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Protein

Gap junction alpha-1 protein

Gene

GJA1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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. 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

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-BTA-190840. Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
R-BTA-190861. Gap junction assembly.
R-BTA-190873. Gap junction degradation.
R-BTA-191647. c-src mediated regulation of Cx43 function and closure of gap junctions.
R-BTA-196025. Formation of annular gap junctions.

Names & Taxonomyi

Protein namesi
Recommended name:
Gap junction alpha-1 protein
Alternative name(s):
Connexin-43
Short name:
Cx43
Vascular smooth muscle connexin-43
Gene namesi
Name:GJA1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 9

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein Sequence analysis
  • Cell junctiongap junction By similarity
  • Endoplasmic reticulum By similarity

  • Note: Localizes at the intercalated disk (ICD) in cardiomyocytes and proper localization at ICD is dependent on TMEM65.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 13CytoplasmicSequence analysisAdd BLAST12
Transmembranei14 – 36HelicalSequence analysisAdd BLAST23
Topological domaini37 – 76ExtracellularSequence analysisAdd BLAST40
Transmembranei77 – 99HelicalSequence analysisAdd BLAST23
Topological domaini100 – 155CytoplasmicSequence analysisAdd BLAST56
Transmembranei156 – 178HelicalSequence analysisAdd BLAST23
Topological domaini179 – 209ExtracellularSequence analysisAdd BLAST31
Transmembranei210 – 232HelicalSequence analysisAdd BLAST23
Topological domaini233 – 383CytoplasmicSequence analysisAdd BLAST151

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000577992 – 383Gap junction alpha-1 proteinAdd BLAST382

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5PhosphoserineBy similarity1
Disulfide bondi54 ↔ 193By similarity
Cross-linki145Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Disulfide bondi188 ↔ 199By similarity
Cross-linki238Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei248PhosphotyrosineBy similarity1
Modified residuei256PhosphoserineBy similarity1
Modified residuei258PhosphoserineBy similarity1
Modified residuei263PhosphoserineBy similarity1
Modified residuei272S-nitrosocysteineBy similarity1
Modified residuei276PhosphothreonineBy similarity1
Modified residuei307PhosphoserineBy similarity1
Modified residuei315PhosphoserineBy similarity1
Modified residuei326Phosphoserine; by CK1By similarity1
Modified residuei327PhosphothreonineBy similarity1
Modified residuei329Phosphoserine; by CK1By similarity1
Modified residuei331Phosphoserine; by CK1By similarity1
Modified residuei345PhosphoserineBy similarity1
Modified residuei366PhosphoserineBy similarity1
Modified residuei369Phosphoserine; by PKC/PRKCG and PKC/PRKCDBy similarity1
Modified residuei370PhosphoserineBy similarity1
Modified residuei374PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-326, Ser-329 and Ser-331 by CK1 modulates gap junction assembly. Phosphorylated at Ser-369 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of gap junction activity. Phosphorylation at Ser-369 by PRKCD triggers its internalization into small vesicles leading to proteasome-mediated degradation (By similarity).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 (By similarity).By similarity

Keywords - PTMi

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

Proteomic databases

PaxDbiP18246.
PeptideAtlasiP18246.
PRIDEiP18246.

Expressioni

Gene expression databases

BgeeiENSBTAG00000001835.

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000002398.

Structurei

3D structure databases

ProteinModelPortaliP18246.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni245 – 383Interaction with NOVBy similarityAdd BLAST139
Regioni265 – 383Interaction with UBQLN4By similarityAdd BLAST119

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF97. Eukaryota.
ENOG4110JTW. LUCA.
GeneTreeiENSGT00840000129674.
HOGENOMiHOG000231127.
HOVERGENiHBG009576.
InParanoidiP18246.
KOiK07372.
OMAiGANVDMH.
OrthoDBiEOG091G0FKH.
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.

P18246-1 [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 EELKVVAQTD GANVDMHLKQ IEIKKFKYGI EEHGKVKMRG
160 170 180 190 200
GLLRTYIISI LFKSVFEVAF LLIQWYIYGF SLSAVYTCKR DPCPHQVDCF
210 220 230 240 250
LSRPTEKTIF IIFMLVVSLV SLALNIIELF YVFFKGVKDR VKGKSDPYHT
260 270 280 290 300
TTGPLSPSKD CGSPKYAYFN GCSSPTAPLS PMSPPGYKLV TGDRNNSSCR
310 320 330 340 350
NYNKQASEQN WANYSAEQNR MGQAGSTISN SHAQPFDFPD DHQNSKKLDA
360 370 380
GHELQPLAIV DQRPSSRASS RASSRPRPDD LEI
Length:383
Mass (Da):43,188
Last modified:January 23, 2007 - v2
Checksum:iB77459AAD14142D8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05535 mRNA. Translation: AAA30459.1.
BC105464 mRNA. Translation: AAI05465.1.
PIRiA36623.
RefSeqiNP_776493.1. NM_174068.2.
UniGeneiBt.15972.

Genome annotation databases

EnsembliENSBTAT00000002398; ENSBTAP00000002398; ENSBTAG00000001835.
GeneIDi281193.
KEGGibta:281193.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05535 mRNA. Translation: AAA30459.1.
BC105464 mRNA. Translation: AAI05465.1.
PIRiA36623.
RefSeqiNP_776493.1. NM_174068.2.
UniGeneiBt.15972.

3D structure databases

ProteinModelPortaliP18246.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000002398.

Proteomic databases

PaxDbiP18246.
PeptideAtlasiP18246.
PRIDEiP18246.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000002398; ENSBTAP00000002398; ENSBTAG00000001835.
GeneIDi281193.
KEGGibta:281193.

Organism-specific databases

CTDi2697.

Phylogenomic databases

eggNOGiENOG410IF97. Eukaryota.
ENOG4110JTW. LUCA.
GeneTreeiENSGT00840000129674.
HOGENOMiHOG000231127.
HOVERGENiHBG009576.
InParanoidiP18246.
KOiK07372.
OMAiGANVDMH.
OrthoDBiEOG091G0FKH.
TreeFamiTF329606.

Enzyme and pathway databases

ReactomeiR-BTA-190840. Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
R-BTA-190861. Gap junction assembly.
R-BTA-190873. Gap junction degradation.
R-BTA-191647. c-src mediated regulation of Cx43 function and closure of gap junctions.
R-BTA-196025. Formation of annular gap junctions.

Gene expression databases

BgeeiENSBTAG00000001835.

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_BOVIN
AccessioniPrimary (citable) accession number: P18246
Secondary accession number(s): Q2KJ91
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.