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P08050 (CXA1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gap junction alpha-1 protein
Alternative name(s):
Connexin-43
Short name=Cx43
Gap junction 43 kDa heart protein
Gene names
Name:Gja1
Synonyms:Cxn-43
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length382 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

A connexon is composed of a hexamer of connexins. Interacts with SGSM3. Interacts with KIAA1432/CIP150. Interacts with CNST and CSNK1D By similarity. Interacts (via C-terminus) with TJP1. Interacts (via C-terminus) with SRC (via SH3 domain). Interacts with UBQLN4. Ref.10 Ref.12 Ref.13

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctiongap junction Ref.13.

Induction

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). Ref.11

Post-translational modification

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. Ref.9

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.

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.

Sequence similarities

Belongs to the connexin family. Alpha-type (group II) subfamily.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Gap junction
Membrane
   DomainTransmembrane
Transmembrane helix
   PTMDisulfide bond
Isopeptide bond
Phosphoprotein
S-nitrosylation
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processATP transport

Inferred from mutant phenotype PubMed 16731531. Source: RGD

adult heart development

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Inferred from mutant phenotype PubMed 17107662. Source: RGD

atrial ventricular junction remodeling

Inferred from electronic annotation. Source: Ensembl

blood vessel morphogenesis

Inferred from electronic annotation. Source: Ensembl

cardiac conduction

Inferred from electronic annotation. Source: Ensembl

cell communication

Inferred from mutant phenotype PubMed 15685554. Source: RGD

cell communication by chemical coupling

Inferred from electronic annotation. Source: Ensembl

cell communication by electrical coupling

Inferred from electronic annotation. Source: Ensembl

cell-cell signaling

Inferred from direct assay PubMed 15048573. Source: RGD

cellular response to mechanical stimulus

Inferred from expression pattern PubMed 10631100. Source: RGD

chronic inflammatory response

Inferred from mutant phenotype PubMed 23165424. Source: RGD

embryonic digit morphogenesis

Inferred from electronic annotation. Source: Ensembl

endothelium development

Inferred from expression pattern PubMed 10990491. Source: RGD

epithelial cell maturation

Inferred from electronic annotation. Source: Ensembl

gap junction assembly

Traceable author statement PubMed 15709751. Source: UniProtKB

heart development

Inferred from expression pattern PubMed 8944820. Source: RGD

heart looping

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

lens development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

milk ejection

Inferred from electronic annotation. Source: Ensembl

negative regulation of cardiac muscle cell proliferation

Inferred from mutant phenotype PubMed 19377854. Source: RGD

negative regulation of cell proliferation

Inferred from direct assay PubMed 12952975. Source: RGD

negative regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

neuron migration

Inferred from electronic annotation. Source: Ensembl

neuron projection morphogenesis

Inferred from mutant phenotype PubMed 16731531. Source: RGD

osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of behavioral fear response

