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Protein

Gap junction alpha-1 protein

Gene

GJA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  • gap junction channel activity Source: BHF-UCL
  • gap junction channel activity involved in cardiac conduction electrical coupling Source: BHF-UCL
  • gap junction channel activity involved in cell communication by electrical coupling Source: BHF-UCL
  • ion transmembrane transporter activity Source: BHF-UCL
  • signal transducer activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-190704. Oligomerization of connexins into connexons.
R-HSA-190827. Transport of connexins along the secretory pathway.
R-HSA-190840. Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
R-HSA-190861. Gap junction assembly.
R-HSA-190873. Gap junction degradation.
R-HSA-191647. c-src mediated regulation of Cx43 function and closure of gap junctions.
R-HSA-196025. Formation of annular gap junctions.
SignaLinkiP17302.
SIGNORiP17302.

Names & Taxonomyi

Protein namesi
Recommended name:
Gap junction alpha-1 protein
Alternative name(s):
Connexin-43
Short name:
Cx43
Gap junction 43 kDa heart protein
Gene namesi
Name:GJA1
Synonyms:GJAL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4274. GJA1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 1312CytoplasmicSequence analysisAdd
BLAST
Transmembranei14 – 3623HelicalSequence analysisAdd
BLAST
Topological domaini37 – 7640ExtracellularSequence analysisAdd
BLAST
Transmembranei77 – 9923HelicalSequence analysisAdd
BLAST
Topological domaini100 – 15455CytoplasmicSequence analysisAdd
BLAST
Transmembranei155 – 17723HelicalSequence analysisAdd
BLAST
Topological domaini178 – 20831ExtracellularSequence analysisAdd
BLAST
Transmembranei209 – 23123HelicalSequence analysisAdd
BLAST
Topological domaini232 – 382151CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • connexon complex Source: ProtInc
  • contractile fiber Source: Ensembl
  • cytosol Source: Ensembl
  • early endosome Source: Ensembl
  • endoplasmic reticulum membrane Source: Reactome
  • extracellular exosome Source: UniProtKB
  • fascia adherens Source: Ensembl
  • focal adhesion Source: UniProtKB
  • gap junction Source: BHF-UCL
  • Golgi apparatus Source: BHF-UCL
  • Golgi-associated vesicle membrane Source: Reactome
  • Golgi membrane Source: Reactome
  • integral component of plasma membrane Source: UniProtKB
  • intercalated disc Source: BHF-UCL
  • intermediate filament Source: Ensembl
  • lateral plasma membrane Source: Ensembl
  • lysosome Source: Ensembl
  • membrane raft Source: BHF-UCL
  • mitochondrial outer membrane Source: Ensembl
  • mitochondrion Source: AgBase
  • multivesicular body Source: Ensembl
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Endoplasmic reticulum, Gap junction, Membrane

Pathology & Biotechi

Involvement in diseasei

Oculodentodigital dysplasia (ODDD)16 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:164200
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti2 – 21G → V in ODDD. 1 Publication
VAR_058990
Natural varianti7 – 71L → V in ODDD. 1 Publication
VAR_058991
Natural varianti11 – 111L → P in ODDD. 2 Publications
Corresponds to variant rs121912969 [ dbSNP | Ensembl ].
VAR_058992
Natural varianti17 – 171Y → S in ODDD. 1 Publication
Corresponds to variant rs104893961 [ dbSNP | Ensembl ].
VAR_015747
Natural varianti18 – 181S → P in ODDD. 1 Publication
Corresponds to variant rs104893962 [ dbSNP | Ensembl ].
VAR_015748
Natural varianti21 – 211G → R in ODDD. 1 Publication
Corresponds to variant rs104893963 [ dbSNP | Ensembl ].
VAR_015749
Natural varianti22 – 221G → E in ODDD. 1 Publication
Corresponds to variant rs104893964 [ dbSNP | Ensembl ].
VAR_015750
Natural varianti23 – 231K → T in ODDD. 1 Publication
VAR_015751
Natural varianti27 – 271S → P in ODDD. 1 Publication
VAR_038356
Natural varianti31 – 311I → M in ODDD. 1 Publication
VAR_038357
Natural varianti40 – 401A → V in ODDD. 4 Publications
VAR_015752
Natural varianti41 – 444Missing in ODDD. 1 Publication
VAR_070439
Natural varianti47 – 471D → H in ODDD. 1 Publication
VAR_071009
Natural varianti49 – 491Q → K in ODDD. 1 Publication
VAR_015753
Natural varianti49 – 491Q → P in ODDD. 1 Publication
VAR_058994
Natural varianti49 – 491Q → QQ in ODDD. 1 Publication
VAR_058995
Natural varianti52 – 521F → FF in ODDD. 1 Publication
VAR_015754
Natural varianti59 – 591P → H in ODDD. 1 Publication
VAR_058996
Natural varianti69 – 691S → Y in ODDD. 1 Publication
VAR_038358
Natural varianti76 – 761R → S in ODDD. 1 Publication
Corresponds to variant rs267606845 [ dbSNP | Ensembl ].
VAR_015755
Natural varianti86 – 861S → Y in ODDD; de novo mutation found in a sporadic case. 1 Publication
VAR_071010
Natural varianti90 – 901L → V in ODDD. 1 Publication
VAR_015756
Natural varianti95 – 951H → R in ODDD. 1 Publication
VAR_058998
Natural varianti96 – 961V → A in ODDD. 1 Publication
VAR_058999
Natural varianti96 – 961V → E in ODDD. 1 Publication
VAR_059000
Natural varianti96 – 961V → M in ODDD. 1 Publication
Corresponds to variant rs28931601 [ dbSNP | Ensembl ].
VAR_059001
Natural varianti98 – 981Y → C in ODDD. 1 Publication
VAR_015757
Natural varianti102 – 1021K → N in ODDD. 1 Publication
VAR_015758
Natural varianti106 – 1061L → P in ODDD. 1 Publication
VAR_059002
Natural varianti106 – 1061L → R in ODDD. 1 Publication
VAR_071011
Natural varianti110 – 1101E → D in ODDD. 1 Publication
VAR_059003
Natural varianti113 – 1131L → P in ODDD. 2 Publications
VAR_038359
Natural varianti130 – 1301I → T in ODDD. 1 Publication
VAR_015759
Natural varianti134 – 1341K → E in ODDD. 1 Publication
VAR_015760
Natural varianti134 – 1341K → N in ODDD. 1 Publication
VAR_038360
Natural varianti138 – 1381G → R in ODDD. 1 Publication
VAR_015761
Natural varianti147 – 1471M → T in ODDD. 1 Publication
VAR_059004
Natural varianti154 – 1541T → A in ODDD. 2 Publications
VAR_059005
Natural varianti154 – 1541T → N in ODDD. 1 Publication
VAR_059006
Natural varianti169 – 1691Missing in ODDD. 1 Publication
VAR_059007
Natural varianti194 – 1941H → P in ODDD; atypical form of ODDD characterized by the predominance of the ocular involvement and by the absence of hand and/or foot syndactyly and absence of any neurologic signs. 1 Publication
Corresponds to variant rs104893966 [ dbSNP | Ensembl ].
VAR_059008
Natural varianti201 – 2011S → F in ODDD. 1 Publication
VAR_059009
Natural varianti202 – 2021R → H in ODDD. 3 Publications
Corresponds to variant rs750294638 [ dbSNP | Ensembl ].
VAR_015762
Natural varianti206 – 2061K → R in ODDD. 1 Publication
Corresponds to variant rs397518464 [ dbSNP | Ensembl ].
VAR_070440
Natural varianti216 – 2161V → L in ODDD. 1 Publication
VAR_015763
Natural varianti220 – 2201S → Y in ODDD. 1 Publication
VAR_059010
Oculodentodigital dysplasia, autosomal recessive (ODDD-AR)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:257850
Syndactyly 3 (SDTY3)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:186100
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti143 – 1431G → S in SDTY3. 1 Publication
Corresponds to variant rs28931600 [ dbSNP | Ensembl ].
VAR_038361
Hypoplastic left heart syndrome 1 (HLHS1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:241550
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti362 – 3621R → Q in HLHS1 and AVSD3; associated with Gln-376 in one individual with atrioventricular septal defect; abolishes phosphorylation by PKA and PKC. 1 Publication
Corresponds to variant rs2227885 [ dbSNP | Ensembl ].
VAR_032924
Natural varianti376 – 3761R → Q in HLHS1 and AVSD3; associated with Gln-362 in one individual with atrioventricular septal defect; abolishes phosphorylation by PKA and PKC. 1 Publication
Corresponds to variant rs104893965 [ dbSNP | Ensembl ].
VAR_032925
Hallermann-Streiff syndrome (HSS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:234100
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti76 – 761R → H in HSS; overlapping features with oculodentodigital dysplasia. 1 Publication
Corresponds to variant rs267606844 [ dbSNP | Ensembl ].
VAR_058997
Atrioventricular septal defect 3 (AVSD3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:600309
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti362 – 3621R → Q in HLHS1 and AVSD3; associated with Gln-376 in one individual with atrioventricular septal defect; abolishes phosphorylation by PKA and PKC. 1 Publication
Corresponds to variant rs2227885 [ dbSNP | Ensembl ].
VAR_032924
Natural varianti376 – 3761R → Q in HLHS1 and AVSD3; associated with Gln-362 in one individual with atrioventricular septal defect; abolishes phosphorylation by PKA and PKC. 1 Publication
Corresponds to variant rs104893965 [ dbSNP | Ensembl ].
VAR_032925
Craniometaphyseal dysplasia, autosomal recessive (CMDR)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:218400
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti239 – 2391R → Q in CMDR. 1 Publication
Corresponds to variant rs764670582 [ dbSNP | Ensembl ].
VAR_070441
Erythrokeratodermia variabilis (EKV)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA genodermatosis characterized by the appearance of two independent skin lesions: transient figurate erythematous patches 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.
See also OMIM:133200
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti44 – 441A → V in EKV; does not localize to intercellular junctions but is retained in the cytoplasm. 1 Publication
Corresponds to variant rs794729675 [ dbSNP | Ensembl ].
VAR_075755
Natural varianti227 – 2271E → D in EKV; does not localize to intercellular junctions but is retained in the cytoplasm. 1 Publication
VAR_075756
Palmoplantar keratoderma and congenital alopecia 1 (PPKCA1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:104100
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti8 – 81G → V in PPKCA1; can form functional gap junctions; results in enhanced hemichannel activity that causes increased cell death. 1 Publication
VAR_075754

Keywords - Diseasei

Cataract, Disease mutation, Hypotrichosis, Palmoplantar keratoderma

Organism-specific databases

MalaCardsiGJA1.
MIMi104100. phenotype.
133200. phenotype.
164200. phenotype.
186100. phenotype.
218400. phenotype.
234100. phenotype.
241550. phenotype.
257850. phenotype.
600309. phenotype.
Orphaneti90636. Autosomal recessive non-syndromic sensorineural deafness type DFNB.
1522. Craniometaphyseal dysplasia.
2248. Hypoplastic left heart syndrome.
2710. Oculodentodigital dysplasia.
93404. Syndactyly type 3.
PharmGKBiPA28685.

Chemistry

DrugBankiDB01136. Carvedilol.

Polymorphism and mutation databases

BioMutaiGJA1.
DMDMi117706.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 382381Gap junction alpha-1 proteinPRO_0000057801Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei5 – 51PhosphoserineBy similarity
Disulfide bondi54 ↔ 1921 Publication
Cross-linki144 – 144Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Disulfide bondi187 ↔ 1981 Publication
Cross-linki237 – 237Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Modified residuei247 – 2471PhosphotyrosineBy similarity
Modified residuei255 – 2551PhosphoserineCombined sources1 Publication
Modified residuei262 – 2621Phosphoserine2 Publications
Modified residuei271 – 2711S-nitrosocysteineBy similarity
Modified residuei275 – 2751PhosphothreonineBy similarity
Modified residuei306 – 3061PhosphoserineBy similarity
Modified residuei314 – 3141PhosphoserineCombined sources
Modified residuei325 – 3251Phosphoserine; by CK11 Publication
Modified residuei326 – 3261PhosphothreonineBy similarity
Modified residuei328 – 3281Phosphoserine; by CK11 Publication
Modified residuei330 – 3301Phosphoserine; by CK11 Publication
Modified residuei344 – 3441PhosphoserineCombined sources
Modified residuei365 – 3651PhosphoserineBy similarity
Modified residuei368 – 3681Phosphoserine; by PKC/PRKCG and PKC/PRKCDBy similarity
Modified residuei369 – 3691PhosphoserineBy similarity
Modified residuei373 – 3731PhosphoserineBy similarity

Post-translational modificationi

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).By similarity3 Publications
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 SENP2.1 Publication
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.

Keywords - PTMi

Disulfide bond, Isopeptide bond, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

EPDiP17302.
MaxQBiP17302.
PaxDbiP17302.
PeptideAtlasiP17302.
PRIDEiP17302.
TopDownProteomicsiP17302.

PTM databases

iPTMnetiP17302.
PhosphoSiteiP17302.

Expressioni

Tissue specificityi

Expressed in the heart and fetal cochlea.1 Publication

Gene expression databases

BgeeiENSG00000152661.
CleanExiHS_GJA1.
GenevisibleiP17302. HS.

Organism-specific databases

HPAiCAB010753.
HPA035097.

Interactioni

Subunit structurei

A connexon is composed of a hexamer of connexins. Interacts (via C-terminus) with TJP1 (By similarity). Interacts (via C-terminus) with SRC (via SH3 domain) (By similarity). Interacts (not ubiquitinated) with UBQLN4 (via UBA domain) (By similarity). Interacts with SGSM3 and CNST (By similarity). Interacts with RIC1/CIP150. Interacts with CSNK1D. Interacts with NOV (PubMed:15181016, PubMed:15213231). Interacts with TMEM65 (By similarity).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DSC2Q02487-12EBI-1103439,EBI-6900677
TJP1Q071573EBI-1103439,EBI-79553

Protein-protein interaction databases

BioGridi108964. 41 interactions.
IntActiP17302. 11 interactions.
MINTiMINT-147603.
STRINGi9606.ENSP00000282561.

Structurei

Secondary structure

1
382
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi240 – 2423Combined sources
Helixi246 – 2538Combined sources
Helixi255 – 2573Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LL2NMR-A234-259[»]
ProteinModelPortaliP17302.
SMRiP17302. Positions 3-382.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni244 – 382139Interaction with NOVBy similarityAdd
BLAST
Regioni264 – 382119Interaction with UBQLN4By similarityAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF97. Eukaryota.
ENOG4110JTW. LUCA.
GeneTreeiENSGT00840000129674.
HOGENOMiHOG000231127.
HOVERGENiHBG009576.
InParanoidiP17302.
KOiK07372.
OMAiGANVDMH.
OrthoDBiEOG091G0FKH.
PhylomeDBiP17302.
TreeFamiTF329606.

Family and domain databases

InterProiIPR000500. Connexin.
IPR002261. Connexin43.
IPR013124. Connexin43_C.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERiPTHR11984. PTHR11984. 1 hit.
PfamiPF00029. Connexin. 1 hit.
PF03508. Connexin43. 1 hit.
[Graphical view]
PRINTSiPR00206. CONNEXIN.
PR01132. CONNEXINA1.
SMARTiSM00037. CNX. 1 hit.
SM01089. Connexin_CCC. 1 hit.
[Graphical view]
PROSITEiPS00407. CONNEXINS_1. 1 hit.
PS00408. CONNEXINS_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P17302-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS
60 70 80 90 100
AFRCNTQQPG CENVCYDKSF PISHVRFWVL QIIFVSVPTL LYLAHVFYVM
110 120 130 140 150
RKEEKLNKKE EELKVAQTDG VNVDMHLKQI EIKKFKYGIE EHGKVKMRGG
160 170 180 190 200
LLRTYIISIL FKSIFEVAFL LIQWYIYGFS LSAVYTCKRD PCPHQVDCFL
210 220 230 240 250
SRPTEKTIFI IFMLVVSLVS LALNIIELFY VFFKGVKDRV KGKSDPYHAT
260 270 280 290 300
SGALSPAKDC GSQKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN
310 320 330 340 350
YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNSKKLAAG
360 370 380
HELQPLAIVD QRPSSRASSR ASSRPRPDDL EI
Length:382
Mass (Da):43,008
Last modified:January 23, 2007 - v2
Checksum:i7DDDAD8040284176
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti2 – 21G → V in ODDD. 1 Publication
VAR_058990
Natural varianti7 – 71L → V in ODDD. 1 Publication
VAR_058991
Natural varianti8 – 81G → V in PPKCA1; can form functional gap junctions; results in enhanced hemichannel activity that causes increased cell death. 1 Publication
VAR_075754
Natural varianti11 – 111L → P in ODDD. 2 Publications
Corresponds to variant rs121912969 [ dbSNP | Ensembl ].
VAR_058992
Natural varianti17 – 171Y → S in ODDD. 1 Publication
Corresponds to variant rs104893961 [ dbSNP | Ensembl ].
VAR_015747
Natural varianti18 – 181S → P in ODDD. 1 Publication
Corresponds to variant rs104893962 [ dbSNP | Ensembl ].
VAR_015748
Natural varianti21 – 211G → R in ODDD. 1 Publication
Corresponds to variant rs104893963 [ dbSNP | Ensembl ].
VAR_015749
Natural varianti22 – 221G → E in ODDD. 1 Publication
Corresponds to variant rs104893964 [ dbSNP | Ensembl ].
VAR_015750
Natural varianti23 – 231K → T in ODDD. 1 Publication
VAR_015751
Natural varianti27 – 271S → P in ODDD. 1 Publication
VAR_038356
Natural varianti31 – 311I → M in ODDD. 1 Publication
VAR_038357
Natural varianti40 – 401A → V in ODDD. 4 Publications
VAR_015752
Natural varianti41 – 444Missing in ODDD. 1 Publication
VAR_070439
Natural varianti41 – 411V → L Found in a patient with hidrotic ectodermal dysplasia, abortive features of oculodentodigital dysplasia and extensive hyperkeratosis of the skin; unknown pathological significance; the patient also carries GJB2 variant H-127. 1 Publication
VAR_058993
Natural varianti44 – 441A → V in EKV; does not localize to intercellular junctions but is retained in the cytoplasm. 1 Publication
Corresponds to variant rs794729675 [ dbSNP | Ensembl ].
VAR_075755
Natural varianti47 – 471D → H in ODDD. 1 Publication
VAR_071009
Natural varianti49 – 491Q → K in ODDD. 1 Publication
VAR_015753
Natural varianti49 – 491Q → P in ODDD. 1 Publication
VAR_058994
Natural varianti49 – 491Q → QQ in ODDD. 1 Publication
VAR_058995
Natural varianti52 – 521F → FF in ODDD. 1 Publication
VAR_015754
Natural varianti59 – 591P → H in ODDD. 1 Publication
VAR_058996
Natural varianti69 – 691S → Y in ODDD. 1 Publication
VAR_038358
Natural varianti76 – 761R → H in HSS; overlapping features with oculodentodigital dysplasia. 1 Publication
Corresponds to variant rs267606844 [ dbSNP | Ensembl ].
VAR_058997
Natural varianti76 – 761R → S in ODDD. 1 Publication
Corresponds to variant rs267606845 [ dbSNP | Ensembl ].
VAR_015755
Natural varianti86 – 861S → Y in ODDD; de novo mutation found in a sporadic case. 1 Publication
VAR_071010
Natural varianti90 – 901L → V in ODDD. 1 Publication
VAR_015756
Natural varianti95 – 951H → R in ODDD. 1 Publication
VAR_058998
Natural varianti96 – 961V → A in ODDD. 1 Publication
VAR_058999
Natural varianti96 – 961V → E in ODDD. 1 Publication
VAR_059000
Natural varianti96 – 961V → M in ODDD. 1 Publication
Corresponds to variant rs28931601 [ dbSNP | Ensembl ].
VAR_059001
Natural varianti98 – 981Y → C in ODDD. 1 Publication
VAR_015757
Natural varianti102 – 1021K → N in ODDD. 1 Publication
VAR_015758
Natural varianti106 – 1061L → P in ODDD. 1 Publication
VAR_059002
Natural varianti106 – 1061L → R in ODDD. 1 Publication
VAR_071011
Natural varianti110 – 1101E → D in ODDD. 1 Publication
VAR_059003
Natural varianti113 – 1131L → P in ODDD. 2 Publications
VAR_038359
Natural varianti124 – 1241D → E.
Corresponds to variant rs2228966 [ dbSNP | Ensembl ].
VAR_014094
Natural varianti130 – 1301I → T in ODDD. 1 Publication
VAR_015759
Natural varianti134 – 1341K → E in ODDD. 1 Publication
VAR_015760
Natural varianti134 – 1341K → N in ODDD. 1 Publication
VAR_038360
Natural varianti138 – 1381G → R in ODDD. 1 Publication
VAR_015761
Natural varianti143 – 1431G → S in SDTY3. 1 Publication
Corresponds to variant rs28931600 [ dbSNP | Ensembl ].
VAR_038361
Natural varianti147 – 1471M → T in ODDD. 1 Publication
VAR_059004
Natural varianti148 – 1481R → Q.1 Publication
Corresponds to variant rs2228960 [ dbSNP | Ensembl ].
VAR_014095
Natural varianti154 – 1541T → A in ODDD. 2 Publications
VAR_059005
Natural varianti154 – 1541T → N in ODDD. 1 Publication
VAR_059006
Natural varianti168 – 1681A → T.
Corresponds to variant rs2228961 [ dbSNP | Ensembl ].
VAR_014096
Natural varianti169 – 1691Missing in ODDD. 1 Publication
VAR_059007
Natural varianti185 – 1851Y → H.
Corresponds to variant rs2228962 [ dbSNP | Ensembl ].
VAR_014097
Natural varianti194 – 1941H → P in ODDD; atypical form of ODDD characterized by the predominance of the ocular involvement and by the absence of hand and/or foot syndactyly and absence of any neurologic signs. 1 Publication
Corresponds to variant rs104893966 [ dbSNP | Ensembl ].
VAR_059008
Natural varianti201 – 2011S → F in ODDD. 1 Publication
VAR_059009
Natural varianti202 – 2021R → C.
Corresponds to variant rs2228964 [ dbSNP | Ensembl ].
VAR_014098
Natural varianti202 – 2021R → H in ODDD. 3 Publications
Corresponds to variant rs750294638 [ dbSNP | Ensembl ].
VAR_015762
Natural varianti204 – 2041T → M.
Corresponds to variant rs2228965 [ dbSNP | Ensembl ].
VAR_014099
Natural varianti206 – 2061K → R in ODDD. 1 Publication
Corresponds to variant rs397518464 [ dbSNP | Ensembl ].
VAR_070440
Natural varianti216 – 2161V → L in ODDD. 1 Publication
VAR_015763
Natural varianti220 – 2201S → Y in ODDD. 1 Publication
VAR_059010
Natural varianti227 – 2271E → D in EKV; does not localize to intercellular junctions but is retained in the cytoplasm. 1 Publication
VAR_075756
Natural varianti239 – 2391R → Q in CMDR. 1 Publication
Corresponds to variant rs764670582 [ dbSNP | Ensembl ].
VAR_070441
Natural varianti239 – 2391R → W in congenital heart malformations. 1 Publication
Corresponds to variant rs2227887 [ dbSNP | Ensembl ].
VAR_014100
Natural varianti251 – 2511S → T in congenital heart malformations. 1 Publication
VAR_059011
Natural varianti253 – 2531A → P in congenital heart malformations. 1 Publication
VAR_059012
Natural varianti253 – 2531A → V.1 Publication
Corresponds to variant rs17653265 [ dbSNP | Ensembl ].
VAR_015764
Natural varianti283 – 2831P → L in congenital heart malformations. 1 Publication
Corresponds to variant rs2228974 [ dbSNP | Ensembl ].
VAR_014101
Natural varianti290 – 2901T → N in congenital heart malformations. 1 Publication
Corresponds to variant rs2227881 [ dbSNP | Ensembl ].
VAR_014102
Natural varianti326 – 3261T → A.1 Publication
VAR_059013
Natural varianti352 – 3521E → G in heart malformations. 1 Publication
VAR_059014
Natural varianti362 – 3621R → Q in HLHS1 and AVSD3; associated with Gln-376 in one individual with atrioventricular septal defect; abolishes phosphorylation by PKA and PKC. 1 Publication
Corresponds to variant rs2227885 [ dbSNP | Ensembl ].
VAR_032924
Natural varianti364 – 3641S → P in heart malformations; shows abnormalities in the regulation of cell-cell communication as compared with cells expressing normal GJA1. 1 Publication
VAR_059015
Natural varianti365 – 3651S → N in heart malformations. 1 Publication
VAR_059016
Natural varianti373 – 3731S → G.1 Publication
VAR_059017
Natural varianti376 – 3761R → Q in HLHS1 and AVSD3; associated with Gln-362 in one individual with atrioventricular septal defect; abolishes phosphorylation by PKA and PKC. 1 Publication
Corresponds to variant rs104893965 [ dbSNP | Ensembl ].
VAR_032925

