the IEA cell junction row. Reactome TAS localization batch (batch 4 of #348).
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|
GO:0022408
negative regulation of cell-cell adhesion
|
IMP
PMID:19653274 Lef-1 isoforms regulate different target genes and reduce ce... |
REMOVE |
Summary: IMP from PMID:19653274 (Jesse et al. 2010): This paper studies Lef-1 isoforms that inhibit E-cadherin expression, reducing cellular aggregation. The IMP annotation of GO:0022408 (negative regulation of cell-cell adhesion) to CDH1 is not supported — E-cadherin is a canonical POSITIVE mediator/regulator of cell-cell adhesion. The paper's phenotype reflects Lef-1-mediated repression of CDH1 transcription leading to reduced adhesion; E-cadherin itself does not negatively regulate cell-cell adhesion in this context.
Reason: Annotation inconsistent with CDH1 biology: E-cadherin is a positive mediator of cell-cell adhesion, not a negative regulator. The Lef-1 paper shows that reducing CDH1 expression reduces adhesion — this is the opposite of CDH1 negatively regulating cell-cell adhesion. This annotation appears to be a misinterpretation of the IMP evidence. Batch 5 of #348.
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|
GO:0030054
cell junction
|
IDA
PMID:19038973 Identification of WNT/beta-CATENIN signaling pathway compone... |
KEEP AS NON CORE |
Summary: IDA from PMID:19038973: Cell junction localization of E-cadherin confirmed experimentally. GO:0030054 cell junction is the broad parent of GO:0005912 adherens junction; the precise core CC is the adherens junction, ACCEPTed elsewhere in this file.
Reason: Broad parent CC — GO:0030054 cell junction is the direct parent of GO:0005912 adherens junction, the precise core CC for E-cadherin (ACCEPTed in this file). A real but non-core annotation: the informative term is the specific adherens junction. Action reconciled with the IEA and TAS GO:0030054 rows in this file (#348).
|
|
GO:0005515
protein binding
|
IPI
PMID:20086044 Vinculin regulates cell-surface E-cadherin expression by bin... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:20086044 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0005912
adherens junction
|
IDA
PMID:20086044 Vinculin regulates cell-surface E-cadherin expression by bin... |
ACCEPT |
Summary: IDA from PMID:20086044: Adherens junction localization confirmed experimentally. Core CC for E-cadherin.
|
|
GO:0071681
cellular response to indole-3-methanol
|
IDA
PMID:10868478 Suppression of breast cancer invasion and migration by indol... |
KEEP AS NON CORE |
Summary: IDA from PMID:10868478 (Meng et al. 2000): Indole-3-carbinol (I3C, a dietary phytochemical from cruciferous vegetables) causes dose-dependent upregulation of E-cadherin and catenin expression in breast cancer cells, suppressing invasion and migration. GO:0071681 (cellular response to indole-3-methanol) captures E-cadherin's transcriptional upregulation in response to this specific dietary compound.
Reason: E-cadherin expression response to indole-3-carbinol is a real but highly context-specific, non-core biological response. E-cadherin's primary function is Ca2+-dependent homophilic cell-cell adhesion. Batch 5 of #348.
|
|
GO:0045295
gamma-catenin binding
|
IPI
PMID:1639850 Plakoglobin, or an 83-kD homologue distinct from beta-cateni... |
ACCEPT |
Summary: IPI from PMID:1639850 (Knudsen and Wheelock 1992): Plakoglobin (gamma-catenin, JUP) co-immunoprecipitates with E-cadherin and N-cadherin. E-cadherin cytoplasmic tail interacts with plakoglobin/gamma-catenin (an 83-kD Drosophila armadillo/plakoglobin-like protein), linking E-cadherin to the cytoskeleton. Gamma-catenin binding is a core MF — plakoglobin is a functional component of the E-cadherin-catenin complex at adherens junctions and desmosomes.
|
|
GO:0043296
apical junction complex
|
IDA
PMID:10460003 Cadherin and catenin expression in normal human bronchial ep... |
KEEP AS NON CORE |
Summary: IDA from PMID:10460003 (Smythe et al. 1999): E-cadherin and catenins detected at apical junction complexes in normal human bronchial epithelium by immunohistochemistry. The apical junction complex (AJC) is the composite apical unit comprising the tight junction, zonula adherens and desmosomes; E-cadherin resides specifically in the zonula adherens sub-compartment, so the annotation is accurate but broader than the precise core CC, GO:0005912 adherens junction.
Reason: Accurate but broader-than-precise CC grouping — the apical junction complex is the composite of tight junction, adherens junction and desmosomes; E-cadherin resides specifically in the zonula adherens, whose precise term GO:0005912 adherens junction is ACCEPTed as core in this file. Action reconciled with the IBA GO:0043296 row in this file (#348).
|
|
GO:0071285
cellular response to lithium ion
|
IDA
PMID:12937339 WNT7a induces E-cadherin in lung cancer cells. |
KEEP AS NON CORE |
Summary: IDA from PMID:12937339 (Ohira et al. 2003): WNT7a induces E-cadherin expression in lung cancer cells. Lithium ion (a GSK-3β inhibitor that mimics Wnt/β-catenin signaling) is used in this study to probe WNT pathway effects on CDH1 expression. GO:0071285 (cellular response to lithium ion) captures E-cadherin's transcriptional induction in response to lithium-mediated Wnt pathway activation.
Reason: CDH1 induction by lithium ion reflects a specific pharmacological activation of WNT signaling, not a core CDH1 function. Lithium response is context-specific and non-core. Batch 5 of #348.
|
|
GO:0005515
protein binding
|
IPI
PMID:19822757 Identification of a physiological E2 module for the human an... |
MARK AS OVER ANNOTATED |
Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:19822757 — non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin partner interactions are already captured in this file by dedicated MF terms (GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical protein binding for the E-cadherin homodimer). Specific alpha-catenin binding (GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin) terms are not yet seeded in this file and should be added in a subsequent batch. Regardless, this generic GO:0005515 IntAct-derived row adds no biological information beyond what partner-specific MF terms (existing or to be added) capture.
Reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin partners are already covered by granular MF terms in this file, and alpha-catenin (GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md, replace generic protein binding with informative partner-specific terms.
|
|
GO:0016342
catenin complex
|
IDA
PMID:18593713 Smad7 stabilizes beta-catenin binding to E-cadherin complex ... |
ACCEPT |
Summary: IDA from PMID:18593713 (Tang et al. 2008): Smad7 stabilizes the beta-catenin-E-cadherin complex at the plasma membrane. The catenin complex (GO:0016342) — comprising E-cadherin, beta-catenin, alpha-catenin, and p120-catenin — is the core protein complex mediating E-cadherin adhesion and cytoskeletal linkage. E-cadherin is the transmembrane scaffold of this complex.
|
|
GO:0005912
adherens junction
|
IDA
PMID:16338932 E-cadherin-dependent transcriptional control of apolipoprote... |
ACCEPT |
Summary: IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin-dependent cell-cell adhesion via adherens junctions studied using chimeric E-cadherin-Fc homophilic surfaces and Caco-2 enterocytes. Adherens junction is the core CC for E-cadherin in intestinal epithelial cells.
|
|
GO:0007156
homophilic cell-cell adhesion
|
NAS
PMID:16338932 E-cadherin-dependent transcriptional control of apolipoprote... |
ACCEPT |
Summary: NAS from PMID:16338932 (Peignon et al. 2006): Homophilic cell-cell adhesion is the foundation for the experimental design (chimeric E-cadherin-Fc surfaces, Caco-2 cell-cell contacts) and is cited as established background knowledge. Homophilic cell-cell adhesion is the definitively core BP for E-cadherin — the basis for all adherens junction-mediated tissue cohesion.
|
|
GO:0015629
actin cytoskeleton
|
IDA
PMID:16338932 E-cadherin-dependent transcriptional control of apolipoprote... |
KEEP AS NON CORE |
Summary: IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin forms complexes with actin ('formation of E-cadherin-actin complexes inducing polarization of Caco-2 enterocytes'). E-cadherin associates with the actin cytoskeleton through alpha-catenin, which links the cadherin-catenin complex to F-actin.
Reason: Actin cytoskeleton localization is real but reflects E-cadherin's indirect connection to actin via alpha-catenin rather than a core CC of E-cadherin itself. Core CC is plasma membrane/adherens junction. Batch 5 of #348.
|
|
GO:0016020
membrane
|
IDA
PMID:16338932 E-cadherin-dependent transcriptional control of apolipoprote... |
MARK AS OVER ANNOTATED |
Summary: IDA from PMID:16338932 (Peignon et al. 2006): GO:0016020 (membrane) is a non-specific parent term for E-cadherin. E-cadherin is a transmembrane protein, but the relevant and informative CC annotation is plasma membrane (GO:0005886) or adherens junction (GO:0005912), both of which are also annotated from this study. The general 'membrane' term adds no biological information beyond what the specific subterm annotations already convey.
Reason: GO:0016020 membrane is over-annotated — an uninformative parent term when more specific descendant CC terms (plasma membrane, adherens junction, lateral plasma membrane) are already annotated from the same paper and evidence. Batch 5 of #348.
|
|
GO:0016328
lateral plasma membrane
|
IDA
PMID:16338932 E-cadherin-dependent transcriptional control of apolipoprote... |
ACCEPT |
Summary: IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin complex formation studied in polarized Caco-2 intestinal epithelial cells where E-cadherin localizes to the lateral plasma membrane forming adherens junctions. Lateral plasma membrane is the canonical CC for E-cadherin in polarized epithelial cells — consistent with PMID:17620337 which describes E-cadherin as 'a ubiquitous component of lateral membranes in epithelial tissues.'
|
|
GO:0045893
positive regulation of DNA-templated transcription
|
IDA
PMID:16338932 E-cadherin-dependent transcriptional control of apolipoprote... |
KEEP AS NON CORE |
Summary: IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin-dependent cell-cell adhesion promotes transcriptional activation of the apoA-IV gene via increased nuclear abundance of HNF4alpha. Positive regulation of transcription is an indirect downstream consequence of E-cadherin-mediated adhesion signaling.
Reason: Transcriptional activation of apoA-IV via HNF4alpha is an indirect downstream effect of E-cadherin signaling in intestinal enterocytes — a context-specific non-core function. E-cadherin's core function is homophilic cell-cell adhesion. Batch 5 of #348.
|
|
GO:0048471
perinuclear region of cytoplasm
|
IDA
PMID:16338932 E-cadherin-dependent transcriptional control of apolipoprote... |
MARK AS OVER ANNOTATED |
Summary: IDA from PMID:16338932 (Peignon et al. 2006): The paper demonstrates that E-cadherin-dependent cell-cell adhesion in Caco-2 enterocytes controls the nuclear abundance of HNF4alpha (hepatic nuclear factor 4alpha), thereby regulating apoA-IV gene transcription. CDH1/E-cadherin itself is a type-I single-pass transmembrane glycoprotein whose canonical localization is the plasma membrane and adherens junction. The paper's experimental finding is about E-cadherin downstream signaling controlling nuclear translocation of HNF4alpha — not about E-cadherin itself localizing to the perinuclear region of cytoplasm. The abstract provides no evidence for E-cadherin perinuclear localization.
Reason: The perinuclear region annotation appears to misattribute the paper's finding about E-cadherin-mediated HNF4alpha nuclear redistribution to a perinuclear localization of E-cadherin itself. HNF4alpha (not CDH1) is the nuclear/perinuclear-region component in this paper. Full-length CDH1 is a plasma-membrane protein; while CTF2/CTF3 cleavage products can translocate to the nucleus in some contexts, this paper does not describe E-cadherin perinuclear localization. MARK_AS_OVER_ANNOTATED: the annotation over-extends the paper's findings about downstream signaling to an unsupported subcellular localization of E-cadherin.
|
|
GO:0050839
cell adhesion molecule binding
|
NAS
PMID:16338932 E-cadherin-dependent transcriptional control of apolipoprote... |
MARK AS OVER ANNOTATED |
Summary: NAS from PMID:16338932 (Peignon et al. 2006): Cell adhesion molecule binding as NAS (Not Ascribed to Source) from a background knowledge statement about E-cadherin adhesion. GO:0050839 (cell adhesion molecule binding) is non-informative for E-cadherin — its specific binding partners (other E-cadherins in trans, beta-catenin, gamma-catenin, ankyrin) are better captured by dedicated terms (GO:0045296 cadherin binding, GO:0008013 beta-catenin binding, GO:0045295 gamma-catenin binding, GO:0030506 ankyrin binding) already annotated in this file.
Reason: GO:0050839 is over-annotated: uninformative parent term when more specific molecular function binding terms for E-cadherin's known partners are separately annotated. Per CLAUDE.md, prefer informative specific terms. Batch 5 of #348.
|
|
GO:0098609
cell-cell adhesion
|
IDA
PMID:16338932 E-cadherin-dependent transcriptional control of apolipoprote... |
ACCEPT |
Summary: IDA from PMID:16338932 (Peignon et al. 2006): Cell-cell adhesion confirmed directly — E-cadherin mediates Caco-2 enterocyte cell-cell adhesion; impairing or enhancing E-cadherin-dependent adhesion modulates apoA-IV transcription. Cell-cell adhesion (GO:0098609) is core BP for E-cadherin.
|
|
GO:0007156
homophilic cell-cell adhesion
|
NAS
PMID:8033105 E-cadherin gene mutations provide clues to diffuse type gast... |
ACCEPT |
Summary: NAS from PMID:8033105: Homophilic cell-cell adhesion is the foundational and defining function of E-cadherin — a classical cadherin mediating Ca2+-dependent homophilic trans-adhesion between cells via strand-swap dimerization of the EC1 domain. This is the core BP and mechanism for E-cadherin's role in epithelial tissue integrity and morphogenesis.
|
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The requested target (UniProt P12830) corresponds to human E‑cadherin, encoded by CDH1 on chromosome 16q22.1, a canonical epithelial classical cadherin and core component of adherens junctions (ghosh2024realtimeanalysisof pages 15-19, samardali2025acomprehensiveliterature pages 1-2). The structure described in recent mechanistic work (single-pass transmembrane glycoprotein with five extracellular cadherin domains) is consistent with a classical cadherin family protein and matches the UniProt-provided cadherin domain context (ghosh2024realtimeanalysisof pages 15-19).
E‑cadherin is a calcium-dependent cell–cell adhesion molecule that organizes epithelial tissue architecture by mediating homophilic adhesion and supporting epithelial integrity and polarity (ghosh2024realtimeanalysisof pages 15-19, samardali2025acomprehensiveliterature pages 2-3).
Recent mechanistic description emphasizes that E‑cadherin is a single-pass transmembrane glycoprotein with extracellular, transmembrane, and intracellular regions, and that its extracellular portion contains five cadherin repeats (EC1–EC5) with calcium-binding sites (ghosh2024realtimeanalysisof pages 15-19).
At the molecular level, homophilic trans-binding is driven primarily by the EC1 domain and proceeds through an X-dimer intermediate followed by formation of a stable strand-swapped dimer, in which a tryptophan side chain from one EC1 inserts into a hydrophobic pocket of the opposing EC1 (ghosh2024realtimeanalysisof pages 15-19). This “strand swapping” mechanism is a central concept in current structural understanding of type I classical cadherin adhesion (ghosh2024realtimeanalysisof pages 15-19).
In epithelia, E‑cadherin is enriched at the plasma membrane and concentrates at adherens junctions where it contributes to epithelial sheet cohesion and tissue architecture (ghosh2024realtimeanalysisof pages 15-19, melo2023theecmand pages 9-10).
A defining functional property of E‑cadherin is that its cytoplasmic region couples adhesive contacts to the actin cytoskeleton via catenins. Experimental/biophysical synthesis emphasizes anchoring through β‑catenin and α‑catenin, enabling transmission of actomyosin forces across junctions (ghosh2024realtimeanalysisof pages 27-29). Broader mechanistic synthesis also highlights interaction with p120‑catenin, and how changes in E‑cadherin availability can alter β‑catenin and p120‑catenin signaling states (samardali2025acomprehensiveliterature pages 7-8).
Beyond static adhesion, E‑cadherin junctions are described as part of a mechanosensitive scaffold: E‑cadherin-based adhesions transmit actomyosin-generated pulling forces through β‑catenin/α‑catenin anchorage, and junction stability can be limited by cytoskeletal anchorage rather than cadherin–cadherin binding strength (ghosh2024realtimeanalysisof pages 27-29). This supports a current view of adherens junctions as force-bearing and force-sensing structures, not merely “glue” (ghosh2024realtimeanalysisof pages 27-29).
Loss or cleavage/downregulation of E‑cadherin can release constraints on β‑catenin signaling; a synthesis of cancer-related mechanisms describes that E‑cadherin loss can permit β‑catenin nuclear translocation with Wnt pathway activation (samardali2025acomprehensiveliterature pages 7-8). The same synthesis notes that redistribution of p120‑catenin can influence RhoA/Rac1 signaling with downstream cytoskeletal and mechanical consequences (samardali2025acomprehensiveliterature pages 7-8).
Reduction of E‑cadherin is repeatedly emphasized as central to EMT-associated loss of epithelial cohesion and increased migratory/invasive behavior. A mechanistic synthesis reports that EMT programs repress E‑cadherin and that such loss contributes to invasion and metastasis (samardali2025acomprehensiveliterature pages 7-8, samardali2025acomprehensiveliterature pages 3-4). A 2024 mechanistic work likewise frames E‑cadherin downregulation as a hallmark of EMT and cancer cell motility changes (ghosh2024realtimeanalysisof pages 27-29).
A 2023 peer-reviewed study combined in vitro extrusion assays using HDGC-associated E‑cadherin mutants with mathematical/computational modeling and concluded that early invasion is not only driven by weakened cell–cell adhesion but is also strongly determined by ECM attachment and 3D tissue architecture (e.g., gland-like cylindrical geometry), which can increase basal extrusion/invasive ability (Melo et al., 2023-11; https://doi.org/10.1038/s42003-023-05482-x) (melo2023theecmand pages 9-10). This line of work represents a shift from viewing CDH1 loss as sufficient for invasion to a multi-factor framework integrating tissue mechanics and geometry (melo2023theecmand pages 9-10).
A 2024 mechanistic analysis using a minimal reconstituted framework (as described in the retrieved text) emphasizes the detailed adhesion mechanism (EC1 X-dimer → strand-swap), actin coupling via catenins, and junction expansion constraints due to lateral membrane pressure/crowding effects, reinforcing a view of E‑cadherin junctions as an emergent physical system supporting mechanotransduction (ghosh2024realtimeanalysisof pages 15-19, ghosh2024realtimeanalysisof pages 27-29). While the venue metadata in the retrieved text is incomplete, the mechanistic content is consistent with modern junction biophysics and complements the 2023 ECM/architecture invasion emphasis (ghosh2024realtimeanalysisof pages 15-19, ghosh2024realtimeanalysisof pages 27-29).
A 2024 narrative review in Hereditary Cancer in Clinical Practice synthesizes newer penetrance estimates and explicitly argues that the risk of advanced diffuse gastric cancer (DGC) in CDH1 pathogenic variant carriers is lower than historically estimated, motivating increased consideration of endoscopic surveillance for selected carriers (van der Sluis et al., 2024-10; https://doi.org/10.1186/s13053-024-00293-5) (sluis2024currentadvancesand pages 2-4, sluis2024currentadvancesand pages 1-2).
Germline CDH1 pathogenic variants are a primary cause of HDGC, and clinical management has historically included prophylactic total gastrectomy (PTG) due to poor detectability and prognosis of invasive DGC (samardali2025acomprehensiveliterature pages 6-7, sluis2024currentadvancesand pages 1-2).
