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P36382 (CXA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gap junction alpha-5 protein
Alternative name(s):
Connexin-40
Short name=Cx40
Gene names
Name:GJA5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length358 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

One 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.

Subunit structure

A connexon is composed of a hexamer of connexins.

Subcellular location

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

Involvement in disease

Atrial standstill (ATST) [MIM:108770]: A rare arrhythmia characterized by the absence of electrical and mechanical activity in the atria. Electrocardiographically, it is characterized by bradycardia, the absence of P waves, and a junctional narrow complex escape rhythm.
Note: The disease may be caused by mutations affecting distinct genetic loci, including the gene represented in this entry. A rare GJA5 genotype has been detected in combination with a mutation in SCN5A in a large family with atrial standstill. Ref.8

Atrial fibrillation, familial, 11 (ATFB11) [MIM:614049]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Sequence similarities

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

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Gap junction
Membrane
   DiseaseAtrial fibrillation
Cardiomyopathy
Disease mutation
   DomainTransmembrane
Transmembrane helix
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processAV node cell to bundle of His cell communication by electrical coupling

Inferred from mutant phenotype PubMed 22247482. Source: BHF-UCL

SA node cell action potential

Inferred from electronic annotation. Source: Ensembl

angiogenesis

Inferred from expression pattern PubMed 11866539. Source: UniProtKB

artery morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

atrial cardiac muscle cell action potential

Inferred from mutant phenotype PubMed 23348765. Source: BHF-UCL

atrial septum development

Inferred from mutant phenotype PubMed 22199024. Source: BHF-UCL

atrial septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

atrial ventricular junction remodeling

Inferred from electronic annotation. Source: Ensembl

bundle of His cell to Purkinje myocyte communication

Inferred from mutant phenotype PubMed 22247482. Source: BHF-UCL

cardiac conduction system development

Inferred from electronic annotation. Source: Ensembl

cell communication by chemical coupling

Inferred from electronic annotation. Source: Ensembl

cell communication by electrical coupling involved in cardiac conduction

Inferred from direct assay Ref.8PubMed 23348765. Source: BHF-UCL

embryonic heart tube development

Inferred from electronic annotation. Source: Ensembl

embryonic limb morphogenesis

Inferred from electronic annotation. Source: Ensembl

endothelium development

Inferred from electronic annotation. Source: Ensembl

foramen ovale closure

Inferred from electronic annotation. Source: Ensembl

gap junction assembly

Inferred from direct assay PubMed 22247482. Source: BHF-UCL

mitral valve development

Inferred from mutant phenotype PubMed 22199024. Source: BHF-UCL

negative regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

negative regulation of glomerular filtration

Inferred from electronic annotation. Source: Ensembl

outflow tract morphogenesis

Inferred from mutant phenotype PubMed 22199024. Source: BHF-UCL

positive regulation of cell communication by chemical coupling

Inferred from electronic annotation. Source: Ensembl

positive regulation of vasoconstriction

Inferred from electronic annotation. Source: Ensembl

positive regulation of vasodilation

Inferred from electronic annotation. Source: Ensembl

potassium ion transport

Inferred from electronic annotation. Source: Ensembl

protein oligomerization

Inferred from electronic annotation. Source: Ensembl

pulmonary valve formation

Inferred from mutant phenotype PubMed 22199024. Source: BHF-UCL

regulation of atrial cardiac muscle cell membrane depolarization

Inferred from mutant phenotype PubMed 22247482PubMed 23348765. Source: BHF-UCL

regulation of cardiac muscle contraction

Inferred from mutant phenotype Ref.8PubMed 22247482PubMed 23348765. Source: BHF-UCL

regulation of heart rate by cardiac conduction

Inferred from electronic annotation. Source: Ensembl

regulation of membrane depolarization during cardiac muscle cell action potential