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52947 mRNA. Translation: CAA37122.1.
M65188 mRNA. Translation: AAA52131.1.
AF151980 Genomic DNA. Translation: AAD37802.2.
CR541660 mRNA. Translation: CAG46461.1.
AK312324 mRNA. Translation: BAG35246.1.
AL139098 Genomic DNA. Translation: CAI20002.1.
CH471051 Genomic DNA. Translation: EAW48178.1.
BC026329 mRNA. Translation: AAH26329.1.
CCDSiCCDS5123.1.
PIRiA35853.
RefSeqiNP_000156.1. NM_000165.4.
UniGeneiHs.700699.
Hs.74471.

Genome annotation databases

EnsembliENST00000282561; ENSP00000282561; ENSG00000152661.
GeneIDi2697.
KEGGihsa:2697.
UCSCiuc003pyr.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52947 mRNA. Translation: CAA37122.1.
M65188 mRNA. Translation: AAA52131.1.
AF151980 Genomic DNA. Translation: AAD37802.2.
CR541660 mRNA. Translation: CAG46461.1.
AK312324 mRNA. Translation: BAG35246.1.
AL139098 Genomic DNA. Translation: CAI20002.1.
CH471051 Genomic DNA. Translation: EAW48178.1.
BC026329 mRNA. Translation: AAH26329.1.
CCDSiCCDS5123.1.
PIRiA35853.
RefSeqiNP_000156.1. NM_000165.4.
UniGeneiHs.700699.
Hs.74471.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LL2NMR-A234-259[»]
ProteinModelPortaliP17302.
SMRiP17302. Positions 3-382.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108964. 41 interactions.
IntActiP17302. 11 interactions.
MINTiMINT-147603.
STRINGi9606.ENSP00000282561.