However, 2024 synthesis highlights a contemporary management challenge: ~30% (around one third) of CDH1 variant carriers decline PTG, often due to major quality-of-life sequelae (e.g., postoperative complications and chronic symptoms) (sluis2024currentadvancesand pages 2-4, sluis2024currentadvancesand pages 1-2). The same review lists common long-term PTG impacts, including substantial mean weight loss (~15–23%) and gastrointestinal/psychosocial effects, which are central to shared decision-making (sluis2024currentadvancesand pages 2-4).
For carriers who defer PTG, expert-center surveillance is recommended; IGCLC-style protocols include targeted biopsies plus ~28–30 random biopsies (sluis2024currentadvancesand pages 2-4). A key implementation issue is sensitivity: detection of early pT1a signet ring cell carcinoma (SRCC) by endoscopy is variable (~20–60% reported in the 2024 synthesis), and modeling suggests random biopsy counts needed for high sensitivity may be impractical (e.g., ~1800 biopsies estimated for 90% detection), supporting an emphasis on targeted lesions and improved recognition frameworks (sluis2024currentadvancesand pages 2-4).
The 2024 review further reports that, in some analyses, targeted biopsies have substantially higher yield than random biopsies (11% vs 0.9%), reinforcing movement toward targeted sampling plus structured histologic/endoscopic interpretation rather than attempting exhaustive random sampling (sluis2024currentadvancesand pages 2-4).
E‑cadherin loss is widely used in tumor pathology contexts as a marker of altered epithelial differentiation/adhesion and is mechanistically linked to invasive phenotypes (ghosh2024realtimeanalysisof pages 27-29, samardali2025acomprehensiveliterature pages 3-4). OpenTargets disease–target associations further reflect extensive disease relevance of CDH1 in cancers (e.g., breast adenocarcinoma, endometrial carcinoma, ovarian cancer) and in “CDH1-related diffuse gastric and lobular breast cancer syndrome” as a disease entity (OpenTargets; accessed via tool output) (OpenTargets Search: -CDH1).
The 2023 Communications Biology work provides explicit evidence that invasion in HDGC models emerges from interplay between defective cell–cell junctions, ECM attachment, and 3D tissue architecture, rather than from loss of adhesion alone (melo2023theecmand pages 9-10). Functionally, this reframes CDH1 as a gatekeeper whose loss creates vulnerability to invasion that is realized under permissive tissue/ECM contexts (melo2023theecmand pages 9-10).
The 2024 HDGC management review synthesizes multiple penetrance estimates, describing a shift from historical ~80% lifetime DGC risk to more recent cohort-derived estimates such as 37–42% (men) and 22–33% (women) in some US cohorts, and even 7–10% irrespective of family history in a more recent study; it also notes that risk can be higher (e.g., ~38%) in high-penetrance families (sluis2024currentadvancesand pages 2-4). The same review highlights that microscopic SRCC foci are common in PTG specimens, yet many individuals may never develop advanced disease, supporting a move away from uniform PTG recommendations toward more individualized approaches (sluis2024currentadvancesand pages 4-5, sluis2024currentadvancesand pages 1-2).
From the 2024 Hereditary Cancer in Clinical Practice review (publication: 2024-10; https://doi.org/10.1186/s13053-024-00293-5):
- Advanced DGC lifetime risk estimates have been revised downward and vary by cohort: 37–42% (men) and 22–33% (women) in some datasets; a recent study reported 7–10% irrespective of family history; risk may be ~38% in high-penetrance families (sluis2024currentadvancesand pages 2-4).
- Lifetime lobular breast cancer risk in women: 37–55% (sluis2024currentadvancesand pages 2-4, sluis2024currentadvancesand pages 1-2).
- PTG refusal/decline: ~30% (sluis2024currentadvancesand pages 2-4, sluis2024currentadvancesand pages 1-2).
- Endoscopic SRCC detection variability: ~20–60% in PTG/HDGC surveillance contexts (sluis2024currentadvancesand pages 2-4).
- Targeted vs random biopsy yield: 11% vs 0.9% (sluis2024currentadvancesand pages 2-4).
Key mechanistic facts for functional annotation include: 5 extracellular cadherin repeats (EC1–EC5), EC1-driven homophilic strand-swap dimerization, and intracellular coupling to actin via catenins (ghosh2024realtimeanalysisof pages 15-19, ghosh2024realtimeanalysisof pages 27-29).
CDH1 (UniProt P12830) encodes E‑cadherin, the canonical epithelial classical cadherin that mediates calcium-dependent homophilic cell–cell adhesion at adherens junctions and couples intercellular contacts to the actin cytoskeleton through catenins, enabling epithelial cohesion and mechanotransduction (ghosh2024realtimeanalysisof pages 15-19, ghosh2024realtimeanalysisof pages 27-29). Loss or functional impairment of E‑cadherin contributes to EMT-associated invasion and alters signaling (including Wnt/β‑catenin and Rho-family GTPase pathways), and germline CDH1 pathogenic variants underlie HDGC, where contemporary (2024) literature supports more individualized management balancing PTG morbidity against surveillance strategies given revised (often lower) estimates of advanced cancer risk (samardali2025acomprehensiveliterature pages 7-8, sluis2024currentadvancesand pages 2-4).
| Category | Evidence-backed summary |
|---|---|
| Identity/aliases | Human CDH1 encodes E-cadherin, a ~120 kDa calcium-dependent cell-cell adhesion glycoprotein also known as epithelial cadherin; this matches the canonical epithelial adherens-junction cadherin described for CDH1 at chromosome 16q22.1 (ghosh2024realtimeanalysisof pages 15-19, samardali2025acomprehensiveliterature pages 1-2). |
| Structure/domains | E-cadherin is a single-pass transmembrane protein with extracellular, transmembrane, and intracellular regions; the ectodomain contains five cadherin repeats (EC1-EC5) with calcium-binding sites, consistent with cadherin-family domain architecture (ghosh2024realtimeanalysisof pages 15-19). |
| Adhesion mechanism | Adhesion is mediated by homophilic trans-interactions between EC1 domains, proceeding through an X-dimer intermediate to a stable strand-swapped dimer in which a tryptophan side chain inserts into the partner EC1 hydrophobic pocket; calcium stabilizes the ectodomain for adhesion (ghosh2024realtimeanalysisof pages 15-19). |
| Localization | E-cadherin localizes mainly at the plasma membrane of epithelial cells, concentrated at adherens junctions, where it maintains epithelial sheet cohesion, polarity, and barrier/tissue architecture (ghosh2024realtimeanalysisof pages 15-19, melo2023theecmand pages 9-10). |
| Key binding partners | Its cytoplasmic tail links to the actin cytoskeleton through catenins, especially β-catenin, α-catenin, and p120-catenin; this coupling is central to junction stability and force transmission (ghosh2024realtimeanalysisof pages 15-19, ghosh2024realtimeanalysisof pages 27-29). |
| Signaling/pathways | Beyond adhesion, CDH1/E-cadherin participates in mechanotransduction and constrains oncogenic signaling; loss of E-cadherin can permit β-catenin nuclear translocation/Wnt signaling, alter RhoA/Rac1 activity via p120-catenin, and is tightly linked to EMT and tumor progression (samardali2025acomprehensiveliterature pages 7-8, ghosh2024realtimeanalysisof pages 27-29). |
| Proteolytic processing/soluble fragments | E-cadherin can undergo proteolytic cleavage/shedding, generating soluble E-cadherin fragments; cleavage releases junctional restraint and can free β-catenin, with reported detection of soluble E-cadherin in cancer-associated biofluids such as urine (ghosh2024realtimeanalysisof pages 27-29). |
| Disease relevance/clinical | Germline CDH1 pathogenic variants cause hereditary diffuse gastric cancer (HDGC) and increase risk of lobular breast cancer. Recent reviews report lower modern estimates for advanced diffuse gastric cancer risk (~13-19%) than historic estimates, while ~30% to one third of carriers decline prophylactic total gastrectomy because of major long-term consequences, motivating expert-center endoscopic surveillance in selected patients (sluis2024currentadvancesand pages 2-4, sluis2024currentadvancesand pages 1-2). |
Table: This table summarizes core functional-annotation facts for human CDH1/E-cadherin (UniProt P12830), including structure, mechanism, localization, partners, pathways, and clinical relevance. It is useful as a compact, evidence-backed reference for the final research report.
References
(ghosh2024realtimeanalysisof pages 15-19): S Ghosh. Real-time analysis of e-cadherin mediated junction formation in cancer cells using a minimal reconstituted system. Unknown journal, 2024.
(samardali2025acomprehensiveliterature pages 1-2): Malik Samardali, Jehad Samardaly, and Ibrahim Shanti. A comprehensive literature review of the cdh1 mutation and its role in gastric cancer. Cureus, May 2025. URL: https://doi.org/10.7759/cureus.85072, doi:10.7759/cureus.85072. This article has 2 citations.
(samardali2025acomprehensiveliterature pages 2-3): Malik Samardali, Jehad Samardaly, and Ibrahim Shanti. A comprehensive literature review of the cdh1 mutation and its role in gastric cancer. Cureus, May 2025. URL: https://doi.org/10.7759/cureus.85072, doi:10.7759/cureus.85072. This article has 2 citations.
(melo2023theecmand pages 9-10): Soraia Melo, Pilar Guerrero, Maurício Moreira Soares, José Rafael Bordin, Fátima Carneiro, Patrícia Carneiro, Maria Beatriz Dias, João Carvalho, Joana Figueiredo, Raquel Seruca, and Rui D. M. Travasso. The ecm and tissue architecture are major determinants of early invasion mediated by e-cadherin dysfunction. Communications Biology, Nov 2023. URL: https://doi.org/10.1038/s42003-023-05482-x, doi:10.1038/s42003-023-05482-x. This article has 15 citations and is from a peer-reviewed journal.
(ghosh2024realtimeanalysisof pages 27-29): S Ghosh. Real-time analysis of e-cadherin mediated junction formation in cancer cells using a minimal reconstituted system. Unknown journal, 2024.
(samardali2025acomprehensiveliterature pages 7-8): Malik Samardali, Jehad Samardaly, and Ibrahim Shanti. A comprehensive literature review of the cdh1 mutation and its role in gastric cancer. Cureus, May 2025. URL: https://doi.org/10.7759/cureus.85072, doi:10.7759/cureus.85072. This article has 2 citations.
(samardali2025acomprehensiveliterature pages 3-4): Malik Samardali, Jehad Samardaly, and Ibrahim Shanti. A comprehensive literature review of the cdh1 mutation and its role in gastric cancer. Cureus, May 2025. URL: https://doi.org/10.7759/cureus.85072, doi:10.7759/cureus.85072. This article has 2 citations.
(sluis2024currentadvancesand pages 2-4): L. van der Sluis, J.M. van Dieren, R.S. van der Post, and T.M. Bisseling. Current advances and challenges in managing hereditary diffuse gastric cancer (hdgc): a narrative review. Hereditary Cancer in Clinical Practice, Oct 2024. URL: https://doi.org/10.1186/s13053-024-00293-5, doi:10.1186/s13053-024-00293-5. This article has 11 citations and is from a peer-reviewed journal.
(sluis2024currentadvancesand pages 1-2): L. van der Sluis, J.M. van Dieren, R.S. van der Post, and T.M. Bisseling. Current advances and challenges in managing hereditary diffuse gastric cancer (hdgc): a narrative review. Hereditary Cancer in Clinical Practice, Oct 2024. URL: https://doi.org/10.1186/s13053-024-00293-5, doi:10.1186/s13053-024-00293-5. This article has 11 citations and is from a peer-reviewed journal.
(samardali2025acomprehensiveliterature pages 6-7): Malik Samardali, Jehad Samardaly, and Ibrahim Shanti. A comprehensive literature review of the cdh1 mutation and its role in gastric cancer. Cureus, May 2025. URL: https://doi.org/10.7759/cureus.85072, doi:10.7759/cureus.85072. This article has 2 citations.
(OpenTargets Search: -CDH1): Open Targets Query (-CDH1, 30 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(sluis2024currentadvancesand pages 4-5): L. van der Sluis, J.M. van Dieren, R.S. van der Post, and T.M. Bisseling. Current advances and challenges in managing hereditary diffuse gastric cancer (hdgc): a narrative review. Hereditary Cancer in Clinical Practice, Oct 2024. URL: https://doi.org/10.1186/s13053-024-00293-5, doi:10.1186/s13053-024-00293-5. This article has 11 citations and is from a peer-reviewed journal.
Provenance note. This is a manually compiled research file. The automated
deep-research providers (Perplexity, OpenAI, Falcon, etc.) were unavailable in
this environment (no API keys; prior runs reported provider timeouts), so per
the repository CLAUDE.md guidance this content is written by hand and named
-deep-research-manual.mdrather than-deep-research-{provider}.md.Every assertion is anchored to a verifiable source: either the UniProt record
(CDH1-uniprot.txt, UniProt P12830) or one of the 73 publications referenced
inCDH1-goa.tsv, all of which are cached locally inpublications/. Supporting
text is quoted verbatim from the cached publication abstracts/full text.
CDH1 is the prototypical "classical" (type I) cadherin. UniProt summarizes its
function as: "Cadherins are calcium-dependent cell adhesion proteins. They
preferentially interact with themselves in a homophilic manner in connecting
cells... CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility
and proliferation of epithelial cells... Has a potent invasive suppressor role"
[UniProt:P12830 FUNCTION, citing PubMed:11976333].
The defining molecular function. Adhesion uses two distinct interfaces:
Single-molecule work shows adhesion begins from monomers, not pre-formed cis
dimers, and that clustering is cooperative:
PMID:19114658
PMID:19114658.
Dimerization proceeds by an induced-fit, two-step mechanism: a weak Ca2+-dependent
"encounter complex" forms first, then strengthens by strand swap.
PMID:19646884
PMID:19646884.
E-cadherin bonds are force-responsive, which lets junctions resist and tune
to mechanical load:
PMID:23112161
PMID:23112161
PMID:23112161.
The cytoplasmic tail nucleates the catenin complex that couples adhesion to
the cytoskeleton. UniProt: "Component of an E-cadherin/catenin adhesion complex
composed of at least E-cadherin/CDH1, beta-catenin/CTNNB1 or gamma-catenin/JUP,
and potentially alpha-catenin/CTNNA1" [UniProt:P12830 SUBUNIT, citing
PubMed:16126725, PubMed:7982500]; the juxtamembrane domain binds CTNND1
(p120-catenin) [UniProt:P12830 SUBUNIT, citing PubMed:15240885].
Beyond forming adherens junctions, E-cadherin seeds desmosome assembly:
Annotation note: desmosome localization (GO:0030057) for CDH1 is a genuine
but organizer/initiator role, not a structural desmosomal-cadherin role — best
treated as a real but non-core (or carefully scoped) annotation.
E-cadherin surface levels are set by a balance of delivery, recycling, endocytosis
and degradation:
Loss of E-cadherin is a hallmark of the epithelial–mesenchymal transition (EMT);
its re-expression drives the reverse (MET). CDH1 itself is a transcriptional
target:
Homophilic E-cadherin engagement is not just structural — it transduces signals
that control gene expression and cell state:
E-cadherin EC1 is hijacked by pathogens:
This is appropriately a non-core function (host receptor co-opted by pathogens),
not part of CDH1's normal physiology.
Synthesis for the eventual core_functions block of CDH1-ai-review.yaml:
GO:0005509 calcium ion binding; GO:0098641 cadherin binding involved in cell-cell adhesion; adherens-junction adhesion BP terms).Likely non-core but genuine: desmosome assembly initiation; outside-in
transcriptional signaling; regulation of cell proliferation; pathogen-receptor
role (microbial infection — should not be a core annotation).
REMOVE.GO:0005515 proteinprotein binding").CDH1-uniprot.txt) — FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, DOMAIN, PTM, DISEASE sections.CDH1-goa.tsv are cached in publications/PMID_<n>.md. Core-function papers used above: 1639850, 8033105, 10725230, 11976333, 12526809, 15689490, 15695390, 16338932, 16882694, 17047063, 17237808, 17620337, 17715295, 18093941, 18593713, 19114658, 19403558, 19604117, 19646884, 19653274, 20086044, 20116244, 20189993, 20859650, 21300292, 21685945, 22158051, 22252131, 22294297, 22750944, 23112161, 24046456, 24424122, 25344754, 25468996, 27760340, 28301459, 29999492.Applied the proven manual-PubMed support-finding workflow (asta deprecated, see issue #1599) to the
14 IBA annotations that lacked independent PMID/DOI support. Several already had a supported_by
entry pointing at the falcon deep-research file (file:...), which is why they were flagged
unsupported — I appended foundational primary PMIDs (verified verbatim against the fetched abstract).
Added independent PMID support to 8 of 14 IBA annotations:
| Term | GO | Reference |
|---|---|---|
| beta-catenin binding | GO:0008013 | PMID:7806582 (β-catenin interacts with E-cadherin) |
| catenin complex | GO:0016342 | PMID:2349235 (uvomorulin/E-cadherin associates with catenins α/β/γ) |
| cadherin binding | GO:0045296 | PMID:20190754 (classical-cadherin strand-swap homophilic binding) |
| cell-cell adhesion mediated by cadherin | GO:0044331 | PMID:3498123 (Nagafuchi/Takeichi 1987) |
| calcium-dependent cell-cell adhesion | GO:0016339 | PMID:3498123 ("Ca2+-dependent intercellular adhesion between epithelial cells") |
| adherens junction | GO:0005912 | PMID:7806582 (E-cadherin in adherens junctions of epithelia) |
| adherens junction organization | GO:0034332 | PMID:3498123 (anti-E-cadherin disperses compact cell colonies) |
| apical junction complex | GO:0043296 | PMID:23643492 (E-cadherin at the epithelial zonula adherens) |
Left unsupported (6) — honest:
Note: unlike the LGALS3 asta run, CDH1's foundational literature (Nagafuchi/Takeichi 1987, the
Ozawa/Kemler catenin papers, Harrison 2010 structure) was trivially recovered by direct PubMed
search — again reinforcing that targeted manual search beats the retrieval-only provider.
id: P12830
gene_symbol: CDH1
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: 'CDH1 encodes E-cadherin (epithelial cadherin), the prototypical type-I
classical cadherin and the principal calcium-dependent cell-cell adhesion molecule
of epithelia. This single-pass transmembrane glycoprotein has five extracellular
cadherin (EC) repeats that bind calcium and mediate homophilic trans-adhesion with
E-cadherin on neighbouring cells, while its cytoplasmic tail nucleates the cadherin-catenin
complex by binding p120-catenin, beta-catenin and gamma-catenin/plakoglobin; alpha-catenin
in turn couples this complex to the cortical actin cytoskeleton. Through these interactions
E-cadherin builds and maintains adherens junctions, establishes epithelial apicobasal
polarity and tissue integrity, and facilitates early desmosome assembly. E-cadherin
is a potent invasion and tumour suppressor: loss of function promotes epithelial-to-mesenchymal
transition and is causative in hereditary diffuse gastric cancer and lobular breast
carcinoma. E-cadherin is additionally exploited as a host cell-surface receptor
by Listeria monocytogenes internalin A.'
alternative_products:
- name: '1'
id: P12830-1
- name: '2'
id: P12830-2
sequence_note: VSP_055586
existing_annotations:
- term:
id: GO:0000902
label: cell morphogenesis
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection from the PANTHER classical cadherin family tree (PTHR24027,
subfamily SF319 Cadherin-1) via GO_REF:0000033. E-cadherin contributes to epithelial
cell morphogenesis because cadherin-mediated adhesion shapes epithelial cells
and is required to establish and maintain epithelial architecture. However,
cell morphogenesis is a broad downstream outcome of the core adhesion and junction-organizing
activity rather than a distinct core function. The precise core CDH1 processes
(calcium-dependent homophilic cell-cell adhesion, cadherin-mediated adhesion,
adherens junction organization) are captured by other rows in this file.
action: KEEP_AS_NON_CORE
reason: 'Real but general developmental/cellular outcome downstream of the core
adhesion function; the precise core processes (GO:0044331 cell-cell adhesion
mediated by cadherin, GO:0034332 adherens junction organization) are ACCEPTed
elsewhere in this batch. Mechanical IBA-PANTHER batch (batch 2 of #348).'
qualifier: involved_in
- term:
id: GO:0016477
label: cell migration
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection from the PANTHER cadherin family tree (PTHR24027) via
GO_REF:0000033. E-cadherin participates in cell migration processes — it is
retained at junctions during collective epithelial migration such as wound healing,
and conversely its loss drives the epithelial-mesenchymal transition that licenses
single-cell motility and invasion. The bare cell migration term carries no directionality,
whereas the best-established directional CDH1 role is suppression of single-cell
migration/invasion, separately captured by the IMP GO:0030336 (negative regulation
of cell migration) row in this file (PMID:16882694). The generic involved_in
cell-migration inference is therefore a real but non-core, context-dependent
association.
action: KEEP_AS_NON_CORE
reason: 'Generic non-directional migration term; the core CDH1 activity is cell-cell
adhesion rather than migration per se, and the directional regulatory role (suppression
of migration/invasion) is captured by GO:0030336 elsewhere in the file. Mechanical
IBA-PANTHER batch (batch 2 of #348).'
qualifier: involved_in
- term:
id: GO:0007043
label: cell-cell junction assembly
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection from the PANTHER classical cadherin family tree (PTHR24027)
via GO_REF:0000033. E-cadherin nucleates assembly of epithelial cell-cell junctions
— homophilic trans-engagement of E-cadherin ectodomains initiates cell-cell
contact, and the cytoplasmic tail recruits the catenins that build the adherens
junction and template subsequent tight-junction and desmosome formation. This
is a core, well-established CDH1 function, consistent with the more specific
GO:0034332 (adherens junction organization) row.
action: ACCEPT
reason: 'Core CDH1 biological process — E-cadherin is the founding adhesion receptor
that initiates epithelial cell-cell junction assembly. Mechanical IBA-PANTHER
batch (batch 2 of #348).'
qualifier: involved_in
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection (is_active_in) from the PANTHER cadherin tree (PTHR24027)
via GO_REF:0000033. E-cadherin is a type-I single-pass transmembrane glycoprotein;
its steady-state location is the plasma membrane and adherens junction, with
only its ~150-residue C-terminal tail exposed to the cytosol. Annotating the
protein as is_active_in the cytoplasm (GO:0005737) is over-broad — it asserts
a generic compartment that does not reflect where the protein resides or acts.
