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Protein

Gap junction alpha-1 protein

Gene

Gja1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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. 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 (PubMed:15181016). Plays an essential role in gap junction communication in the ventricles (PubMed:26403541).3 Publications
Connexin 43 is possibly the ATP-induced pore of mouse macrophages.1 Publication

GO - Molecular functioni

  • beta-tubulin binding Source: MGI
  • connexin binding Source: MGI
  • disordered domain specific binding Source: MGI
  • gap junction channel activity Source: MGI
  • gap junction channel activity involved in cardiac conduction electrical coupling Source: UniProtKB
  • gap junction channel activity involved in cell communication by electrical coupling Source: MGI
  • ion transmembrane transporter activity Source: MGI
  • PDZ domain binding Source: MGI
  • protein domain specific binding Source: MGI
  • protein tyrosine kinase binding Source: CAFA
  • scaffold protein binding Source: CAFA
  • SH3 domain binding Source: MGI
  • signaling receptor binding Source: MGI

GO - Biological processi

  • adult heart development Source: MGI
  • apoptotic process Source: MGI
  • ATP transport Source: MGI
  • atrial ventricular junction remodeling Source: MGI
  • blood vessel morphogenesis Source: MGI
  • cardiac conduction Source: MGI
  • cell-cell junction organization Source: MGI
  • cell-cell signaling Source: MGI
  • cell communication Source: MGI
  • cell communication by chemical coupling Source: MGI
  • cell communication by electrical coupling Source: MGI
  • cellular response to mechanical stimulus Source: Ensembl
  • cellular response to parathyroid hormone stimulus Source: Ensembl
  • cellular response to pH Source: CAFA
  • chronic inflammatory response Source: MGI
  • decidualization Source: Ensembl
  • embryonic digit morphogenesis Source: MGI
  • embryonic heart tube development Source: MGI
  • endothelium development Source: Ensembl
  • epicardial cell to mesenchymal cell transition Source: DFLAT
  • epididymis development Source: Ensembl
  • epithelial cell maturation Source: MGI
  • establishment of epithelial cell polarity Source: DFLAT
  • heart development Source: MGI
  • heart looping Source: MGI
  • in utero embryonic development Source: MGI
  • ion transmembrane transport Source: MGI
  • lens development in camera-type eye Source: MGI
  • milk ejection reflex Source: MGI
  • negative regulation of cardiac muscle cell proliferation Source: MGI
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of DNA biosynthetic process Source: MGI
  • negative regulation of endothelial cell proliferation Source: MGI
  • negative regulation of gene expression Source: MGI
  • negative regulation of wound healing Source: MGI
  • neuron migration Source: MGI
  • neuron projection morphogenesis Source: MGI
  • osteoblast differentiation Source: MGI
  • positive regulation of behavioral fear response Source: MGI
  • positive regulation of blood vessel diameter Source: MGI
  • positive regulation of cell communication by chemical coupling Source: MGI
  • positive regulation of cytosolic calcium ion concentration Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of glomerular filtration Source: MGI
  • positive regulation of insulin secretion Source: MGI
  • positive regulation of osteoblast differentiation Source: MGI
  • positive regulation of protein catabolic process Source: MGI
  • positive regulation of striated muscle tissue development Source: MGI
  • positive regulation of vasoconstriction Source: MGI
  • protein complex oligomerization Source: MGI
  • regulation of atrial cardiac muscle cell membrane depolarization Source: MGI
  • regulation of bicellular tight junction assembly Source: MGI
  • regulation of blood vessel remodeling Source: DFLAT
  • regulation of bone mineralization Source: MGI
  • regulation of bone remodeling Source: MGI
  • regulation of calcium ion transport Source: MGI
  • regulation of heart contraction Source: MGI
  • regulation of transmembrane transporter activity Source: MGI
  • regulation of ventricular cardiac muscle cell membrane depolarization Source: MGI
  • regulation of ventricular cardiac muscle cell membrane repolarization Source: MGI
  • response to fluid shear stress Source: Ensembl
  • response to glucose Source: Ensembl
  • response to ischemia Source: Ensembl
  • response to lipopolysaccharide Source: Ensembl
  • response to peptide hormone Source: Ensembl
  • response to pH Source: MGI
  • response to retinoic acid Source: Ensembl
  • signal transduction Source: MGI
  • skeletal muscle tissue regeneration Source: MGI
  • transmembrane transport Source: MGI
  • vascular transport Source: MGI

Enzyme and pathway databases

ReactomeiR-MMU-190840 Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane
R-MMU-190861 Gap junction assembly
R-MMU-190873 Gap junction degradation
R-MMU-191647 c-src mediated regulation of Cx43 function and closure of gap junctions
R-MMU-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
Gap junction 43 kDa heart protein
Gene namesi
Name:Gja1
Synonyms:Cxn-43
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:95713 Gja1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 13CytoplasmicSequence analysisAdd BLAST13
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

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

Mutant mice die shortly after birth.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000578021 – 382Gap junction alpha-1 proteinAdd BLAST382

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 residuei247PhosphotyrosineCombined sources1
Modified residuei255PhosphoserineBy similarity1
Modified residuei257PhosphoserineBy similarity1
Modified residuei262PhosphoserineBy similarity1
Modified residuei271S-nitrosocysteine1 Publication1
Modified residuei275PhosphothreonineCombined sources1
Modified residuei306PhosphoserineCombined sources1
Modified residuei314PhosphoserineCombined sources1
Modified residuei325PhosphoserineCombined sources1
Modified residuei326PhosphothreonineCombined sources1
Modified residuei328PhosphoserineCombined sources1
Modified residuei330PhosphoserineCombined sources1
Modified residuei341PhosphoserineCombined sources1
Modified residuei365PhosphoserineCombined sources1
Modified residuei368Phosphoserine; by PKC/PRKCG and PKC/PRKCDCombined sources1 Publication1
Modified residuei369PhosphoserineCombined sources1
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.1 Publication

Keywords - PTMi

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

Proteomic databases

PaxDbiP23242
PeptideAtlasiP23242
PRIDEiP23242

PTM databases

iPTMnetiP23242
PhosphoSitePlusiP23242

Expressioni

Tissue specificityi

Expressed in heart, non-sensory epithelial cells, and in fibrocytes of the spiral ligament and the spiral limbus. Expressed in bladder smooth muscle cells (at protein level). Expressed in astrocytes (at protein level) (PubMed:15213231).4 Publications

Developmental stagei

At 7.5 dpc, expressed in the embryo, but not in the extraembryonic region containing the ectoplacental cone.1 Publication

Inductioni

In bladder smooth muscle cells, exhibits night/day variations with low levels during the sleep phase, at circadian time (CT) 4-12 (at protein level). Down-regulation during the night allows increase in bladder capacity, avoiding disturbance of sleep by micturition. Expression starts to increase around CT12 and forms a plateau during the active phase (CT16-24) (at protein level). Circadian transcription is activated by NR1D1. Up-regulated by SP1 and SP3.1 Publication

Gene expression databases

BgeeiENSMUSG00000050953
CleanExiMM_GJA1
ExpressionAtlasiP23242 baseline and differential
GenevisibleiP23242 MM

Interactioni

Subunit structurei

A connexon is composed of a hexamer of connexins. Interacts with CSNK1D (By similarity). Interacts with RIC1/CIP150 (By similarity). 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). Interacts with CNST. Interacts with SGSM3. Interacts with NOV (By similarity). Interacts with TMEM65 (PubMed:26403541).By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • beta-tubulin binding Source: MGI
  • connexin binding Source: MGI
  • disordered domain specific binding Source: MGI
  • PDZ domain binding Source: MGI
  • protein domain specific binding Source: MGI
  • protein tyrosine kinase binding Source: CAFA
  • scaffold protein binding Source: CAFA
  • SH3 domain binding Source: MGI
  • signaling receptor binding Source: MGI