Inferred from electronic annotation. Source: Ensembl

regulation of renin secretion into blood stream

Inferred from electronic annotation. Source: Ensembl

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

septum primum development

Inferred from electronic annotation. Source: Ensembl

skeletal system development

Inferred from electronic annotation. Source: Ensembl

transmembrane transport

Inferred from direct assay PubMed 23348765. Source: GOC

vasomotion

Inferred from electronic annotation. Source: Ensembl

ventricular cardiac muscle cell action potential

Inferred from electronic annotation. Source: Ensembl

ventricular septum development

Inferred from mutant phenotype PubMed 22199024. Source: BHF-UCL

ventricular septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell projection

Inferred from electronic annotation. Source: Ensembl

connexon complex

Inferred from direct assay PubMed 22247482. Source: BHF-UCL

gap junction

Inferred from direct assay PubMed 23348765. Source: BHF-UCL

integral component of plasma membrane

Inferred from direct assay PubMed 22247482. Source: BHF-UCL

intercalated disc

Inferred from direct assay Ref.8. Source: BHF-UCL

   Molecular_functiongap junction channel activity involved in AV node cell-bundle of His cell electrical coupling

Inferred from direct assay PubMed 22247482. Source: BHF-UCL

gap junction channel activity involved in cardiac conduction electrical coupling

Inferred from direct assay PubMed 23348765. Source: BHF-UCL

gap junction hemi-channel activity

Inferred from direct assay PubMed 23348765. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 358358Gap junction alpha-5 protein
PRO_0000057819

Regions

Topological domain1 – 1919Cytoplasmic Potential
Transmembrane20 – 4021Helical; Potential
Topological domain41 – 7636Extracellular Potential
Transmembrane77 – 9721Helical; Potential
Topological domain98 – 16467Cytoplasmic Potential
Transmembrane165 – 18521Helical; Potential
Topological domain186 – 20520Extracellular Potential
Transmembrane206 – 22621Helical; Potential
Topological domain227 – 358132Cytoplasmic Potential

Natural variations

Natural variant851V → I in ATFB11. Ref.9
VAR_066249
Natural variant881P → S in ATST; somatic. Ref.8
VAR_035013
Natural variant961A → S in ATST. Ref.8
Corresponds to variant rs121434557 [ dbSNP | Ensembl ].
VAR_035014
Natural variant2211L → I in ATFB11. Ref.9
VAR_066250
Natural variant2291L → M in ATFB11. Ref.9
VAR_066251

Sequences

Sequence LengthMass (Da)Tools
P36382 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: DE9DD863C130229A

FASTA35840,380
        10         20         30         40         50         60 
MGDWSFLGNF LEEVHKHSTV VGKVWLTVLF IFRMLVLGTA AESSWGDEQA DFRCDTIQPG 

        70         80         90        100        110        120 
CQNVCYDQAF PISHIRYWVL QIIFVSTPSL VYMGHAMHTV RMQEKRKLRE AERAKEVRGS 

       130        140        150        160        170        180 
GSYEYPVAEK AELSCWEEGN GRIALQGTLL NTYVCSILIR TTMEVGFIVG QYFIYGIFLT 

       190        200        210        220        230        240 
TLHVCRRSPC PHPVNCYVSR PTEKNVFIVF MLAVAALSLL LSLAELYHLG WKKIRQRFVK 

       250        260        270        280        290        300 
PRQHMAKCQL SGPSVGIVQS CTPPPDFNQC LENGPGGKFF NPFSNNMASQ QNTDNLVTEQ 

