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GJA1 phospho S368

OverviewProducts

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. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph. 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. Plays an essential role in gap junction communication in the ventricles (By similarity).

Involvement in disease

Oculodentodigital dysplasia

ODDD

A disease characterized by a typical facial appearance and variable involvement of the eyes, dentition, and fingers. Characteristic facial features include a narrow, pinched nose with hypoplastic alae nasi, prominent columella and thin anteverted nares together with a narrow nasal bridge, and prominent epicanthic folds giving the impression of hypertelorism. The teeth are usually small and carious. Typical eye findings include microphthalmia and microcornea. The characteristic digital malformation is complete syndactyly of the fourth and fifth fingers (syndactyly type III) but the third finger may be involved and associated camptodactyly is a common finding. Cardiac abnormalities are observed in rare instances.

None

The disease is caused by variants affecting the gene represented in this entry.

Oculodentodigital dysplasia, autosomal recessive

ODDD-AR

A disease characterized by a typical facial appearance and variable involvement of the eyes, dentition, and fingers. Characteristic facial features include a narrow, pinched nose with hypoplastic alae nasi, prominent columella and thin anteverted nares together with a narrow nasal bridge, and prominent epicanthic folds giving the impression of hypertelorism. The teeth are usually small and carious. Typical eye findings include microphthalmia and microcornea. The characteristic digital malformation is complete syndactyly of the fourth and fifth fingers (syndactyly type III) but the third finger may be involved and associated camptodactyly is a common finding. Cardiac abnormalities are observed in rare instances.

None

The disease is caused by variants affecting the gene represented in this entry.

Syndactyly 3

SDTY3

A form of syndactyly, a congenital anomaly of the hand or foot marked by persistence of the webbing between adjacent digits that are more or less completely attached. In SDTY3, there is usually complete and bilateral syndactyly between the fourth and fifth fingers. Usually it is soft tissue syndactyly but occasionally the distal phalanges are fused. The fifth finger is short with absent or rudimentary middle phalanx. The feet are not affected.

None

The disease may be caused by variants affecting the gene represented in this entry.

Hypoplastic left heart syndrome 1

HLHS1

A syndrome due to defective development of the aorta proximal to the entrance of the ductus arteriosus, and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium, right ventricle, and pulmonary artery are enlarged.

None

The disease is caused by variants affecting the gene represented in this entry.

Hallermann-Streiff syndrome

HSS

A disorder characterized by a typical skull shape (brachycephaly with frontal bossing), hypotrichosis, microphthalmia, cataracts, beaked nose, micrognathia, skin atrophy, dental anomalies and proportionate short stature. Mental retardation is present in a minority of cases.

None

The disease is caused by variants affecting the gene represented in this entry.

Atrioventricular septal defect 3

AVSD3

A congenital heart malformation characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. The complete form involves underdevelopment of the lower part of the atrial septum and the upper part of the ventricular septum; the valve itself is also shared. A less severe form, known as ostium primum atrial septal defect, is characterized by separate atrioventricular valvar orifices despite a common junction.

None

The disease is caused by variants affecting the gene represented in this entry.

Craniometaphyseal dysplasia, autosomal recessive

CMDR

An osteochondrodysplasia characterized by hyperostosis and sclerosis of the craniofacial bones associated with abnormal modeling of the metaphyses. Sclerosis of the skull may lead to asymmetry of the mandible, as well as to cranial nerve compression, that may finally result in hearing loss and facial palsy.

None

The disease is caused by variants affecting the gene represented in this entry.

Erythrokeratodermia variabilis et progressiva 3

EKVP3

A form of erythrokeratodermia variabilis et progressiva, a genodermatosis characterized by the coexistence of two independent skin lesions: transient erythema and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases.

None

The disease is caused by variants affecting the gene represented in this entry.

Palmoplantar keratoderma and congenital alopecia 1

PPKCA1

A rare autosomal dominant disorder characterized by severe hyperkeratosis of the palms and soles, and congenital hypotrichosis or alopecia. Dystrophic nail changes occur in some patients.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylated at Ser-368 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of gap junction activity (By similarity). Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly. Phosphorylation at Ser-368 by PRKCD triggers its internalization into small vesicles leading to proteasome-mediated degradation (By similarity).

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.

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.

Acetylated in the developing cortex; leading to delocalization from the cell membrane.

Sequence similarities

Belongs to the connexin family. Alpha-type (group II) subfamily.

Tissue specificity

Expressed in the heart and fetal cochlea.

Cellular localization

  • Cell membrane
  • Multi-pass membrane protein
  • Cell junction
  • Gap junction
  • Endoplasmic reticulum
  • Localizes at the intercalated disk (ICD) in cardiomyocytes and the proper localization at ICD is dependent on TMEM65.

Alternative names

  • Gap junction alpha-1 protein
  • Connexin-43
  • Gap junction 43 kDa heart protein
  • Cx43
  • GJA1
  • GJAL

Database links

Target type

Proteins

Primary research area

Neuroscience

Molecular weight

43008Da