ID:CXA1_HUMAN DESCRIPTION: RecName: Full=Gap junction alpha-1 protein; AltName: Full=Connexin-43; Short=Cx43; AltName: Full=Gap junction 43 kDa heart protein; 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). SUBUNIT: A connexon is composed of a hexamer of connexins. Interacts (via C-terminus) with TJP1. Interacts (via C-terminus) with SRC (via SH3 domain). Interacts with UBQLN4 (By similarity). Interacts with SGSM3. Interacts with KIAA1432/CIP150. Interacts with CNST and CSNK1D. SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Cell junction, gap junction. TISSUE SPECIFICITY: Expressed in the heart and fetal cochlea. PTM: 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. 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. DISEASE: Defects in GJA1 are the cause of oculodentodigital dysplasia (ODDD) [MIM:164200]; also known as oculodentoosseous dysplasia. ODDD is a highly penetrant syndrome presenting with craniofacial (ocular, nasal, dental) and limb dysmorphisms, spastic paraplegia, and neurodegeneration. Craniofacial anomalies tipically include a thin nose with hypoplastic alae nasi, small anteverted nares, prominent columnella, and microcephaly. Brittle nails and hair abnormalities of hypotrichosis and slow growth are present. Ocular defects include microphthalmia, microcornea, cataracts, glaucoma, and optic atrophy. Syndactyly type 3 and conductive deafness can occur in some cases. Cardiac abnormalities are observed in rare instances. DISEASE: Defects in GJA1 are the cause of oculodentodigital dysplasia, autosomal recessive (ODDD-AR) [MIM:257850]. DISEASE: Defects in GJA1 may be the cause of syndactyly type 3 (SDTY3) [MIM:186100]. Syndactyly is an autosomal dominant trait and is the most common congenital anomaly of the hand or foot. It is marked by persistence of the webbing between adjacent digits, so they are more or less completely attached. In this type 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. DISEASE: Defects in GJA1 are a cause of hypoplastic left heart syndrome type 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. DISEASE: Defects in GJA1 are a cause of Hallermann-Streiff syndrome (HSS) [MIM:234100]. HSS is 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. DISEASE: Defects in GJA1 are a cause of atrioventricular septal defect type 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. A less severe form, known as ostium primum atrial septal defect, has a deficiency of the atrial septum. SIMILARITY: Belongs to the connexin family. Alpha-type (group II) subfamily. CAUTION: PubMed:7715640 reported a mutation Pro-364 linked to congenital heart diseases. PubMed:8873667 later shown that it is an artifact. CAUTION: PubMed:11741837 reported 2 mutations (Phe-11 and Ala-24) linked to non-syndromic autosomal recessive deafness (DFNBG). These mutations have subsequently been shown (PubMed:12457340) to involve the pseudogene of connexin-43 located on chromosome 5. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GJA1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P17302
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: 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:0022857 transmembrane transporter activity GO:0030165 PDZ domain binding GO:0048487 beta-tubulin binding GO:0071253 connexin binding GO:0086075 gap junction channel activity involved in cardiac conduction electrical coupling GO:0097110 scaffold protein binding GO:0097718 disordered domain specific binding GO:1903763 gap junction channel activity involved in cell communication by electrical coupling GO:1990782 protein tyrosine kinase 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:0002931 response to ischemia GO:0003104 positive regulation of glomerular filtration GO:0003158 endothelium development GO:0003294 atrial ventricular junction remodeling 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:0022898 regulation of transmembrane transporter activity GO:0030308 negative regulation of cell growth GO:0030500 regulation of bone mineralization GO:0032024 positive regulation of insulin secretion GO:0032496 response to lipopolysaccharide GO:0032526 response to retinoic acid 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:0045216 cell-cell junction organization GO:0045669 positive regulation of osteoblast differentiation GO:0045732 positive regulation of protein catabolic process GO:0045844 positive regulation of striated muscle tissue development GO:0045907 positive regulation of vasoconstriction GO:0046697 decidualization 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 reflex 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:0061045 negative regulation of wound healing GO:0061337 cardiac conduction GO:0071260 cellular response to mechanical stimulus GO:0071374 cellular response to parathyroid hormone stimulus GO:0071467 cellular response to pH GO:0086014 atrial cardiac muscle cell action potential GO:0086064 cell communication by electrical coupling involved in cardiac conduction GO:2000279 negative regulation of DNA biosynthetic process GO:2000810 regulation of bicellular tight junction assembly GO:2000987 positive regulation of behavioral fear response
