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Protein

Gap junction alpha-5 protein

Gene

GJA5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. gap junction channel activity involved in AV node cell-bundle of His cell electrical coupling Source: BHF-UCL
  2. gap junction channel activity involved in cardiac conduction electrical coupling Source: BHF-UCL
  3. gap junction hemi-channel activity Source: BHF-UCL

GO - Biological processi

  1. angiogenesis Source: UniProtKB
  2. artery morphogenesis Source: BHF-UCL
  3. atrial septum development Source: BHF-UCL
  4. atrial septum morphogenesis Source: Ensembl
  5. atrial ventricular junction remodeling Source: Ensembl
  6. AV node cell to bundle of His cell communication by electrical coupling Source: BHF-UCL
  7. bundle of His cell to Purkinje myocyte communication by electrical coupling Source: BHF-UCL
  8. cardiac conduction system development Source: Ensembl
  9. cell communication by chemical coupling Source: Ensembl
  10. cell communication by electrical coupling involved in cardiac conduction Source: BHF-UCL
  11. embryonic heart tube development Source: Ensembl
  12. embryonic limb morphogenesis Source: Ensembl
  13. endothelium development Source: Ensembl
  14. foramen ovale closure Source: Ensembl
  15. gap junction assembly Source: BHF-UCL
  16. mitral valve development Source: BHF-UCL
  17. negative regulation of blood pressure Source: Ensembl
  18. negative regulation of glomerular filtration Source: Ensembl
  19. outflow tract morphogenesis Source: BHF-UCL
  20. positive regulation of cell communication by chemical coupling Source: Ensembl
  21. positive regulation of vasoconstriction Source: Ensembl
  22. positive regulation of vasodilation Source: Ensembl
  23. potassium ion transport Source: Ensembl
  24. protein oligomerization Source: Ensembl
  25. pulmonary valve formation Source: BHF-UCL
  26. regulation of atrial cardiac muscle cell action potential Source: BHF-UCL
  27. regulation of atrial cardiac muscle cell membrane depolarization Source: BHF-UCL
  28. regulation of AV node cell action potential Source: BHF-UCL
  29. regulation of bundle of His cell action potential Source: BHF-UCL
  30. regulation of cardiac muscle contraction Source: BHF-UCL
  31. regulation of heart rate by cardiac conduction Source: Ensembl
  32. regulation of membrane depolarization during cardiac muscle cell action potential Source: Ensembl
  33. regulation of Purkinje myocyte action potential Source: BHF-UCL
  34. regulation of renin secretion into blood stream Source: Ensembl
  35. regulation of ventricular cardiac muscle cell membrane depolarization Source: Ensembl
  36. regulation of ventricular cardiac muscle cell membrane repolarization Source: Ensembl
  37. SA node cell action potential Source: Ensembl
  38. septum primum development Source: Ensembl
  39. skeletal system development Source: Ensembl
  40. vasomotion Source: Ensembl
  41. ventricular cardiac muscle cell action potential Source: Ensembl
  42. ventricular septum development Source: BHF-UCL
  43. ventricular septum morphogenesis Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_9509. Gap junction assembly.

Names & Taxonomyi

Protein namesi
Recommended name:
Gap junction alpha-5 protein
Alternative name(s):
Connexin-40
Short name:
Cx40
Gene namesi
Name:GJA5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:4279. GJA5.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1919CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei20 – 4021HelicalSequence AnalysisAdd
BLAST
Topological domaini41 – 7636ExtracellularSequence AnalysisAdd
BLAST
Transmembranei77 – 9721HelicalSequence AnalysisAdd
BLAST
Topological domaini98 – 16467CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei165 – 18521HelicalSequence AnalysisAdd
BLAST
Topological domaini186 – 20520ExtracellularSequence AnalysisAdd
BLAST
Transmembranei206 – 22621HelicalSequence AnalysisAdd
BLAST
Topological domaini227 – 358132CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell projection Source: Ensembl
  2. connexon complex Source: BHF-UCL
  3. gap junction Source: BHF-UCL
  4. integral component of plasma membrane Source: BHF-UCL
  5. intercalated disc Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Gap junction, Membrane

Pathology & Biotechi

Involvement in diseasei

Atrial standstill 1 (ATRST1)1 Publication

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.

Disease descriptionA 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.

See also OMIM:108770
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti88 – 881P → S in ATRST1; somatic. 1 Publication
VAR_035013
Natural varianti96 – 961A → S in ATRST1. 1 Publication
Corresponds to variant rs121434557 [ dbSNP | Ensembl ].
VAR_035014
Atrial fibrillation, familial, 11 (ATFB11)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:614049
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti85 – 851V → I in ATFB11. 1 Publication
VAR_066249
Natural varianti221 – 2211L → I in ATFB11. 1 Publication
VAR_066250
Natural varianti229 – 2291L → M in ATFB11. 1 Publication
VAR_066251

Keywords - Diseasei

Atrial fibrillation, Cardiomyopathy, Disease mutation

Organism-specific databases

MIMi108770. phenotype.
614049. phenotype.
Orphaneti334. Familial atrial fibrillation.
3303. Tetralogy of Fallot.
PharmGKBiPA28690.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 358358Gap junction alpha-5 proteinPRO_0000057819Add
BLAST

Proteomic databases

PaxDbiP36382.
PRIDEiP36382.

PTM databases

PhosphoSiteiP36382.

Expressioni

Gene expression databases

BgeeiP36382.
CleanExiHS_GJA5.
ExpressionAtlasiP36382. baseline and differential.
GenevestigatoriP36382.

Organism-specific databases

HPAiCAB013080.

Interactioni

Subunit structurei

A connexon is composed of a hexamer of connexins.

Protein-protein interaction databases

BioGridi108969. 4 interactions.
IntActiP36382. 3 interactions.
MINTiMINT-1454178.
STRINGi9606.ENSP00000271348.

Structurei

3D structure databases

ProteinModelPortaliP36382.
SMRiP36382. Positions 3-229, 252-358.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG45265.
HOGENOMiHOG000231127.
HOVERGENiHBG009576.
InParanoidiP36382.
KOiK07614.
OMAiHKHSTVI.
OrthoDBiEOG7P2XSS.
PhylomeDBiP36382.
TreeFamiTF329606.

Family and domain databases

InterProiIPR000500. Connexin.
IPR002264. Connexin40.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERiPTHR11984. PTHR11984. 1 hit.
PTHR11984:SF13. PTHR11984:SF13. 1 hit.
PfamiPF00029. Connexin. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]
PRINTSiPR00206. CONNEXIN.
PR01135. CONNEXINA5.
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.

P36382-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGDWSFLGNF LEEVHKHSTV VGKVWLTVLF IFRMLVLGTA AESSWGDEQA
60 70 80 90 100
DFRCDTIQPG CQNVCYDQAF PISHIRYWVL QIIFVSTPSL VYMGHAMHTV
110 120 130 140 150
RMQEKRKLRE AERAKEVRGS GSYEYPVAEK AELSCWEEGN GRIALQGTLL
160 170 180 190 200
NTYVCSILIR TTMEVGFIVG QYFIYGIFLT TLHVCRRSPC PHPVNCYVSR
210 220 230 240 250
PTEKNVFIVF MLAVAALSLL LSLAELYHLG WKKIRQRFVK PRQHMAKCQL
260 270 280 290 300
SGPSVGIVQS CTPPPDFNQC LENGPGGKFF NPFSNNMASQ QNTDNLVTEQ
310 320 330 340 350
VRGQEQTPGE GFIQVRYGQK PEVPNGVSPG HRLPHGYHSD KRRLSKASSK

ARSDDLSV
Length:358
Mass (Da):40,380
Last modified:January 23, 2007 - v3
Checksum:iDE9DD863C130229A
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti85 – 851V → I in ATFB11. 1 Publication
VAR_066249
Natural varianti88 – 881P → S in ATRST1; somatic. 1 Publication
VAR_035013
Natural varianti96 – 961A → S in ATRST1. 1 Publication
Corresponds to variant rs121434557 [ dbSNP | Ensembl ].
VAR_035014
Natural varianti221 – 2211L → I in ATFB11. 1 Publication
VAR_066250
Natural varianti229 – 2291L → M in ATFB11. 1 Publication
VAR_066251

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS929.1.
PIRiI38429.
RefSeqiNP_005257.2. NM_005266.6.
NP_859054.1. NM_181703.3.
XP_005273008.1. XM_005272951.2.
UniGeneiHs.447968.

Genome annotation databases

EnsembliENST00000579774; ENSP00000463851; ENSG00000265107.
ENST00000621517; ENSP00000484552; ENSG00000265107.
GeneIDi2702.
KEGGihsa:2702.
UCSCiuc001eps.1. human.

Polymorphism databases

DMDMi8928556.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS929.1.
PIRiI38429.
RefSeqiNP_005257.2. NM_005266.6.
NP_859054.1. NM_181703.3.
XP_005273008.1. XM_005272951.2.
UniGeneiHs.447968.

3D structure databases

ProteinModelPortaliP36382.
SMRiP36382. Positions 3-229, 252-358.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108969. 4 interactions.
IntActiP36382. 3 interactions.
MINTiMINT-1454178.
STRINGi9606.ENSP00000271348.

Chemistry

GuidetoPHARMACOLOGYi726.

PTM databases

PhosphoSiteiP36382.

Polymorphism databases

DMDMi8928556.

Proteomic databases

PaxDbiP36382.
PRIDEiP36382.

Protocols and materials databases

DNASUi2702.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000579774; ENSP00000463851; ENSG00000265107.
ENST00000621517; ENSP00000484552; ENSG00000265107.
GeneIDi2702.
KEGGihsa:2702.
UCSCiuc001eps.1. human.

Organism-specific databases

CTDi2702.
GeneCardsiGC01M147228.
HGNCiHGNC:4279. GJA5.
HPAiCAB013080.
MIMi108770. phenotype.
121013. gene.
614049. phenotype.
neXtProtiNX_P36382.
Orphaneti334. Familial atrial fibrillation.
3303. Tetralogy of Fallot.
PharmGKBiPA28690.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG45265.
HOGENOMiHOG000231127.
HOVERGENiHBG009576.
InParanoidiP36382.
KOiK07614.
OMAiHKHSTVI.
OrthoDBiEOG7P2XSS.
PhylomeDBiP36382.
TreeFamiTF329606.

Enzyme and pathway databases

ReactomeiREACT_9509. Gap junction assembly.

Miscellaneous databases

ChiTaRSiGJA5. human.
GeneWikiiGJA5.
GenomeRNAii2702.
NextBioi10682.
PROiP36382.
SOURCEiSearch...

Gene expression databases

BgeeiP36382.
CleanExiHS_GJA5.
ExpressionAtlasiP36382. baseline and differential.
GenevestigatoriP36382.

Family and domain databases

InterProiIPR000500. Connexin.
IPR002264. Connexin40.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERiPTHR11984. PTHR11984. 1 hit.
PTHR11984:SF13. PTHR11984:SF13. 1 hit.
PfamiPF00029. Connexin. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]
PRINTSiPR00206. CONNEXIN.
PR01135. CONNEXINA5.
SMARTiSM00037. CNX. 1 hit.
SM01089. Connexin_CCC. 1 hit.
[Graphical view]
PROSITEiPS00407. CONNEXINS_1. 1 hit.
PS00408. CONNEXINS_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. Beyer E.C., Christensen E.A.
    Submitted (SEP-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 (FEB-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(1998) [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 (SEP-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.
    , 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(2005) [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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Placenta.
  8. Cited for: VARIANTS ATRST1 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(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS ATFB11 ILE-85; ILE-221 AND MET-229.

Entry informationi

Entry nameiCXA5_HUMAN
AccessioniPrimary (citable) accession number: P36382
Secondary accession number(s): Q5T3B6, Q5U0N6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: January 23, 2007
Last modified: April 1, 2015
This is version 142 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.