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Protein

Gap junction alpha-1 protein

Gene

GJA1

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 4 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...

Names & Taxonomyi

Protein namesi
Recommended name:
Gap junction alpha-1 protein
Alternative name(s):
Connexin-43
Short name:
Cx43
Gene namesi
Name:GJA1
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

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 the 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 – 154CytoplasmicSequence analysisAdd BLAST55
Transmembranei155 – 177HelicalSequence analysisAdd BLAST23
Topological domaini178 – 208ExtracellularSequence analysisAdd BLAST31
Transmembranei209 – 231HelicalSequence analysisAdd BLAST23
Topological domaini232 – 382CytoplasmicSequence 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_00000578002 – 382Gap junction alpha-1 proteinAdd BLAST381

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5PhosphoserineBy similarity1
Disulfide bondi54 ↔ 192By similarity
Cross-linki144Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Disulfide bondi187 ↔ 198By similarity
Cross-linki237Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei247PhosphotyrosineBy similarity1
Modified residuei255PhosphoserineBy similarity1
Modified residuei257PhosphoserineBy similarity1
Modified residuei262PhosphoserineBy similarity1
Modified residuei271S-nitrosocysteineBy similarity1
Modified residuei275PhosphothreonineBy similarity1
Modified residuei306PhosphoserineBy similarity1
Modified residuei314PhosphoserineBy similarity1
Modified residuei325Phosphoserine; by CK1By similarity1
Modified residuei326PhosphothreonineBy similarity1
Modified residuei328Phosphoserine; by CK1By similarity1
Modified residuei330Phosphoserine; by CK1By similarity1
Modified residuei344PhosphoserineBy similarity1
Modified residuei365PhosphoserineBy similarity1
Modified residuei368Phosphoserine; by PKC/PRKCG and PKC/PRKCDBy similarity1
Modified residuei369PhosphoserineBy similarity1
Modified residuei373PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly. 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 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
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

PaxDbiQ6S9C0.

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

STRINGi9615.ENSCAFP00000041768.

Structurei

3D structure databases

ProteinModelPortaliQ6S9C0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni244 – 382Interaction with NOVBy similarityAdd BLAST139
Regioni264 – 382Interaction with UBQLN4By similarityAdd BLAST119

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF97. Eukaryota.
ENOG4110JTW. LUCA.
HOVERGENiHBG009576.
InParanoidiQ6S9C0.

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.

Q6S9C0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGGWSALAKL LGKVQAYSPA GGKVWLSVLF IFRILLLGTA VESAWGDEQS
60 70 80 90 100
AFRCNTQQPG CENVCYDKSF PISHVRFWVL QIIFVSVPTL LYLAHVFYVM
110 120 130 140 150
RKEEKLNKKE EELKVAQTDG ANVDMHLKQI EIKKFKYGIE EHGKVKMRGG
160 170 180 190 200
LLRTYIISIL FKSVFEVAFL LIQWYIYGFS LSAVYTCKRE PCPHQVDCFL
210 220 230 240 250
SRPTEKTIFI IFMLVVSLVS LALNIIELFY VFFKGVKDRV KGQSDPYHAT
260 270 280 290 300
TGPLSPSKDC GSPEYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN
310 320 330 340 350
YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNSKKLAAG
360 370 380
HELQPLAIVD QRPSSRASSR ASSRPRPDDL EI
Length:382
Mass (Da):42,900
Last modified:January 23, 2007 - v3
Checksum:i949669D6E3743828
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY462223 mRNA. Translation: AAR25626.1.
UniGeneiCfa.119.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY462223 mRNA. Translation: AAR25626.1.
UniGeneiCfa.119.

3D structure databases

ProteinModelPortaliQ6S9C0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000041768.

Proteomic databases

PaxDbiQ6S9C0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiENOG410IF97. Eukaryota.
ENOG4110JTW. LUCA.
HOVERGENiHBG009576.
InParanoidiQ6S9C0.

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_CANLF
AccessioniPrimary (citable) accession number: Q6S9C0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 83 of the entry and version 3 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.