UniProt functional annotation for P15116



	UniProt functional annotation for P15116

UniProt code: P15116.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell (PubMed:2762814, PubMed:11433297, PubMed:17988630, PubMed:9655503, PubMed:25253890). 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). CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density. {ECO:0000269|PubMed:11433297, ECO:0000269|PubMed:17988630, ECO:0000269|PubMed:24952463, ECO:0000269|PubMed:25253890, ECO:0000269|PubMed:26750727, ECO:0000269|PubMed:2762814, ECO:0000269|PubMed:9655503}.

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). {ECO:0000250|UniProtKB:P19022, ECO:0000250|UniProtKB:Q9Z1Y3, ECO:0000269|PubMed:11433297, ECO:0000269|PubMed:21300292, ECO:0000269|PubMed:23392350, ECO:0000269|PubMed:25253890}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:17988630, ECO:0000269|PubMed:26403541, ECO:0000269|PubMed:9655503}; Single-pass type I membrane protein {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000269|PubMed:23392350}. Cell junction {ECO:0000269|PubMed:26750727}. Cell surface {ECO:0000269|PubMed:25232112, ECO:0000269|PubMed:9655503}. Note=Colocalizes with TMEM65 at the intercalated disk in cardiomyocytes (PubMed:26403541). Colocalizes with OBSCN at the intercalated disk and sarcolemma in cardiomyocytes (PubMed:23392350). {ECO:0000269|PubMed:23392350, ECO:0000269|PubMed:26403541}.

Tissue specificity: Expressed in cardiac muscle (at protein level). {ECO:0000269|PubMed:23392350}.

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). {ECO:0000269|PubMed:23001562, ECO:0000269|PubMed:31650526, ECO:0000269|PubMed:8879495}.

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. {ECO:0000269|PubMed:21300292, ECO:0000269|PubMed:21366346}.

Ptm: 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). {ECO:0000269|PubMed:19805319, ECO:0000269|PubMed:24952463}.

Ptm: May be phosphorylated by OBSCN. {ECO:0000269|PubMed:23392350}.

Ptm: O-glycosylated on Ser and Thr residues. {ECO:0000269|PubMed:21300292}.

Disruption phenotype: Embryonic lethality. {ECO:0000269|PubMed:24952463}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell (PubMed:2762814, PubMed:11433297, PubMed:17988630, PubMed:9655503, PubMed:25253890). 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). CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density. {ECO:0000269\|PubMed:11433297, ECO:0000269\|PubMed:17988630, ECO:0000269\|PubMed:24952463, ECO:0000269\|PubMed:25253890, ECO:0000269\|PubMed:26750727, ECO:0000269\|PubMed:2762814, ECO:0000269\|PubMed:9655503}.


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). {ECO:0000250\|UniProtKB:P19022, ECO:0000250\|UniProtKB:Q9Z1Y3, ECO:0000269\|PubMed:11433297, ECO:0000269\|PubMed:21300292, ECO:0000269\|PubMed:23392350, ECO:0000269\|PubMed:25253890}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:17988630, ECO:0000269\|PubMed:26403541, ECO:0000269\|PubMed:9655503}; Single-pass type I membrane protein {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000269\|PubMed:23392350}. Cell junction {ECO:0000269\|PubMed:26750727}. Cell surface {ECO:0000269\|PubMed:25232112, ECO:0000269\|PubMed:9655503}. Note=Colocalizes with TMEM65 at the intercalated disk in cardiomyocytes (PubMed:26403541). Colocalizes with OBSCN at the intercalated disk and sarcolemma in cardiomyocytes (PubMed:23392350). {ECO:0000269\|PubMed:23392350, ECO:0000269\|PubMed:26403541}.
Tissue specificity:		Expressed in cardiac muscle (at protein level). {ECO:0000269\|PubMed:23392350}.
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). {ECO:0000269\|PubMed:23001562, ECO:0000269\|PubMed:31650526, ECO:0000269\|PubMed:8879495}.
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. {ECO:0000269\|PubMed:21300292, ECO:0000269\|PubMed:21366346}.
Ptm:		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). {ECO:0000269\|PubMed:19805319, ECO:0000269\|PubMed:24952463}.
Ptm:		May be phosphorylated by OBSCN. {ECO:0000269\|PubMed:23392350}.
Ptm:		O-glycosylated on Ser and Thr residues. {ECO:0000269\|PubMed:21300292}.
Disruption phenotype:		Embryonic lethality. {ECO:0000269\|PubMed:24952463}.