       310        320        330        340        350 
VRGQEQTPGE GFIQVRYGQK PEVPNGVSPG HRLPHGYHSD KRRLSKASSK ARSDDLSV 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of two human cardiac gap junction proteins, connexin40 and connexin45."
Kanter H.L., Saffitz J.E., Beyer E.C.
J. Mol. Cell. Cardiol. 26:861-868(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]Beyer E.C., Christensen E.A.
Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Nucleotide sequence of protein-coding region of human connexin 40 gene."
Lin H.H., Jin N., Kiang D.T.
Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Sporadic cases of dilated cardiomyopathies associated with atrioventricular conduction defects are not linked to mutation within the connexins 40 and 43 genes."
Haefliger J.-A., Goy J.J., Waeber G.
Eur. Heart J. 20:1843-1843(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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: Placenta.
[8]"Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation."
Gollob M.H., Jones D.L., Krahn A.D., Danis L., Gong X.Q., Shao Q., Liu X., Veinot J.P., Tang A.S., Stewart A.F., Tesson F., Klein G.J., Yee R., Skanes A.C., Guiraudon G.M., Ebihara L., Bai D.
N. Engl. J. Med. 354:2677-2688(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ATST SER-88 AND SER-96.
[9]"Novel connexin40 missense mutations in patients with familial atrial fibrillation."
Yang Y.Q., Liu X., Zhang X.L., Wang X.H., Tan H.W., Shi H.F., Jiang W.F., Fang W.Y.
Europace 12:1421-1427(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ATFB11 ILE-85; ILE-221 AND MET-229.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U03486 Genomic DNA. Translation: AAA60457.2.
L34954 Genomic DNA. Translation: AAA91833.1.
AF151979 Genomic DNA. Translation: AAD37801.1.
BT019415 mRNA. Translation: AAV38222.1.
BT019416 mRNA. Translation: AAV38223.1.
AL365260 Genomic DNA. Translation: CAI14124.1.
AL365260 Genomic DNA. Translation: CAI14125.1.
BC013313 mRNA. Translation: AAH13313.1.
PIRI38429.
RefSeqNP_005257.2. NM_005266.6.
NP_859054.1. NM_181703.3.
XP_005273008.1. XM_005272951.2.
UniGeneHs.447968.

3D structure databases

ProteinModelPortalP36382.
SMRP36382. Positions 3-229, 252-358.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108969. 4 interactions.
IntActP36382. 3 interactions.
MINTMINT-1454178.
STRING9606.ENSP00000271348.

Chemistry

GuidetoPHARMACOLOGY726.

PTM databases

PhosphoSiteP36382.

Polymorphism databases

DMDM8928556.

Proteomic databases

PaxDbP36382.
PRIDEP36382.

Protocols and materials databases

DNASU2702.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000271348; ENSP00000271348; ENSG00000143140.
ENST00000369237; ENSP00000358240; ENSG00000143140.
ENST00000430508; ENSP00000407645; ENSG00000143140.
GeneID2702.
KEGGhsa:2702.
UCSCuc001eps.1. human.

Organism-specific databases

CTD2702.
GeneCardsGC01M147228.
HGNCHGNC:4279. GJA5.
HPACAB013080.
MIM108770. phenotype.
121013. gene.
614049. phenotype.
neXtProtNX_P36382.
Orphanet1344. Atrial stand still.
334. Familial atrial fibrillation.
3303. Tetralogy of Fallot.
PharmGKBPA28690.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG45265.
HOGENOMHOG000231127.
HOVERGENHBG009576.
InParanoidP36382.
KOK07614.
OMADWSFLGE.
OrthoDBEOG7P2XSS.
PhylomeDBP36382.
TreeFamTF329606.

Enzyme and pathway databases

ReactomeREACT_11123. Membrane Trafficking.

Gene expression databases

BgeeP36382.
CleanExHS_GJA5.
GenevestigatorP36382.

Family and domain databases

InterProIPR000500. Connexin.
IPR002264. Connexin40.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERPTHR11984. PTHR11984. 1 hit.
PTHR11984:SF13. PTHR11984:SF13. 1 hit.
PfamPF00029. Connexin. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]
PRINTSPR00206. CONNEXIN.
PR01135. CONNEXINA5.
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

GeneWikiGJA5.
GenomeRNAi2702.
NextBio10682.
PROP36382.
SOURCESearch...

Entry information

Entry nameCXA5_HUMAN
AccessionPrimary (citable) accession number: P36382
Secondary accession number(s): Q5T3B6, Q5U0N6
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 131 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM