UniProt functional annotation for P08050



	UniProt functional annotation for P08050

UniProt code: P08050.

Organism: Rattus norvegicus (Rat).

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

Function: Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract (By similarity). May play a role in cell growth inhibition through the regulation of NOV expression and localization (PubMed:15181016). Plays an essential role in gap junction communication in the ventricles (By similarity). {ECO:0000250|UniProtKB:P23242, ECO:0000269|PubMed:15181016}.

Subunit: A connexon is composed of a hexamer of connexins (PubMed:1371548). Interacts with SGSM3 (By similarity). Interacts with RIC1/CIP150 (By similarity). Interacts with CNST and CSNK1D (By similarity). Interacts (via C-terminus) with TJP1 (PubMed:15492000, PubMed:18636092). Interacts (via C-terminus) with SRC (via SH3 domain) (PubMed:15492000). Interacts (not ubiquitinated) with UBQLN4 (via UBA domain) (PubMed:20127391). Interacts with NOV (PubMed:15181016, PubMed:15213231). Interacts with TMEM65 (By similarity). {ECO:0000250|UniProtKB:P17302, ECO:0000250|UniProtKB:P23242, ECO:0000269|PubMed:1371548, ECO:0000269|PubMed:15181016, ECO:0000269|PubMed:15213231, ECO:0000269|PubMed:15492000, ECO:0000269|PubMed:18636092, ECO:0000269|PubMed:20127391}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:18636092}; Multi-pass membrane protein {ECO:0000255}. Cell junction, gap junction {ECO:0000269|PubMed:15213231, ECO:0000269|PubMed:18636092, ECO:0000269|PubMed:2472402}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P23242}. Note=Localizes at the intercalated disk (ICD) in cardiomyocytes and the proper localization at ICD is dependent on TMEM65. {ECO:0000250|UniProtKB:P23242}.

Tissue specificity: Detected in ventricle and atrium (at protein level). {ECO:0000269|PubMed:2472402}.

Induction: In bladder smooth muscle cells, exhibits night/day variations with low levels during the sleep phase, at circadian time (CT) 4-8 (at protein level). Expression starts to increase around CT12 and forms a plateau during the active phase (CT16-24) (at protein level). {ECO:0000269|PubMed:22549838}.

Ptm: Contains at least one intramolecular disulfide bond.

Ptm: Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly. Phosphorylated at Ser-368 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of gap junction activity (By similarity). Phosphorylation at Ser-368 by PRKCD triggers its internalization into small vesicles leading to proteasome-mediated degradation (PubMed:24500718). {ECO:0000250|UniProtKB:P17302, ECO:0000250|UniProtKB:Q6TYA7, ECO:0000269|PubMed:24500718}.

Ptm: Sumoylated with SUMO1, SUMO2 and SUMO3, which may regulate the level of functional Cx43 gap junctions at the plasma membrane. May be desumoylated by SENP1 or SENP2 (By similarity). {ECO:0000250|UniProtKB:P17302}.

Ptm: S-nitrosylation at Cys-271 is enriched at the muscle endothelial gap junction in arteries, it augments channel permeability and may regulate of smooth muscle cell to endothelial cell communication. {ECO:0000250|UniProtKB:P23242}.

Ptm: Acetylated in the developing cortex; leading to delocalization from the cell membrane. {ECO:0000250|UniProtKB:P23242}.

Similarity: Belongs to the connexin family. Alpha-type (group II) subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract (By similarity). May play a role in cell growth inhibition through the regulation of NOV expression and localization (PubMed:15181016). Plays an essential role in gap junction communication in the ventricles (By similarity). {ECO:0000250\|UniProtKB:P23242, ECO:0000269\|PubMed:15181016}.


Subunit:		A connexon is composed of a hexamer of connexins (PubMed:1371548). Interacts with SGSM3 (By similarity). Interacts with RIC1/CIP150 (By similarity). Interacts with CNST and CSNK1D (By similarity). Interacts (via C-terminus) with TJP1 (PubMed:15492000, PubMed:18636092). Interacts (via C-terminus) with SRC (via SH3 domain) (PubMed:15492000). Interacts (not ubiquitinated) with UBQLN4 (via UBA domain) (PubMed:20127391). Interacts with NOV (PubMed:15181016, PubMed:15213231). Interacts with TMEM65 (By similarity). {ECO:0000250\|UniProtKB:P17302, ECO:0000250\|UniProtKB:P23242, ECO:0000269\|PubMed:1371548, ECO:0000269\|PubMed:15181016, ECO:0000269\|PubMed:15213231, ECO:0000269\|PubMed:15492000, ECO:0000269\|PubMed:18636092, ECO:0000269\|PubMed:20127391}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:18636092}; Multi-pass membrane protein {ECO:0000255}. Cell junction, gap junction {ECO:0000269\|PubMed:15213231, ECO:0000269\|PubMed:18636092, ECO:0000269\|PubMed:2472402}. Endoplasmic reticulum {ECO:0000250\|UniProtKB:P23242}. Note=Localizes at the intercalated disk (ICD) in cardiomyocytes and the proper localization at ICD is dependent on TMEM65. {ECO:0000250\|UniProtKB:P23242}.
Tissue specificity:		Detected in ventricle and atrium (at protein level). {ECO:0000269\|PubMed:2472402}.
Induction:		In bladder smooth muscle cells, exhibits night/day variations with low levels during the sleep phase, at circadian time (CT) 4-8 (at protein level). Expression starts to increase around CT12 and forms a plateau during the active phase (CT16-24) (at protein level). {ECO:0000269\|PubMed:22549838}.
Ptm:		Contains at least one intramolecular disulfide bond.
Ptm:		Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly. Phosphorylated at Ser-368 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of gap junction activity (By similarity). Phosphorylation at Ser-368 by PRKCD triggers its internalization into small vesicles leading to proteasome-mediated degradation (PubMed:24500718). {ECO:0000250\|UniProtKB:P17302, ECO:0000250\|UniProtKB:Q6TYA7, ECO:0000269\|PubMed:24500718}.
Ptm:		Sumoylated with SUMO1, SUMO2 and SUMO3, which may regulate the level of functional Cx43 gap junctions at the plasma membrane. May be desumoylated by SENP1 or SENP2 (By similarity). {ECO:0000250\|UniProtKB:P17302}.
Ptm:		S-nitrosylation at Cys-271 is enriched at the muscle endothelial gap junction in arteries, it augments channel permeability and may regulate of smooth muscle cell to endothelial cell communication. {ECO:0000250\|UniProtKB:P23242}.
Ptm:		Acetylated in the developing cortex; leading to delocalization from the cell membrane. {ECO:0000250\|UniProtKB:P23242}.
Similarity:		Belongs to the connexin family. Alpha-type (group II) subfamily. {ECO:0000305}.