Nidogen-1 (also called entactin) is a critical basement membrane glycoprotein that functions as an architectural linker protein bridging the laminin and collagen IV networks. The 1247 amino acid protein contains three globular domains (G1, G2, G3) connected by rod-like segments with EGF-like repeats. The G2 domain binds with high affinity to the laminin gamma-1 chain, while the G3 domain binds collagen IV. Nidogen-1 also binds perlecan and fibulins, serving as a central organizing element in basement membrane assembly. This bridging function is essential for basement membrane structural integrity across diverse tissues including skin, muscle, and nervous system. The protein is ubiquitously expressed in basement membranes throughout the body and represents one of the core structural constituents of the basement membrane extracellular matrix.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Nidogen-1 contains multiple calcium-binding EGF-like domains in its central rod region, as indicated by InterPro domain annotations. UniProt features annotate calcium-binding EGF-like domains at positions 710-751 and 802-840. Reason: This is a legitimate molecular function supported by domain architecture. Nidogen-1 contains calcium-binding EGF-like repeats in the rod domain connecting G2 and G3 globules, as confirmed by InterPro annotations and UniProt features. PMID:2119632 notes "The molecule binds calcium ions" as one of nidogen's properties. While not the core bridging function, calcium binding may play a role in maintaining structural integrity. Supporting Evidence: GO_REF:0000002 InterPro domain IPR001881 (EGF-like calcium-binding domain) and IPR018097 (EGF calcium-binding domain conserved site) mapped to NID1 PMID:2119632 The molecule binds calcium ions and supports cell adhesion. However, its major function may be the assembly of the basement membrane. |
| GO:0005576 extracellular region | IEA GO_REF:0000117 | ACCEPT | Summary: Nidogen-1 is a secreted protein localized to the extracellular space, specifically in basement membranes. This is an accurate but overly general localization term. Reason: This annotation is correct but the more specific terms basement membrane (GO:0005604) and extracellular matrix (GO:0031012) are preferable. However, as a parent term this remains valid and useful for broad queries. UniProt clearly states secreted extracellular space location. Supporting Evidence: GO_REF:0000117 ARBA machine learning model prediction based on sequence features |
| GO:0005604 basement membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Nidogen-1 is a ubiquitous and integral component of basement membranes. This is THE primary localization for this protein. Reason: This is absolutely correct and represents the core localization of nidogen-1. Basement membrane localization is fundamental to nidogen-1's function as a structural linker. UniProt annotation explicitly states "Secreted, extracellular space, extracellular matrix, basement membrane" and emphasizes nidogen-1 is "widely distributed in basement membranes." Supporting Evidence: GO_REF:0000120 Combined automated annotation methods including orthology to mouse UniProtKB:P10493 and SubCell localization SL-0025 (basement membrane) file:human/NID1/NID1-deep-research-falcon.md Falcon synthesis supports nidogen-1 as a secreted glycoprotein deposited broadly in basement membranes. |
| GO:0007155 cell adhesion | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Cell adhesion is a consequence of basement membrane organization and ECM structural function. This is a plausible but indirect annotation. Reason: While nidogen-1 supports cell adhesion indirectly by organizing the basement membrane ECM to which cells adhere, this is not its direct molecular function. PMID:2119632 mentions "supports cell adhesion" and PMID:3794389 examines "Effect of basement membrane entactin on epidermal cell attachment and growth," but the primary function is ECM structural organization. The cell adhesion effects are secondary to the structural role. This annotation is acceptable but represents a downstream consequence rather than core function. Supporting Evidence: GO_REF:0000043 Based on UniProtKB keyword KW-0130 (Cell adhesion) PMID:2119632 The molecule binds calcium ions and supports cell adhesion. However, its major function may be the assembly of the basement membrane. |
| GO:0007160 cell-matrix adhesion | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Cell-matrix adhesion is supported by nidogen-1's role in organizing the basement membrane matrix that mediates cell-ECM interactions. Reason: Similar to cell adhesion (GO:0007155), this represents a consequence of nidogen-1's structural role rather than its direct function. The InterPro NIDO domain (IPR003886) is associated with cell-matrix interactions, but nidogen-1's primary role is as a structural bridge between laminin and collagen IV networks. Cell-matrix adhesion is mediated by the organized basement membrane that nidogen-1 helps assemble. Keep as non-core. Supporting Evidence: GO_REF:0000002 InterPro domain IPR003886 (NIDO domain) mapped to process involved in cell-matrix adhesion |
