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Details on Person UniProt:P12830 CDH1
| Class:Id | ReferenceGeneProduct:51210 |
|---|---|
| _chainChangeLog | signal peptide:1-22 added on Fri February 6 2015;propeptide:23-154 added on Fri February 6 2015;chain:155-882 added on Fri February 6 2015;chain:701-882 added on Fri February 6 2015;chain:732-882 added on Fri February 6 2015;chain:751-882 added on Fri February 6 2015 |
| _displayName | UniProt:P12830 CDH1 |
| _timestamp | 2026-02-20 22:30:14 |
| chain | signal peptide:1-22 propeptide:23-154 chain:155-882 chain:701-882 chain:732-882 chain:751-882 |
| checksum | E427118043A13C67 |
| comment | FUNCTION Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells (PubMed:11976333). Promotes organization of radial actin fiber structure and cellular response to contractile forces, via its interaction with AMOTL2 which facilitates anchoring of radial actin fibers to CDH1 junction complexes at the cell membrane (By similarity). Plays a role in the early stages of desmosome cell-cell junction formation via facilitating the recruitment of DSG2 and DSP to desmosome plaques (PubMed:29999492). Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7.FUNCTION E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production.FUNCTION (Microbial infection) Serves as a receptor for Listeria monocytogenes; internalin A (InlA) binds to this protein and promotes uptake of the bacteria.SUBUNIT Homodimer; disulfide-linked (PubMed:11856755). Component of an E-cadherin/ catenin adhesion complex composed of at least E-cadherin/CDH1, beta-catenin/CTNNB1 or gamma-catenin/JUP, and potentially alpha-catenin/CTNNA1; the complex is located to adherens junctions (PubMed:16126725, PubMed:7982500). Found in a complex composed of CDH1, RAP1A and PKP3; PKP3 acts as a scaffold protein within the complex, the complex is required for CDH1 localization to mature desmosome cell junctions (PubMed:25208567). Interacts with the TRPV4 and CTNNB1 complex (By similarity). Interacts with CTNND1 (PubMed:15240885). The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex (By similarity). Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1 (By similarity). Interaction with PSEN1, cleaves CDH1 resulting in the disassociation of cadherin-based adherens junctions (CAJs) (PubMed:11226248, PubMed:16126725). Interacts with AJAP1 and DLGAP5 (PubMed:14595118, PubMed:14699157). Interacts with TBC1D2 (PubMed:20116244). Interacts with LIMA1 (PubMed:18093941). Interacts with CAV1. Interacts with PIP5K1C (PubMed:17261850). Interacts with RAB8B (By similarity). Interacts with RAPGEF2 (By similarity). Interacts with DDR1; this stabilizes CDH1 at the cell surface and inhibits its internalization (PubMed:20432435). Interacts with KLRG1 (PubMed:19604491). Forms a ternary complex composed of ADAM10, CADH1 and EPHA4; within the complex, CADH1 is cleaved by ADAM10 which disrupts adherens junctions (By similarity). Interacts with SPEF1 (PubMed:31473225). Interacts with CTNNB1 and PKP2 (PubMed:11790773). Interacts with AMOTL2; the interaction may facilitate binding of radial actin fibers to cell junction complexes (By similarity). Interacts with DSG3; the interaction is required for CDH1 localization to developing adherens junctions (PubMed:22294297).SUBUNIT (Microbial infection) Interacts with L.monocytogenes InlA (PubMed:12526809, PubMed:17540170, PubMed:17715295). The formation of the complex between InlA and cadherin-1 is calcium-dependent (PubMed:12526809).INTERACTION Colocalizes with DLGAP5 at sites of cell-cell contact in intestinal epithelial cells. Anchored to actin microfilaments through association with alpha-, beta- and gamma-catenin. Sequential proteolysis induced by apoptosis or calcium influx, results in translocation from sites of cell-cell contact to