P15116 · CADH2_MOUSE
- ProteinCadherin-2
- GeneCdh2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids906 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell (PubMed:11433297, PubMed:17988630, PubMed:25253890, PubMed:2762814, PubMed:9655503).
Cadherins may thus contribute to the sorting of heterogeneous cell types. Acts as a regulator of neural stem cells quiescence by mediating anchorage of neural stem cells to ependymocytes in the adult subependymal zone: upon cleavage by MMP24, CDH2-mediated anchorage is affected, leading to modulate neural stem cell quiescence (PubMed:24952463).
Plays a role in cell-to-cell junction formation between pancreatic beta cells and neural crest stem (NCS) cells, promoting the formation of processes by NCS cells (PubMed:26750727).
Required for proper neurite branching. Required for pre- and postsynaptic organization (By similarity).
CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density
Cadherins may thus contribute to the sorting of heterogeneous cell types. Acts as a regulator of neural stem cells quiescence by mediating anchorage of neural stem cells to ependymocytes in the adult subependymal zone: upon cleavage by MMP24, CDH2-mediated anchorage is affected, leading to modulate neural stem cell quiescence (PubMed:24952463).
Plays a role in cell-to-cell junction formation between pancreatic beta cells and neural crest stem (NCS) cells, promoting the formation of processes by NCS cells (PubMed:26750727).
Required for proper neurite branching. Required for pre- and postsynaptic organization (By similarity).
CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 170 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 170 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 226 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 228 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 228 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 259 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 260 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Binding site | 261 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 262 | Ca2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 262 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 263 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 293 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 295 | Ca2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 301 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 353 | Ca2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCadherin-2
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP15116
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 160-724 | Extracellular | ||||
Sequence: DWVIPPINLPENSRGPFPQELVRIRSDRDKNLSLRYSVTGPGADQPPTGIFIINPISGQLSVTKPLDRELIARFHLRAHAVDINGNQVENPIDIVINVIDMNDNRPEFLHQVWNGSVPEGSKPGTYVMTVTAIDADDPNALNGMLRYRILSQAPSTPSPNMFTINNETGDIITVAAGLDREKVQQYTLIIQATDMEGNPTYGLSNTATAVITVTDVNDNPPEFTAMTFYGEVPENRVDVIVANLTVTDKDQPHTPAWNAAYRISGGDPTGRFAILTDPNSNDGLVTVVKPIDFETNRMFVLTVAAENQVPLAKGIQHPPQSTATVSVTVIDVNENPYFAPNPKIIRQEEGLHAGTMLTTLTAQDPDRYMQQNIRYTKLSDPANWLKIDPVNGQITTIAVLDRESPNVKNNIYNATFLASDNGIPPMSGTGTLQIYLLDINDNAPQVLPQEAETCETPEPNSINITALDYDIDPNAGPFAFDLPLSPVTIKRNWTINRLNGDFAQLNLKIKFLEAGIYEVPIIITDSGNPPKSNISILRVKVCQCDSNGDCTDVDRIVGAGLGTGA | ||||||
Transmembrane | 725-745 | Helical | ||||
Sequence: IIAILLCIIILLILVLMFVVW | ||||||
Topological domain | 746-906 | Cytoplasmic | ||||
Sequence: MKRRDKERQAKQLLIDPEDDVRDNILKYDEEGGGEEDQDYDLSQLQQPDTVEPDAIKPVGIRRLDERPIHAEPQYPVRSAAPHPGDIGDFINEGLKAADNDPTAPPYDSLLVFDYEGSGSTAGSLSSLNSSSSGGDQDYDYLNDWGPRFKKLADMYGGGDD |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Embryonic lethality.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 150 | CRISPR/Cas9-mutated knockin mice manifest motor-associated features of hyperactivity such as greater traveling distance, increased velocity and prolonged mobility time compared with control mice. Synaptic release is attenuated in neuron from mutant mice and synaptic vesicle clusters size is reduced in presynaptic terminals. | ||||
Sequence: H → Y | ||||||
Mutagenesis | 161 | Loss of calcium-dependent cell-cell adhesion. | ||||
Sequence: W → A or Y | ||||||
Mutagenesis | 161 | Loss of dimerization; when associated with E-173. | ||||
Sequence: W → A | ||||||
Mutagenesis | 162 | Decreased calcium-dependent cell-cell adhesion. | ||||
Sequence: V → A | ||||||
Mutagenesis | 173 | Loss of dimerization; when associated with A-161. | ||||
Sequence: R → E | ||||||
Mutagenesis | 237 | Loss of calcium-dependent cell-cell adhesion. | ||||
Sequence: A → M | ||||||
Mutagenesis | 239 | Loss of calcium-dependent cell-cell adhesion. | ||||
Sequence: A → M | ||||||
Mutagenesis | 262 | Abolishes dimerization. | ||||
Sequence: D → A | ||||||
Mutagenesis | 293 | Severely impaired the binding of calcium to all three sites. | ||||
Sequence: D → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 23 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, propeptide, chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-25 | |||||
Sequence: MCRIAGAPRTLLPLLAALLQASVEA | ||||||
Propeptide | PRO_0000003733 | 26-159 | ||||
Sequence: SGEIALCKTGFPEDVYSAVLPKDVHEGQPLLNVKFSNCNRKRKVQYESSEPADFKVDEDGTVYAVRSFPLTAEQAKFLIYAQDKETQEKWQVAVNLSREPTLTEEPMKEPHEIEEIVFPRQLAKHSGALQRQKR | ||||||
Chain | PRO_0000003734 | 160-906 | Cadherin-2 | |||
Sequence: DWVIPPINLPENSRGPFPQELVRIRSDRDKNLSLRYSVTGPGADQPPTGIFIINPISGQLSVTKPLDRELIARFHLRAHAVDINGNQVENPIDIVINVIDMNDNRPEFLHQVWNGSVPEGSKPGTYVMTVTAIDADDPNALNGMLRYRILSQAPSTPSPNMFTINNETGDIITVAAGLDREKVQQYTLIIQATDMEGNPTYGLSNTATAVITVTDVNDNPPEFTAMTFYGEVPENRVDVIVANLTVTDKDQPHTPAWNAAYRISGGDPTGRFAILTDPNSNDGLVTVVKPIDFETNRMFVLTVAAENQVPLAKGIQHPPQSTATVSVTVIDVNENPYFAPNPKIIRQEEGLHAGTMLTTLTAQDPDRYMQQNIRYTKLSDPANWLKIDPVNGQITTIAVLDRESPNVKNNIYNATFLASDNGIPPMSGTGTLQIYLLDINDNAPQVLPQEAETCETPEPNSINITALDYDIDPNAGPFAFDLPLSPVTIKRNWTINRLNGDFAQLNLKIKFLEAGIYEVPIIITDSGNPPKSNISILRVKVCQCDSNGDCTDVDRIVGAGLGTGAIIAILLCIIILLILVLMFVVWMKRRDKERQAKQLLIDPEDDVRDNILKYDEEGGGEEDQDYDLSQLQQPDTVEPDAIKPVGIRRLDERPIHAEPQYPVRSAAPHPGDIGDFINEGLKAADNDPTAPPYDSLLVFDYEGSGSTAGSLSSLNSSSSGGDQDYDYLNDWGPRFKKLADMYGGGDD | ||||||
Glycosylation | 190 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 273 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 325 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 402 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 572 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 651 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 692 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Cleaved by MMP24 (PubMed:19805319, PubMed:24952463).
Ectodomain cleavage leads to the generation of a soluble 90 kDa N-terminal soluble fragment and a 45 kDa membrane-bound C-terminal fragment 1 (CTF1), which is further cleaved by gamma-secretase into a 35 kDa (PubMed:24952463).
Cleavage in neural stem cells by MMP24 affects CDH2-mediated anchorage of neural stem cells to ependymocytes in the adult subependymal zone, leading to modulate neural stem cell quiescence (PubMed:24952463).
Ectodomain cleavage leads to the generation of a soluble 90 kDa N-terminal soluble fragment and a 45 kDa membrane-bound C-terminal fragment 1 (CTF1), which is further cleaved by gamma-secretase into a 35 kDa (PubMed:24952463).
Cleavage in neural stem cells by MMP24 affects CDH2-mediated anchorage of neural stem cells to ependymocytes in the adult subependymal zone, leading to modulate neural stem cell quiescence (PubMed:24952463).
May be phosphorylated by OBSCN.
O-glycosylated on Ser and Thr residues.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in cardiac muscle (at protein level).
Developmental stage
Expressed at all stages of testicular development with the highest expression levels found in testes of 21-day-old mice (PubMed:8879495).
Expressed at the outer limiting membrane of the retina at 3 months of age (PubMed:23001562).
Expression is restricted to the lens stalk region between 10 and 11 dpc. At later stages (17.5 dpc), it is expressed in the developing lens and corneal endothelium (PubMed:31650526).
Expressed at the outer limiting membrane of the retina at 3 months of age (PubMed:23001562).
Expression is restricted to the lens stalk region between 10 and 11 dpc. At later stages (17.5 dpc), it is expressed in the developing lens and corneal endothelium (PubMed:31650526).
Gene expression databases
Interaction
Subunit
Homodimer (via extracellular region) (PubMed:21300292, PubMed:25253890).