| GO:0043236 laminin binding | IEA GO_REF:0000117 | ACCEPT | Summary: Laminin binding via the G2 domain is one of THE core molecular functions of nidogen-1. High-affinity binding to laminin gamma-1 chain is critical for basement membrane assembly. Reason: This is absolutely a core molecular function. The G2 domain of nidogen-1 binds with high affinity to the laminin gamma-1 chain. PMID:22952693 extensively characterizes nidogen-1 binding to laminin and shows cathepsin S cleavage impairs this interaction. PMID:23948589 structural study confirms "the interaction is mediated solely by the C-terminal domains" for laminin-nidogen complex. UniProt function states nidogen-1 is "tightly associated with laminin." This is essential for the bridging function. Supporting Evidence: GO_REF:0000117 ARBA machine learning model ARBA00086571 predicting laminin binding PMID:22952693 Nid-1 was cleaved within its G2 and G3 globular domains that are both involved in interactions with other BM components. Binding assays with soluble and immobilized ligands indicated that catS altered the formation of complexes between nid-1 and other BM components. PMID:23948589 The ab initio shape reconstruction of the complex between nidogen-1 and the laminin gamma-1 short arm confirms that the interaction is mediated solely by the C-terminal domains file:human/NID1/NID1-deep-research-falcon.md Falcon synthesis supports laminin binding as part of the nidogen-1 basement membrane bridging function. |
| GO:0071711 basement membrane organization | IEA GO_REF:0000117 | ACCEPT | Summary: Basement membrane organization is THE core biological process for nidogen-1. It serves as the central organizing element linking laminin and collagen IV networks. Reason: This is the primary biological process annotation for nidogen-1. PMID:2119632 states "its major function may be the assembly of the basement membrane" and describes nidogen as serving "as a bridge between the two most abundant molecules in the basement membrane." PMID:22952693 describes nidogens as playing "a central role in the supramolecular organization of the basal laminae in tissues such as skin, muscle, lung and the nervous system." This is THE defining function of nidogen-1. Supporting Evidence: GO_REF:0000117 ARBA machine learning model ARBA00085295 predicting basement membrane organization PMID:2119632 However, its major function may be the assembly of the basement membrane. PMID:22952693 Both nidogens play a central role in the supramolecular organization of the basal laminae in tissues such as skin, muscle, lung and the nervous system file:human/NID1/NID1-deep-research-falcon.md Falcon synthesis identifies basement membrane organization as the primary biological process for nidogen-1. |
| GO:0005518 collagen binding | IEA GO_REF:0000120 | ACCEPT | Summary: Collagen IV binding via the G3 domain is one of THE core molecular functions of nidogen-1, essential for bridging laminin to collagen IV networks. Reason: This is absolutely a core molecular function. The G3 domain binds collagen IV. PMID:2119632 states "This same region is also believed to be responsible for the attachment of entactin to type IV collagen at approximately 80 nm from its carboxyl noncollagenous end." PMID:22952693 demonstrates cathepsin cleavage within G3 impairs collagen binding. UniProt function notes nidogen "Also binds to collagen IV." This collagen IV binding is the other half of nidogen-1's critical bridging function. Supporting Evidence: GO_REF:0000120 Automated annotation based on orthology to mouse (UniProtKB:P10493, ensembl:ENSMUSP00000005532) with combined evidence PMID:2119632 Entactin therefore could serve as a bridge between the two most abundant molecules in the basement membrane. PMID:22952693 Cleavage sites were identified within G2 and G3 globular domains that are both involved in interactions with other BM components (type IV collagen, laminin, perlecan) file:human/NID1/NID1-deep-research-falcon.md Falcon synthesis supports collagen IV binding as a core component of nidogen-1-mediated basement membrane network bridging. |
| GO:0031012 extracellular matrix | IEA GO_REF:0000107 | ACCEPT | Summary: Nidogen-1 is an integral structural component of the extracellular matrix, specifically the basement membrane ECM. Reason: This is accurate and appropriate. Basement membrane (GO:0005604) is a child term of extracellular matrix (GO:0031012), so this parent term is valid. Nidogen-1 is one of the major ECM proteins. UniProt emphasizes ECM localization, and PMID:22952693 describes nidogen's role in "extracellular matrix (ECM)" turnover and organization. This is a good general ECM annotation. Supporting Evidence: GO_REF:0000107 Ensembl automatic transfer from ortholog mouse UniProtKB:P10493 (ensembl:ENSMUSP00000005532) PMID:22952693 Both nidogens play a central role in the supramolecular organization of the basal laminae in tissues such as skin, muscle, lung and the nervous system |
