GJA1
GeneName
GJA1
Summary
GJA1, also known as Cx43 or connexin 43, is a 43kDa protein that is predominantly expressed in the heart and various tissues including bone and the central nervous system. It is a member of the connexin family and plays a critical role in forming gap junctions, which facilitate direct intercellular communication through the transfer of ions and small molecules. GJA1 is localised at the plasma membrane and cell junctions, particularly in intercalated discs of cardiac muscle cells, where it is essential for cardiac conduction and synchronisation of heartbeats. Additionally, it participates in various cellular processes such as cell signalling, cytoskeletal interactions, and the maintenance of the blood-brain barrier.
Importance
GJA1 is relevant to: - Cardiac health as it is crucial for electrical coupling and synchronisation of cardiac muscle contractions - Bone development and remodelling due to its role in cell communication and signalling in osteoblasts and osteoclasts - Neurobiology, particularly in maintaining the integrity of the blood-brain barrier and facilitating communication between glial cells and neurons - Various diseases, including cardiac arrhythmias and osteopathies, highlighting its potential as a therapeutic target in regenerative medicine and tissue engineering
Top Products
For researchers investigating GJA1, we recommend two excellent primary antibodies that cater to a variety of applications. The first is the well-cited polyclonal antibody, Anti-Connexin 43 / GJA1 antibody - Intercellular Junction Marker (ab11370). This antibody has garnered 368 citations, reflecting its reliability and trust within the research community. It is validated for use in Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC), making it a versatile choice for your studies. Notably, it has also been validated in knockout models, ensuring its effectiveness in specific experimental contexts.Additionally, we offer the recombinant antibody, Anti-Connexin 43 / GJA1 antibody [EPR22955-101] (ab235585). This product is suitable for WB, IHC, and immunoprecipitation (IP), providing researchers with the batch-to-batch consistency that recombinant antibodies are known for. With 17 citations, it is gaining traction in the field and serves as a reliable option for those studying GJA1. Together, these antibodies provide robust tools for exploring the role of GJA1 in intercellular communication.
Abcam Product Citation Summary
The data indicates that GJA1 (also known as Cx43) is being extensively studied in various contexts, particularly in relation to cardiac and neurological conditions. The use of Abcam antibodies in both Western blotting and immunohistochemistry highlights the importance of GJA1 in understanding cellular mechanisms in diseases such as myocardial injury, cerebral ischemia, and the effects of estrogen signaling. The studies predominantly involve human and rat models, suggesting a focus on translational research that may have implications for human health.
Abcam Product Citation Table
Function
Structural component of the gap junction, a specialized intercellular structure consisting of a cluster of closely packed pairs of transmembrane channels, the connexons, that allow passage of small molecules and electrical signals between neighboring cells (By similarity). Forms homotypic and heterotypic channels gated by transjunctional voltage (By similarity). May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph (Probable). 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 the conductive system of ventricular myocardium and heart morphogenesis (By similarity). May play a role in cell growth inhibition through the regulation of NOV expression and localization (By similarity). Involved in intercellular innate immune signaling (PubMed:24077100, PubMed:31992625, PubMed:40010341). Mediates translocation of 2',3'-cGAMP and 2',5'-oligoadenylates (2-5A) second messengers from virus-infected cells to macrophages and uninfected neighboring cells to propagate and amplify the antiviral immune response (PubMed:24077100, PubMed:31992625, PubMed:40010341).
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 may be 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. Intellectual disability is present in a minority of cases.
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). Phosphorylation by MAPK1/MAPK3 at Ser-279 and Ser-282 leads to increased ubiquitination and lysosomal degradation (By similarity).
Ubiquitination results in lysosomal degradation.
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 at intercalated disks in the heart (at protein level) (PubMed:11741837, PubMed:18662195, PubMed:38375917). Expressed in the fetal cochlea (PubMed:11741837).
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Cell junction
- Gap junction
- Endoplasmic reticulum
- Cell junction
- Localizes at the intercalated disk (ICD) between two adjacent cardiomyocytes and the proper localization at ICD is dependent on TMEM65.
Alternative names
GJAL, GJA1, Gap junction alpha-1 protein, Connexin-43, Gap junction 43 kDa heart protein, Cx43