UniProt functional annotation for O60716



	UniProt functional annotation for O60716

UniProt code: O60716.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:14610055, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:20371349}.

Subunit: Belongs to a multiprotein cell-cell adhesion complex that also contains E-cadherin/CDH1, alpha-catenin/CTNNA1, beta-catenin/CTNNB1, and gamma-catenin/JUP (PubMed:20371349, PubMed:15240885). Component of a cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1 (PubMed:28051089). Binds to the C-terminal fragment of PSEN1 and mutually competes for CDH1. Interacts with ZBTB33 (PubMed:10207085). Interacts with GLIS2 (PubMed:17344476). Interacts with FER (PubMed:7623846). Interacts with NANOS1 (via N-terminal region) (PubMed:17047063). Interacts (via N-terminus) with GNA12; the interaction regulates CDH1-mediated cell-cell adhesion (PubMed:15240885). Interacts with GNA13 (PubMed:15240885). Interacts with CCDC85B (PubMed:25009281). Interacts with PLPP3; negatively regulates the PLPP3-mediated stabilization of CTNNB1 (PubMed:20123964). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:15240885, ECO:0000269|PubMed:17047063, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:20123964, ECO:0000269|PubMed:20371349, ECO:0000269|PubMed:25009281, ECO:0000269|PubMed:28051089, ECO:0000269|PubMed:7623846}.

Subcellular location: Cell junction, adherens junction {ECO:0000269|PubMed:11896187}. Cytoplasm {ECO:0000269|PubMed:15240885, ECO:0000269|PubMed:17047063}. Nucleus {ECO:0000269|PubMed:11896187, ECO:0000269|PubMed:17115030}. Cell membrane {ECO:0000269|PubMed:15240885, ECO:0000269|PubMed:17047063}. Note=Interaction with GLIS2 promotes nuclear translocation (By similarity). Detected at cell-cell contacts (PubMed:15240885, PubMed:17047063). NANOS1 induces its translocation from sites of cell- cell contact to the cytoplasm (PubMed:17047063). CDH1 enhances cell membrane localization (PubMed:15240885). Isoforms 4A and 1AB are excluded from the nucleus (PubMed:11896187). {ECO:0000250|UniProtKB:P30999, ECO:0000269|PubMed:11896187, ECO:0000269|PubMed:15240885, ECO:0000269|PubMed:17047063}.

Subcellular location: [Isoform 1A]: Nucleus {ECO:0000269|PubMed:11896187}.

Subcellular location: [Isoform 2A]: Nucleus {ECO:0000269|PubMed:11896187}.

Subcellular location: [Isoform 3A]: Nucleus {ECO:0000269|PubMed:11896187}.

Tissue specificity: Expressed in vascular endothelium. Melanocytes and melanoma cells primarily express the long isoform 1A, whereas keratinocytes express shorter isoforms, especially 3A. The shortest isoform 4A, is detected in normal keratinocytes and melanocytes, and generally lost from cells derived from squamous cell carcinomas or melanomas. The C-terminal alternatively spliced exon B is present in the p120ctn transcripts in the colon, intestine and prostate, but lost in several tumor tissues derived from these organs. {ECO:0000269|PubMed:11896187, ECO:0000269|PubMed:14699141}.

Induction: Induced in vascular endothelium by wounding. This effect is potentiated by prior laminar shear stress, which enhances wound closure. {ECO:0000269|PubMed:14699141}.

Domain: A possible nuclear localization signal exists in all isoforms where Asp-626--631-Arg are deleted.

Domain: ARM repeats 1 to 5 mediate interaction with cadherins.

Ptm: Phosphorylated by FER and other protein-tyrosine kinases. Phosphorylated at Ser-288 by PAK5. Dephosphorylated by PTPRJ. {ECO:0000269|PubMed:12370829, ECO:0000269|PubMed:17194753, ECO:0000269|PubMed:20564219, ECO:0000269|PubMed:7623846}.

Disease: Blepharocheilodontic syndrome 2 (BCDS2) [MIM:617681]: A form of blepharocheilodontic syndrome, a rare autosomal dominant disorder. It is characterized by lower eyelid ectropion, upper eyelid distichiasis, euryblepharon, bilateral cleft lip and palate, and features of ectodermal dysplasia, including hair anomalies, conical teeth and tooth agenesis. An additional rare manifestation is imperforate anus. There is considerable phenotypic variability among affected individuals. {ECO:0000269|PubMed:28301459}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the beta-catenin family. {ECO:0000305}.

Sequence caution: Sequence=BAA20838.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269\|PubMed:10207085, ECO:0000269\|PubMed:14610055, ECO:0000269\|PubMed:17344476, ECO:0000269\|PubMed:20371349}.


