InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: GJA1

Summary

InnateDB Protein

IDBP-95986.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

GJA1

Protein Name

gap junction protein, alpha 1, 43kDa

Synonyms

AVSD3; CMDR; CX43; GJAL; HLHS1; HSS; ODDD;

Species

Homo sapiens

Ensembl Protein

ENSP00000282561

InnateDB Gene

IDBG-95984 (GJA1)

Protein Structure

UniProt Annotation

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). {ECO:0000250}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:22411987}; Multi-pass membrane protein {ECO:0000269PubMed:22411987}. Cell junction, gap junction {ECO:0000269PubMed:22411987}.

Disease Associations

Oculodentodigital dysplasia (ODDD) [MIM:164200]: 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. {ECO:0000269PubMed:12457340, ECO:0000269PubMed:14729836, ECO:0000269PubMed:15108203, ECO:0000269PubMed:15637728, ECO:0000269PubMed:16219735, ECO:0000269PubMed:16222672, ECO:0000269PubMed:16378922, ECO:0000269PubMed:16709485, ECO:0000269PubMed:16813608, ECO:0000269PubMed:16816024, ECO:0000269PubMed:17509830, ECO:0000269PubMed:18161618, ECO:0000269PubMed:19338053, ECO:0000269PubMed:21670345, ECO:0000269PubMed:23550541, ECO:0000269PubMed:24508941}. Note=The disease is caused by mutations affecting the gene represented in this entry.Oculodentodigital dysplasia, autosomal recessive (ODDD- AR) [MIM:257850]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry.Syndactyly 3 (SDTY3) [MIM:186100]: 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. {ECO:0000269PubMed:14729836}. Note=The disease may be caused by mutations affecting the gene represented in this entry.Hypoplastic left heart syndrome 1 (HLHS1) [MIM:241550]: 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. {ECO:0000269PubMed:11470490}. Note=The disease is caused by mutations affecting the gene represented in this entry.Hallermann-Streiff syndrome (HSS) [MIM:234100]: 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. {ECO:0000269PubMed:14974090}. Note=The disease is caused by mutations affecting the gene represented in this entry.Atrioventricular septal defect 3 (AVSD3) [MIM:600309]: 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. {ECO:0000269PubMed:11470490}. Note=The disease is caused by mutations affecting the gene represented in this entry.Craniometaphyseal dysplasia, autosomal recessive (CMDR) [MIM:218400]: 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. {ECO:0000269PubMed:23951358}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in the heart and fetal cochlea. {ECO:0000269PubMed:11741837}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 34 experimentally validated interaction(s) in this database.
They are also associated with 18 interaction(s) predicted by orthology.

Experimentally validated
Total	34 [view]
Protein-Protein	32 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	18 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004871	signal transducer activity
GO:0005102	receptor binding
GO:0005243	gap junction channel activity
GO:0005515	protein binding
GO:0015075	ion transmembrane transporter activity
GO:0017124	SH3 domain binding
GO:0019904	protein domain specific binding
GO:0030165	PDZ domain binding
GO:0048487	beta-tubulin binding
GO:0071253	connexin binding
GO:0097110	scaffold protein binding

Biological Process

GO:0001649	osteoblast differentiation
GO:0001701	in utero embryonic development
GO:0001764	neuron migration
GO:0001937	negative regulation of endothelial cell proliferation
GO:0001947	heart looping
GO:0002070	epithelial cell maturation
GO:0002088	lens development in camera-type eye
GO:0002544	chronic inflammatory response
GO:0003104	positive regulation of glomerular filtration
GO:0003158	endothelium development
GO:0003294	atrial ventricular junction remodeling
GO:0006810	transport
GO:0006915	apoptotic process
GO:0006936	muscle contraction
GO:0007154	cell communication
GO:0007165	signal transduction
GO:0007204	positive regulation of cytosolic calcium ion concentration
GO:0007267	cell-cell signaling
GO:0007507	heart development
GO:0007512	adult heart development
GO:0008016	regulation of heart contraction
GO:0008285	negative regulation of cell proliferation
GO:0009268	response to pH
GO:0009749	response to glucose
GO:0010232	vascular transport
GO:0010628	positive regulation of gene expression
GO:0010629	negative regulation of gene expression
GO:0010643	cell communication by chemical coupling
GO:0010644	cell communication by electrical coupling
GO:0010652	positive regulation of cell communication by chemical coupling
GO:0015867	ATP transport
GO:0016264	gap junction assembly
GO:0030500	regulation of bone mineralization
GO:0032024	positive regulation of insulin secretion
GO:0034220	ion transmembrane transport
GO:0034405	response to fluid shear stress
GO:0035050	embryonic heart tube development
GO:0042733	embryonic digit morphogenesis
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043403	skeletal muscle tissue regeneration
GO:0043434	response to peptide hormone
GO:0045087	innate immune response (InnateDB)
GO:0045216	cell-cell junction organization
GO:0045732	positive regulation of protein catabolic process
GO:0045844	positive regulation of striated muscle tissue development
GO:0045907	positive regulation of vasoconstriction
GO:0045909	positive regulation of vasodilation
GO:0046850	regulation of bone remodeling
GO:0048514	blood vessel morphogenesis
GO:0048812	neuron projection morphogenesis
GO:0051259	protein oligomerization
GO:0051924	regulation of calcium ion transport
GO:0055085	transmembrane transport
GO:0060044	negative regulation of cardiac muscle cell proliferation
GO:0060156	milk ejection
GO:0060307	regulation of ventricular cardiac muscle cell membrane repolarization
GO:0060371	regulation of atrial cardiac muscle cell membrane depolarization
GO:0060373	regulation of ventricular cardiac muscle cell membrane depolarization
GO:0061024	membrane organization
GO:0061045	negative regulation of wound healing
GO:0061337	cardiac conduction
GO:0071260	cellular response to mechanical stimulus
GO:0086014	atrial cardiac muscle cell action potential
GO:2000279	negative regulation of DNA biosynthetic process
GO:2000810	regulation of tight junction assembly
GO:2000987	positive regulation of behavioral fear response

Cellular Component

GO:0000139	Golgi membrane
GO:0005737	cytoplasm
GO:0005741	mitochondrial outer membrane
GO:0005764	lysosome
GO:0005768	endosome
GO:0005769	early endosome
GO:0005770	late endosome
GO:0005771	multivesicular body
GO:0005789	endoplasmic reticulum membrane
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005882	intermediate filament
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0005911	cell-cell junction
GO:0005916	fascia adherens
GO:0005921	gap junction
GO:0005922	connexon complex
GO:0014704	intercalated disc
GO:0016020	membrane
GO:0016324	apical plasma membrane
GO:0016328	lateral plasma membrane
GO:0030054	cell junction
GO:0030660	Golgi-associated vesicle membrane
GO:0043292	contractile fiber
GO:0045121	membrane raft
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000500 Connexin
IPR002261 Gap junction alpha-1 protein (Cx43)
IPR013092 Connexin, N-terminal
IPR013124 Gap junction alpha-1 protein (Cx43), C-terminal
IPR019570 Gap junction protein, cysteine-rich domain

PFAM

PF00029
PF03508
PF10582

PRINTS

PR00206
PR01132

PIRSF

SMART

SM00037
SM01089

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt