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Protein

Gap junction alpha-1 protein

Gene

Gja1

Organism
Rattus norvegicus (Rat)
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. 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 (By similarity). 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 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • connexin binding Source: RGD
  • gap junction channel activity Source: RGD
  • gap junction channel activity involved in cell communication by electrical coupling Source: Ensembl
  • ion transmembrane transporter activity Source: Ensembl
  • PDZ domain binding Source: RGD
  • protein domain specific binding Source: RGD
  • SH3 domain binding Source: RGD
  • signal transducer activity Source: Ensembl

GO - Biological processi

  • adult heart development Source: Ensembl
  • apoptotic process Source: RGD
  • ATP transport Source: RGD
  • atrial ventricular junction remodeling Source: Ensembl
  • blood vessel morphogenesis Source: Ensembl
  • cardiac conduction Source: Ensembl
  • cell-cell signaling Source: RGD
  • cell communication Source: RGD
  • cell communication by chemical coupling Source: Ensembl
  • cellular response to mechanical stimulus Source: RGD
  • chronic inflammatory response Source: RGD
  • embryonic digit morphogenesis Source: Ensembl
  • endothelium development Source: RGD
  • epithelial cell maturation Source: Ensembl
  • gap junction assembly Source: UniProtKB
  • heart development Source: RGD
  • heart looping Source: Ensembl
  • in utero embryonic development Source: Ensembl
  • lens development in camera-type eye Source: Ensembl
  • milk ejection Source: Ensembl
  • negative regulation of cardiac muscle cell proliferation Source: RGD
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cell proliferation Source: RGD
  • negative regulation of DNA biosynthetic process Source: RGD
  • negative regulation of endothelial cell proliferation Source: RGD
  • negative regulation of gene expression Source: Ensembl
  • negative regulation of wound healing Source: RGD
  • neuron migration Source: Ensembl
  • neuron projection morphogenesis Source: RGD
  • osteoblast differentiation Source: Ensembl
  • positive regulation of behavioral fear response Source: RGD
  • positive regulation of cell communication by chemical coupling Source: RGD
  • positive regulation of cytosolic calcium ion concentration Source: RGD
  • positive regulation of gene expression Source: Ensembl
  • positive regulation of glomerular filtration Source: RGD
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  • positive regulation of insulin secretion Source: RGD
  • positive regulation of osteoblast differentiation Source: Ensembl
  • positive regulation of protein catabolic process Source: RGD
  • positive regulation of striated muscle tissue development Source: Ensembl
  • positive regulation of vasoconstriction Source: RGD
  • positive regulation of vasodilation Source: RGD
  • protein oligomerization Source: RGD
  • regulation of atrial cardiac muscle cell membrane depolarization Source: Ensembl
  • regulation of bicellular tight junction assembly Source: RGD
  • regulation of bone mineralization Source: Ensembl
  • regulation of bone remodeling Source: Ensembl
  • regulation of calcium ion transport Source: RGD
  • regulation of ventricular cardiac muscle cell membrane depolarization Source: Ensembl
  • regulation of ventricular cardiac muscle cell membrane repolarization Source: Ensembl
  • response to fluid shear stress Source: RGD
  • response to glucose Source: RGD
  • response to peptide hormone Source: RGD
  • response to pH Source: RGD
  • skeletal muscle tissue regeneration Source: Ensembl
  • transmembrane transport Source: RGD
  • vascular transport Source: RGD
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-RNO-190704. Oligomerization of connexins into connexons.
R-RNO-190827. Transport of connexins along the secretory pathway.
R-RNO-190840. Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
R-RNO-190861. Gap junction assembly.
R-RNO-190873. Gap junction degradation.
R-RNO-191647. c-src mediated regulation of Cx43 function and closure of gap junctions.
R-RNO-196025. Formation of annular gap junctions.
R-RNO-215126. Transport of connexins along the secretory pathway.