| GO:0043237 laminin-1 binding | IEA GO_REF:0000107 | ACCEPT | Summary: Laminin-1 (laminin-111, alpha1beta1gamma1) binding is a specific instance of nidogen-1's laminin binding activity. The binding is to the gamma-1 chain shared across multiple laminin isoforms. Reason: This is a more specific child term of laminin binding (GO:0043236). Nidogen-1 binds to the gamma-1 chain of laminins, including laminin-1 (laminin-111). PMID:22952693 notes that nidogen-1 "is more resistant to degradation when complexed with laminin-111 (alpha1beta1gamma1) (the binding site for nidogens locates in gamma 1 chain)." Since the binding site is on the gamma-1 chain, nidogen-1 can bind various laminins containing gamma-1. This specific annotation to laminin-1 is valid. Supporting Evidence: GO_REF:0000107 Ensembl automatic transfer from ortholog mouse UniProtKB:P10493 PMID:22952693 Isolated nid-1 is readily hydrolyzed by serine proteases and metalloproteinases (MMPs) [9]β[13], however it is more resistant to degradation when complexed with laminin-111 (Ξ±1Ξ²1Ξ³1) (the binding site for nidogens locates in gamma 1 chain) [14] |
| GO:0050840 extracellular matrix binding | IEA GO_REF:0000107 | ACCEPT | Summary: Nidogen-1 binds multiple ECM components including laminin, collagen IV, and perlecan. This is a valid general ECM binding annotation. Reason: This parent term appropriately captures nidogen-1's multiple ECM binding activities. It binds laminin (GO:0043236), collagen IV (GO:0005518), and perlecan (GO:0043394). PMID:22952693 describes nidogen-1 as having "several binding sites (localized to its G2 and G3 domains) for other BM components." UniProt states it "Also binds to collagen IV and perlecan." This general ECM binding term is appropriate given the multiple specific binding partners. Supporting Evidence: GO_REF:0000107 Ensembl automatic transfer from ortholog mouse UniProtKB:P10493 PMID:22952693 Though nid-1 cannot self-assemble, unlike most ECM molecules, it has several binding sites (localized to its G2 and G3 domains) for other BM components. |
| GO:0071944 cell periphery | IEA GO_REF:0000107 | REMOVE | Summary: Cell periphery is an overly general and imprecise localization for nidogen-1, which is specifically secreted into the extracellular space. Reason: This annotation is misleading. GO:0071944 (cell periphery) includes both plasma membrane and cell wall, which are not appropriate for nidogen-1. Nidogen-1 is a secreted protein that localizes to the extracellular basement membrane, not to cellular membranes or cell periphery structures. While the basement membrane is adjacent to cells, "cell periphery" suggests association with the cell surface itself rather than the extracellular space. The more specific terms basement membrane (GO:0005604) and extracellular matrix (GO:0031012) are far more appropriate. This appears to be an overly broad IEA annotation that should be removed. Supporting Evidence: GO_REF:0000107 Ensembl automatic transfer from ortholog, but the annotation is not appropriate for a secreted ECM protein |
| GO:0031012 extracellular matrix | HDA PMID:23658023 Comparative proteomic analysis of supportive and unsupportiv... | ACCEPT | Summary: High-throughput detection of nidogen-1 in ECM preparations from human embryonic stem cell cultures. Confirms ECM localization. Reason: This HDA (high-throughput direct assay) evidence from proteomics confirms nidogen-1 presence in purified extracellular matrix samples. PMID:23658023 title is "Comparative proteomic analysis of supportive and unsupportive extracellular matrix substrates for human embryonic stem cell maintenance." Detection of nidogen-1 in ECM preparations validates its ECM localization. This complements other ECM annotations with experimental proteomics data. Supporting Evidence: PMID:23658023 Comparative proteomic analysis of supportive and unsupportive extracellular matrix substrates for human embryonic stem cell maintenance |
| GO:0005604 basement membrane | NAS PMID:1678389 Cross-linking of laminin-nidogen complexes by tissue transgl... | ACCEPT | Summary: Study on cross-linking of laminin-nidogen complexes by transglutaminase for basement membrane stabilization. Confirms basement membrane localization. Reason: PMID:1678389 title is "Cross-linking of laminin-nidogen complexes by tissue transglutaminase. A novel mechanism for basement membrane stabilization." This NAS (non-traceable author statement) annotation is from ComplexPortal curation based on published literature describing nidogen-1 in basement membrane context. The annotation is well-supported and basement membrane is THE primary localization for nidogen-1. Supporting Evidence: PMID:1678389 Cross-linking of laminin-nidogen complexes by tissue transglutaminase |
| GO:0045785 positive regulation of cell adhesion | NAS PMID:3794389 Effect of basement membrane entactin on epidermal cell attac... | KEEP AS NON CORE | Summary: Study examining entactin effects on epidermal cell attachment and growth. This represents indirect downstream effects of ECM organization. Reason: PMID:3794389 title is "Effect of basement membrane entactin on epidermal cell attachment and growth." While nidogen-1 does enhance cell adhesion by organizing the basement membrane substrate, this is a regulatory/downstream effect rather than its direct core function. The annotation is from ComplexPortal NAS curation. Similar to GO:0007155 (cell adhesion), this represents a consequence of nidogen-1's structural organizing role. Keep as non-core function. Supporting Evidence: PMID:3794389 Effect of basement membrane entactin on epidermal cell attachment and growth |
| GO:0051149 positive regulation of muscle cell differentiation | NAS PMID:26555376 Impaired primary mouse myotube formation on crosslinked type... | KEEP AS NON CORE | Summary: Study showing laminin and entactin enhance impaired myotube formation on collagen. This is a tissue-specific developmental effect. Reason: PMID:26555376 title is "Impaired primary mouse myotube formation on crosslinked type I collagen films is enhanced by laminin and entactin." This describes a specific role in muscle cell differentiation, which is a specialized context-dependent function. While valid, this represents a developmental/tissue-specific process rather than nidogen-1's core structural bridging function. ComplexPortal NAS annotation. This is peripheral to core function - keep as non-core. Supporting Evidence: PMID:26555376 Impaired primary mouse myotube formation on crosslinked type I collagen films is enhanced by laminin and entactin. |
| GO:0098637 protein complex involved in cell-matrix adhesion | NAS PMID:3109910 Laminin-nidogen complex. Extraction with chelating agents an... | ACCEPT | Summary: Study on laminin-nidogen complex extraction and structural characterization. Nidogen-1 is part of complexes mediating cell-matrix interactions. Reason: PMID:3109910 title is "Laminin-nidogen complex. Extraction with chelating agents and structural characterization." This ComplexPortal NAS annotation describes nidogen-1 as part of the laminin-nidogen complex that mediates cell-matrix adhesion. While cell adhesion is downstream of the structural role, the complex itself is a valid annotation. The laminin-nidogen complex is a well-characterized structural unit that does mediate cell-ECM interactions. Accept as valid complex annotation. Supporting Evidence: PMID:3109910 Large quantities of intact laminin-nidogen complex could be extracted from a mouse tumor basement membrane with a physiological buffer containing EDTA. |
| GO:0110011 regulation of basement membrane organization | NAS PMID:2119632 Entactin: structure and function. | ACCEPT | Summary: Classic review on entactin structure and function emphasizing basement membrane assembly role. Core regulatory function. Reason: PMID:2119632 is the key review "Entactin structure and function" that established nidogen-1's role in basement membrane assembly. States "its major function may be the assembly of the basement membrane" and "Entactin therefore could serve as a bridge between the two most abundant molecules in the basement membrane." This is THE central function of nidogen-1 - regulating/organizing basement membrane structure. ComplexPortal NAS curation is well-supported. This is core function. Supporting Evidence: PMID:2119632 However, its major function may be the assembly of the basement membrane. |
| GO:2001046 positive regulation of integrin-mediated signaling pathway | NAS PMID:23948589 Structural elucidation of full-length nidogen and the lamini... | KEEP AS NON CORE | Summary: Structural study of full-length nidogen and laminin-nidogen complex. The annotation about integrin signaling is inferential. Reason: PMID:23948589 is the structural study "Structural elucidation of full-length nidogen and the laminin-nidogen complex in solution." While this paper characterizes the structure, the connection to integrin-mediated signaling is indirect - the organized basement membrane containing laminin-nidogen complexes provides a substrate for integrin binding and signaling. This is a downstream regulatory effect rather than direct function. ComplexPortal NAS annotation infers signaling effects. Keep as non-core. Supporting Evidence: PMID:23948589 Nidogen-1 is a key basement membrane protein that is required for many biological activities. |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: Nidogen-1 is an integral structural component of basement membrane ECM. This is THE core molecular function. Reason: Extracellular matrix structural constituent (GO:0005201) perfectly captures nidogen-1's core function as a structural bridging protein in basement membranes. Multiple RCA (inferred from reviewed computational analysis) annotations from ECM proteomics studies all support this function. This is the most appropriate molecular function term for nidogen-1. Supporting Evidence: PMID:28675934 The extracellular matrix (ECM) is a complex meshwork of insoluble fibrillar proteins file:human/NID1/NID1-deep-research-falcon.md Falcon synthesis supports nidogen-1 as an extracellular matrix structural linker between laminin, collagen IV, and perlecan networks. |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: Proteomics detection of nidogen-1 in ECM preparations. Reason: HDA evidence from proteomics confirming ECM localization. Accept as valid. Supporting Evidence: PMID:28675934 Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics. |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | ACCEPT | Summary: ECM structural constituent annotation from varicose vein ECM proteomics. Reason: RCA evidence from ECM proteomics. This is core function. Accept. Supporting Evidence: PMID:27068509 The proteomics analysis revealed the presence of >150 extracellular matrix proteins, of which 48 had not been previously detected in venous tissue |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: ECM structural constituent from glycoproteomics study. Reason: RCA evidence from ECM glycoproteomics. Core function. Accept. Supporting Evidence: PMID:27559042 RESULTS: ECM-related glycoproteins were identified in left and right atrial appendages from the same patients |
| GO:0005201 extracellular matrix structural constituent | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to orthologs. Reason: ISS (inferred from sequence or structural similarity) annotation transferring this core function from orthologs. This is appropriate for the conserved structural function. Accept. Supporting Evidence: GO_REF:0000024 Manual transfer of experimentally verified GO annotation to orthologs by curator judgment |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: ECM structural constituent from aorta ECM proteomics. Reason: RCA evidence from aortic ECM proteomics. Core function. Accept. Supporting Evidence: PMID:20551380 Proteomics characterization of extracellular space components in the human aorta |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: ECM structural constituent from colon cancer metastasis ECM proteomics. Reason: RCA evidence from cancer ECM proteomics. Core function. Accept. Supporting Evidence: PMID:25037231 We have been able to identify consistent changes in the ECM of i) colon tumors as compared with normal colon ECM; ii) primary tumors as compared with metastases derived from them |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: ECM localization from cancer proteomics. Reason: HDA proteomics evidence for ECM localization. Accept. Supporting Evidence: PMID:25037231 The ECM protein signatures of metastatic primary colon carcinomas and metastases to liver defined in this study |
| GO:0031012 extracellular matrix | HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | ACCEPT | Summary: ECM localization from varicose vein proteomics. Reason: HDA proteomics evidence for ECM localization. Accept. Supporting Evidence: PMID:27068509 Extracellular matrix proteins were enriched from venous tissues |
| GO:0031012 extracellular matrix | HDA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: ECM localization from glycoproteomics. Reason: HDA proteomics evidence for ECM localization. Accept. Supporting Evidence: PMID:27559042 Atrial specimens were analyzed by mass spectrometry after extraction of ECM proteins and enrichment for glycoproteins |
| GO:0031012 extracellular matrix | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: ECM localization from aorta proteomics. Reason: HDA proteomics evidence for ECM localization. Accept. Supporting Evidence: PMID:20551380 Nidogen-1NID1_HUMAN136566415.0101 |
| GO:0031012 extracellular matrix | ISS PMID:22261194 Proteomics analysis of cardiac extracellular matrix remodeli... | ACCEPT | Summary: ECM localization inferred from similarity. Reason: ISS annotation for ECM localization based on orthology. Accept. Supporting Evidence: PMID:22261194 Proteomics analysis of cardiac extracellular matrix remodeling in a porcine model of ischemia/reperfusion injury |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Detection of nidogen-1 in extracellular exosomes from urine proteomics. Non-core peripheral localization. Reason: While nidogen-1 can be detected in exosome preparations, this is not a primary or functional localization. Exosomes may contain basement membrane fragments or contamination from ECM. The core localization is basement membrane. Mark as non-core. Supporting Evidence: PMID:23533145 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine |
| GO:0005604 basement membrane | IDA PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | ACCEPT | Summary: Direct experimental evidence (IDA) for basement membrane localization from PMID:22952693 study. Reason: This is IDA (inferred from direct assay) experimental evidence for THE core localization of nidogen-1. PMID:22952693 directly demonstrates nidogen-1 in basement membranes. This is the gold standard evidence type. Absolutely accept. Supporting Evidence: PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to basement membrane partners |
