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 β 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 β 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 β 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 β 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 β 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 **Ξ²βcatenin and Ξ±βcatenin**, 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 β 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 β 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 Eβcadherin is a **calcium-dependent cellβcell 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 β 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 **p120βcatenin**, and how changes in Eβcadherin availability can alter Ξ²βcatenin and p120βcatenin 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 β 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 β 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-Ξ΄ subfamily binding; there is no separate "p120-catenin binding" term. The term is used here for CTNND1 (p120/Ξ΄1-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 β 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 β 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 Eβcadherin-based adhesions transmit **actomyosin-generated pulling forces** through Ξ²βcatenin/Ξ±βcatenin anchorage, and junction stability can be limited by cytoskeletal anchorage rather than cadherinβcadherin 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 β 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, Eβcadherin 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 β 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 β 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 Eβcadherin is a **calcium-dependent cellβcell 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 β 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 (EC1βEC5)** 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 β 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 β 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 β 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 β 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, Eβcadherin 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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) β 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 β 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 β 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 β 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 β 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). |
| 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 β 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: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 β 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: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 β 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:16212417 Biosensor-based micro-affinity purification for the proteomi... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:16212417 β 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: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 β 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: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 β 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: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 β 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: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 β 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:17715295 Thermodynamically reengineering the listerial invasion compl... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:17715295 β 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: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 β 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: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 β 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:19016843 Molecular basis of actin reorganization promoted by binding ... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:19016843 β 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: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 β 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: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 β 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: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 β 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:20951947 Pharmacologic inhibition of the anaphase-promoting complex i... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:20951947 β 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: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 β 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:22056988 Nuclear PKM2 regulates Ξ²-catenin transactivation upon EGFR a... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22056988 β 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:22158051 Tumor suppressor Alpha B-crystallin (CRYAB) associates with ... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22158051 β 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: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 β 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:22750944 Centralspindlin and Ξ±-catenin regulate Rho signalling at the... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:22750944 β 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:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | MARK AS OVER ANNOTATED | Summary: Generic 'protein binding' (GO:0005515) IPI evidence from PMID:24189400 β 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: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 β 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: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 β 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 β 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 β 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: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 β 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 β 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 β 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 β 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 β 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: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 β 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 β 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 β 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 β 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: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 β 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 β 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 β notably the single-molecule force spectroscopy of PMID:19114658 β and by UniProt, which documents CDH1 as a disulfide-linked homodimer (PubMed:11856755). ACCEPT. |
| 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 β unlike the generic GO:0005515 protein binding rows removed in batch 1. UniProt documents CDH1 as a disulfide-linked homodimer (PubMed:11856755). ACCEPT. |
| 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). |
| 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 β 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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). |
| 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 β 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). |
| 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 Ξ²-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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 Eβcadherin 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 β 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 β 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 β 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) β an actin-rich protrusion at the leading edge of migrating cells β 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 β 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 β 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 β 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 β 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). |
| 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). |
| 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). |
| 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 β 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: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 β 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. |
| 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. |
| 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. |
| 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 β distinct from generic protein binding, ankyrin links E-cadherin to the spectrin/actin cytoskeleton. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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 β 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 β 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. |
| 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 β 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 β 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 β 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 β 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-3Ξ² inhibitor that mimics Wnt/Ξ²-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 β 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) β comprising E-cadherin, beta-catenin, alpha-catenin, and p120-catenin β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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 β 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. |
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