Can also form heterodimers with other cadherins (via extracellular region) (PubMed:25253890).
Dimerization occurs in trans, i.e. with a cadherin chain from another cell (PubMed:21300292, PubMed:25253890).
Interacts with CDCP1 (By similarity).
Interacts with PCDH8; this complex may also include TAOK2 (By similarity).
The interaction with PCDH8 may lead to internalization through TAOK2/p38 MAPK pathway (By similarity).
Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN (PubMed:11433297).
May interact with OBSCN (via protein kinase domain 2) (PubMed:23392350).
Interacts with FBXO45 (By similarity).
Can also form heterodimers with other cadherins (via extracellular region) (PubMed:25253890).
Dimerization occurs in trans, i.e. with a cadherin chain from another cell (PubMed:21300292, PubMed:25253890).
Interacts with CDCP1 (By similarity).
Interacts with PCDH8; this complex may also include TAOK2 (By similarity).
The interaction with PCDH8 may lead to internalization through TAOK2/p38 MAPK pathway (By similarity).
Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN (PubMed:11433297).
May interact with OBSCN (via protein kinase domain 2) (PubMed:23392350).
Interacts with FBXO45 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P15116 | Cdh2 P15116 | 4 | EBI-397974, EBI-397974 | |
XENO | P15116 | PTPN1 P18031 | 3 | EBI-397974, EBI-968788 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 160-267 | Cadherin 1 | ||||
Sequence: DWVIPPINLPENSRGPFPQELVRIRSDRDKNLSLRYSVTGPGADQPPTGIFIINPISGQLSVTKPLDRELIARFHLRAHAVDINGNQVENPIDIVINVIDMNDNRPEF | ||||||
Domain | 268-382 | Cadherin 2 | ||||
Sequence: LHQVWNGSVPEGSKPGTYVMTVTAIDADDPNALNGMLRYRILSQAPSTPSPNMFTINNETGDIITVAAGLDREKVQQYTLIIQATDMEGNPTYGLSNTATAVITVTDVNDNPPEF | ||||||
Domain | 383-497 | Cadherin 3 | ||||
Sequence: TAMTFYGEVPENRVDVIVANLTVTDKDQPHTPAWNAAYRISGGDPTGRFAILTDPNSNDGLVTVVKPIDFETNRMFVLTVAAENQVPLAKGIQHPPQSTATVSVTVIDVNENPYF | ||||||
Domain | 498-603 | Cadherin 4 | ||||
Sequence: APNPKIIRQEEGLHAGTMLTTLTAQDPDRYMQQNIRYTKLSDPANWLKIDPVNGQITTIAVLDRESPNVKNNIYNATFLASDNGIPPMSGTGTLQIYLLDINDNAP | ||||||
Domain | 604-717 | Cadherin 5 | ||||
Sequence: QVLPQEAETCETPEPNSINITALDYDIDPNAGPFAFDLPLSPVTIKRNWTINRLNGDFAQLNLKIKFLEAGIYEVPIIITDSGNPPKSNISILRVKVCQCDSNGDCTDVDRIVG | ||||||
Region | 863-883 | Disordered | ||||
Sequence: SGSTAGSLSSLNSSSSGGDQD | ||||||
Compositional bias | 864-883 | Polar residues | ||||
Sequence: GSTAGSLSSLNSSSSGGDQD |
Domain
Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. Calcium-binding sites are occupied sequentially in the order of site 3, then site 2 and site 1.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length906
- Mass (Da)99,796
- Last updated2011-07-27 v2
- ChecksumBDAB8063A23E1F13
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
D3YYT0 | D3YYT0_MOUSE | Cdh2 | 849 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 7-9 | in Ref. 1; AAA37353 | ||||
Sequence: APR → GRG | ||||||
Sequence conflict | 565-567 | in Ref. 1; AAA37353 | ||||
Sequence: NVK → YVQ | ||||||
Sequence conflict | 624 | in Ref. 1; AAA37353 | ||||
Sequence: T → A | ||||||
Compositional bias | 864-883 | Polar residues | ||||
Sequence: GSTAGSLSSLNSSSSGGDQD |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M31131 EMBL· GenBank· DDBJ | AAA37353.1 EMBL· GenBank· DDBJ | mRNA | ||
AB008811 EMBL· GenBank· DDBJ | BAA23549.1 EMBL· GenBank· DDBJ | mRNA | ||
S45011 EMBL· GenBank· DDBJ | AAB23356.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH466557 EMBL· GenBank· DDBJ | EDK96930.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC022107 EMBL· GenBank· DDBJ | AAH22107.1 EMBL· GenBank· DDBJ | mRNA |