Protein family/group databases

TCDBi1.A.24.1.1. the gap junction-forming connexin (connexin) family.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi2690. Gja1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 13Cytoplasmic1 PublicationAdd BLAST12
Transmembranei14 – 36HelicalCuratedAdd BLAST23
Topological domaini37 – 76Extracellular1 PublicationAdd BLAST40
Transmembranei77 – 99HelicalCuratedAdd BLAST23
Topological domaini100 – 154Cytoplasmic1 PublicationAdd BLAST55
Transmembranei155 – 177HelicalCuratedAdd BLAST23
Topological domaini178 – 208Extracellular1 PublicationAdd BLAST31
Transmembranei209 – 231HelicalCuratedAdd BLAST23
Topological domaini232 – 382Cytoplasmic1 PublicationAdd BLAST151

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • connexin complex Source: RGD
  • contractile fiber Source: Ensembl
  • cytoplasm Source: RGD
  • cytosol Source: Ensembl
  • early endosome Source: RGD
  • endoplasmic reticulum membrane Source: Reactome
  • endosome Source: RGD
  • extracellular exosome Source: Ensembl
  • fascia adherens Source: RGD
  • focal adhesion Source: Ensembl
  • gap junction Source: UniProtKB
  • Golgi apparatus Source: BHF-UCL
  • Golgi-associated vesicle membrane Source: Reactome
  • Golgi membrane Source: Reactome
  • integral component of plasma membrane Source: UniProtKB
  • intermediate filament Source: Ensembl
  • late endosome Source: RGD
  • lateral plasma membrane Source: Ensembl
  • lysosome Source: RGD
  • membrane Source: MGI
  • membrane raft Source: BHF-UCL
  • mitochondrial outer membrane Source: RGD
  • multivesicular body Source: RGD
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi368S → A: Loss of phosphorylation by PKC/PRKCD. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00000578042 – 382Gap junction alpha-1 proteinAdd BLAST381

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5PhosphoserineCombined sources1
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 residuei257PhosphoserineCombined sources1
Modified residuei262PhosphoserineBy similarity1
Modified residuei271S-nitrosocysteineBy similarity1
Modified residuei275PhosphothreonineBy similarity1
Modified residuei306PhosphoserineCombined sources1
Modified residuei314PhosphoserineCombined sources1
Modified residuei325PhosphoserineCombined sources1
Modified residuei326PhosphothreonineCombined sources1
Modified residuei328PhosphoserineCombined sources1
Modified residuei330PhosphoserineCombined sources1
Modified residuei365Phosphoserine1 Publication1
Modified residuei368Phosphoserine; by PKC/PRKCG and PKC/PRKCD1 Publication1 Publication1
Modified residuei369Phosphoserine1 Publication1
Modified residuei373Phosphoserine1 Publication1

Post-translational modificationi

Contains at least one intramolecular disulfide bond.
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 (By similarity). Phosphorylation at Ser-368 by PRKCD triggers its internalization into small vesicles leading to proteasome-mediated degradation (PubMed:24500718).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

Proteomic databases

PaxDbiP08050.
PRIDEiP08050.

PTM databases

iPTMnetiP08050.
PhosphoSitePlusiP08050.

Expressioni

Inductioni

In bladder smooth muscle cells, exhibits night/day variations with low levels during the sleep phase, at circadian time (CT) 4-8 (at protein level). Expression starts to increase around CT12 and forms a plateau during the active phase (CT16-24) (at protein level).1 Publication

Gene expression databases

BgeeiENSRNOG00000000805.
GenevisibleiP08050. RN.

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). Interacts with NOV (PubMed:15181016, PubMed:15213231). Interacts with TMEM65 (By similarity).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Kcnj8Q636644EBI-476947,EBI-6991142
Sgsm3Q8VCZ64EBI-476947,EBI-525155From a different organism.
UBQLN4Q9NRR52EBI-476947,EBI-711226From a different organism.

GO - Molecular functioni

  • connexin binding Source: RGD
  • PDZ domain binding Source: RGD
  • protein domain specific binding Source: RGD
  • SH3 domain binding Source: RGD

Protein-protein interaction databases

BioGridi246562. 116 interactors.
DIPiDIP-34793N.
IntActiP08050. 12 interactors.
MINTiMINT-1791096.
STRINGi10116.ENSRNOP00000001054.