Chemistry

DrugBankiDB01136. Carvedilol.

PTM databases

iPTMnetiP17302.
PhosphoSiteiP17302.

Polymorphism and mutation databases

BioMutaiGJA1.
DMDMi117706.

Proteomic databases

EPDiP17302.
MaxQBiP17302.
PaxDbiP17302.
PeptideAtlasiP17302.
PRIDEiP17302.
TopDownProteomicsiP17302.

Protocols and materials databases

DNASUi2697.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282561; ENSP00000282561; ENSG00000152661.
GeneIDi2697.
KEGGihsa:2697.
UCSCiuc003pyr.4. human.

Organism-specific databases

CTDi2697.
GeneCardsiGJA1.
HGNCiHGNC:4274. GJA1.
HPAiCAB010753.
HPA035097.
MalaCardsiGJA1.
MIMi104100. phenotype.
121014. gene.
133200. phenotype.
164200. phenotype.
186100. phenotype.
218400. phenotype.
234100. phenotype.
241550. phenotype.
257850. phenotype.
600309. phenotype.
neXtProtiNX_P17302.
Orphaneti90636. Autosomal recessive non-syndromic sensorineural deafness type DFNB.
1522. Craniometaphyseal dysplasia.
2248. Hypoplastic left heart syndrome.
2710. Oculodentodigital dysplasia.
93404. Syndactyly type 3.
PharmGKBiPA28685.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF97. Eukaryota.
ENOG4110JTW. LUCA.
GeneTreeiENSGT00840000129674.
HOGENOMiHOG000231127.
HOVERGENiHBG009576.
InParanoidiP17302.
KOiK07372.
OMAiGANVDMH.
OrthoDBiEOG091G0FKH.
PhylomeDBiP17302.
TreeFamiTF329606.

Enzyme and pathway databases

ReactomeiR-HSA-190704. Oligomerization of connexins into connexons.
R-HSA-190827. Transport of connexins along the secretory pathway.
R-HSA-190840. Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
R-HSA-190861. Gap junction assembly.
R-HSA-190873. Gap junction degradation.
R-HSA-191647. c-src mediated regulation of Cx43 function and closure of gap junctions.
R-HSA-196025. Formation of annular gap junctions.
SignaLinkiP17302.
SIGNORiP17302.

Miscellaneous databases

ChiTaRSiGJA1. human.
GeneWikiiGJA1.
GenomeRNAii2697.
PROiP17302.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000152661.
CleanExiHS_GJA1.
GenevisibleiP17302. HS.

Family and domain databases

InterProiIPR000500. Connexin.
IPR002261. Connexin43.
IPR013124. Connexin43_C.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERiPTHR11984. PTHR11984. 1 hit.
PfamiPF00029. Connexin. 1 hit.
PF03508. Connexin43. 1 hit.
[Graphical view]
PRINTSiPR00206. CONNEXIN.
PR01132. CONNEXINA1.
SMARTiSM00037. CNX. 1 hit.
SM01089. Connexin_CCC. 1 hit.
[Graphical view]
PROSITEiPS00407. CONNEXINS_1. 1 hit.
PS00408. CONNEXINS_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCXA1_HUMAN
AccessioniPrimary (citable) accession number: P17302
Secondary accession number(s): B2R5U9, Q6FHU1, Q9Y5I8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 203 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

PubMed:7715640 reported a mutation Pro-364 linked to congenital heart diseases. PubMed:8873667 later shown that it is an artifact.Curated
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 5.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.