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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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 1312CytoplasmicSequence analysisAdd
BLAST
Transmembranei14 – 3623HelicalSequence analysisAdd
BLAST
Topological domaini37 – 7640ExtracellularSequence analysisAdd
BLAST
Transmembranei77 – 9923HelicalSequence analysisAdd
BLAST
Topological domaini100 – 15556CytoplasmicSequence analysisAdd
BLAST
Transmembranei156 – 17823HelicalSequence analysisAdd
BLAST
Topological domaini179 – 20931ExtracellularSequence analysisAdd
BLAST
Transmembranei210 – 23223HelicalSequence analysisAdd
BLAST
Topological domaini233 – 383151CytoplasmicSequence analysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 383382Gap junction alpha-1 proteinPRO_0000057799Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei5 – 51PhosphoserineBy similarity
Disulfide bondi54 ↔ 193By similarity
Cross-linki145 – 145Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Disulfide bondi188 ↔ 199By similarity
Cross-linki238 – 238Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei248 – 2481PhosphotyrosineBy similarity
Modified residuei256 – 2561PhosphoserineBy similarity
Modified residuei258 – 2581PhosphoserineBy similarity
Modified residuei263 – 2631PhosphoserineBy similarity
Modified residuei272 – 2721S-nitrosocysteineBy similarity
Modified residuei276 – 2761PhosphothreonineBy similarity
Modified residuei307 – 3071PhosphoserineBy similarity
Modified residuei315 – 3151PhosphoserineBy similarity
Modified residuei326 – 3261Phosphoserine; by CK1By similarity
Modified residuei327 – 3271PhosphothreonineBy similarity
Modified residuei329 – 3291Phosphoserine; by CK1By similarity
Modified residuei331 – 3311Phosphoserine; by CK1By similarity
Modified residuei345 – 3451PhosphoserineBy similarity
Modified residuei366 – 3661PhosphoserineBy similarity
Modified residuei369 – 3691Phosphoserine; by PKC/PRKCG and PKC/PRKCDBy similarity
Modified residuei370 – 3701PhosphoserineBy similarity
Modified residuei374 – 3741PhosphoserineBy similarity

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.
PRIDEiP18246.

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.
SMRiP18246. Positions 253-383.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni245 – 383139Interaction with NOVBy similarityAdd
BLAST
Regioni265 – 383119Interaction with UBQLN4By similarityAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF97. Eukaryota.
ENOG4110JTW. LUCA.
GeneTreeiENSGT00840000129674.
HOGENOMiHOG000231127.
HOVERGENiHBG009576.
InParanoidiP18246.
KOiK07372.
OMAiGANVDMH.
OrthoDBiEOG7P2XSS.
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.
SMRiP18246. Positions 253-383.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000002398.

Proteomic databases

PaxDbiP18246.
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.
OrthoDBiEOG7P2XSS.
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.

Miscellaneous databases

NextBioi20805250.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of a gap junctional protein from vascular smooth muscle and expression in two-cell mouse embryos."
    Lash J.A., Critser E.S., Pressler M.L.
    J. Biol. Chem. 265:13113-13117(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. NIH - Mammalian Gene Collection (MGC) project
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Thymus.

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: May 11, 2016
This is version 133 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.