the cytoplasm. Colocalizes with RAB11A endosomes during its transport from the Golgi apparatus to the plasma membrane. Recruited to desmosomes at the initial assembly phase and also accumulates progressively at mature desmosome cell-cell junctions (PubMed:25208567, PubMed:29999492). Localizes to cell-cell contacts as keratinocyte differentiation progresses (By similarity).ALTERNATIVE PRODUCTS Expressed in granuloma macrophages (at protein level) (PubMed:27760340). Expressed in the skin (at protein level) (PubMed:22294297). Expressed in the liver (PubMed:3263290).INDUCTION Induced in the hours following cyclic mechanical strain in keratinocytes (PubMed:31835537). Expression is repressed by MACROD1 (PubMed:17893710).DOMAIN Three calcium ions are usually bound at the interface of each cadherin domain and strengthen the connections, imparting a strong curvature to the full-length ectodomain.PTM During apoptosis or with calcium influx, cleaved by a membrane-bound metalloproteinase (ADAM10), PS1/gamma-secretase and caspase-3 (PubMed:10597309, PubMed:11076937, PubMed:11953314). Processing by the metalloproteinase, induced by calcium influx, causes disruption of cell-cell adhesion and the subsequent release of beta-catenin into the cytoplasm (PubMed:10597309). The residual membrane-tethered cleavage product is rapidly degraded via an intracellular proteolytic pathway (PubMed:10597309). Cleavage by caspase-3 releases the cytoplasmic tail resulting in disintegration of the actin microfilament system (PubMed:11076937). The gamma-secretase-mediated cleavage promotes disassembly of adherens junctions (PubMed:11953314). During development of the cochlear organ of Corti, cleavage by ADAM10 at adherens junctions promotes pillar cell separation (By similarity).PTM N-glycosylation at Asn-637 is essential for expression, folding and trafficking. Addition of bisecting N-acetylglucosamine by MGAT3 modulates its cell membrane location (PubMed:19403558).PTM Ubiquitinated by a SCF complex containing SKP2, which requires prior phosphorylation by CK1/CSNK1A1. Ubiquitinated by CBLL1/HAKAI, requires prior phosphorylation at Tyr-754.PTM O-glycosylated. O-manosylated by TMTC1, TMTC2, TMTC3 or TMTC4. Thr-285 and Thr-509 are O-mannosylated by TMTC2 or TMTC4 but not TMTC1 or TMTC3.PTM (Microbial infection) Cleaved by S.pyogenes SpeB protease; leading to its degradation (PubMed:23532847). Degradation by SpeB promotes bacterial translocation across the host epithelial barrier (PubMed:23532847).DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry. Heterozygous CDH1 germline mutations are responsible for familial cases of diffuse gastric cancer. Somatic mutations has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE The gene represented in this entry may be involved in disease pathogenesis.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS May play a role in blister formation in Pemphigus vulgaris patients, expression is lost at sites of cell-cell contact between the basal and suprabasal layers in blisters and immediately adjacent to blisters.SEQUENCE CAUTION E-cadherin entry |
| description | recommendedName: fullName evidence="75"Cadherin-1 alternativeName: CAM 120/80 alternativeName: fullName evidence="74"Epithelial cadherin shortName evidence="75"E-cadherin alternativeName: fullName evidence="72"Uvomorulin cdAntigenNameCD324/cdAntigenName component recommendedName: E-Cad/CTF1 /component component recommendedName: E-Cad/CTF2 /component component recommendedName: E-Cad/CTF3 /component |
| geneName | CDH1 CDHE UVO |
| identifier | P12830 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Calcium Cell adhesion Cell junction Cell membrane Cleavage on pair of basic residues Cytoplasm Direct protein sequencing Disease variant Disulfide bond Ectodermal dysplasia Endosome Glycoprotein Golgi apparatus Membrane Metal-binding Phosphoprotein Proteomics identification Reference proteome Repeat Signal Transmembrane Transmembrane helix Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | CDH1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8987710] ENSEMBL:ENSG00000039068 CDH1 [Homo sapiens] |
| secondaryIdentifier | CADH1_HUMAN A8K1U7 Q13799 Q14216 Q15855 Q16194 Q4PJ14 Q9UII8 |
| sequenceLength | 882 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8972720] UniProt:P12830-1 CDH1 [Homo sapiens] [ReferenceIsoform:8972721] UniProt:P12830-2 CDH1 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:198003] CDH1(155-882) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:202919] CDH1(1-882) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:202929] CDH1(751-882) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:202940] CDH1(155-750) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2534158] CDH1(701-882) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:2534244] CDH1(155-700) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:3827997] CDH1(732-882) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:3828039] CDH1(155-731) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:8876938] p-Y753,Y754-CDH1(155-882) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:8877002] Ub-K,p-Y753,Y754-CDH1(155-882) [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:8876942] O4'-phospho-L-tyrosine at 753 [ModifiedResidue:8876945] O4'-phospho-L-tyrosine at 754 [GroupModifiedResidue:8877007] ubiquitinylated lysine (Ub [cytosol]) at unknown position [GroupModifiedResidue:9932173] N4-(N-acetylamino)glucosyl-L-asparagine (N-{alpha-Glc-(1->2)-alpha-Glc-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-(alpha-Man-(1->2)-alpha-Man-(1->3)-(alpha-Man-(1->2)-alpha-Man-(1->6))-alpha-Man-(1->6))-beta-Man-(1->4)-beta-GlcNAc-(1->4)-beta-GlcNAc}-yl group (ChEBI:59084)) at 558 [GroupModifiedResidue:9932174] N4-(N-acetylamino)glucosyl-L-asparagine (N-{alpha-Glc-(1->2)-alpha-Glc-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-(alpha-Man-(1->2)-alpha-Man-(1->3)-(alpha-Man-(1->2)-alpha-Man-(1->6))-alpha-Man-(1->6))-beta-Man-(1->4)-beta-GlcNAc-(1->4)-beta-GlcNAc}-yl group (ChEBI:59084)) at 570 [GroupModifiedResidue:9932175] N4-(N-acetylamino)glucosyl-L-asparagine (N-{alpha-Glc-(1->2)-alpha-Glc-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-(alpha-Man-(1->2)-alpha-Man-(1->3)-(alpha-Man-(1->2)-alpha-Man-(1->6))-alpha-Man-(1->6))-beta-Man-(1->4)-beta-GlcNAc-(1->4)-beta-GlcNAc}-yl group (ChEBI:59084)) at 637 [GroupModifiedResidue:9932177] N4-(N-acetylamino)glucosyl-L-asparagine (N-{alpha-Glc-(1->2)-alpha-Glc-(1->3)-alpha-Glc-(1->3)-alpha-Man-(1->2)-alpha-Man-(1->2)-alpha-Man-(1->3)-(alpha-Man-(1->2)-alpha-Man-(1->3)-(alpha-Man-(1->2)-alpha-Man-(1->6))-alpha-Man-(1->6))-beta-Man-(1->4)-beta-GlcNAc-(1->4)-beta-GlcNAc}-yl group (ChEBI:59084)) at 622 [GroupModifiedResidue:9932339] N4-(N-acetylamino)glucosyl-L-asparagine (N-(α-Glc-(1→3)-α-Glc-(1→3)-α-Man-(1→2)-α-Man-(1→2)-α-Man-(1→3)-(α-Man-(1→2)-α-Man-(1→3)-(α-Man-(1→2)-α-Man-(1→6))-α-Man-(1→6))-β-Man-(1→4)-β-GlcNAc-(1→4)-β-GlcNAc)-L-Asn residue) at 637 [GroupModifiedResidue:9932343] N4-(N-acetylamino)glucosyl-L-asparagine (N-(α-Glc-(1→3)-α-Glc-(1→3)-α-Man-(1→2)-α-Man-(1→2)-α-Man-(1→3)-(α-Man-(1→2)-α-Man-(1→3)-(α-Man-(1→2)-α-Man-(1→6))-α-Man-(1→6))-β-Man-(1→4)-β-GlcNAc-(1→4)-β-GlcNAc)-L-Asn residue) at 570 [GroupModifiedResidue:9932345] N4-(N-acetylamino)glucosyl-L-asparagine (N-(α-Glc-(1→3)-α-Glc-(1→3)-α-Man-(1→2)-α-Man-(1→2)-α-Man-(1→3)-(α-Man-(1→2)-α-Man-(1→3)-(α-Man-(1→2)-α-Man-(1→6))-α-Man-(1→6))-β-Man-(1→4)-β-GlcNAc-(1→4)-β-GlcNAc)-L-Asn residue) at 558 |
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No pathways have been reviewed or authored by UniProt:P12830 CDH1 (51210)