Inferred from mutant phenotype PubMed 22665389. Source: RGD

positive regulation of cell communication by chemical coupling

Inferred from mutant phenotype PubMed 15678088. Source: RGD

positive regulation of cytosolic calcium ion concentration

Inferred from mutant phenotype PubMed 22577485. Source: RGD

positive regulation of gene expression

Inferred from electronic annotation. Source: Ensembl

positive regulation of glomerular filtration

Inferred from mutant phenotype PubMed 18046320. Source: RGD

positive regulation of protein catabolic process

Inferred from direct assay PubMed 12952975. Source: RGD

positive regulation of striated muscle tissue development

Inferred from electronic annotation. Source: Ensembl

positive regulation of vasoconstriction

Inferred from mutant phenotype PubMed 21414209. Source: RGD

positive regulation of vasodilation

Inferred from mutant phenotype PubMed 15301736. Source: RGD

protein oligomerization

Inferred from direct assay PubMed 11557558PubMed 15817491. Source: RGD

regulation of atrial cardiac muscle cell membrane depolarization

Inferred from electronic annotation. Source: Ensembl

regulation of bone mineralization

Inferred from electronic annotation. Source: Ensembl

regulation of bone remodeling

Inferred from electronic annotation. Source: Ensembl

regulation of calcium ion transport

Inferred from mutant phenotype PubMed 16878174. Source: RGD

regulation of tight junction assembly

Inferred from mutant phenotype PubMed 19509333. Source: RGD

regulation of ventricular cardiac muscle cell membrane depolarization

Inferred from electronic annotation. Source: Ensembl

regulation of ventricular cardiac muscle cell membrane repolarization

Inferred from electronic annotation. Source: Ensembl

response to fluid shear stress

Inferred from expression pattern PubMed 15558296. Source: RGD

response to glucose

Inferred from expression pattern PubMed 21567444. Source: RGD

response to pH

Inferred from direct assay PubMed 14699011. Source: RGD

response to peptide hormone

Inferred from expression pattern PubMed 12700188. Source: RGD

skeletal muscle tissue regeneration

Inferred from electronic annotation. Source: Ensembl

transmembrane transport

Inferred from direct assay PubMed 15048573PubMed 16731531. Source: GOC

vascular transport

Inferred from mutant phenotype PubMed 16878174. Source: RGD

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 18162583. Source: BHF-UCL

Golgi membrane

Traceable author statement. Source: Reactome

Golgi-associated vesicle membrane

Traceable author statement. Source: Reactome

apical plasma membrane

Inferred from electronic annotation. Source: Ensembl

connexon complex

Inferred from direct assay PubMed 15048573PubMed 16731531PubMed 9851942. Source: RGD

contractile fiber

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 16731531. Source: RGD

cytosol

Inferred from electronic annotation. Source: Ensembl

early endosome

Inferred from direct assay PubMed 16162097. Source: RGD

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

endosome

Inferred from direct assay PubMed 19808888. Source: RGD

fascia adherens

Inferred from direct assay PubMed 16515795PubMed 9851942. Source: RGD

gap junction

Inferred from direct assay PubMed 15709751. Source: UniProtKB

integral component of plasma membrane

Traceable author statement PubMed 15709751. Source: UniProtKB

intermediate filament

Inferred from electronic annotation. Source: Ensembl

late endosome

Inferred from direct assay PubMed 16162097. Source: RGD

lateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

lysosome

Inferred from direct assay PubMed 16162097. Source: RGD

membrane

Inferred from direct assay PubMed 19723622. Source: MGI

membrane raft

Inferred from direct assay PubMed 18162583. Source: BHF-UCL

mitochondrial outer membrane

Inferred from direct assay PubMed 17107662. Source: RGD

multivesicular body

Inferred from direct assay PubMed 16162097. Source: RGD

plasma membrane

Inferred from direct assay PubMed 18162583. Source: BHF-UCL

   Molecular_functionPDZ domain binding

Inferred from physical interaction PubMed 15980428. Source: RGD

SH3 domain binding

Inferred from physical interaction PubMed 14699011. Source: RGD

connexin binding

Inferred from physical interaction PubMed 11557558. Source: RGD

gap junction channel activity

Inferred from direct assay PubMed 15048573PubMed 16731531. Source: RGD

protein binding

Inferred from physical interaction PubMed 15709751. Source: IntAct

protein domain specific binding

Inferred from direct assay PubMed 17008717. Source: RGD

signal transducer activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sgsm3Q8VCZ64EBI-476947,EBI-525155From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5 Ref.6
Chain2 – 382381Gap junction alpha-1 protein
PRO_0000057804

Regions

Topological domain2 – 1312Cytoplasmic Probable
Transmembrane14 – 3623Helical; Probable
Topological domain37 – 7640Extracellular Probable
Transmembrane77 – 9923Helical; Probable
Topological domain100 – 15455Cytoplasmic Probable
Transmembrane155 – 17723Helical; Probable
Topological domain178 – 20831Extracellular Probable
Transmembrane209 – 23123Helical; Probable
Topological domain232 – 382151Cytoplasmic Probable

Amino acid modifications

Modified residue2471Phosphotyrosine By similarity
Modified residue2551Phosphoserine By similarity
Modified residue2621Phosphoserine By similarity
Modified residue2711S-nitrosocysteine By similarity
Modified residue3061Phosphoserine By similarity
Modified residue3141Phosphoserine By similarity
Modified residue3251Phosphoserine; by CK1 By similarity
Modified residue3281Phosphoserine; by CK1 By similarity
Modified residue3301Phosphoserine; by CK1 By similarity
Modified residue3651Phosphoserine Ref.9
Modified residue3681Phosphoserine; by PKC/PRKCG Probable
Modified residue3691Phosphoserine Ref.9
Modified residue3731Phosphoserine Ref.9
Disulfide bond54 ↔ 192 By similarity
Disulfide bond187 ↔ 198 By similarity
Cross-link144Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link237Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Experimental info

Sequence conflict21G → A AA sequence Ref.5
Sequence conflict161A → T no nucleotide entry Ref.2
Sequence conflict281V → I AA sequence Ref.5

Secondary structure

.................. 382
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08050 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 0196416EA6A69490

FASTA38243,031
        10         20         30         40         50         60 
MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS AFRCNTQQPG 

        70         80         90        100        110        120 
CENVCYDKSF PISHVRFWVL QIIFVSVPTL LYLAHVFYVM RKEEKLNKKE EELKVAQTDG 

       130        140        150        160        170        180 
VNVEMHLKQI EIKKFKYGIE EHGKVKMRGG LLRTYIISIL FKSVFEVAFL LIQWYIYGFS 

       190        200        210        220        230        240 
LSAVYTCKRD PCPHQVDCFL SRPTEKTIFI IFMLVVSLVS LALNIIELFY VFFKGVKDRV 

       250        260        270        280        290        300 
KGRSDPYHAT TGPLSPSKDC GSPKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN 

       310        320        330        340        350        360 
YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNAKKVAAG HELQPLAIVD 