The accurate localizations (plasma membrane, adherens junction, lateral plasma
membrane) are captured by other rows in this file.
action: MARK_AS_OVER_ANNOTATED
reason: 'Over-broad CC for a single-pass transmembrane plasma-membrane protein;
cytoplasm is not entirely wrong (the cytoplasmic tail faces the cytosol) but
does not reflect the protein actual residence or site of action. More precise
CC terms (GO:0005886 plasma membrane, GO:0005912 adherens junction, GO:0016328
lateral plasma membrane) are present in the file. Mechanical IBA-PANTHER batch
(batch 2 of #348).'
qualifier: is_active_in
- term:
id: GO:0008013
label: beta-catenin binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033.
The E-cadherin cytoplasmic catenin-binding domain directly binds beta-catenin
(CTNNB1); this interaction links the cadherin to the actin cytoskeleton via
alpha-catenin and is the molecular basis of the cadherin-catenin complex. Independently
supported within this file by IPI/IDA evidence on this same term (PMID:18593713,
Smad7 stabilizes beta-catenin binding to the E-cadherin complex; PMID:17620337)
and by Reactome TAS rows describing CDH1-CTNNB1 complex formation.
action: ACCEPT
reason: 'Canonical core CDH1 molecular function — direct beta-catenin binding
by the cadherin cytoplasmic tail is the defining interaction of the cadherin-catenin
complex. Corroborated by IPI (PMID:18593713) and IDA (PMID:17620337) evidence
on this exact term elsewhere in the file. Mechanical IBA-PANTHER batch (batch
2 of #348).'
supported_by:
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: Experimental/biophysical synthesis emphasizes anchoring through
**β‑catenin and α‑catenin**, enabling transmission of actomyosin forces across
junctions
- reference_id: PMID:7806582
supporting_text: "beta-Catenin is involved in the formation of adherens junctions of mammalian epithelia. It interacts with the cell adhesion molecule E-cadherin"
qualifier: enables
- term:
id: GO:0044331
label: cell-cell adhesion mediated by cadherin
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection from the PANTHER classical cadherin tree (PTHR24027) via
GO_REF:0000033. Cadherin-mediated cell-cell adhesion is the defining function
of E-cadherin — calcium-dependent homophilic trans-interaction of ectodomains
between adjacent epithelial cells. This is the central core CDH1 process. Independently
supported in this file by IDA evidence on the same term (PMID:18593713) and
by the crystallographic adhesion-architecture reference PMID:21300292.
action: ACCEPT
reason: 'Defining core biological process of E-cadherin — homophilic cadherin-mediated
cell-cell adhesion. Corroborated by IDA evidence on this exact term (PMID:18593713)
elsewhere in the file. Mechanical IBA-PANTHER batch (batch 2 of #348).'
supported_by:
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: E‑cadherin is a **calcium-dependent cell–cell adhesion molecule**
that organizes epithelial tissue architecture by mediating **homophilic adhesion**
and supporting epithelial integrity and polarity
- reference_id: PMID:3498123
supporting_text: "E-cadherin is a cell surface glycoprotein responsible for Ca2+-dependent intercellular adhesion between epithelial cells"
qualifier: involved_in
- term:
id: GO:0016342
label: catenin complex
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection (part_of) from the PANTHER cadherin tree (PTHR24027) via
GO_REF:0000033. E-cadherin is the transmembrane core of the cadherin-catenin
(catenin) complex; its cytoplasmic tail scaffolds beta-catenin and gamma-catenin
and, via alpha-catenin, the actin cytoskeleton. Independently supported in this
file by IDA evidence on the same GO:0016342 term (PMID:18593713).
action: ACCEPT
reason: 'Core CDH1 cellular component — E-cadherin is the obligate transmembrane
component of the catenin complex. Corroborated by IDA evidence on this exact
term (PMID:18593713) elsewhere in the file. Mechanical IBA-PANTHER batch (batch
2 of #348).'
supported_by:
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: Broader mechanistic synthesis also highlights interaction with
**p120‑catenin**, and how changes in E‑cadherin availability can alter β‑catenin
and p120‑catenin signaling states
- reference_id: PMID:2349235
supporting_text: "the cytoplasmic region of the cell adhesion molecule uvomorulin associates with three proteins named catenin alpha, beta, and gamma"
qualifier: part_of
- term:
id: GO:0045296
label: cadherin binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033.
E-cadherin engages in cadherin binding through calcium-dependent homophilic
trans- and cis-interactions of its ectodomain (the EC1 strand-swap dimer interface),
the mechanistic basis of homophilic cell-cell adhesion. Independently supported
in this file by HDA evidence on the same term (PMID:25468996, the E-cadherin
interactome) and the crystallographic reference PMID:21300292.
action: ACCEPT
reason: 'Core CDH1 molecular function — homophilic cadherin-cadherin binding via
the ectodomain is the adhesive activity of E-cadherin. Corroborated by HDA evidence
on this exact term (PMID:25468996) elsewhere in the file. Mechanical IBA-PANTHER
batch (batch 2 of #348).'
supported_by:
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: '**homophilic trans-binding** is driven primarily by the **EC1
domain** and proceeds through an **X-dimer intermediate** followed by formation
of a stable **strand-swapped dimer**, in which a **tryptophan side chain from
one EC1 inserts into a hydrophobic pocket** of the opposing EC1'
- reference_id: PMID:20190754
supporting_text: "Crystal structures of classical cadherins have revealed two dimeric configurations. In the first, N-terminal beta-strands of EC1 domains 'swap' between partner molecules."
qualifier: enables
- term:
id: GO:0070097
label: delta-catenin binding
evidence_type: IPI
original_reference_id: PMID:15240885
review:
summary: 'NEW annotation. The juxtamembrane domain (JMD) of E-cadherin''s cytoplasmic tail directly binds p120-catenin (CTNND1) at a site distinct from the C-terminal beta-catenin-binding domain. UniProt cites Krakstad et al. 2004 (PMID:15240885) as the primary reference for "INTERACTION WITH CTNND1" (CDH1-uniprot.txt line 300); Fig. 5B coimmunoprecipitates E-cadherin with p120-catenin in L cells in the context of Galpha12 overexpression (with Galpha12 increasing the association), and the Discussion explicitly references the established direct binding of p120ctn to the juxtamembrane region of E-cadherin (the citation context UniProt relies on when listing this paper). The CDH1-CTNND1 interaction is independently documented in UniProt (P12830 SUBUNIT: "Interacts with CTNND1"; binding-site feature "Required for binding CTNND1 and PSEN1") and by four IntAct/UniProt-curated IPI records against CTNND1/O60716 in this file''s GOA (PMID:10725230, PMID:19604117, PMID:33961781, PMID:34591612). Mariner et al. 2000 (PMID:10725230) provides supporting JMD-localization context by showing that ARVCF competes with p120 for the same JMD site. Mechanistically, p120-catenin binding masks a dileucine endocytic motif in the JMD and stabilizes E-cadherin at the plasma membrane, controlling cadherin surface levels, turnover, and adhesion strength — a direct molecular function distinct from beta-catenin binding (GO:0008013, a core function here). Term-usage note: GO:0070097 "delta-catenin binding" is the only available granular GO term for catenin-δ subfamily binding; there is no separate "p120-catenin binding" term. The term is used here for CTNND1 (p120/δ1-catenin) following the convention already established across all 39 GO:0005515 over-annotation rows in this file (e.g. line 285: "delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)"), and consistent with the GO definition "Binding to the delta subunit of the catenin complex."'
action: NEW
reason: 'Direct, well-supported molecular function (p120-catenin binding at the juxtamembrane domain) currently captured only as uninformative generic protein binding; promoting it to GO:0070097 implements the partner-specific replacement flagged across the GO:0005515 CTNND1 IPI rows of this file. Reference set was tightened after PR review: original_reference_id updated to UniProt''s primary direct reference PMID:15240885 (was PMID:10725230, an ARVCF competition assay that only indirectly implies p120 binding), and PMID:24424122 (a suppressor-tRNA therapy paper) was dropped from the summary, leaving only the four IPI records that clearly target CTNND1/O60716. Alpha-catenin binding (GO:0045294) is intentionally NOT proposed, because alpha-catenin associates with E-cadherin indirectly via beta-catenin rather than by direct binding to CDH1.'
- term:
id: GO:0034332
label: adherens junction organization
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection from the PANTHER classical cadherin tree (PTHR24027) via
GO_REF:0000033. E-cadherin is the founding component that organizes the epithelial
adherens junction — clustering of trans-engaged cadherins together with recruitment
of the catenin-actin module assembles and maintains the zonula adherens. Independently
supported in this file by IMP evidence on the same term (PMID:21724833).
action: ACCEPT
reason: 'Core CDH1 biological process — E-cadherin organizes the adherens junction.
Corroborated by IMP evidence on this exact term (PMID:21724833) elsewhere in
the file. Mechanical IBA-PANTHER batch (batch 2 of #348).'
supported_by:
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: E‑cadherin-based adhesions transmit **actomyosin-generated
pulling forces** through β‑catenin/α‑catenin anchorage, and junction stability
can be limited by cytoskeletal anchorage rather than cadherin–cadherin binding
strength
- reference_id: PMID:3498123
supporting_text: "blocking the action of E-cadherin by monoclonal antibodies causes dispersion of compact cell colonies"
qualifier: involved_in
- term:
id: GO:0005912
label: adherens junction
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection (is_active_in) from the PANTHER classical cadherin tree
(PTHR24027) via GO_REF:0000033. The adherens junction (zonula adherens) is the
principal site of E-cadherin residence and function in epithelial cells. This
is a core CDH1 cellular component, independently supported in this file by multiple
IDA rows on the same term (PMID:22294297, PMID:18343367, PMID:27760340, PMID:24046456,
PMID:20086044, PMID:16338932).
action: ACCEPT
reason: 'Core CDH1 cellular component — the adherens junction is the defining
site of E-cadherin localization and activity, corroborated by numerous IDA rows
on this exact term in the file. Mechanical IBA-PANTHER batch (batch 2 of #348).'
supported_by:
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: In epithelia, E‑cadherin is enriched at the **plasma membrane**
and concentrates at **adherens junctions** where it contributes to epithelial
sheet cohesion and tissue architecture
- reference_id: PMID:7806582
supporting_text: "beta-Catenin is involved in the formation of adherens junctions of mammalian epithelia. It interacts with the cell adhesion molecule E-cadherin"
qualifier: is_active_in
- term:
id: GO:0007416
label: synapse assembly
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection from the PANTHER cadherin tree (PTHR24027) via GO_REF:0000033,
originating from the broad ancestral node PTN000616414. Classical cadherins
contribute to synapse assembly and stabilization in the nervous system, and
E-cadherin has documented roles at neuronal synapses; however, for the canonical
epithelial CDH1 this is a tissue-specific, non-core context rather than a defining
function. The core CDH1 role is epithelial cell-cell adhesion at adherens junctions.
action: KEEP_AS_NON_CORE
reason: 'Tissue/cell-type-specific neuronal context (synapse assembly) rather
than a core epithelial CDH1 function; projected from a broad ancestral PANTHER
node. Mechanical IBA-PANTHER batch (batch 2 of #348).'
qualifier: involved_in
- term:
id: GO:0016339
label: calcium-dependent cell-cell adhesion
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection from the PANTHER classical cadherin tree (PTHR24027) via
GO_REF:0000033. E-cadherin adhesion is strictly calcium-dependent — Ca2+ ions
bridge the linker regions between extracellular cadherin (EC) domains, rigidifying
the ectodomain into the conformation competent for homophilic trans-binding.
GO:0016339 (attachment of one cell to another via adhesion molecules that require
calcium) precisely describes the core CDH1 adhesive process. Consistent with
the IEA GO:0005509 (calcium ion binding) row in this file.
action: ACCEPT
reason: 'Core CDH1 biological process — calcium-dependent homophilic cell-cell
adhesion is the defining activity of E-cadherin. Mechanical IBA-PANTHER batch
(batch 2 of #348).'
supported_by:
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: E‑cadherin is a **calcium-dependent cell–cell adhesion molecule**
that organizes epithelial tissue architecture by mediating **homophilic adhesion**
and supporting epithelial integrity and polarity
- reference_id: PMID:3498123
supporting_text: "E-cadherin is a cell surface glycoprotein responsible for Ca2+-dependent intercellular adhesion between epithelial cells"
qualifier: involved_in
- term:
id: GO:0016600
label: flotillin complex
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA projection (part_of) from the PANTHER cadherin tree (PTHR24027) via
GO_REF:0000033, from the broad ancestral node PTN000616414. GO:0016600 (flotillin
complex) is defined as a protein complex containing flotillin-1 and flotillin-2
(and possibly associated proteins). E-cadherin is recruited to flotillin-rich
membrane microdomains that stabilize cadherins at cell-cell junctions (shown
experimentally in PMID:24046456, the separate IDA GO:0016600 row in this file),
but it is not a constitutive flotillin subunit. Annotating E-cadherin as part_of
the flotillin complex by phylogenetic inference overstates this microdomain
association into structural complex membership. (The IDA flotillin row, PMID:24046456,
is left PENDING for a later batch.)
action: MARK_AS_OVER_ANNOTATED
reason: 'The part_of qualifier overstates a membrane-microdomain association as
structural membership of the flotillin-1/-2 complex; E-cadherin is recruited
to flotillin microdomains but is not a flotillin-complex subunit. Not entirely
wrong (flotillin-microdomain localization is experimentally supported by PMID:24046456)
but an over-annotation as an IBA part_of inference. Mechanical IBA-PANTHER batch
(batch 2 of #348).'
qualifier: part_of
- term:
id: GO:0043296
label: apical junction complex
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
supported_by:
- reference_id: PMID:23643492
supporting_text: "E-cadherin supports steady-state Rho signaling at the epithelial zonula adherens"
summary: IBA projection (is_active_in) from the PANTHER cadherin tree (PTHR24027)
via GO_REF:0000033, from the broad ancestral node PTN000616414. The apical junction
complex (GO:0043296) is the composite apical unit comprising the tight junction,
the zonula adherens and desmosomes. E-cadherin is the core of the zonula adherens,
one of the three constituents of the apical junction complex, so the annotation
is not wrong; however, the precise and core CDH1 cellular component is the adherens
junction itself (GO:0005912, ACCEPTed in this batch), and the broader composite
grouping is best treated as non-core.
action: KEEP_AS_NON_CORE
reason: 'Accurate but broader-than-precise CC grouping; the precise core localization
is GO:0005912 adherens junction. E-cadherin resides specifically in the zonula
adherens sub-compartment of the apical junction complex. Mechanical IBA-PANTHER
batch (batch 2 of #348).'
qualifier: is_active_in
- term:
id: GO:0005509
label: calcium ion binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
action: ACCEPT
summary: 'IEA from InterPro2GO (GO_REF:0000002): E-cadherin has five extracellular
cadherin (EC) domains, each pair bridged by three Ca2+ ions at the domain linker
regions. Ca2+ binding rigidifies the extracellular domain into a rod-like conformation
required for homophilic trans-dimerisation and cell-cell adhesion. Calcium ion
binding is therefore a core molecular activity of CDH1, corroborated by the
IBA GO:0016339 (calcium-dependent cell-cell adhesion) ACCEPT in this file.'
reason: 'Core CDH1 molecular function — Ca2+ binding via the EC-domain linkers
is an obligate step in homophilic cadherin adhesion. IEA batch (batch 3 of #348).'
supported_by:
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: extracellular portion contains **five cadherin repeats (EC1–EC5)**
with **calcium-binding sites**
qualifier: enables
- term:
id: GO:0005576
label: extracellular region
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
action: ACCEPT
summary: 'IEA from UniProt-GOA (GO_REF:0000044): CDH1 is a type-I single-pass
transmembrane glycoprotein with a large N-terminal extracellular segment comprising
five EC repeat domains (EC1-EC5). The ectodomain is entirely extracellular and
constitutes the adhesion-competent portion of the protein.'
reason: 'Core CDH1 cellular component — the large EC1-EC5 ectodomain occupies
the extracellular region and is the adhesion-active portion of the protein.
IEA batch (batch 3 of #348).'
qualifier: located_in
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from UniProt-GOA (GO_REF:0000044): CDH1 is a type-I single-pass
transmembrane glycoprotein whose steady-state localization is the plasma membrane
and adherens junction. Only the ~150-residue C-terminal cytoplasmic tail faces
the cytosol; the protein does not reside in or act within the cytoplasm as a
compartment. More precise CC terms (GO:0005886 plasma membrane, GO:0005912 adherens
junction) are accepted elsewhere in this file. Consistent with MARK_AS_OVER_ANNOTATED
on the IBA GO:0005737 row.'
reason: 'Over-broad CC for a single-pass transmembrane plasma-membrane protein;
only the cytoplasmic tail faces the cytosol; more precise CC terms (plasma membrane,
adherens junction) are accepted elsewhere. IEA batch (batch 3 of #348).'
qualifier: located_in
- term:
id: GO:0005768
label: endosome
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
action: KEEP_AS_NON_CORE
summary: 'IEA from UniProt-GOA (GO_REF:0000044): CDH1/E-cadherin undergoes clathrin-mediated
endocytosis and is trafficked through early endosomes during junction remodelling
and in response to growth factor signalling. Endosomal localisation is real
but is a trafficking/turnover context rather than the site of CDH1 core adhesion
and junction-organising function.'
reason: 'Real but non-core CC — endosomal localisation reflects CDH1 endocytic
turnover/recycling rather than core adhesion function; primary sites of CDH1
activity are plasma membrane and adherens junction. IEA batch (batch 3 of #348).'
qualifier: located_in
- term:
id: GO:0005794
label: Golgi apparatus
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
action: KEEP_AS_NON_CORE
summary: 'IEA from UniProt-GOA (GO_REF:0000044): CDH1 is glycosylated and processed
in the Golgi apparatus as part of the secretory pathway before reaching the
plasma membrane. Golgi localisation is real but represents a transient biosynthetic/processing
compartment rather than a site of CDH1 function.'
reason: 'Real but non-core CC — Golgi is a transient biosynthetic/processing compartment
for CDH1 maturation; core localisation and function are at the plasma membrane
and adherens junction. IEA batch (batch 3 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
action: ACCEPT
summary: 'IEA from UniProt keyword mapping (GO_REF:0000120): The plasma membrane
is the primary site of CDH1/E-cadherin localization and function. E-cadherin
concentrates at the lateral/basolateral plasma membrane of epithelial cells,
where it mediates homophilic trans-dimerisation and cell-cell adhesion. Consistent
with experimental IDA and TAS evidence on the same term elsewhere in this file.'
reason: 'Core CDH1 cellular component — the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity. IEA batch (batch
3 of #348).'
supported_by:
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: In epithelia, E‑cadherin is enriched at the **plasma membrane**
and concentrates at **adherens junctions** where it contributes to epithelial
sheet cohesion and tissue architecture
qualifier: located_in
- term:
id: GO:0005912
label: adherens junction
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
action: ACCEPT
summary: 'IEA from UniProt-GOA (GO_REF:0000044): The adherens junction is the
principal and defining site of CDH1/E-cadherin localization and function in
epithelial cells. E-cadherin is the core transmembrane component of the cadherin-catenin
complex at the adherens junction. Already ACCEPTed for the IBA annotation (GO_REF:0000033)
in this file.'
reason: 'Core CDH1 cellular component — the adherens junction is the defining
site of CDH1 localization and activity; consistent with IBA ACCEPT on this term
elsewhere in the file. IEA batch (batch 3 of #348).'
qualifier: located_in
- term:
id: GO:0007155
label: cell adhesion
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
action: ACCEPT
summary: 'IEA from InterPro2GO (GO_REF:0000002): Cell adhesion is the defining
biological process of CDH1/E-cadherin. E-cadherin mediates calcium-dependent
homophilic cell-cell adhesion between epithelial cells and is the founding member
of the classical cadherin family.'
reason: 'Core CDH1 biological process — cell adhesion is the defining function
of E-cadherin. IEA batch (batch 3 of #348).'
qualifier: involved_in
- term:
id: GO:0007156
label: homophilic cell-cell adhesion
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
action: ACCEPT
summary: 'IEA from InterPro2GO (GO_REF:0000002): Homophilic cell-cell adhesion
is the specific core mechanism of CDH1 — E-cadherin engages in calcium-dependent
homophilic trans-dimerisation with E-cadherin on adjacent cells, forming the
molecular basis of epithelial cell-cell adhesion.'
reason: 'Core CDH1 biological process — homophilic cell-cell adhesion via the
ectodomain strand-swap mechanism is the defining activity of E-cadherin. IEA
batch (batch 3 of #348).'
supported_by:
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: '**homophilic trans-binding** is driven primarily by the **EC1
domain** and proceeds through an **X-dimer intermediate** followed by formation
of a stable **strand-swapped dimer**, in which a **tryptophan side chain from
one EC1 inserts into a hydrophobic pocket** of the opposing EC1'
qualifier: involved_in
- term:
id: GO:0016020
label: membrane
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from InterPro2GO (GO_REF:0000002): CDH1 is a single-pass transmembrane
glycoprotein and is associated with membranes. However, GO:0016020 membrane
is a broad parent term. The precise CC annotations for CDH1 are GO:0005886 plasma
membrane (core, ACCEPTed) and GO:0005912 adherens junction. The generic membrane
annotation does not add information beyond the more specific terms.'
reason: GO:0016020 membrane is an uninformative broad parent term — CDH1 is a
single-pass transmembrane protein but the informative CC terms are GO:0005886
plasma membrane and GO:0005912 adherens junction (both ACCEPTed elsewhere);
the generic membrane term adds no annotation value. Consistent with the MARK_AS_OVER_ANNOTATED
treatment of the equally generic GO:0005737 cytoplasm rows. Action reconciled
with the IDA GO:0016020 row in this file (#348).
qualifier: located_in
- term:
id: GO:0030054
label: cell junction
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
action: KEEP_AS_NON_CORE
summary: 'IEA from HGNC (GO_REF:0000117): CDH1 localizes to cell junctions. However,
GO:0030054 cell junction is a broad parent term; the more specific and informative
CC annotation is GO:0005912 adherens junction (ACCEPTed in this file), which
is the precise junction type where E-cadherin resides and functions.'
reason: 'Broad parent CC — CDH1 localises to cell junctions but the precise junction
type is the adherens junction (GO:0005912, accepted elsewhere); the broad parent
term adds no annotation value. IEA batch (batch 3 of #348).'
qualifier: located_in
- term:
id: GO:0030057
label: desmosome
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
action: KEEP_AS_NON_CORE
summary: 'IEA from UniProt-GOA (GO_REF:0000044, the UniProtKB Subcellular Location
keyword-to-GO mapping — not generic cadherin-family domain mapping): CDH1/E-cadherin
localizes to desmosomes. UniProt P12830 curates "Cell junction, desmosome" as
an experimentally-supported subcellular location (ECO:0000269|PubMed:25208567,
PubMed:29999492, PubMed:33596089), and E-cadherin plays a role in the early
stages of desmosome cell-cell junction formation by facilitating recruitment
of DSG2 and DSP to desmosome plaques (PubMed:29999492). CDH1 is not itself a
desmosomal cadherin (those are the desmogleins/desmocollins), but its desmosome
localization and early-assembly role are genuine biology, not an over-annotation.
This is peripheral to the core E-cadherin function at the adherens junction
(GO:0005912, ACCEPTed in this file). Two IDA annotations on this term (PMID:33596089,
PMID:29999492) and an IMP on GO:0002159 desmosome assembly (PMID:29999492) are
PENDING for review in a later batch and should be reviewed consistently as KEEP_AS_NON_CORE.'
reason: 'GO_REF:0000044 propagates UniProt''s curated, experimentally-supported
"Cell junction, desmosome" subcellular location (ECO:0000269|PubMed:25208567/29999492/33596089)
— it is not generic domain mapping, and the desmosome localization plus early-desmosome-assembly
role are genuine but peripheral to the core adherens-junction function of E-cadherin.
Corrects the prior MARK_AS_OVER_ANNOTATED decision after a UniProt fact-check
(see issue #348). IEA batch (batch 3 of #348) follow-up.'
qualifier: located_in
- term:
id: GO:0034329
label: cell junction assembly
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
action: KEEP_AS_NON_CORE
summary: 'IEA from HGNC (GO_REF:0000117): CDH1 participates in cell junction assembly
— E-cadherin nucleates adherens junction assembly and via the catenin complex
templates subsequent tight junction assembly. GO:0034329 cell junction assembly
is valid but is a broad parent of GO:0007043 cell-cell junction assembly (already
ACCEPTed via IBA in this file).'
reason: 'Valid but broad parent BP — CDH1 participates in cell junction assembly
but the precise term GO:0007043 cell-cell junction assembly is already ACCEPTed
via IBA; broad parent adds no annotation value. IEA batch (batch 3 of #348).'
qualifier: involved_in
- term:
id: GO:0098609
label: cell-cell adhesion
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
action: ACCEPT
summary: 'IEA from InterPro2GO (GO_REF:0000002): Cell-cell adhesion is the core
biological process of CDH1/E-cadherin — the protein mediates calcium-dependent
homophilic cell-cell adhesion between adjacent epithelial cells. Consistent
with GO:0007155 cell adhesion (also ACCEPTed) and GO:0044331 cell-cell adhesion
mediated by cadherin (ACCEPTed via IBA in this file).'
reason: 'Core CDH1 biological process — cell-cell adhesion is the defining function
of E-cadherin; consistent with GO:0044331 (IBA ACCEPT) and GO:0007155 (IEA ACCEPT).
IEA batch (batch 3 of #348).'
qualifier: involved_in
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:11401320
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:11401320
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:12526809
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:12526809
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:15695390
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:15695390
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16212417
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:16212417
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:16983094
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:16983094
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17220478
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:17220478
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17237808
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:17237808
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17274640
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:17274640
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17715295
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:17715295
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18093941
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:18093941
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18593713
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:18593713
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19016843
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:19016843
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19604117
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:19604117
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19732724
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:19732724
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20802534
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:20802534
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20951947
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:20951947
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21685945
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:21685945
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22056988
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22056988
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22158051
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22158051
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22252131
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22252131
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22750944
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22750944
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24189400
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:24189400
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24424122
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:24424122
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24658140
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:24658140
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25241761
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:25241761
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25344754
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:25344754
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:31980649
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:31980649
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:32814053
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:32814053
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:33961781
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:33961781
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:34591612
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:34591612
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:35271311
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:35271311
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:19114658
review:
summary: CDH1 homodimerization documented by single-molecule force spectroscopy
(Zhang et al. 2009, PNAS). This study directly measured E-cadherin trans-dimerization
at the single-molecule level, confirming homophilic binding between CDH1 ectodomains
and characterizing binding cooperativity. CDH1 identical protein binding is
the molecular basis of homophilic cadherin-mediated cell adhesion.
action: ACCEPT
reason: CDH1 homodimerization (identical protein binding) is the molecular basis
of homophilic cadherin adhesion. This is a well-established, specific, and biologically
meaningful annotation — unlike the generic GO:0005515 protein binding rows removed
in batch 1. UniProt documents CDH1 as a disulfide-linked homodimer (PubMed:11856755).
ACCEPT.
qualifier: enables
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:19646884
review:
summary: CDH1 homodimerization detected by IntAct-curated physical interaction
experiment (PMID:19646884). CDH1 identical protein binding reflects the well-established
homophilic trans-dimerization mechanism that underlies cadherin-mediated cell-cell
adhesion. UniProt documents CDH1 as a disulfide-linked homodimer.
action: ACCEPT
reason: CDH1 homodimerization (identical protein binding) is the molecular basis
of homophilic cadherin adhesion. This is a well-established, specific, and biologically
meaningful annotation — unlike the generic GO:0005515 protein binding rows removed
in batch 1. UniProt documents CDH1 as a disulfide-linked homodimer (PubMed:11856755).
ACCEPT.
qualifier: enables
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:21300292
review:
summary: CDH1 homodimerization detected by IntAct-curated physical interaction
experiment (PMID:21300292). CDH1 identical protein binding reflects the well-established
homophilic trans-dimerization mechanism that underlies cadherin-mediated cell-cell
adhesion.
action: ACCEPT
reason: CDH1 homodimerization (identical protein binding) is the molecular basis
of homophilic cadherin adhesion. This is a well-established, specific, and biologically
meaningful annotation — unlike the generic GO:0005515 protein binding rows removed
in batch 1. UniProt documents CDH1 as a disulfide-linked homodimer (PubMed:11856755).
ACCEPT.
qualifier: enables
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:23112161
review:
summary: CDH1 homodimerization detected by IntAct-curated physical interaction
experiment (PMID:23112161). CDH1 identical protein binding reflects the well-established
homophilic trans-dimerization mechanism that underlies cadherin-mediated cell-cell
adhesion.
action: ACCEPT
reason: CDH1 homodimerization (identical protein binding) is the molecular basis
of homophilic cadherin adhesion. This is a well-established, specific, and biologically
meaningful annotation — unlike the generic GO:0005515 protein binding rows removed
in batch 1. UniProt documents CDH1 as a disulfide-linked homodimer (PubMed:11856755).
ACCEPT.
qualifier: enables
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:24725409
review:
summary: This GO:0042802 identical-protein-binding annotation derives from an
IntAct-curated interaction in Crawley et al. 2014 (PMID:24725409, Cell), a study
primarily about PCDH24/MLPCDH protocadherin-based intermicrovillar adhesion
driving intestinal brush border assembly. CDH1/E-cadherin is not a subject of
that paper — it appears only as a positive control in a bead aggregation assay
(Fig. 4B,C), where E-cadherin ectodomain-coated beads formed large aggregates,
demonstrating robust homophilic adhesion. The paper explicitly excludes CDH1
from further study because E-cadherin localizes to the basolateral compartment
rather than the brush border. The bead-aggregation control nonetheless confirms
CDH1 homophilic (identical protein) binding, consistent with the well-established
homophilic trans-dimerization mechanism underlying cadherin-mediated cell-cell
adhesion.
action: ACCEPT
reason: CDH1 homodimerization (identical protein binding) is the molecular basis
of homophilic cadherin adhesion — a well-established, specific, and biologically
meaningful annotation, unlike the generic GO:0005515 protein binding rows removed
in batch 1. PMID:24725409 is not a dedicated CDH1 study (E-cadherin serves only
as a bead-aggregation positive control there), but that control is genuine supporting
data, and CDH1 homophilic binding is independently established by the other
GO:0042802 IPI entries — notably the single-molecule force spectroscopy of PMID:19114658
— and by UniProt, which documents CDH1 as a disulfide-linked homodimer (PubMed:11856755).
ACCEPT.
qualifier: enables
- term:
id: GO:0042802
label: identical protein binding
evidence_type: IPI
original_reference_id: PMID:35922511
review:
summary: CDH1 homodimerization detected in a physical wiring screen of the human
immune system (Shilts et al. 2022, Nature). CDH1 identical protein binding reflects
the well-established homophilic trans-dimerization mechanism that underlies
cadherin-mediated cell-cell adhesion; this large-scale screen provides additional
proteomics-level support for CDH1 self-interaction.
action: ACCEPT
reason: CDH1 homodimerization (identical protein binding) is the molecular basis
of homophilic cadherin adhesion. This is a well-established, specific, and biologically
meaningful annotation — unlike the generic GO:0005515 protein binding rows removed
in batch 1. UniProt documents CDH1 as a disulfide-linked homodimer (PubMed:11856755).
ACCEPT.
qualifier: enables
- term:
id: GO:0007416
label: synapse assembly
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: KEEP_AS_NON_CORE
summary: 'IEA from Ensembl (GO_REF:0000107): Synapse assembly is a neural cadherin
function attributed to CDH1 by Ensembl electronic propagation from neural cadherin
subfamilies. E-cadherin has documented roles at neuronal synapses in neural
tissue contexts, but this is a tissue-specific non-core context for canonical
epithelial CDH1. Consistent with the IBA annotation on this same term (KEEP_AS_NON_CORE)
in this file.'
reason: 'Tissue/cell-type-specific neuronal context rather than a core epithelial
CDH1 function; consistent with IBA KEEP_AS_NON_CORE on this term. IEA batch
(batch 3 of #348).'
qualifier: involved_in
- term:
id: GO:0008013
label: beta-catenin binding
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
action: ACCEPT
summary: 'IEA from UniProt keyword mapping (GO_REF:0000120): Beta-catenin binding
by the CDH1 cytoplasmic tail is the canonical molecular mechanism of the cadherin-catenin
complex. The E-cadherin cytoplasmic domain directly binds beta-catenin (CTNNB1);
this interaction links the cadherin to the actin cytoskeleton via alpha-catenin
and is the basis of the adherens junction. Already ACCEPTed for the IBA annotation
in this file.'
reason: 'Core CDH1 molecular function — beta-catenin binding by the cytoplasmic
domain is the canonical interaction of the cadherin-catenin complex; consistent
with IBA ACCEPT on this term. IEA batch (batch 3 of #348).'
qualifier: enables
- term:
id: GO:0009410
label: response to xenobiotic stimulus
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from Ensembl (GO_REF:0000107): There is no established direct role
for CDH1/E-cadherin in responding to xenobiotic stimuli. CDH1 expression may
change after toxic/xenobiotic exposure in some organisms as a secondary transcriptional
effect, but this does not constitute a direct CDH1 molecular function in xenobiotic
sensing or response.'
reason: 'No direct CDH1 role in xenobiotic response; Ensembl IEA likely propagated
from toxicology studies where CDH1 expression changed as a secondary effect;
not a core CDH1 function. IEA batch (batch 3 of #348).'
qualifier: involved_in
- term:
id: GO:0009636
label: response to toxic substance
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from Ensembl (GO_REF:0000107): Response to toxic substance is not
a CDH1 core function. CDH1/E-cadherin is a cell-cell adhesion molecule; its
expression may change under toxic conditions as a secondary effect but this
does not constitute a direct CDH1 molecular function. Co-propagated with GO:0009410
from the same Ensembl ortholog source.'
reason: 'No direct CDH1 role in toxic-substance response; co-propagated with GO:0009410
from Ensembl; secondary CDH1 expression changes under toxic conditions are not
a core CDH1 function. IEA batch (batch 3 of #348).'
qualifier: involved_in
- term:
id: GO:0021983
label: pituitary gland development
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from Ensembl (GO_REF:0000107): Pituitary gland development is not
a core CDH1 function. CDH1/E-cadherin may be expressed in pituitary cells but
pituitary gland development is a tissue-specific, context-dependent association
rather than a defining function of E-cadherin. Likely propagated from a pituitary-expressing
cadherin ortholog annotation.'
reason: 'Tissue-specific context not representing a core CDH1 function; CDH1 may
be expressed in pituitary but pituitary gland development is not a defining
E-cadherin activity; Ensembl electronic propagation. IEA batch (batch 3 of #348).'
qualifier: involved_in
- term:
id: GO:0030517
label: negative regulation of axon extension
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from Ensembl (GO_REF:0000107): Negative regulation of axon extension
is a neural cadherin function (N-cadherin/CDH2 and type II cadherins mediate
contact-inhibition of axon extension). CDH1/E-cadherin is primarily an epithelial
adhesion molecule; this Ensembl IEA annotation was propagated from a neural
cadherin subfamily annotation.'
reason: 'Neural cadherin function attributed to epithelial CDH1 by Ensembl propagation;
negative regulation of axon extension is mediated by neural cadherins (CDH2
etc.), not CDH1. IEA batch (batch 3 of #348).'
qualifier: involved_in
- term:
id: GO:0031175
label: neuron projection development
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from Ensembl (GO_REF:0000107): Neuron projection development is
a neural cadherin function. CDH1/E-cadherin is an epithelial cell adhesion molecule;
neuron projection development is not a core CDH1 function. Propagated from neural
cadherin annotations, analogous to the synapse assembly and axon extension IEA
annotations in this batch.'
reason: 'Neural cadherin function attributed to epithelial CDH1 by Ensembl propagation;
neuron projection development is not a core E-cadherin function. IEA batch (batch
3 of #348).'
qualifier: involved_in
- term:
id: GO:0071503
label: response to heparin
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from Ensembl (GO_REF:0000107): Response to heparin is not a CDH1
core function. CDH1/E-cadherin adhesion does not depend on heparin and there
is no established CDH1-specific role in heparin sensing or response. This Ensembl
IEA annotation likely reflects non-specific propagation from another cadherin
family member or indirect experimental observation.'
reason: 'No established CDH1 role in heparin response; Ensembl electronic propagation
from a non-CDH1 cadherin or indirect experimental observation. IEA batch (batch
3 of #348).'
qualifier: involved_in
- term:
id: GO:0098794
label: postsynapse
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from Ensembl (GO_REF:0000107): The postsynapse is a neural compartment
at excitatory and inhibitory synapses. CDH1/E-cadherin is not a canonical postsynaptic
protein; this GO location is associated with neural cadherins (CDH2) and protocadherins.