Subunit:		Belongs to a multiprotein cell-cell adhesion complex that also contains E-cadherin/CDH1, alpha-catenin/CTNNA1, beta-catenin/CTNNB1, and gamma-catenin/JUP (PubMed:20371349, PubMed:15240885). Component of a cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1 (PubMed:28051089). Binds to the C-terminal fragment of PSEN1 and mutually competes for CDH1. Interacts with ZBTB33 (PubMed:10207085). Interacts with GLIS2 (PubMed:17344476). Interacts with FER (PubMed:7623846). Interacts with NANOS1 (via N-terminal region) (PubMed:17047063). Interacts (via N-terminus) with GNA12; the interaction regulates CDH1-mediated cell-cell adhesion (PubMed:15240885). Interacts with GNA13 (PubMed:15240885). Interacts with CCDC85B (PubMed:25009281). Interacts with PLPP3; negatively regulates the PLPP3-mediated stabilization of CTNNB1 (PubMed:20123964). {ECO:0000269\|PubMed:10207085, ECO:0000269\|PubMed:15240885, ECO:0000269\|PubMed:17047063, ECO:0000269\|PubMed:17344476, ECO:0000269\|PubMed:20123964, ECO:0000269\|PubMed:20371349, ECO:0000269\|PubMed:25009281, ECO:0000269\|PubMed:28051089, ECO:0000269\|PubMed:7623846}.
Subcellular location:		Cell junction, adherens junction {ECO:0000269\|PubMed:11896187}. Cytoplasm {ECO:0000269\|PubMed:15240885, ECO:0000269\|PubMed:17047063}. Nucleus {ECO:0000269\|PubMed:11896187, ECO:0000269\|PubMed:17115030}. Cell membrane {ECO:0000269\|PubMed:15240885, ECO:0000269\|PubMed:17047063}. Note=Interaction with GLIS2 promotes nuclear translocation (By similarity). Detected at cell-cell contacts (PubMed:15240885, PubMed:17047063). NANOS1 induces its translocation from sites of cell- cell contact to the cytoplasm (PubMed:17047063). CDH1 enhances cell membrane localization (PubMed:15240885). Isoforms 4A and 1AB are excluded from the nucleus (PubMed:11896187). {ECO:0000250\|UniProtKB:P30999, ECO:0000269\|PubMed:11896187, ECO:0000269\|PubMed:15240885, ECO:0000269\|PubMed:17047063}.
Subcellular location:		[Isoform 1A]: Nucleus {ECO:0000269\|PubMed:11896187}.
Subcellular location:		[Isoform 2A]: Nucleus {ECO:0000269\|PubMed:11896187}.
Subcellular location:		[Isoform 3A]: Nucleus {ECO:0000269\|PubMed:11896187}.
Tissue specificity:		Expressed in vascular endothelium. Melanocytes and melanoma cells primarily express the long isoform 1A, whereas keratinocytes express shorter isoforms, especially 3A. The shortest isoform 4A, is detected in normal keratinocytes and melanocytes, and generally lost from cells derived from squamous cell carcinomas or melanomas. The C-terminal alternatively spliced exon B is present in the p120ctn transcripts in the colon, intestine and prostate, but lost in several tumor tissues derived from these organs. {ECO:0000269\|PubMed:11896187, ECO:0000269\|PubMed:14699141}.
Induction:		Induced in vascular endothelium by wounding. This effect is potentiated by prior laminar shear stress, which enhances wound closure. {ECO:0000269\|PubMed:14699141}.
Domain:		A possible nuclear localization signal exists in all isoforms where Asp-626--631-Arg are deleted.
Domain:		ARM repeats 1 to 5 mediate interaction with cadherins.
Ptm:		Phosphorylated by FER and other protein-tyrosine kinases. Phosphorylated at Ser-288 by PAK5. Dephosphorylated by PTPRJ. {ECO:0000269\|PubMed:12370829, ECO:0000269\|PubMed:17194753, ECO:0000269\|PubMed:20564219, ECO:0000269\|PubMed:7623846}.
Disease:		Blepharocheilodontic syndrome 2 (BCDS2) [MIM:617681]: A form of blepharocheilodontic syndrome, a rare autosomal dominant disorder. It is characterized by lower eyelid ectropion, upper eyelid distichiasis, euryblepharon, bilateral cleft lip and palate, and features of ectodermal dysplasia, including hair anomalies, conical teeth and tooth agenesis. An additional rare manifestation is imperforate anus. There is considerable phenotypic variability among affected individuals. {ECO:0000269\|PubMed:28301459}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the beta-catenin family. {ECO:0000305}.
Sequence caution:		Sequence=BAA20838.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};