HW061161 - JP 2012529430-A/36: METHODS FOR TREATING CHRONIC KIDNEY DISEASE. JA482116 - Sequence 99 from Patent WO2011072091. JB251969 - Sequence 36 from Patent EP2440214. JE980408 - Sequence 99 from Patent EP2862929. LP764868 - Sequence 36 from Patent EP3276004. HH837108 - Sequence 35 from Patent EP2231168. HI214749 - Sequence 35 from Patent EP2076526. HV601551 - JP 2011500003-A/35: Novel siRNA Structures. HV856624 - JP 2010507387-A/35: Novel siRNAs and Methods of Use Thereof. HW165111 - JP 2013102767-A/35: Novel siRNA's and Use Thereof. HW675619 - JP 2014210789-A/35: Novel siRNA Structures. HW835307 - JP 2015051004-A/35: Novel siRNA's and Use Thereof. JA538150 - Sequence 35 from Patent EP2371958. AK312324 - Homo sapiens cDNA, FLJ92636, Homo sapiens gap junction protein, alpha 1, 43kDa (connexin 43)(GJA1), mRNA. AK297764 - Homo sapiens cDNA FLJ51901 complete cds, highly similar to Gap junction alpha-1 protein. AK223289 - Homo sapiens mRNA for connexin 43 variant, clone: SYN08454. AK294670 - Homo sapiens cDNA FLJ50955 complete cds, highly similar to Gap junction alpha-1 protein. AK297402 - Homo sapiens cDNA FLJ50990 complete cds, highly similar to Gap junction alpha-1 protein. AK309377 - Homo sapiens cDNA, FLJ99418. AK316159 - Homo sapiens cDNA, FLJ79058 complete cds, highly similar to Gap junction alpha-1 protein. AK295460 - Homo sapiens cDNA FLJ53043 complete cds, highly similar to Gap junction alpha-1 protein. AK297761 - Homo sapiens cDNA FLJ57333 complete cds, highly similar to Gap junction alpha-1 protein. AK309490 - Homo sapiens cDNA, FLJ99531. JA670489 - Sequence 5 from Patent EP2387612. M65188 - Human connexin 43 (GJA1, Cx43) mRNA, complete cds. X52947 - Human mRNA for cardiac gap junction protein. BC026329 - Homo sapiens gap junction protein, alpha 1, 43kDa, mRNA (cDNA clone MGC:26323 IMAGE:4794131), complete cds. JD433017 - Sequence 414041 from Patent EP1572962. JD563232 - Sequence 544256 from Patent EP1572962. JD226090 - Sequence 207114 from Patent EP1572962. JD196410 - Sequence 177434 from Patent EP1572962. JD359258 - Sequence 340282 from Patent EP1572962. CU693216 - Synthetic construct Homo sapiens gateway clone IMAGE:100019169 5' read GJA1 mRNA. AB464551 - Synthetic construct DNA, clone: pF1KB9852, Homo sapiens GJA1 gene for gap junction protein, alpha 1, 43kDa, without stop codon, in Flexi system. DQ895611 - Synthetic construct Homo sapiens clone IMAGE:100010071; FLH185943.01L; RZPDo839G12147D gap junction protein, alpha 1, 43kDa (connexin 43) (GJA1) gene, encodes complete protein. KJ896880 - Synthetic construct Homo sapiens clone ccsbBroadEn_06274 GJA1 gene, encodes complete protein. KR709453 - Synthetic construct Homo sapiens clone CCSBHm_00002356 GJA1 (GJA1) mRNA, encodes complete protein. KR709454 - Synthetic construct Homo sapiens clone CCSBHm_00002385 GJA1 (GJA1) mRNA, encodes complete protein. DQ893649 - Synthetic construct clone IMAGE:100006279; FLH185947.01X; RZPDo839G12148D gap junction protein, alpha 1, 43kDa (connexin 43) (GJA1) gene, encodes complete protein. CR541660 - Homo sapiens full open reading frame cDNA clone RZPDo834A1127D for gene GJA1, gap junction protein, alpha 1, 43kDa (connexin 43); complete cds, without stopcodon. JD449035 - Sequence 430059 from Patent EP1572962. JD108183 - Sequence 89207 from Patent EP1572962. JD544451 - Sequence 525475 from Patent EP1572962. JD485900 - Sequence 466924 from Patent EP1572962. JD223495 - Sequence 204519 from Patent EP1572962. JD485976 - Sequence 467000 from Patent EP1572962. JD545018 - Sequence 526042 from Patent EP1572962. JD222552 - Sequence 203576 from Patent EP1572962. JD290949 - Sequence 271973 from Patent EP1572962. JD551358 - Sequence 532382 from Patent EP1572962. JD551155 - Sequence 532179 from Patent EP1572962. JD323676 - Sequence 304700 from Patent EP1572962. JD354663 - Sequence 335687 from Patent EP1572962. JD263358 - Sequence 244382 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_gsk3Pathway - Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages
Reactome (by CSHL, EBI, and GO)
Protein P17302 (Reactome details) participates in the following event(s):
R-HSA-190662 Connexin oligomerization in Trans-Golgi Network (TGN) R-HSA-190686 Transport of connexins to the Trans-Golgi Network (TGN) R-HSA-190877 Insertion of connexons into the plasma membrane resulting in the formation of hemi-channels R-HSA-190520 Association of Golgi transport vesicles with microtubules R-HSA-190541 Association of Cx43 with TJP1 R-HSA-190782 Budding of connexon-containing transport vesicles from the Golgi R-HSA-190788 Formation of junctional channels R-HSA-191654 c-src associates with Cx43 in gap junctions R-HSA-191737 Docking of connexons into junctional, double-membrane spanning channels R-HSA-191636 Phosphorylation of Cx43 by c-src R-HSA-191656 Closure of gap junction R-HSA-190790 Assembly of gap junction plaques R-HSA-196026 Dab2 is recruited to the junctional plaques R-HSA-196017 Dynamin is recruited to the gap junction plaque R-HSA-190519 Internalization of gap junction plaques R-HSA-190704 Oligomerization of connexins into connexons R-HSA-190827 Transport of connexins along the secretory pathway R-HSA-190861 Gap junction assembly R-HSA-190840 Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane R-HSA-191647 c-src mediated regulation of Cx43 function and closure of gap junctions R-HSA-190828 Gap junction trafficking R-HSA-190872 Transport of connexons to the plasma membrane R-HSA-191650 Regulation of gap junction activity R-HSA-157858 Gap junction trafficking and regulation R-HSA-199991 Membrane Trafficking R-HSA-5653656 Vesicle-mediated transport R-HSA-196025 Formation of annular gap junctions R-HSA-190873 Gap junction degradation
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