This Ensembl IEA annotation was propagated from neural cadherin annotations.'
reason: 'Neural synaptic CC attributed to epithelial CDH1 by Ensembl propagation;
CDH1 is not a postsynaptic component; this location is specific to neural/synaptic
cadherins. IEA batch (batch 3 of #348).'
qualifier: is_active_in
- term:
id: GO:0098978
label: glutamatergic synapse
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from Ensembl (GO_REF:0000107): The glutamatergic synapse is a specific
neural compartment. CDH1/E-cadherin is not a glutamatergic synapse component;
this is a neural cadherin function. Propagated from neural cadherin family annotations
in the same batch as GO:0098794 postsynapse and GO:0007416 synapse assembly.'
reason: 'Neural synaptic CC attributed to epithelial CDH1 by Ensembl propagation;
CDH1 is not a glutamatergic synapse component. IEA batch (batch 3 of #348).'
qualifier: is_active_in
- term:
id: GO:0099576
label: regulation of protein catabolic process at postsynapse, modulating synaptic
transmission
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from Ensembl (GO_REF:0000107): Regulation of protein catabolic process
at the postsynapse is a highly specific neural synaptic process. CDH1/E-cadherin
is not a canonical synaptic protein and does not regulate postsynaptic protein
catabolism. This IEA annotation was propagated from neural cadherin annotations.'
reason: 'Highly specific neural synaptic process attributed to epithelial CDH1
by Ensembl propagation; CDH1 does not regulate postsynaptic protein catabolism.
IEA batch (batch 3 of #348).'
qualifier: involved_in
- term:
id: GO:0140459
label: response to Gram-positive bacterium
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IEA from Ensembl (GO_REF:0000107): While CDH1/E-cadherin is the host
receptor for Listeria monocytogenes (a Gram-positive bacterium) via the bacterial
internalin InlA, this represents pathogen exploitation of a host cell-surface
receptor, not a core CDH1 biological function. Annotating CDH1 as responding
to Gram-positive bacteria conflates bacterial hijacking of a host receptor with
an intrinsic CDH1 function.'
reason: 'Pathogen exploitation (Listeria InlA uses CDH1 as an invasion receptor)
is not a core CDH1 function; annotating CDH1 as responding to Gram-positive
bacteria conflates bacterial hijacking with intrinsic receptor function. IEA
batch (batch 3 of #348).'
qualifier: involved_in
- term:
id: GO:1990782
label: protein tyrosine kinase binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
action: KEEP_AS_NON_CORE
summary: 'IEA from Ensembl (GO_REF:0000107): CDH1/E-cadherin cytoplasmic domain
interactions with protein tyrosine kinases (PTKs) are documented — Src family
kinases phosphorylate the CDH1 cytoplasmic tail and regulate E-cadherin adhesion,
and receptor tyrosine kinases including EGFR/HER2 interact with CDH1. However,
protein tyrosine kinase binding is a regulatory modulation of the core adhesion
activity, not a core CDH1 molecular function. IEA evidence from Ensembl provides
lower confidence than direct experimental evidence.'
reason: 'CDH1 cytoplasmic tail interacts with Src/EGFR/HER2 PTKs modulating E-cadherin
function, but PTK binding is a regulatory modulation rather than a core CDH1
MF; lower-confidence Ensembl IEA. IEA batch (batch 3 of #348).'
qualifier: enables
- term:
id: GO:0005576
label: extracellular region
evidence_type: IDA
original_reference_id: PMID:34742300
review:
action: ACCEPT
summary: 'IDA from PMID:34742300 (Bernegger et al. 2021): H. pylori HtrA protease
cleaves E-cadherin''s extracellular ectodomain, directly confirming the extracellular
localization of E-cadherin''s cadherin repeat domains. The ectodomain''s extracellular
region is core to E-cadherin''s homophilic trans-adhesion mechanism.'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:36309486
review:
action: ACCEPT
summary: 'IDA from PMID:36309486 (Myo Min KK et al. 2022): E-cadherin plasma membrane
localization confirmed in islet/epithelial context. Plasma membrane is the canonical
and core localization for functional E-cadherin mediating cell-cell adhesion.'
qualifier: located_in
- term:
id: GO:0030057
label: desmosome
evidence_type: IDA
original_reference_id: PMID:33596089
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:33596089 (Raya-Sandino et al. 2021): E-cadherin is detected
at desmosomes in intestinal epithelial cells in the context of desmocollin-2
regulation of adhesion. Consistent with the direct evidence in PMID:29999492
that E-cadherin is enriched in nascent desmosomes but diminishes as desmosomes
mature; E-cadherin facilitates desmosome assembly but is not a stable resident
of mature desmosome structures.'
reason: 'E-cadherin appears at nascent desmosomal contacts as part of junction
initiation (its trans-adhesion recruits desmosomal cadherins), but mature desmosomes
are composed primarily of desmoglein/desmocollin — not E-cadherin. Desmosomal
localization is a transient non-core CC. Batch 5 of #348.'
qualifier: located_in
- term:
id: GO:0005794
label: Golgi apparatus
evidence_type: IDA
original_reference_id: GO_REF:0000052
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from GO_REF:0000052 (UniProtKB keyword-to-GO mapping): E-cadherin
transits through the Golgi apparatus during biosynthesis and post-translational
N-glycosylation (critical for correct E-cadherin folding and function). Golgi
localization is a real but non-core CC reflecting biosynthetic/trafficking transit.'
reason: 'Golgi localization is part of the E-cadherin biosynthetic pathway, not
its core adhesive function site. Core CC is plasma membrane/adherens junction.
Batch 5 of #348.'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: GO_REF:0000052
review:
action: ACCEPT
summary: 'IDA from GO_REF:0000052 (UniProtKB keyword-to-GO mapping): Plasma membrane
localization is the canonical site for functional E-cadherin. E-cadherin is
a type-I transmembrane protein whose extracellular cadherin domains mediate
homophilic trans-adhesion at the plasma membrane — unambiguously core CC.'
qualifier: located_in
- term:
id: GO:0030054
label: cell junction
evidence_type: IDA
original_reference_id: GO_REF:0000052
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from GO_REF:0000052 (UniProtKB keyword-to-GO mapping): E-cadherin
is the canonical adhesion receptor at cell-cell junctions. GO:0030054 cell junction
is the broad parent of GO:0005912 adherens junction; it is a valid CC annotation
but the precise core localization is the adherens junction, ACCEPTed elsewhere
in this file.'
reason: 'Broad parent CC — GO:0030054 cell junction is the direct parent of GO:0005912
adherens junction, the precise core CC for E-cadherin (ACCEPTed in this file).
A real but non-core annotation: the informative term is the specific adherens
junction. Action reconciled with the IEA and TAS GO:0030054 rows in this file
(#348).'
qualifier: located_in
- term:
id: GO:0005768
label: endosome
evidence_type: EXP
original_reference_id: PMID:15689490
review:
action: KEEP_AS_NON_CORE
summary: 'EXP from PMID:15689490 (Lock and Stow 2005): Rab11-positive recycling
endosomes are an intermediate compartment for post-Golgi trafficking and exocytic
delivery of E-cadherin to the basolateral plasma membrane. Endosomal localization
is real and functionally important for E-cadherin surface delivery, but represents
trafficking transit rather than the core functional site.'
reason: 'E-cadherin transits through recycling endosomes during biosynthetic delivery
to the basolateral membrane — a real but non-core CC. Core localization is at
the plasma membrane/adherens junction. Batch 5 of #348.'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: EXP
original_reference_id: PMID:19403558
review:
action: ACCEPT
summary: 'EXP from PMID:19403558 (Pinho et al. 2009): GnT-III knockdown causes
membrane de-localization of E-cadherin leading to cytoplasmic accumulation,
confirming that plasma membrane is the normal core localization of E-cadherin.
Wild-type E-cadherin is robustly present at the plasma membrane.'
qualifier: located_in
- term:
id: GO:0098631
label: cell adhesion mediator activity
evidence_type: IDA
original_reference_id: PMID:11976333
review:
action: ACCEPT
summary: 'IDA from PMID:11976333 (Meigs et al. 2002): Galpha12/13 negatively regulate
the adhesive functions of E-cadherin. The cell-adhesion-mediator-activity annotation
is directly supported — E-cadherin functions as a cell adhesion mediator, and
Galpha12/13 block cadherin-mediated cell adhesion in K562 and breast cancer
cells. Cell adhesion mediator activity is core MF for E-cadherin.'
qualifier: enables
- term:
id: GO:0005765
label: lysosomal membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9935547
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9935547): Endocytosed, ubiquitinated CDH1/E-cadherin
is sorted to lysosomes for degradation as part of junction turnover and downregulation.
Lysosomal localization is real but reflects CDH1 degradative turnover rather
than the site of its core adhesion function.'
reason: 'Real but non-core CC -- lysosomal localization reflects CDH1 degradative
turnover; core localization and function are at the plasma membrane and adherens
junction. Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005765
label: lysosomal membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9935552
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9935552): Endocytosed, ubiquitinated CDH1/E-cadherin
is sorted to lysosomes for degradation as part of junction turnover and downregulation.
Lysosomal localization is real but reflects CDH1 degradative turnover rather
than the site of its core adhesion function.'
reason: 'Real but non-core CC -- lysosomal localization reflects CDH1 degradative
turnover; core localization and function are at the plasma membrane and adherens
junction. Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934752
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9934752): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934753
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9934753): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0031901
label: early endosome membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934752
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9934752): CDH1/E-cadherin undergoes clathrin-mediated
endocytosis and is trafficked through early endosomes during junction remodelling,
recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination).
Early endosome localization is real but reflects CDH1 trafficking/turnover rather
than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE
on the IEA endosome annotation in this file.'
reason: 'Real but non-core CC -- early endosome localization reflects CDH1 endocytic
trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row.
Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0031901
label: early endosome membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9935552
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9935552): CDH1/E-cadherin undergoes clathrin-mediated
endocytosis and is trafficked through early endosomes during junction remodelling,
recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination).
Early endosome localization is real but reflects CDH1 trafficking/turnover rather
than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE
on the IEA endosome annotation in this file.'
reason: 'Real but non-core CC -- early endosome localization reflects CDH1 endocytic
trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row.
Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934751
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9934751): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934755
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9934755): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9766227
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9766227): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934584
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9934584): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0031901
label: early endosome membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9766223
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9766223): CDH1/E-cadherin undergoes clathrin-mediated
endocytosis and is trafficked through early endosomes during junction remodelling,
recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination).
Early endosome localization is real but reflects CDH1 trafficking/turnover rather
than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE
on the IEA endosome annotation in this file.'
reason: 'Real but non-core CC -- early endosome localization reflects CDH1 endocytic
trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row.
Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0031901
label: early endosome membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934584
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9934584): CDH1/E-cadherin undergoes clathrin-mediated
endocytosis and is trafficked through early endosomes during junction remodelling,
recycling, and degradative sorting (e.g. following CBLL1/Hakai-mediated ubiquitination).
Early endosome localization is real but reflects CDH1 trafficking/turnover rather
than the site of its core adhesion function. Consistent with KEEP_AS_NON_CORE
on the IEA endosome annotation in this file.'
reason: 'Real but non-core CC -- early endosome localization reflects CDH1 endocytic
trafficking/turnover; consistent with KEEP_AS_NON_CORE on the IEA endosome row.
Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9766219
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9766219): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9816278
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9816278): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9817325
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9817325): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9817330
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9817330): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934294
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9934294): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934410
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9934410): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934411
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9934411): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934486
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9934486): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0000139
label: Golgi membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9816275
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9816275): CDH1/E-cadherin transits and is further
processed/glycosylated in the Golgi apparatus en route from the ER to the plasma
membrane. Golgi localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function. Consistent
with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.'
reason: 'Real but non-core CC -- the Golgi is a transient biosynthetic/processing
compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA
Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0000139
label: Golgi membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9816278
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9816278): CDH1/E-cadherin transits and is further
processed/glycosylated in the Golgi apparatus en route from the ER to the plasma
membrane. Golgi localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function. Consistent
with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.'
reason: 'Real but non-core CC -- the Golgi is a transient biosynthetic/processing
compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA
Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0000139
label: Golgi membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9934330
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9934330): CDH1/E-cadherin transits and is further
processed/glycosylated in the Golgi apparatus en route from the ER to the plasma
membrane. Golgi localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function. Consistent
with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.'
reason: 'Real but non-core CC -- the Golgi is a transient biosynthetic/processing
compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA
Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0000139
label: Golgi membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9935209
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9935209): CDH1/E-cadherin transits and is further
processed/glycosylated in the Golgi apparatus en route from the ER to the plasma
membrane. Golgi localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function. Consistent
with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.'
reason: 'Real but non-core CC -- the Golgi is a transient biosynthetic/processing
compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA
Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005796
label: Golgi lumen
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9816275
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9816275): CDH1/E-cadherin transits and is further
processed/glycosylated in the Golgi apparatus en route from the ER to the plasma
membrane. Golgi localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function. Consistent
with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.'
reason: 'Real but non-core CC -- the Golgi is a transient biosynthetic/processing
compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA
Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0000139
label: Golgi membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9816273
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9816273): CDH1/E-cadherin transits and is further
processed/glycosylated in the Golgi apparatus en route from the ER to the plasma
membrane. Golgi localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function. Consistent
with KEEP_AS_NON_CORE on the IEA Golgi apparatus annotation in this file.'
reason: 'Real but non-core CC -- the Golgi is a transient biosynthetic/processing
compartment for CDH1 maturation; consistent with KEEP_AS_NON_CORE on the IEA
Golgi apparatus row. Reactome TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9816273
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9816273): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9933194
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9933194): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9933380
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9933380): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9816277
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9816277): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9932352
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9932352): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9932913
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9932913): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9932988
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9932988): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9816276
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9816276): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9932344
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9932344): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005788
label: endoplasmic reticulum lumen
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9932162
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9932162): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9932162
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9932162): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0002159
label: desmosome assembly
evidence_type: IMP
original_reference_id: PMID:29999492
review:
action: KEEP_AS_NON_CORE
summary: 'IMP from PMID:29999492 (Shafraz et al. 2018): E-cadherin cis-dimerization
site (Leu-175) is required for efficient desmoglein-2 (Dsg2) recruitment and
desmosome assembly in keratinocytes. E-cadherin facilitates desmosome assembly
by initially recruiting Dsg2 via a direct Ca2+-independent heterophilic interaction,
with Ecad levels in desmosomes decreasing as junctions mature.'
reason: 'E-cadherin''s role in desmosome assembly is real but non-core — it facilitates
early desmosomal junction initiation as an auxiliary function. E-cadherin''s
primary role is adherens junction formation and homophilic cadherin-mediated
cell-cell adhesion. Batch 5 of #348.'
qualifier: involved_in
- term:
id: GO:0030057
label: desmosome
evidence_type: IDA
original_reference_id: PMID:29999492
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:29999492 (Shafraz et al. 2018): Super-resolution imaging
shows E-cadherin is enriched in nascent desmosomes (1 hr after Ca2+ switch),
declining 50% as desmosomes mature by 18 hr. E-cadherin transiently localizes
to nascent desmosomal sites where it recruits Dsg2, but is displaced from mature
desmosomes.'
reason: 'Desmosomal localization is transient and non-core for E-cadherin — it
functions to nucleate early junction formation but is not a permanent resident
of mature desmosomes (desmoglein/desmocollin are the stable components). Core
CC is plasma membrane/adherens junction. Batch 5 of #348.'
qualifier: located_in
- term:
id: GO:1903829
label: positive regulation of protein localization
evidence_type: IMP
original_reference_id: PMID:29999492
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IMP from PMID:29999492 (Shafraz et al. 2018): E-cadherin promotes Dsg2
localization to intercellular contacts, supporting positive regulation of protein
localization. However, GO:1903829 (positive regulation of protein localization)
is too general — this specific function is better captured by the co-annotated
GO:0002159 (desmosome assembly) from the same paper and same experiment.'
reason: 'GO:1903829 is an overly broad parent term; the actual function is promotion
of desmosomal cadherin (Dsg2) localization to nascent junctions, captured more
specifically by GO:0002159 desmosome assembly. Per CLAUDE.md: prefer informative
specific terms. Batch 5 of #348.'
qualifier: involved_in
- term:
id: GO:0008013
label: beta-catenin binding
evidence_type: IPI
original_reference_id: PMID:18593713
review:
action: ACCEPT
summary: 'IPI from PMID:18593713 (Tang et al. 2008): Smad7 stabilizes the beta-catenin-E-cadherin
complex at the plasma membrane. E-cadherin physically binds beta-catenin through
its cytoplasmic tail — this is the canonical CDH1-CTNNB1 armadillo repeat interaction
that links E-cadherin to the actin cytoskeleton via alpha-catenin. Beta-catenin
binding is core MF for E-cadherin.'
qualifier: enables
- term:
id: GO:0044331
label: cell-cell adhesion mediated by cadherin
evidence_type: IDA
original_reference_id: PMID:18593713
review:
action: ACCEPT
summary: 'IDA from PMID:18593713 (Tang et al. 2008): Smad7 promotes cell-cell
adhesion by increasing the beta-catenin-E-cadherin complex level at the plasma
membrane. Cell-cell adhesion mediated by cadherin is the defining core BP for
E-cadherin, confirmed in this study through perturbation of the cadherin complex.'
qualifier: involved_in
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22294297
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22294297
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:22294297
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IDA from PMID:22294297 (Tsang et al. 2012): The paper studies how non-junctional
Dsg3 regulates Src and E-cadherin junction assembly. GO:0005737 (cytoplasm)
for E-cadherin is over-annotated — E-cadherin has a cytoplasmic tail engaged
at the adherens junction, but annotating the entire cytoplasm as E-cadherin''s
CC is non-informative and too general. The more informative and specific CC
is GO:0005912 (adherens junction), which is also annotated from this paper.'
reason: 'GO:0005737 cytoplasm is a highly non-specific CC for a transmembrane
protein like E-cadherin whose cytoplasmic domain localizes to the adherens junction
plaque; the adherens junction annotation from the same study captures the relevant
specificity. Batch 5 of #348.'
qualifier: located_in
- term:
id: GO:0005912
label: adherens junction
evidence_type: IDA
original_reference_id: PMID:22294297
review:
action: ACCEPT
summary: 'IDA from PMID:22294297 (Tsang et al. 2012): Non-junctional Dsg3 regulates
Src and E-cadherin adherens junction formation. Adherens junction is the core
CC for functional E-cadherin — E-cadherin organizes with beta-catenin, alpha-catenin,
and p120-catenin at adherens junctions to mediate epithelial cell-cell adhesion.'
qualifier: located_in
- term:
id: GO:0005912
label: adherens junction
evidence_type: IDA
original_reference_id: PMID:18343367
review:
action: ACCEPT
summary: 'IDA from PMID:18343367: Adherens junction localization of E-cadherin
confirmed experimentally. Core CC for E-cadherin — adherens junctions are the
primary site of E-cadherin-mediated cell-cell adhesion in epithelial cells.'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:20859650
review:
action: ACCEPT
summary: 'IDA from PMID:20859650: Plasma membrane localization of E-cadherin confirmed.
Core CC — E-cadherin is a type-I transmembrane protein that localizes to the
basolateral plasma membrane of epithelial cells where it mediates homophilic
adhesion.'
qualifier: located_in
- term:
id: GO:0005912
label: adherens junction
evidence_type: IDA
original_reference_id: PMID:27760340
review:
action: ACCEPT
summary: 'IDA from PMID:27760340: Adherens junction localization confirmed experimentally.
Core CC for E-cadherin.'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9768614
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9768614): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9768618
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from Reactome (R-HSA-9768618): As a secretory-pathway transmembrane
glycoprotein, pro-CDH1/E-cadherin is co-translationally inserted into, N-glycosylated,
and folded within the endoplasmic reticulum before transport to the Golgi and
plasma membrane. ER localization is real but represents a transient biosynthetic/processing
compartment rather than the site of CDH1 core adhesion function.'
reason: 'Real but non-core CC -- the endoplasmic reticulum is a transient biosynthetic/folding
compartment for CDH1 maturation; core localization and function are at the plasma
membrane and adherens junction. Reactome TAS localization batch (batch 4 of
#348).'
qualifier: located_in
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:11790773
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:11790773
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:10725230
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:10725230
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0034332
label: adherens junction organization
evidence_type: IMP
original_reference_id: PMID:21724833
review:
action: ACCEPT
summary: 'IMP from PMID:21724833 (Lin et al. 2011): PTPN23 knockdown increases
E-cadherin internalization and impairs adherens junction integrity, identifying
E-cadherin as a key regulator/component of adherens junction organization. E-cadherin
is the core structural component whose proper trafficking and membrane retention
is essential for adherens junction maintenance.'
qualifier: involved_in
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:31473225
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:31473225
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0010468
label: regulation of gene expression
evidence_type: IMP
original_reference_id: PMID:19403558
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IMP from PMID:19403558 (Pinho et al. 2009): Wild-type E-cadherin regulates
MGAT3 (GnT-III) gene transcription. While E-cadherin can influence downstream
gene expression programs (e.g., via beta-catenin sequestration or epithelial
differentiation signaling), GO:0010468 (regulation of gene expression) is far
too general an annotation for this specific MGAT3-regulatory phenotype. If retained,
a more specific term like ''regulation of gene transcription by E-cadherin''
would be needed, but no such specific GO term exists; the general parent is
non-informative.'
reason: 'Over-annotated: the specific CDH1 regulatory activity on MGAT3 transcription
is a very narrow context-specific function, not a general gene-expression regulatory
role of E-cadherin. GO:0010468 is too broad to be informative for curation.
Batch 5 of #348.'
qualifier: involved_in
- term:
id: GO:0030336
label: negative regulation of cell migration
evidence_type: IMP
original_reference_id: PMID:16882694
review:
action: ACCEPT
summary: 'IMP from PMID:16882694: E-cadherin mutant phenotype supports its role
as negative regulator of cell migration. E-cadherin is a well-established suppressor
of epithelial cell migration and invasion — loss of E-cadherin is a hallmark
of EMT and tumor invasion. This is a core BP function of E-cadherin.'
supported_by:
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: EMT programs repress E‑cadherin and that such loss contributes
to invasion and metastasis
qualifier: involved_in
- term:
id: GO:0045296
label: cadherin binding
evidence_type: HDA
original_reference_id: PMID:25468996
review:
action: ACCEPT
summary: 'HDA from PMID:25468996 (Guo et al. 2014): E-cadherin interactome quantitative
proteomics using proximity biotinylation (BioID). Cadherin binding is confirmed
— E-cadherin mediates homophilic trans-adhesion by binding to E-cadherin on
opposing cells (strand-swap dimer) and to other cadherin family members. Cadherin
binding is core MF for E-cadherin.'
qualifier: enables
- term:
id: GO:0042307
label: positive regulation of protein import into nucleus
evidence_type: IDA
original_reference_id: PMID:16338932
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin-dependent cell-cell
adhesion controls nuclear abundance of HNF4alpha in Caco-2 enterocytes, linking
E-cadherin engagement to increased nuclear import of this transcription factor.
This is an indirect downstream signaling consequence of E-cadherin adhesion,
not a direct E-cadherin MF.'
reason: 'Positive regulation of protein import into nucleus is an indirect consequence
of E-cadherin-mediated adhesion signaling (via HNF4alpha redistribution), not
a core CDH1 function. E-cadherin''s primary role is cell-cell adhesion at adherens
junctions. Batch 5 of #348.'
qualifier: involved_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:28301459
review:
action: ACCEPT
summary: 'IDA from PMID:28301459: Plasma membrane localization of E-cadherin confirmed
experimentally. Core CC.'
qualifier: located_in
- term:
id: GO:0030054
label: cell junction
evidence_type: IDA
original_reference_id: PMID:28169360
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:28169360: Cell junction localization of E-cadherin confirmed
experimentally. GO:0030054 cell junction is the broad parent of GO:0005912 adherens
junction; the precise core CC is the adherens junction, ACCEPTed elsewhere in
this file.'
reason: 'Broad parent CC — GO:0030054 cell junction is the direct parent of GO:0005912
adherens junction, the precise core CC for E-cadherin (ACCEPTed in this file).
A real but non-core annotation: the informative term is the specific adherens
junction. Action reconciled with the IEA and TAS GO:0030054 rows in this file
(#348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8876948
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-8876948): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8876993
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-8876993): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8877003
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-8877003): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005912
label: adherens junction
evidence_type: IDA
original_reference_id: PMID:24046456
review:
action: ACCEPT
summary: 'IDA from PMID:24046456 (Guillaume et al. 2013): Flotillins stabilize
E-cadherin at cell-cell junctions; flotillin and E-cadherin complexes co-localize
at CCJs. Adherens junction is confirmed as core CC for E-cadherin.'
qualifier: located_in
- term:
id: GO:0016600
label: flotillin complex
evidence_type: IDA
original_reference_id: PMID:24046456
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IDA from PMID:24046456 (Guillaume et al. 2013): E-cadherin and flotillin
1/2 are ''constitutively associated at the plasma membrane'' and co-localize
at cell-cell junctions. E-cadherin associates with flotillin-containing lipid
raft microdomains at CCJs; flotillins are required for cadherin stabilization
at CCJs.'
reason: E-cadherin is recruited to flotillin-1/-2 membrane microdomains that stabilize
cadherins at cell-cell junctions (PMID:24046456), but it is not a structural
subunit of the flotillin complex. The part_of GO:0016600 qualifier overstates
this microdomain association as constitutive complex membership — not entirely
wrong but an over-annotation. Action reconciled with the IBA GO:0016600 row
in this file (#348).
qualifier: part_of
- term:
id: GO:0030027
label: lamellipodium
evidence_type: IDA
original_reference_id: PMID:24046456
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IDA from PMID:24046456 (Guillaume et al. 2013): The paper describes
flotillin 1/2 as new partners of the cadherin complex that stabilize E-cadherin
at cell-cell junctions (CCJs). The abstract focuses exclusively on CCJ biology:
flotillins co-localize with cadherins at CCJs, are required for cadherin recruitment
to CCJs, and mediate cadherin association with GM1-containing plasma membrane
microdomains. Lamellipodium (GO:0030027) — an actin-rich protrusion at the leading
edge of migrating cells — is mechanistically and spatially distinct from a stable
epithelial CCJ. The abstract makes no mention of lamellipodia.'
reason: The paper is entirely about E-cadherin stabilization at CCJs via flotillin
microdomains; the abstract contains no evidence for E-cadherin in lamellipodia.
CDH1 core CC is the adherens junction/plasma membrane (both ACCEPTed in this
file). Lamellipodium is a migrating-cell leading-edge structure mechanistically
distinct from the stable epithelial CCJ context studied in this paper. The annotation
is not supported by the abstract and is inconsistent with the paper's experimental
focus. MARK_AS_OVER_ANNOTATED rather than REMOVE because full text was not accessible,
but abstract evidence strongly argues against this localization.
qualifier: located_in
- term:
id: GO:0030864
label: cortical actin cytoskeleton
evidence_type: IDA
original_reference_id: PMID:24046456
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:24046456 (Guillaume et al. 2013): Cadherin and flotillin
complexes are associated with F-actin bundles at cell-cell junctions via flotillin
microdomains. E-cadherin associates with the cortical actin cytoskeleton through
catenin-actin linkages (alpha-catenin links the cadherin-catenin complex to
F-actin).'
reason: 'Cortical actin association is mechanistically real for E-cadherin (via
alpha-catenin) but represents the actin-anchoring support for adherens junctions,
not a core CDH1 CC. Core CC is the adherens junction/plasma membrane. Batch
5 of #348.'
qualifier: colocalizes_with
- term:
id: GO:0050839
label: cell adhesion molecule binding
evidence_type: IPI
original_reference_id: PMID:21724833
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IPI from PMID:21724833 (Lin et al. 2011): E-cadherin identified as a
direct substrate of PTPN23, implying physical interaction. GO:0050839 (cell
adhesion molecule binding) is too general — E-cadherin''s specific binding partners
relevant to its adhesion function are more informatively captured by GO:0008013
(beta-catenin binding), GO:0045296 (cadherin binding), and GO:0045295 (gamma-catenin
binding) already annotated in this file.'
reason: 'GO:0050839 cell adhesion molecule binding is uninformative relative to
specific partner terms; PTPN23 is a phosphatase, not a canonical cell adhesion
molecule. Per CLAUDE.md, prefer specific functional interaction terms over generic
binding. Batch 5 of #348.'
qualifier: enables
- term:
id: GO:0070062
label: extracellular exosome
evidence_type: HDA
original_reference_id: PMID:23533145
review:
action: KEEP_AS_NON_CORE
summary: 'HDA from PMID:23533145 (Principe et al. 2013): E-cadherin identified
by shotgun proteomics in exosomes from expressed prostatic secretions. E-cadherin
as a type-I transmembrane surface glycoprotein can be shed in membrane vesicles/exosomes;
exosomal release of E-cadherin (or its ectodomain fragments) is real but represents
a minor non-core aspect of E-cadherin biology.'
reason: 'Extracellular exosome localization is a non-core CC reflecting passive
vesicular shedding or secretion of E-cadherin/ectodomain fragments. Core localization
is at the plasma membrane/adherens junction in epithelial cells. HDA evidence
from large-scale proteomics. Batch 5 of #348.'
qualifier: located_in
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23086448
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:23086448
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0072659
label: protein localization to plasma membrane
evidence_type: IMP
original_reference_id: PMID:20859650
review:
action: KEEP_AS_NON_CORE
summary: 'IMP from PMID:20859650: Mutant phenotype supports E-cadherin''s role
in protein localization to plasma membrane — loss of E-cadherin or related perturbation
affects surface delivery. E-cadherin localization to the plasma membrane is
actively regulated by trafficking machinery (Rab11, ankyrin-G, spectrin), and
E-cadherin mutant phenotype informs this process.'
reason: 'Protein localization to plasma membrane is a real function related to
E-cadherin trafficking, but it is non-core — the core BP is cell-cell adhesion
and adherens junction organization, not the localization machinery itself. Batch
5 of #348.'
qualifier: involved_in
- term:
id: GO:0005576
label: extracellular region
evidence_type: TAS
original_reference_id: Reactome:R-HSA-3827958
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-3827958): CDH1/E-cadherin has a large N-terminal
ectodomain (EC1-EC5) that occupies the extracellular space, and proteolytic
shedding (e.g. by MMP9/KLK7) releases a soluble extracellular ectodomain fragment.
Consistent with the extracellular region annotation ACCEPTed on IEA evidence
elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the EC1-EC5 ectodomain occupies the extracellular
region and the shed soluble ectodomain is an extracellular fragment; consistent
with extracellular region ACCEPT on IEA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005576
label: extracellular region
evidence_type: TAS
original_reference_id: Reactome:R-HSA-4224014
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-4224014): CDH1/E-cadherin has a large N-terminal
ectodomain (EC1-EC5) that occupies the extracellular space, and proteolytic
shedding (e.g. by MMP9/KLK7) releases a soluble extracellular ectodomain fragment.
Consistent with the extracellular region annotation ACCEPTed on IEA evidence
elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the EC1-EC5 ectodomain occupies the extracellular
region and the shed soluble ectodomain is an extracellular fragment; consistent
with extracellular region ACCEPT on IEA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-3827958
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-3827958): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-4224014
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-4224014): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-NUL-2534209
review:
action: ACCEPT
summary: 'TAS from Reactome (R-NUL-2534209): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-202939
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-202939): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-265422
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-265422): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-419001
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-419001): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-419002
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-419002): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5672304
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-5672304): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8876497
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-8876497): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9825774
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9825774): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9926527
review:
action: ACCEPT
summary: 'TAS from Reactome (R-HSA-9926527): The plasma membrane is the primary
steady-state localization of CDH1/E-cadherin. As a type-I single-pass transmembrane
glycoprotein, mature E-cadherin resides at the lateral/basolateral plasma membrane
of epithelial cells, where it mediates calcium-dependent homophilic trans-dimerisation
and cell-cell adhesion. Consistent with the plasma membrane annotations ACCEPTed
on IEA and IDA evidence elsewhere in this file.'
reason: 'Core CDH1 cellular component -- the lateral/basolateral plasma membrane
is the primary site of CDH1 localization and adhesive activity; consistent with
plasma membrane ACCEPT on IEA/IDA evidence elsewhere in this file. Reactome
TAS localization batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19038973
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:19038973
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005802
label: trans-Golgi network
evidence_type: IMP
original_reference_id: PMID:17620337
review:
action: KEEP_AS_NON_CORE
summary: 'IMP from PMID:17620337 (Kizhatil et al. 2007): Ankyrin-G and beta-2-spectrin
are required for exit of E-cadherin from the trans-Golgi network in a microtubule-dependent
pathway. TGN is the staging point for post-Golgi trafficking of newly synthesized
E-cadherin to the lateral plasma membrane.'
reason: 'Trans-Golgi network localization is non-core — reflects biosynthetic
trafficking transit of E-cadherin before its delivery to the lateral plasma
membrane. Core CC is plasma membrane/adherens junction. Batch 5 of #348.'
qualifier: located_in
- term:
id: GO:0008013
label: beta-catenin binding
evidence_type: IDA
original_reference_id: PMID:17620337
review:
action: ACCEPT
summary: 'IDA from PMID:17620337 (Kizhatil et al. 2007): Ankyrin-G binds to the
cytoplasmic domain of E-cadherin at a conserved site distinct from beta-catenin;
ankyrin-G recruits beta-2-spectrin to E-cadherin-beta-catenin complexes. This
study provides independent experimental confirmation that E-cadherin directly
binds beta-catenin (IDA from the ankyrin study, co-IP evidence). Beta-catenin
binding is core MF for E-cadherin.'
qualifier: enables
- term:
id: GO:0016328
label: lateral plasma membrane
evidence_type: IDA
original_reference_id: PMID:17620337
review:
action: ACCEPT
summary: 'IDA from PMID:17620337 (Kizhatil et al. 2007): ''E-cadherin is a ubiquitous
component of lateral membranes in epithelial tissues.'' Ankyrin-G and beta-2-spectrin
are required for accumulation of E-cadherin at the lateral membrane. Lateral
plasma membrane is the core CC of E-cadherin in epithelial cells.'
qualifier: located_in
- term:
id: GO:0030506
label: ankyrin binding
evidence_type: IPI
original_reference_id: PMID:17620337
review:
action: ACCEPT
summary: 'IPI from PMID:17620337 (Kizhatil et al. 2007): Ankyrin-G (ANK3) binds
to the cytoplasmic domain of E-cadherin at a conserved site distinct from beta-catenin;
this ankyrin-G interaction is required for lateral membrane accumulation and
exit from the TGN. Ankyrin binding (GO:0030506) is a specific and informative
MF — distinct from generic protein binding, ankyrin links E-cadherin to the
spectrin/actin cytoskeleton.'
qualifier: enables
- term:
id: GO:0072659
label: protein localization to plasma membrane
evidence_type: IDA
original_reference_id: PMID:17620337
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:17620337 (Kizhatil et al. 2007): Ankyrin-G and beta-2-spectrin
regulate E-cadherin''s localization to the lateral plasma membrane; their loss
causes mistargeting. E-cadherin localization to plasma membrane is real but
this BP annotation captures the trafficking/targeting aspect rather than the
core adhesion function.'
reason: 'Protein localization to plasma membrane is a mechanistic support function
for E-cadherin trafficking, not its core BP. Core BP is cell-cell adhesion and
adherens junction organization. Non-core context: ankyrin/spectrin-dependent
lateral membrane targeting. Batch 5 of #348.'
qualifier: involved_in
- term:
id: GO:0032794
label: GTPase activating protein binding
evidence_type: IPI
original_reference_id: PMID:20116244
review:
action: KEEP_AS_NON_CORE
summary: 'IPI from PMID:20116244 (Frasa et al. 2010): Armus is a TBC/RabGAP protein
that integrates Arf6, Rac1, and Rab7 signaling during E-cadherin junction disassembly.
E-cadherin co-immunoprecipitates with Armus (a GTPase activating protein for
Rab7), suggesting physical association. E-cadherin''s association with Armus/RabGAP
is part of the junction disassembly/degradation pathway.'
reason: 'GTPase activating protein binding by E-cadherin reflects its participation
in junction disassembly/endocytic degradation pathways, not a core MF. Core
function is homophilic adhesion at adherens junctions. Batch 5 of #348.'
qualifier: enables
- term:
id: GO:0009898
label: cytoplasmic side of plasma membrane
evidence_type: IDA
original_reference_id: PMID:20189993
review:
action: ACCEPT
summary: 'IDA from PMID:20189993: E-cadherin''s cytoplasmic domain localizes to
the cytoplasmic side of the plasma membrane where it interacts with beta-catenin,
alpha-catenin, and p120-catenin. As a type-I transmembrane protein, E-cadherin''s
cytoplasmic tail is definitively on the cytoplasmic side of the plasma membrane,
making this a correct CC annotation.'
qualifier: located_in
- term:
id: GO:0030054
label: cell junction
evidence_type: TAS
original_reference_id: PMID:17047063
review:
action: KEEP_AS_NON_CORE
summary: 'TAS from PMID:17047063: CDH1/E-cadherin localizes to cell junctions.
GO:0030054 cell junction is a broad parent term; the precise and informative
CC annotation is GO:0005912 adherens junction (ACCEPTed in this file), the specific
junction type where E-cadherin resides and functions. Consistent with KEEP_AS_NON_CORE
on the IEA cell junction annotation in this file.'
reason: 'Real but non-core CC -- CDH1 localizes to cell junctions but the precise
junction type is the adherens junction (GO:0005912, accepted elsewhere); consistent
with KEEP_AS_NON_CORE on the IEA cell junction row. Reactome TAS localization
batch (batch 4 of #348).'
qualifier: located_in
- term:
id: GO:0022408
label: negative regulation of cell-cell adhesion
evidence_type: IMP
original_reference_id: PMID:19653274
review:
action: REMOVE
summary: 'IMP from PMID:19653274 (Jesse et al. 2010): This paper studies Lef-1
isoforms that inhibit E-cadherin expression, reducing cellular aggregation.
The IMP annotation of GO:0022408 (negative regulation of cell-cell adhesion)
to CDH1 is not supported — E-cadherin is a canonical POSITIVE mediator/regulator
of cell-cell adhesion. The paper''s phenotype reflects Lef-1-mediated repression
of CDH1 transcription leading to reduced adhesion; E-cadherin itself does not
negatively regulate cell-cell adhesion in this context.'
reason: 'Annotation inconsistent with CDH1 biology: E-cadherin is a positive mediator
of cell-cell adhesion, not a negative regulator. The Lef-1 paper shows that
reducing CDH1 expression reduces adhesion — this is the opposite of CDH1 negatively
regulating cell-cell adhesion. This annotation appears to be a misinterpretation
of the IMP evidence. Batch 5 of #348.'
qualifier: involved_in
- term:
id: GO:0030054
label: cell junction
evidence_type: IDA
original_reference_id: PMID:19038973
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:19038973: Cell junction localization of E-cadherin confirmed
experimentally. GO:0030054 cell junction is the broad parent of GO:0005912 adherens
junction; the precise core CC is the adherens junction, ACCEPTed elsewhere in
this file.'
reason: 'Broad parent CC — GO:0030054 cell junction is the direct parent of GO:0005912
adherens junction, the precise core CC for E-cadherin (ACCEPTed in this file).
A real but non-core annotation: the informative term is the specific adherens
junction. Action reconciled with the IEA and TAS GO:0030054 rows in this file
(#348).'
qualifier: located_in
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20086044
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:20086044
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0005912
label: adherens junction
evidence_type: IDA
original_reference_id: PMID:20086044
review:
action: ACCEPT
summary: 'IDA from PMID:20086044: Adherens junction localization confirmed experimentally.
Core CC for E-cadherin.'
qualifier: located_in
- term:
id: GO:0071681
label: cellular response to indole-3-methanol
evidence_type: IDA
original_reference_id: PMID:10868478
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:10868478 (Meng et al. 2000): Indole-3-carbinol (I3C, a
dietary phytochemical from cruciferous vegetables) causes dose-dependent upregulation
of E-cadherin and catenin expression in breast cancer cells, suppressing invasion
and migration. GO:0071681 (cellular response to indole-3-methanol) captures
E-cadherin''s transcriptional upregulation in response to this specific dietary
compound.'
reason: 'E-cadherin expression response to indole-3-carbinol is a real but highly
context-specific, non-core biological response. E-cadherin''s primary function
is Ca2+-dependent homophilic cell-cell adhesion. Batch 5 of #348.'
qualifier: involved_in
- term:
id: GO:0045295
label: gamma-catenin binding
evidence_type: IPI
original_reference_id: PMID:1639850
review:
action: ACCEPT
summary: 'IPI from PMID:1639850 (Knudsen and Wheelock 1992): Plakoglobin (gamma-catenin,
JUP) co-immunoprecipitates with E-cadherin and N-cadherin. E-cadherin cytoplasmic
tail interacts with plakoglobin/gamma-catenin (an 83-kD Drosophila armadillo/plakoglobin-like
protein), linking E-cadherin to the cytoskeleton. Gamma-catenin binding is a
core MF — plakoglobin is a functional component of the E-cadherin-catenin complex
at adherens junctions and desmosomes.'
qualifier: enables
- term:
id: GO:0043296
label: apical junction complex
evidence_type: IDA
original_reference_id: PMID:10460003
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:10460003 (Smythe et al. 1999): E-cadherin and catenins
detected at apical junction complexes in normal human bronchial epithelium by
immunohistochemistry. The apical junction complex (AJC) is the composite apical
unit comprising the tight junction, zonula adherens and desmosomes; E-cadherin
resides specifically in the zonula adherens sub-compartment, so the annotation
is accurate but broader than the precise core CC, GO:0005912 adherens junction.'
reason: Accurate but broader-than-precise CC grouping — the apical junction complex
is the composite of tight junction, adherens junction and desmosomes; E-cadherin
resides specifically in the zonula adherens, whose precise term GO:0005912 adherens
junction is ACCEPTed as core in this file. Action reconciled with the IBA GO:0043296
row in this file (#348).
qualifier: located_in
- term:
id: GO:0071285
label: cellular response to lithium ion
evidence_type: IDA
original_reference_id: PMID:12937339
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:12937339 (Ohira et al. 2003): WNT7a induces E-cadherin
expression in lung cancer cells. Lithium ion (a GSK-3β inhibitor that mimics
Wnt/β-catenin signaling) is used in this study to probe WNT pathway effects
on CDH1 expression. GO:0071285 (cellular response to lithium ion) captures E-cadherin''s
transcriptional induction in response to lithium-mediated Wnt pathway activation.'
reason: 'CDH1 induction by lithium ion reflects a specific pharmacological activation
of WNT signaling, not a core CDH1 function. Lithium response is context-specific
and non-core. Batch 5 of #348.'
qualifier: involved_in
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19822757
review:
summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:19822757
— non-informative per CLAUDE.md curation guidance. CDH1's beta-catenin and cadherin
partner interactions are already captured in this file by dedicated MF terms
(GO:0008013 beta-catenin binding, GO:0045296 cadherin binding, GO:0042802 identical
protein binding for the E-cadherin homodimer). Specific alpha-catenin binding
(GO:0045294, for CTNNA1) and delta-catenin binding (GO:0070097, for CTNND1/p120-catenin)
terms are not yet seeded in this file and should be added in a subsequent batch.
Regardless, this generic GO:0005515 IntAct-derived row adds no biological information
beyond what partner-specific MF terms (existing or to be added) capture.
action: MARK_AS_OVER_ANNOTATED
reason: Generic 'protein binding' is uninformative; CDH1's beta-catenin and cadherin
partners are already covered by granular MF terms in this file, and alpha-catenin
(GO:0045294) and delta-catenin (GO:0070097) binding terms should be added in
a subsequent batch to cover the CTNNA1 and CTNND1 IPI partners. Per CLAUDE.md,
replace generic protein binding with informative partner-specific terms.
qualifier: enables
- term:
id: GO:0016342
label: catenin complex
evidence_type: IDA
original_reference_id: PMID:18593713
review:
action: ACCEPT
summary: 'IDA from PMID:18593713 (Tang et al. 2008): Smad7 stabilizes the beta-catenin-E-cadherin
complex at the plasma membrane. The catenin complex (GO:0016342) — comprising
E-cadherin, beta-catenin, alpha-catenin, and p120-catenin — is the core protein
complex mediating E-cadherin adhesion and cytoskeletal linkage. E-cadherin is
the transmembrane scaffold of this complex.'
qualifier: part_of
- term:
id: GO:0005912
label: adherens junction
evidence_type: IDA
original_reference_id: PMID:16338932
review:
action: ACCEPT
summary: 'IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin-dependent cell-cell
adhesion via adherens junctions studied using chimeric E-cadherin-Fc homophilic
surfaces and Caco-2 enterocytes. Adherens junction is the core CC for E-cadherin
in intestinal epithelial cells.'
qualifier: located_in
- term:
id: GO:0007156
label: homophilic cell-cell adhesion
evidence_type: NAS
original_reference_id: PMID:16338932
review:
action: ACCEPT
summary: 'NAS from PMID:16338932 (Peignon et al. 2006): Homophilic cell-cell adhesion
is the foundation for the experimental design (chimeric E-cadherin-Fc surfaces,
Caco-2 cell-cell contacts) and is cited as established background knowledge.
Homophilic cell-cell adhesion is the definitively core BP for E-cadherin — the
basis for all adherens junction-mediated tissue cohesion.'
qualifier: involved_in
- term:
id: GO:0015629
label: actin cytoskeleton
evidence_type: IDA
original_reference_id: PMID:16338932
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin forms complexes
with actin (''formation of E-cadherin-actin complexes inducing polarization
of Caco-2 enterocytes''). E-cadherin associates with the actin cytoskeleton
through alpha-catenin, which links the cadherin-catenin complex to F-actin.'
reason: 'Actin cytoskeleton localization is real but reflects E-cadherin''s indirect
connection to actin via alpha-catenin rather than a core CC of E-cadherin itself.
Core CC is plasma membrane/adherens junction. Batch 5 of #348.'
qualifier: located_in
- term:
id: GO:0016020
label: membrane
evidence_type: IDA
original_reference_id: PMID:16338932
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IDA from PMID:16338932 (Peignon et al. 2006): GO:0016020 (membrane)
is a non-specific parent term for E-cadherin. E-cadherin is a transmembrane
protein, but the relevant and informative CC annotation is plasma membrane (GO:0005886)
or adherens junction (GO:0005912), both of which are also annotated from this
study. The general ''membrane'' term adds no biological information beyond what
the specific subterm annotations already convey.'
reason: 'GO:0016020 membrane is over-annotated — an uninformative parent term
when more specific descendant CC terms (plasma membrane, adherens junction,
lateral plasma membrane) are already annotated from the same paper and evidence.
Batch 5 of #348.'
qualifier: located_in
- term:
id: GO:0016328
label: lateral plasma membrane
evidence_type: IDA
original_reference_id: PMID:16338932
review:
action: ACCEPT
summary: 'IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin complex formation
studied in polarized Caco-2 intestinal epithelial cells where E-cadherin localizes
to the lateral plasma membrane forming adherens junctions. Lateral plasma membrane
is the canonical CC for E-cadherin in polarized epithelial cells — consistent
with PMID:17620337 which describes E-cadherin as ''a ubiquitous component of
lateral membranes in epithelial tissues.'''
qualifier: located_in
- term:
id: GO:0045893
label: positive regulation of DNA-templated transcription
evidence_type: IDA
original_reference_id: PMID:16338932
review:
action: KEEP_AS_NON_CORE
summary: 'IDA from PMID:16338932 (Peignon et al. 2006): E-cadherin-dependent cell-cell
adhesion promotes transcriptional activation of the apoA-IV gene via increased
nuclear abundance of HNF4alpha. Positive regulation of transcription is an indirect
downstream consequence of E-cadherin-mediated adhesion signaling.'
reason: 'Transcriptional activation of apoA-IV via HNF4alpha is an indirect downstream
effect of E-cadherin signaling in intestinal enterocytes — a context-specific
non-core function. E-cadherin''s core function is homophilic cell-cell adhesion.
Batch 5 of #348.'
qualifier: involved_in
- term:
id: GO:0048471
label: perinuclear region of cytoplasm
evidence_type: IDA
original_reference_id: PMID:16338932
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'IDA from PMID:16338932 (Peignon et al. 2006): The paper demonstrates
that E-cadherin-dependent cell-cell adhesion in Caco-2 enterocytes controls
the nuclear abundance of HNF4alpha (hepatic nuclear factor 4alpha), thereby
regulating apoA-IV gene transcription. CDH1/E-cadherin itself is a type-I single-pass
transmembrane glycoprotein whose canonical localization is the plasma membrane
and adherens junction. The paper''s experimental finding is about E-cadherin
downstream signaling controlling nuclear translocation of HNF4alpha — not about
E-cadherin itself localizing to the perinuclear region of cytoplasm. The abstract
provides no evidence for E-cadherin perinuclear localization.'
reason: 'The perinuclear region annotation appears to misattribute the paper''s
finding about E-cadherin-mediated HNF4alpha nuclear redistribution to a perinuclear
localization of E-cadherin itself. HNF4alpha (not CDH1) is the nuclear/perinuclear-region
component in this paper. Full-length CDH1 is a plasma-membrane protein; while
CTF2/CTF3 cleavage products can translocate to the nucleus in some contexts,
this paper does not describe E-cadherin perinuclear localization. MARK_AS_OVER_ANNOTATED:
the annotation over-extends the paper''s findings about downstream signaling
to an unsupported subcellular localization of E-cadherin.'
qualifier: located_in
- term:
id: GO:0050839
label: cell adhesion molecule binding
evidence_type: NAS
original_reference_id: PMID:16338932
review:
action: MARK_AS_OVER_ANNOTATED
summary: 'NAS from PMID:16338932 (Peignon et al. 2006): Cell adhesion molecule
binding as NAS (Not Ascribed to Source) from a background knowledge statement
about E-cadherin adhesion. GO:0050839 (cell adhesion molecule binding) is non-informative
for E-cadherin — its specific binding partners (other E-cadherins in trans,
beta-catenin, gamma-catenin, ankyrin) are better captured by dedicated terms
(GO:0045296 cadherin binding, GO:0008013 beta-catenin binding, GO:0045295 gamma-catenin
binding, GO:0030506 ankyrin binding) already annotated in this file.'
reason: 'GO:0050839 is over-annotated: uninformative parent term when more specific
molecular function binding terms for E-cadherin''s known partners are separately
annotated. Per CLAUDE.md, prefer informative specific terms. Batch 5 of #348.'
qualifier: enables
- term:
id: GO:0098609
label: cell-cell adhesion
evidence_type: IDA
original_reference_id: PMID:16338932
review:
action: ACCEPT
summary: 'IDA from PMID:16338932 (Peignon et al. 2006): Cell-cell adhesion confirmed
directly — E-cadherin mediates Caco-2 enterocyte cell-cell adhesion; impairing
or enhancing E-cadherin-dependent adhesion modulates apoA-IV transcription.
Cell-cell adhesion (GO:0098609) is core BP for E-cadherin.'
qualifier: involved_in
- term:
id: GO:0007156
label: homophilic cell-cell adhesion
evidence_type: NAS
original_reference_id: PMID:8033105
review:
action: ACCEPT
summary: 'NAS from PMID:8033105: Homophilic cell-cell adhesion is the foundational
and defining function of E-cadherin — a classical cadherin mediating Ca2+-dependent
homophilic trans-adhesion between cells via strand-swap dimerization of the
EC1 domain. This is the core BP and mechanism for E-cadherin''s role in epithelial
tissue integrity and morphogenesis.'
qualifier: involved_in
references:
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title: Gene Ontology annotation through association of InterPro records with GO
terms
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping, accompanied by conservative changes to GO terms applied by
UniProt
findings: []
- id: GO_REF:0000052
title: Gene Ontology annotation based on curation of immunofluorescence data
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to
orthologs using Ensembl Compara
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:10460003
title: Cadherin and catenin expression in normal human bronchial epithelium and
non-small cell lung cancer.
findings: []
- id: PMID:10725230
title: ARVCF localizes to the nucleus and adherens junction and is mutually exclusive
with p120(ctn) in E-cadherin complexes.
findings: []
- id: PMID:10868478
title: 'Suppression of breast cancer invasion and migration by indole-3-carbinol:
associated with up-regulation of BRCA1 and E-cadherin/catenin complexes.'
findings: []
- id: PMID:11401320
title: FGF-1 and FGF-2 modulate the E-cadherin/catenin system in pancreatic adenocarcinoma
cell lines.
findings: []
- id: PMID:11790773
title: Protein binding and functional characterization of plakophilin 2. Evidence
for its diverse roles in desmosomes and beta -catenin signaling.
findings: []
- id: PMID:11976333
title: Galpha12 and Galpha13 negatively regulate the adhesive functions of cadherin.
findings: []
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title: Structure of internalin, a major invasion protein of Listeria monocytogenes,
in complex with its human receptor E-cadherin.
findings: []
- id: PMID:12937339
title: WNT7a induces E-cadherin in lung cancer cells.
findings: []
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title: A role for Galpha12/Galpha13 in p120ctn regulation.
findings: []
- id: PMID:15689490
title: Rab11 in recycling endosomes regulates the sorting and basolateral transport
of E-cadherin.
findings: []
- id: PMID:15695390
title: E-cadherin phosphorylation by protein kinase D1/protein kinase C{mu} is associated
with altered cellular aggregation and motility in prostate cancer.
findings: []
- id: PMID:16212417
title: Biosensor-based micro-affinity purification for the proteomic analysis of
protein complexes.
findings: []
- id: PMID:16338932
title: 'E-cadherin-dependent transcriptional control of apolipoprotein A-IV gene
expression in intestinal epithelial cells: a role for the hepatic nuclear factor
4.'
findings: []
- id: PMID:1639850
title: Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts
with E-cadherin and N-cadherin.
findings: []
- id: PMID:16882694
title: Regulation of epithelial wound closure and intercellular adhesion by interaction
of AF6 with actin cytoskeleton.
findings: []
- id: PMID:16983094
title: The von Hippel-Lindau tumor suppressor gene product represses oncogenic beta-catenin
signaling in renal carcinoma cells.
findings: []
- id: PMID:17047063
title: E-cadherin regulates human Nanos1, which interacts with p120ctn and induces
tumor cell migration and invasion.
findings: []
- id: PMID:17220478
title: Proteomics analysis of the interactome of N-myc downstream regulated gene
1 and its interactions with the androgen response program in prostate cancer cells.
findings: []
- id: PMID:17237808
title: Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin
signal that promotes intestinal transdifferentiation in gastric epithelial cells.
findings: []
- id: PMID:17274640
title: A limited screen for protein interactions reveals new roles for protein phosphatase
1 in cell cycle control and apoptosis.
findings: []
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title: Ankyrin-G is a molecular partner of E-cadherin in epithelial cells and early
embryos.
findings: []
- id: PMID:17715295
title: Thermodynamically reengineering the listerial invasion complex InlA/E-cadherin.
findings: []
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title: EPLIN mediates linkage of the cadherin catenin complex to F-actin and stabilizes
the circumferential actin belt.
findings: []
- id: PMID:18343367
title: 'P120-catenin is a novel desmoglein 3 interacting partner: identification
of the p120-catenin association site of desmoglein 3.'
findings: []
- id: PMID:18593713
title: Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes
cell-cell adhesion.
findings: []
- id: PMID:19016843
title: Molecular basis of actin reorganization promoted by binding of enterohaemorrhagic
Escherichia coli EspB to alpha-catenin.
findings: []
- id: PMID:19038973
title: Identification of WNT/beta-CATENIN signaling pathway components in human
cumulus cells.
findings: []
- id: PMID:19114658
title: Resolving cadherin interactions and binding cooperativity at the single-molecule
level.
findings: []
- id: PMID:19403558
title: The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional
modifications of E-cadherin.
findings: []
- id: PMID:19604117
title: CagA associates with c-Met, E-cadherin, and p120-catenin in a multiproteic
complex that suppresses Helicobacter pylori-induced cell-invasive phenotype.
findings: []
- id: PMID:19646884
title: Characterizing the initial encounter complex in cadherin adhesion.
findings: []
- id: PMID:19653274
title: Lef-1 isoforms regulate different target genes and reduce cellular adhesion.
findings: []
- id: PMID:19732724
title: The Tensin-3 protein, including its SH2 domain, is phosphorylated by Src
and contributes to tumorigenesis and metastasis.
findings: []
- id: PMID:19822757
title: Identification of a physiological E2 module for the human anaphase-promoting
complex.
findings: []
- id: PMID:20086044
title: Vinculin regulates cell-surface E-cadherin expression by binding to beta-catenin.
findings: []
- id: PMID:20116244
title: Armus is a Rac1 effector that inactivates Rab7 and regulates E-cadherin degradation.
findings: []
- id: PMID:20189993
title: GATA3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal
transition.
findings: []
- id: PMID:20802534
title: Hypoxia and cell cycle regulation of the von Hippel-Lindau tumor suppressor.
findings: []
- id: PMID:20859650
title: E-cadherin and plakoglobin recruit plakophilin3 to the cell border to initiate
desmosome assembly.
findings: []
- id: PMID:20951947
title: Pharmacologic inhibition of the anaphase-promoting complex induces a spindle
checkpoint-dependent mitotic arrest in the absence of spindle damage.
findings: []
- id: PMID:21300292
title: The extracellular architecture of adherens junctions revealed by crystal
structures of type I cadherins.
findings: []
- id: PMID:21685945
title: Rack1 promotes epithelial cell-cell adhesion by regulating E-cadherin endocytosis.
findings: []
- id: PMID:21724833
title: Identification of PTPN23 as a novel regulator of cell invasion in mammary
epithelial cells from a loss-of-function screen of the 'PTP-ome'.
findings: []
- id: PMID:22056988
title: Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation.
findings: []
- id: PMID:22158051
title: Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin
adherens junction and impairs NPC progression-associated properties.
findings: []
- id: PMID:22252131
title: Structure of a novel phosphotyrosine-binding domain in Hakai that targets
E-cadherin.
findings: []
- id: PMID:22294297
title: Non-junctional human desmoglein 3 acts as an upstream regulator of Src in
E-cadherin adhesion, a pathway possibly involved in the pathogenesis of pemphigus
vulgaris.
findings: []
- id: PMID:22750944
title: Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula
adherens.
findings: []
- id: PMID:23086448
title: The CD46-Jagged1 interaction is critical for human TH1 immunity.
findings: []
- id: PMID:23112161
title: Ideal, catch, and slip bonds in cadherin adhesion.
findings: []
- id: PMID:23533145
title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
secretions in urine.
findings: []
- id: PMID:24046456
title: Flotillin microdomains stabilize cadherins at cell-cell junctions.
findings: []
- id: PMID:24189400
title: Perturbation of the mutated EGFR interactome identifies vulnerabilities and
resistance mechanisms.
findings: []
- id: PMID:24424122
title: Rescue of wild-type E-cadherin expression from nonsense-mutated cancer cells
by a suppressor-tRNA.
findings: []
- id: PMID:24658140
title: The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein
interactions in human cells.
findings: []
- id: PMID:24725409
title: Intestinal brush border assembly driven by protocadherin-based intermicrovillar
adhesion.
findings: []
- id: PMID:25241761
title: Using an in situ proximity ligation assay to systematically profile endogenous
protein-protein interactions in a pathway network.
findings: []
- id: PMID:25344754
title: ASPP2 controls epithelial plasticity and inhibits metastasis through β-catenin-dependent
regulation of ZEB1.
findings: []
- id: PMID:25468996
title: E-cadherin interactome complexity and robustness resolved by quantitative
proteomics.
findings: []
- id: PMID:27760340
title: Macrophage Epithelial Reprogramming Underlies Mycobacterial Granuloma Formation
and Promotes Infection.
findings: []
- id: PMID:28169360
title: Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo signaling
pathway.
findings: []
- id: PMID:28301459
title: Blepharocheilodontic syndrome is a CDH1 pathway-related disorder due to mutations
in CDH1 and CTNND1.
findings: []
- id: PMID:29999492
title: E-cadherin binds to desmoglein to facilitate desmosome assembly.
findings: []
- id: PMID:31473225
title: Sperm Flagellar 1 Binds Actin in Intestinal Epithelial Cells and Contributes
to Formation of Filopodia and Lamellipodia.
findings: []
- id: PMID:31980649
title: Extensive rewiring of the EGFR network in colorectal cancer cells expressing
transforming levels of KRAS(G13D).
findings: []
- id: PMID:32814053
title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
and Uncovers Widespread Protein Aggregation in Affected Brains.
findings: []
- id: PMID:33596089
title: Regulation of intestinal epithelial intercellular adhesion and barrier function
by desmosomal cadherin desmocollin-2.
findings: []
- id: PMID:33961781
title: Dual proteome-scale networks reveal cell-specific remodeling of the human
interactome.
findings: []
- id: PMID:34591612
title: A protein interaction landscape of breast cancer.
findings: []
- id: PMID:34742300
title: Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA
in epithelial cells.
findings: []
- id: PMID:35271311
title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
findings: []
- id: PMID:35922511
title: A physical wiring diagram for the human immune system.
findings: []
- id: PMID:36309486
title: Desmoglein-2 is important for islet function and β-cell survival.
findings: []
- id: PMID:8033105
title: E-cadherin gene mutations provide clues to diffuse type gastric carcinomas.
findings: []
- id: Reactome:R-HSA-202939
title: Caspase-mediated cleavage of E-Cadherin
findings: []
- id: Reactome:R-HSA-265422
title: Interaction of integrin alphaEbeta7 with Cadherin-1
findings: []
- id: Reactome:R-HSA-3827958
title: E-cadherin degradation by MMP9, KLK7
findings: []
- id: Reactome:R-HSA-419001
title: Connection of adjacent cells through calcium-dependent trans-dimerization
of cadherin
findings: []
- id: Reactome:R-HSA-419002
title: Interaction of cadherin with Beta/gamma catenin, alpha catenin and p120 catenin
findings: []
- id: Reactome:R-HSA-4224014
title: E-cadherin degradation by ADAM10, ADAM15
findings: []
- id: Reactome:R-HSA-5672304
title: IQGAP1 binds CDH1:CTTNB1:CTTNA1 and MEN1
findings: []
- id: Reactome:R-HSA-8876497
title: InlA binds CDH1
findings: []
- id: Reactome:R-HSA-8876948
title: SRC phosphorylates InlA-bound CDH1 and CTNNB1
findings: []
- id: Reactome:R-HSA-8876993
title: CBLL1 binds SRC-phosphorylated CDH1 complex
findings: []
- id: Reactome:R-HSA-8877003
title: CBLL1 ubiqutinates the InlA-bound CDH1 complex
findings: []
- id: Reactome:R-HSA-9766219
title: MDM2 binds CDH1
findings: []
- id: Reactome:R-HSA-9766223
title: Proteasome-dependent degradation of ubiquitinated CDH1
findings: []
- id: Reactome:R-HSA-9766227
title: MDM2 mediates CDH1 ubiquitination
findings: []
- id: Reactome:R-HSA-9768614
title: miR-9 inhibits CDH1 mRNA translation
findings: []
- id: Reactome:R-HSA-9768618
title: miR-10b inhibits CDH1 mRNA translation
findings: []
- id: Reactome:R-HSA-9816273
title: CDH1 translocates from ER to Golgi
findings: []
- id: Reactome:R-HSA-9816275
title: CDH1 is proteolytically cleaved in Golgi
findings: []
- id: Reactome:R-HSA-9816276
title: CDH1 is N-glycosylated on asparagine residues in endoplasmic reticulum
findings: []
- id: Reactome:R-HSA-9816277
title: CDH1 is O-manosylated
findings: []
- id: Reactome:R-HSA-9816278
title: CDH1 translocates to the plasma membrane
findings: []
- id: Reactome:R-HSA-9817325
title: CDH1 associates with CTNND1
findings: []
- id: Reactome:R-HSA-9817330
title: CDH1:CTNNB1 complex binds CTNNA1
findings: []
- id: Reactome:R-HSA-9825774
title: SNAI2 and TBX3 repress CDH1 gene expression during melanocyte development
findings: []
- id: Reactome:R-HSA-9926527
title: MITF-M-dependent CDH1 gene expression
findings: []
- id: Reactome:R-HSA-9932162
title: Removal of CDH1 signal peptide
findings: []
- id: Reactome:R-HSA-9932344
title: MOGS removes terminal glucose from Glu3Man9GlcNAc2-CDH1
findings: []
- id: Reactome:R-HSA-9932352
title: Glucosidase II removes glucose residue from Glu2Man9GlucNAc2-CDH1
findings: []
- id: Reactome:R-HSA-9932913
title: Glucosidase II removes glucose residue from Glu1Man9GlucNAc2-CDH1
findings: []
- id: Reactome:R-HSA-9932988
title: CANX binds Glu1Man9GlcNAc2-CDH1
findings: []
- id: Reactome:R-HSA-9933194
title: CTNNB1, JUP bind CDH1
findings: []
- id: Reactome:R-HSA-9933380
title: Cytosolic tail of CDH1 is phosphorylated
findings: []
- id: Reactome:R-HSA-9934294
title: CDH1-associated CTNNA1 binds VCL
findings: []
- id: Reactome:R-HSA-9934330
title: CDH1:CTNNB1,JUP complex binds to ANK3
findings: []
- id: Reactome:R-HSA-9934410
title: CDH1 forms homotypic trans-dimers
findings: []
- id: Reactome:R-HSA-9934411
title: CDH1 forms cis-clusters
findings: []
- id: Reactome:R-HSA-9934486
title: CDH1-associated CTNNA1 binds F-actin
findings: []
- id: Reactome:R-HSA-9934584
title: The complex of MDM2 and CDH1 translocates to early endosomes
findings: []
- id: Reactome:R-HSA-9934751
title: CDH1 is phosphorylated on tyrosine residues
findings: []
- id: Reactome:R-HSA-9934752
title: Ubiquitinated CDH1 is endocytosed
findings: []
- id: Reactome:R-HSA-9934753
title: CBLL1 ubiquitinates CDH1
findings: []
- id: Reactome:R-HSA-9934755
title: CBLL1 binds p-Y-CDH1
findings: []
- id: Reactome:R-HSA-9935209
title: CDH1 binds to PIP5K1C
findings: []
- id: Reactome:R-HSA-9935547
title: Lysosomal degradation of ubiquitinated CDH1
findings: []
- id: Reactome:R-HSA-9935552
title: Ubiquitinated CDH1 translocates to lysosomes for degradation
findings: []
- id: Reactome:R-NUL-2534209
title: E-cadherin strand dimer degradation by PS1
findings: []
- id: file:human/CDH1/CDH1-uniprot.txt
title: UniProt record for human CDH1 (P12830)
findings:
- statement: Cadherins, including E-cadherin/CDH1, are calcium-dependent cell adhesion
proteins.
supporting_text: Cadherins are calcium-dependent cell adhesion proteins
- statement: E-cadherin mediates homophilic cell-cell adhesion by preferentially
interacting with itself.
supporting_text: They preferentially interact with themselves in a homophilic
manner in connecting cells
- statement: E-cadherin is a component of an E-cadherin/catenin adhesion complex
containing beta-catenin or gamma-catenin, located at adherens junctions.
supporting_text: beta-catenin/CTNNB1 or gamma-catenin/JUP
- id: file:human/CDH1/CDH1-deep-research-manual.md
title: Manual deep research summary for human CDH1 (E-cadherin)
findings:
- statement: E-cadherin mediates calcium-dependent homophilic trans-adhesion via
strand-swap dimerization between EC1 domains on apposing cells; trans interactions
are sufficient for aggregation while cis interactions are additionally required
for junction assembly.
supporting_text: EC1 domains of each protomer closely interact and symmetrically
exchange their N-terminal β-strands, which contain a conserved tryptophan residue,
Trp2; trans interactions are sufficient to mediate aggregation, while cis interactions
are further required for assembly of junctions
- statement: The cytoplasmic tail of E-cadherin nucleates the cadherin-catenin complex
by binding beta-catenin/plakoglobin and p120-catenin, coupling homophilic adhesion
to the cortical actin cytoskeleton via alpha-catenin and adaptor proteins.
supporting_text: Component of an E-cadherin/catenin adhesion complex; the juxtamembrane
domain binds CTNND1 (p120-catenin); alpha-catenin links the complex to F-actin
via adaptor proteins including EPLIN and AF6/afadin
- id: file:human/CDH1/CDH1-deep-research-falcon.md
title: Falcon deep research report on CDH1
findings:
- statement: E-cadherin is a calcium-dependent cell-cell adhesion molecule that
organizes epithelial tissue architecture via homophilic adhesion, supporting
epithelial integrity and polarity.
supporting_text: E‑cadherin is a **calcium-dependent cell–cell adhesion molecule**
that organizes epithelial tissue architecture by mediating **homophilic adhesion**
and supporting epithelial integrity and polarity
- statement: The E-cadherin ectodomain is composed of five extracellular cadherin
repeats (EC1-EC5) containing calcium-binding sites that rigidify the ectodomain
for adhesion.
supporting_text: extracellular portion contains **five cadherin repeats (EC1–EC5)**
with **calcium-binding sites**
- statement: Homophilic adhesion proceeds through an EC1-mediated X-dimer intermediate
to a stable strand-swapped dimer in which a tryptophan from one EC1 inserts
into the hydrophobic pocket of the opposing EC1.
supporting_text: '**homophilic trans-binding** is driven primarily by the **EC1
domain** and proceeds through an **X-dimer intermediate** followed by formation
of a stable **strand-swapped dimer**, in which a **tryptophan side chain from
one EC1 inserts into a hydrophobic pocket** of the opposing EC1'
- statement: In epithelia, E-cadherin is enriched at the plasma membrane and concentrates
at adherens junctions, where it maintains epithelial sheet cohesion and tissue
architecture.
supporting_text: In epithelia, E‑cadherin is enriched at the **plasma membrane**
and concentrates at **adherens junctions** where it contributes to epithelial
sheet cohesion and tissue architecture
- statement: The E-cadherin cytoplasmic tail is anchored to the actin cytoskeleton
through beta-catenin and alpha-catenin, enabling transmission of actomyosin
forces across junctions.
supporting_text: Experimental/biophysical synthesis emphasizes anchoring through
**β‑catenin and α‑catenin**, enabling transmission of actomyosin forces across
junctions
- statement: E-cadherin also interacts with p120-catenin, and changes in E-cadherin
availability can alter beta-catenin and p120-catenin signaling states.
supporting_text: Broader mechanistic synthesis also highlights interaction with
**p120‑catenin**, and how changes in E‑cadherin availability can alter β‑catenin
and p120‑catenin signaling states
- statement: Adherens junctions formed by E-cadherin act as a mechanosensitive scaffold,
transmitting actomyosin-generated pulling forces via beta-catenin/alpha-catenin
anchorage rather than functioning as static "glue".
supporting_text: E‑cadherin-based adhesions transmit **actomyosin-generated pulling
forces** through β‑catenin/α‑catenin anchorage, and junction stability can be
limited by cytoskeletal anchorage rather than cadherin–cadherin binding strength
- statement: Loss or downregulation of E-cadherin can release beta-catenin to permit
nuclear translocation and Wnt pathway activation, and can alter RhoA/Rac1 signaling
via redistribution of p120-catenin.
supporting_text: a synthesis of cancer-related mechanisms describes that E‑cadherin
loss can permit **β‑catenin nuclear translocation** with **Wnt pathway activation**
(samardali2025acomprehensiveliterature pages 7-8). The same synthesis notes
that redistribution of **p120‑catenin** can influence **RhoA/Rac1** signaling
- statement: EMT programs repress E-cadherin, and this loss contributes to invasion
and metastasis; E-cadherin downregulation is a hallmark of EMT and cancer cell
motility changes.
supporting_text: EMT programs repress E‑cadherin and that such loss contributes
to invasion and metastasis
- statement: Germline CDH1 pathogenic variants are a primary cause of hereditary
diffuse gastric cancer (HDGC), with clinical management historically including
prophylactic total gastrectomy.
supporting_text: Germline **CDH1 pathogenic variants** are a primary cause of
**HDGC**, and clinical management has historically included **prophylactic total
gastrectomy (PTG)**
- statement: E-cadherin loss is necessary but not sufficient for invasive progression;
invasion in HDGC models emerges from the interplay between defective cell-cell
junctions, ECM attachment, and 3D tissue architecture.
supporting_text: invasion in HDGC models emerges from interplay between **defective
cell-cell junctions**, **ECM attachment**, and **3D tissue architecture**, rather
than from loss of adhesion alone
- statement: E-cadherin can undergo proteolytic cleavage/shedding, generating soluble
E-cadherin fragments; cleavage releases junctional restraint and can free beta-catenin.
supporting_text: E-cadherin can undergo **proteolytic cleavage/shedding**, generating
**soluble E-cadherin fragments**; cleavage releases junctional restraint and
can free β-catenin
- id: PMID:7806582
title: "E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton."
findings: []
- id: PMID:2349235
title: "Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule."
findings: []
- id: PMID:3498123
title: "Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA."
findings: []
- id: PMID:20190754
title: "Two-step adhesive binding by classical cadherins."
findings: []
- id: PMID:23643492
title: "E-cadherin supports steady-state Rho signaling at the epithelial zonula adherens."
findings: []
core_functions:
- description: E-cadherin engages in calcium-dependent homophilic trans-interaction
with E-cadherin molecules on adjacent epithelial cells through its five extracellular
cadherin (EC) repeats. This homophilic binding is the molecular basis of E-cadherin-mediated
cell-cell adhesion and the nucleation of adherens junctions.
molecular_function:
id: GO:0045296
label: cadherin binding
supported_by:
- reference_id: file:human/CDH1/CDH1-uniprot.txt
supporting_text: They preferentially interact with themselves in a homophilic
manner in connecting cells
- reference_id: file:human/CDH1/CDH1-deep-research-manual.md
supporting_text: EC1 domains of each protomer closely interact and symmetrically
exchange their N-terminal β-strands, which contain a conserved tryptophan residue,
Trp2; trans interactions are sufficient to mediate aggregation, while cis interactions
are further required for assembly of junctions
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: '**homophilic trans-binding** is driven primarily by the **EC1
domain** and proceeds through an **X-dimer intermediate** followed by formation
of a stable **strand-swapped dimer**, in which a **tryptophan side chain from
one EC1 inserts into a hydrophobic pocket** of the opposing EC1'
locations:
- id: GO:0016328
label: lateral plasma membrane
- id: GO:0005912
label: adherens junction
directly_involved_in:
- id: GO:0007156
label: homophilic cell-cell adhesion
- description: The C-terminal cytoplasmic domain of E-cadherin binds beta-catenin
(and gamma-catenin/plakoglobin), forming the cadherin-catenin complex. This complex
couples E-cadherin to the cortical actin cytoskeleton via alpha-catenin, mechanically
linking cell-cell adhesion to the cytoskeleton and stabilizing adherens junctions.
molecular_function:
id: GO:0008013
label: beta-catenin binding
supported_by:
- reference_id: file:human/CDH1/CDH1-uniprot.txt
supporting_text: beta-catenin/CTNNB1 or gamma-catenin/JUP
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: Experimental/biophysical synthesis emphasizes anchoring through
**β‑catenin and α‑catenin**, enabling transmission of actomyosin forces across
junctions
locations:
- id: GO:0016328
label: lateral plasma membrane
- id: GO:0005912
label: adherens junction
directly_involved_in:
- id: GO:0034332
label: adherens junction organization
- description: The juxtamembrane domain of E-cadherin's cytoplasmic tail binds p120-catenin
(CTNND1/delta-catenin) at a site distinct from the C-terminal beta-catenin-binding domain.
p120-catenin binding masks a dileucine endocytic motif and stabilizes E-cadherin at the
plasma membrane, thereby controlling cadherin surface levels, turnover, and adhesion
strength.
molecular_function:
id: GO:0070097
label: delta-catenin binding
supported_by:
- reference_id: PMID:15240885
supporting_text: The binding of p120 ctn to the juxtamembrane region of E-cadherin
has been shown to mediate stronger cell-cell adhesion and to support resistance
to detachment of cells
- reference_id: file:human/CDH1/CDH1-uniprot.txt
supporting_text: Interacts with CTNND1
- reference_id: file:human/CDH1/CDH1-deep-research-manual.md
supporting_text: the juxtamembrane domain binds CTNND1
locations:
- id: GO:0016328
label: lateral plasma membrane
- id: GO:0005912
label: adherens junction
directly_involved_in:
- id: GO:0034332
label: adherens junction organization
- description: Calcium ions bind at the linker regions between E-cadherin's extracellular
cadherin repeats, rigidifying the ectodomain into the conformation required for
homophilic trans-adhesion; cadherin-mediated cell-cell adhesion is strictly calcium-dependent.
molecular_function:
id: GO:0005509
label: calcium ion binding
supported_by:
- reference_id: file:human/CDH1/CDH1-uniprot.txt
supporting_text: Cadherins are calcium-dependent cell adhesion proteins
- reference_id: file:human/CDH1/CDH1-deep-research-falcon.md
supporting_text: extracellular portion contains **five cadherin repeats (EC1–EC5)**
with **calcium-binding sites**
locations:
- id: GO:0016328
label: lateral plasma membrane
directly_involved_in:
- id: GO:0007156
label: homophilic cell-cell adhesion