Protein-protein interaction databases

BioGridi199923, 11 interactors
DIPiDIP-29207N
IntActiP23242, 30 interactors
MINTiP23242
STRINGi10090.ENSMUSP00000064536

Structurei

3D structure databases

ProteinModelPortaliP23242
SMRiP23242
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni244 – 382Interaction with NOVBy similarityAdd BLAST139
Regioni264 – 382Interaction with UBQLN41 PublicationAdd BLAST119

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF97 Eukaryota
ENOG4110JTW LUCA
GeneTreeiENSGT00910000143998
HOVERGENiHBG009576
InParanoidiP23242
KOiK07372
OMAiGANVDMH
OrthoDBiEOG091G0FKH
PhylomeDBiP23242
TreeFamiTF329606

Family and domain databases

Gene3Di1.20.1440.80, 1 hit
1.20.5.1130, 1 hit
InterProiView protein in InterPro
IPR035091 Alpha_helix_dom_sf
IPR000500 Connexin
IPR002261 Connexin43
IPR013124 Connexin43_C
IPR034634 Connexin_C
IPR019570 Connexin_CCC
IPR017990 Connexin_CS
IPR013092 Connexin_N
IPR038359 Connexin_N_sf
PANTHERiPTHR11984 PTHR11984, 1 hit
PTHR11984:SF33 PTHR11984:SF33, 1 hit
PfamiView protein in Pfam
PF00029 Connexin, 1 hit
PF03508 Connexin43, 1 hit
PRINTSiPR00206 CONNEXIN
PR01132 CONNEXINA1
SMARTiView protein in SMART
SM00037 CNX, 1 hit
SM01089 Connexin_CCC, 1 hit
SUPFAMiSSF118220 SSF118220, 1 hit
PROSITEiView protein in PROSITE
PS00407 CONNEXINS_1, 1 hit
PS00408 CONNEXINS_2, 1 hit

Sequencei

Sequence statusi: Complete.

P23242-1 [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 KGRSDPYHAT
260 270 280 290 300
TGPLSPSKDC GSPKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN
310 320 330 340 350
YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD SQNAKKVAAG
360 370 380
HELQPLAIVD QRPSSRASSR ASSRPRPDDL EI
Length:382
Mass (Da):43,004
Last modified:January 23, 2007 - v2
Checksum:i018DCB461FA69490
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti21G → V in BAC26375 (PubMed:16141072).Curated1
Sequence conflicti320M → T in AAA53027 (PubMed:1318884).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M61896 Genomic DNA Translation: AAA37444.1
M63801 mRNA Translation: AAA53027.1
X62836 Genomic DNA Translation: CAA44640.1
X61576 mRNA Translation: CAA43778.1
AK029291 mRNA Translation: BAC26375.1
AK036979 mRNA Translation: BAC29656.1
AK145692 mRNA Translation: BAE26592.1
AK165986 mRNA Translation: BAE38502.1
CT010327 mRNA Translation: CAJ18535.1
CH466540 Genomic DNA Translation: EDL05108.1
BC006894 mRNA Translation: AAH06894.1
CCDSiCCDS23851.1
PIRiA39802
RefSeqiNP_034418.1, NM_010288.3
UniGeneiMm.378921

Genome annotation databases

EnsembliENSMUST00000068581; ENSMUSP00000064536; ENSMUSG00000050953
ENSMUST00000220069; ENSMUSP00000151620; ENSMUSG00000050953
GeneIDi14609
KEGGimmu:14609
UCSCiuc007fcc.2 mouse

Similar proteinsi

Entry informationi

Entry nameiCXA1_MOUSE
AccessioniPrimary (citable) accession number: P23242
Secondary accession number(s): Q544I7, Q8CE05
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: January 23, 2007
Last modified: June 20, 2018
This is version 195 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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