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Protein

Gap junction alpha-1 protein

Gene

GJA1

Organism
Oryctolagus cuniculus (Rabbit)
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. 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...

Names & Taxonomyi

Protein namesi
Recommended name:
Gap junction alpha-1 protein
Alternative name(s):
Connexin-43
Short name:
Cx43
Gene namesi
Name:GJA1
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Chromosome 12

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 – 15455CytoplasmicSequence analysisAdd
BLAST
Transmembranei155 – 17723HelicalSequence analysisAdd
BLAST
Topological domaini178 – 20831ExtracellularSequence analysisAdd
BLAST
Transmembranei209 – 23123HelicalSequence analysisAdd
BLAST
Topological domaini232 – 382151CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi368 – 3681S → A: Loss of phosphorylation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 382381Gap junction alpha-1 proteinPRO_0000313001Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei5 – 51PhosphoserineBy similarity
Disulfide bondi54 ↔ 192By similarity
Cross-linki144 – 144Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Disulfide bondi187 ↔ 198By similarity
Cross-linki237 – 237Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei247 – 2471PhosphotyrosineBy similarity
Modified residuei255 – 2551PhosphoserineBy similarity
Modified residuei257 – 2571PhosphoserineBy similarity
Modified residuei262 – 2621PhosphoserineBy similarity
Modified residuei271 – 2711S-nitrosocysteineBy similarity
Modified residuei275 – 2751PhosphothreonineBy similarity
Modified residuei306 – 3061PhosphoserineBy similarity
Modified residuei314 – 3141PhosphoserineBy similarity
Modified residuei325 – 3251Phosphoserine; by CK1By similarity
Modified residuei326 – 3261PhosphothreonineBy similarity
Modified residuei328 – 3281Phosphoserine; by CK1By similarity
Modified residuei330 – 3301Phosphoserine; by CK1By similarity
Modified residuei344 – 3441PhosphoserineBy similarity
Modified residuei365 – 3651PhosphoserineBy similarity
Modified residuei368 – 3681Phosphoserine; by PKC/PRKCG and PKC/PRKCDBy similarity1 Publication
Modified residuei369 – 3691PhosphoserineBy similarity
Modified residuei373 – 3731PhosphoserineBy similarity

Post-translational modificationi

Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly (By similarity). Phosphorylated at Ser-368 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of gap junction activity. Phosphorylation at Ser-368 by PRKCD triggers its internalization into small vesicles leading to proteasome-mediated degradation (By similarity).By similarity1 Publication
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
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

PTM databases

iPTMnetiQ6TYA7.

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

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000019547.

Structurei

3D structure databases

ProteinModelPortaliQ6TYA7.
SMRiQ6TYA7. Positions 252-382.
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.
InParanoidiQ6TYA7.
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.

Q6TYA7-1 [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 VNVEMHLKQI EIKKFKYGIE EHGKVKMRGG
160 170 180 190 200
LLRTYIISIL FKSVFEVAFL LIQWYIYGFS LSAVYTCKRD PCPHQVDCFL
210 220 230 240 250
SRPTEKTIFI IFMLVVSLVS LALNIIELFY VFFKGVKDRV KGKSDPYHAT
260 270 280 290 300
TGPLSPSKDC GSPKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN
310 320 330 340 350
YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNSKKLAAG
360 370 380
HELQPLAIVD QRPSSRASSR ASSRPRPDDL EI
Length:382
Mass (Da):43,033
Last modified:July 5, 2004 - v1
Checksum:iCAFEF68793025077
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY382590 Genomic DNA. Translation: AAR33084.1.
RefSeqiNP_001185877.1. NM_001198948.1.
XP_008261519.1. XM_008263297.1.
UniGeneiOcu.1384.

Genome annotation databases

EnsembliENSOCUT00000009321; ENSOCUP00000019547; ENSOCUG00000009324.
GeneIDi100008935.
KEGGiocu:100008935.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY382590 Genomic DNA. Translation: AAR33084.1.
RefSeqiNP_001185877.1. NM_001198948.1.
XP_008261519.1. XM_008263297.1.
UniGeneiOcu.1384.

3D structure databases

ProteinModelPortaliQ6TYA7.
SMRiQ6TYA7. Positions 252-382.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000019547.

PTM databases

iPTMnetiQ6TYA7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSOCUT00000009321; ENSOCUP00000019547; ENSOCUG00000009324.
GeneIDi100008935.
KEGGiocu:100008935.

Organism-specific databases

CTDi2697.

Phylogenomic databases

eggNOGiENOG410IF97. Eukaryota.
ENOG4110JTW. LUCA.
GeneTreeiENSGT00840000129674.
HOGENOMiHOG000231127.
HOVERGENiHBG009576.
InParanoidiQ6TYA7.
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]
ProtoNetiSearch...

Publicationsi

  1. "Connexin43 orthologues in vertebrates: phylogeny from fish to man."
    van der Heyden M.A., van Eijk M., Wilders R., de Bakker J.M., Opthof T.
    Dev. Genes Evol. 214:261-266(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Oxidative activation of protein kinase Cgamma through the C1 domain. Effects on gap junctions."
    Lin D., Takemoto D.J.
    J. Biol. Chem. 280:13682-13693(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-368, MUTAGENESIS OF SER-368.

Entry informationi

Entry nameiCXA1_RABIT
AccessioniPrimary (citable) accession number: Q6TYA7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: July 5, 2004
Last modified: May 11, 2016
This is version 80 of the entry and version 1 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.