| GO:0043394 proteoglycan binding | IPI PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | ACCEPT | Summary: IPI experimental evidence showing nidogen-1 interacts with perlecan proteoglycan. Core binding function. Reason: This is IPI (inferred from physical interaction) evidence specifically showing nidogen-1 binds proteoglycans including perlecan (UniProtKB:Q05793). Perlecan binding is part of nidogen-1's bridging function in basement membranes. UniProt states nidogen "Also binds to...perlecan." This is a core molecular function. Accept. Supporting Evidence: PMID:22952693 Cleavage sites were identified within G2 and G3 globular domains that are both involved in interactions with other BM components (type IV collagen, laminin, perlecan) file:human/NID1/NID1-deep-research-falcon.md Falcon synthesis supports perlecan/proteoglycan association as part of nidogen-1 basement membrane stabilization. |
| GO:0005518 collagen binding | IDA PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | ACCEPT | Summary: IDA experimental evidence for collagen IV binding. THE core molecular function for bridging. Reason: This is IDA (direct assay) experimental evidence for collagen binding, one of THE two essential binding activities (along with laminin binding) that define nidogen-1's bridging function. PMID:22952693 directly demonstrates collagen binding and shows cathepsin cleavage impairs it. This is absolutely core function. Accept. Supporting Evidence: PMID:22952693 Cleavage sites were identified within G2 and G3 globular domains that are both involved in interactions with other BM components (type IV collagen, laminin, perlecan) file:human/NID1/NID1-deep-research-falcon.md Falcon synthesis supports collagen IV binding as a core component of nidogen-1 basement membrane bridging. |
| GO:0043236 laminin binding | IDA PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | ACCEPT | Summary: IDA experimental evidence for laminin binding. THE core molecular function for bridging. Reason: This is IDA (direct assay) experimental evidence for laminin binding, one of THE two essential binding activities that define nidogen-1's bridging function. PMID:22952693 directly demonstrates laminin binding and shows cathepsin cleavage impairs it. This is absolutely core function. Accept. Supporting Evidence: PMID:22952693 Cleavage sites were identified within G2 and G3 globular domains that are both involved in interactions with other BM components file:human/NID1/NID1-deep-research-falcon.md Falcon synthesis supports laminin binding as a core nidogen-1 molecular interaction in basement membranes. |
| GO:0071711 basement membrane organization | TAS PMID:22952693 Cleavage of nidogen-1 by cathepsin S impairs its binding to ... | ACCEPT | Summary: TAS evidence for basement membrane organization. THE core biological process. Reason: This is TAS (traceable author statement) evidence for THE defining biological process of nidogen-1. PMID:22952693 describes nidogen's central role in basement membrane supramolecular organization. This is the primary process annotation. Accept. Supporting Evidence: PMID:22952693 Both nidogens play a central role in the supramolecular organization of the basal laminae in tissues file:human/NID1/NID1-deep-research-falcon.md Falcon synthesis supports nidogen-1 as a linker protein that organizes laminin and collagen IV basement membrane networks. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Detection of nidogen-1 in urinary exosome proteomics. Non-core peripheral localization. Reason: Duplicate of previous exosome annotation. While detected in exosome preparations, this is not a primary functional localization. Mark as non-core. Supporting Evidence: PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-3791319 | ACCEPT | Summary: Reactome pathway annotation for NID1 degradation by MMP19. Confirms extracellular localization. Reason: Reactome TAS annotation based on pathway R-HSA-3791319 (NID1 degradation by MMP19). Confirms nidogen-1 is in extracellular space where it can be cleaved by secreted proteases. Accept as valid general localization. Supporting Evidence: Reactome:R-HSA-3791319 Nidogen-1 (entactin) is a member of the nidogen family of basement membrane glycoproteins |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2426450 | ACCEPT | Summary: Reactome pathway annotation for Laminins-Nidogens binding collagen IV. Confirms extracellular localization. Reason: Reactome TAS annotation based on pathway R-HSA-2426450 (Laminins:Nidogens binds collagen type IV networks). This pathway describes THE core function of nidogen-1 bridging laminin and collagen IV in the extracellular space. Accept as valid. Supporting Evidence: Reactome:R-HSA-2426450 Laminin-bound nidogens can bind to type IV collagen (Aumailey et al. 1989, 1993, Fox et al. 1991, Reinhardt et al. 1993, Ries et al. 2001, Bechtel et al. 2012) |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)