       370        380 
QRPSSRASSR ASSRPRPDDL EI 

« Hide

References

« Hide 'large scale' references
[1]"Connexin43: a protein from rat heart homologous to a gap junction protein from liver."
Beyer E.C., Paul D.L., Goodenough D.A.
J. Cell Biol. 105:2621-2629(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Molecular cloning of a rat uterine gap junction protein and analysis of gene expression during gestation."
Lang L.M., Beyer E.C., Schwartz A.L., Gitlin J.D.
Am. J. Physiol. 260:E787-E793(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Uterus.
[3]Ma L.X., Peng Y.W.
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Heart.
[5]"The Mr 28,000 gap junction proteins from rat heart and liver are different but related."
Nicholson B.J., Gros D.B., Kent S.B.H., Hood L.E., Revel J.-P.
J. Biol. Chem. 260:6514-6517(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-33.
Tissue: Heart.
[6]"Affinity purification of a rat-brain junctional protein, connexin 43."
Dupont E., el Aoumari A., Fromaget C., Briand J.-C., Gros D.
Eur. J. Biochem. 200:263-270(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-16.
Tissue: Brain.
[7]"Connexon integrity is maintained by non-covalent bonds: intramolecular disulfide bonds link the extracellular domains in rat connexin-43."
John S.A., Revel J.-P.
Biochem. Biophys. Res. Commun. 178:1312-1318(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS.
[8]"Membrane topology and quaternary structure of cardiac gap junction ion channels."
Yeager M., Gilula N.B.
J. Mol. Biol. 223:929-948(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY.
[9]"Identification and functional analysis of novel phosphorylation sites in Cx43 in rat primary granulosa cells."
Yogo K., Ogawa T., Akiyama M., Ishida N., Takeya T.
FEBS Lett. 531:132-136(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-365; SER-368; SER-369 AND SER-373.
[10]"NMR structure note: UBA domain of CIP75."
Kieken F., Spagnol G., Su V., Lau A.F., Sorgen P.L.
J. Biomol. NMR 46:245-250(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBQLN4.
[11]"Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm."
Negoro H., Kanematsu A., Doi M., Suadicani S.O., Matsuo M., Imamura M., Okinami T., Nishikawa N., Oura T., Matsui S., Seo K., Tainaka M., Urabe S., Kiyokage E., Todo T., Okamura H., Tabata Y., Ogawa O.
Nat. Commun. 3:809-809(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[12]"Structural changes in the carboxyl terminus of the gap junction protein connexin43 indicates signaling between binding domains for c-Src and zonula occludens-1."
Sorgen P.L., Duffy H.S., Sahoo P., Coombs W., Delmar M., Spray D.C.
J. Biol. Chem. 279:54695-54701(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 255-381, INTERACTION WITH TJP1 AND SRC.
[13]"Domain-swapped dimerization of ZO-1 PDZ2 generates specific and regulatory connexin43-binding sites."
Chen J., Pan L., Wei Z., Zhao Y., Zhang M.
EMBO J. 27:2113-2123(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 374-382 IN COMPLEX WITH TJP1, SUBCELLULAR LOCATION, INTERACTION WITH TJP1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X06656 mRNA. Translation: CAA29855.1.
AY324140 mRNA. Translation: AAP88589.1.
BC081842 mRNA. Translation: AAH81842.1.
PIRA24047.
S00532.
RefSeqNP_036699.1. NM_012567.2.
XP_006256564.1. XM_006256502.1.
XP_006256565.1. XM_006256503.1.
UniGeneRn.10346.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1R5SNMR-A255-382[»]
3CYYX-ray2.40C/D374-382[»]
DisProtDP00278.
ProteinModelPortalP08050.
SMRP08050. Positions 252-382.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid246562. 116 interactions.
DIPDIP-34793N.
IntActP08050. 8 interactions.
MINTMINT-1791096.

Protein family/group databases

TCDB1.A.24.1.1. the gap junction-forming connexin (connexin) family.

PTM databases

PhosphoSiteP08050.

Proteomic databases

PaxDbP08050.
PRIDEP08050.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000001054; ENSRNOP00000001054; ENSRNOG00000000805.
GeneID24392.
KEGGrno:24392.
UCSCRGD:2690. rat.

Organism-specific databases

CTD2697.
RGD2690. Gja1.

Phylogenomic databases

eggNOGNOG45368.
GeneTreeENSGT00740000115305.
HOGENOMHOG000231127.
HOVERGENHBG009576.
InParanoidP08050.
KOK07372.
OMAGANVDMH.
OrthoDBEOG7P2XSS.
PhylomeDBP08050.
TreeFamTF329606.

Enzyme and pathway databases

ReactomeREACT_12587. Transport of connexins along the secretory pathway.

Gene expression databases

ArrayExpressP08050.
GenevestigatorP08050.

Family and domain databases

InterProIPR000500. Connexin.
IPR002261. Connexin43.
IPR013124. Connexin43_C.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERPTHR11984. PTHR11984. 1 hit.
PfamPF00029. Connexin. 1 hit.
PF03508. Connexin43. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]
PRINTSPR00206. CONNEXIN.
PR01132. CONNEXINA1.
SMARTSM00037. CNX. 1 hit.
SM01089. Connexin_CCC. 1 hit.
[Graphical view]
PROSITEPS00407. CONNEXINS_1. 1 hit.
PS00408. CONNEXINS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP08050.
NextBio603181.
PROP08050.

Entry information

Entry nameCXA1_RAT
AccessionPrimary (citable) accession number: P08050
Secondary accession number(s): Q53ZE1
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: June 11, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references