Structurei

Secondary structure

1382
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni256 – 259Combined sources4
Beta strandi263 – 265Combined sources3
Beta strandi283 – 285Combined sources3
Beta strandi297 – 300Combined sources4
Helixi317 – 325Combined sources9
Helixi342 – 348Combined sources7
Turni349 – 352Combined sources4
Beta strandi360 – 362Combined sources3
Turni366 – 370Combined sources5
Beta strandi379 – 381Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1R5SNMR-A255-382[»]
2N8TNMR-B276-289[»]
3CYYX-ray2.40C/D374-382[»]
DisProtiDP00278.
ProteinModelPortaliP08050.
SMRiP08050.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08050.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni244 – 382Interaction with NOV2 PublicationsAdd BLAST139
Regioni264 – 382Interaction with UBQLN4By similarityAdd BLAST119

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF97. Eukaryota.
ENOG4110JTW. LUCA.
GeneTreeiENSGT00840000129674.
HOGENOMiHOG000231127.
HOVERGENiHBG009576.
InParanoidiP08050.
KOiK07372.
OMAiGANVDMH.
OrthoDBiEOG091G0FKH.
PhylomeDBiP08050.
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.

P08050-1 [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 NQNAKKVAAG
360 370 380
HELQPLAIVD QRPSSRASSR ASSRPRPDDL EI
Length:382
Mass (Da):43,031
Last modified:January 23, 2007 - v2
Checksum:i0196416EA6A69490
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2G → A AA sequence (PubMed:2987225).Curated1
Sequence conflicti16A → T no nucleotide entry (PubMed:1852114).Curated1
Sequence conflicti28V → I AA sequence (PubMed:2987225).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06656 mRNA. Translation: CAA29855.1.
AY324140 mRNA. Translation: AAP88589.1.
BC081842 mRNA. Translation: AAH81842.1.
PIRiA24047.
S00532.
RefSeqiNP_036699.1. NM_012567.2.
UniGeneiRn.10346.

Genome annotation databases

EnsembliENSRNOT00000001054; ENSRNOP00000001054; ENSRNOG00000000805.
GeneIDi24392.
KEGGirno:24392.
UCSCiRGD:2690. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06656 mRNA. Translation: CAA29855.1.
AY324140 mRNA. Translation: AAP88589.1.
BC081842 mRNA. Translation: AAH81842.1.
PIRiA24047.
S00532.
RefSeqiNP_036699.1. NM_012567.2.
UniGeneiRn.10346.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1R5SNMR-A255-382[»]
2N8TNMR-B276-289[»]
3CYYX-ray2.40C/D374-382[»]
DisProtiDP00278.
ProteinModelPortaliP08050.
SMRiP08050.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246562. 116 interactors.
DIPiDIP-34793N.
IntActiP08050. 12 interactors.
MINTiMINT-1791096.
STRINGi10116.ENSRNOP00000001054.

Protein family/group databases

TCDBi1.A.24.1.1. the gap junction-forming connexin (connexin) family.

PTM databases

iPTMnetiP08050.
PhosphoSitePlusiP08050.

Proteomic databases

PaxDbiP08050.
PRIDEiP08050.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000001054; ENSRNOP00000001054; ENSRNOG00000000805.
GeneIDi24392.
KEGGirno:24392.
UCSCiRGD:2690. rat.

Organism-specific databases

CTDi2697.
RGDi2690. Gja1.

Phylogenomic databases

eggNOGiENOG410IF97. Eukaryota.
ENOG4110JTW. LUCA.
GeneTreeiENSGT00840000129674.
HOGENOMiHOG000231127.
HOVERGENiHBG009576.
InParanoidiP08050.
KOiK07372.
OMAiGANVDMH.
OrthoDBiEOG091G0FKH.
PhylomeDBiP08050.
TreeFamiTF329606.

Enzyme and pathway databases

ReactomeiR-RNO-190704. Oligomerization of connexins into connexons.
R-RNO-190827. Transport of connexins along the secretory pathway.
R-RNO-190840. Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
R-RNO-190861. Gap junction assembly.
R-RNO-190873. Gap junction degradation.
R-RNO-191647. c-src mediated regulation of Cx43 function and closure of gap junctions.
R-RNO-196025. Formation of annular gap junctions.
R-RNO-215126. Transport of connexins along the secretory pathway.

Miscellaneous databases

EvolutionaryTraceiP08050.
PROiP08050.

Gene expression databases

BgeeiENSRNOG00000000805.
GenevisibleiP08050. RN.

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_RAT
AccessioniPrimary (citable) accession number: P08050
Secondary accession number(s): Q53ZE1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 171 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.