P36382 (CXA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gap junction alpha-5 protein

Alternative name(s):
Connexin-40
Short name=Cx40

Gene names

Name:

GJA5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	358 AA.
Sequence status	Complete.
Protein existence	Evidence 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 junction › gap junction.
Involvement in disease	Familial atrial standstill (FAS) [MIM:108770]: Atrial standstill is an extremely 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 Familial atrial fibrillation 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 component	Cell junction Cell membrane Gap junction Membrane
Disease	Atrial fibrillation Disease mutation
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from expression pattern PubMed 11866539. Source: UniProtKB artery morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL atrial septum development Inferred from mutant phenotype PubMed 22199024. Source: BHF-UCL atrial septum morphogenesis Inferred from electronic annotation. Source: Compara atrial ventricular junction remodeling Inferred from electronic annotation. Source: Compara 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: Compara embryonic heart tube development Inferred from electronic annotation. Source: Compara embryonic limb morphogenesis Inferred from electronic annotation. Source: Compara foramen ovale closure Inferred from electronic annotation. Source: Compara gap junction assembly Inferred from direct assay PubMed 22247482. Source: BHF-UCL mitral valve development Inferred from mutant phenotype PubMed 22199024. Source: BHF-UCL outflow tract morphogenesis Inferred from mutant phenotype PubMed 22199024. Source: BHF-UCL pulmonary valve formation Inferred from mutant phenotype PubMed 22199024. Source: BHF-UCL regulation of SA node cell action potential Inferred from electronic annotation. Source: Compara regulation of atrial cardiac muscle cell action potential Inferred from mutant phenotype PubMed 23348765. Source: BHF-UCL regulation of atrial cardiac muscle cell membrane depolarization Inferred from mutant phenotype PubMed 22247482PubMed 23348765. Source: BHF-UCL regulation of heart rate by cardiac conduction Inferred from electronic annotation. Source: Compara regulation of membrane depolarization involved in regulation of cardiac muscle cell action potential Inferred from electronic annotation. Source: Compara regulation of renin secretion into blood stream Inferred from electronic annotation. Source: Compara regulation of vasodilation Inferred from electronic annotation. Source: Compara regulation of ventricular cardiac muscle cell action potential Inferred from electronic annotation. Source: Compara regulation of ventricular cardiac muscle cell membrane depolarization Inferred from electronic annotation. Source: Compara regulation of ventricular cardiac muscle cell membrane repolarization Inferred from electronic annotation. Source: Compara renal system process involved in regulation of systemic arterial blood pressure Inferred from electronic annotation. Source: Compara septum primum development Inferred from electronic annotation. Source: Compara skeletal system development Inferred from electronic annotation. Source: Compara ventricular septum development Inferred from mutant phenotype PubMed 22199024. Source: BHF-UCL ventricular septum morphogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	connexon complex Inferred from direct assay PubMed 22247482. Source: BHF-UCL integral to plasma membrane Inferred from direct assay PubMed 22247482. Source: BHF-UCL intercalated disc Inferred from direct assay Ref.8. Source: BHF-UCL
Molecular_function	gap 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 hemi-channel activity Inferred from direct assay PubMed 23348765. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 358	358	Gap junction alpha-5 protein		PRO_0000057819
Regions
	Topological domain	1 – 19	19	Cytoplasmic Potential
	Transmembrane	20 – 40	21	Helical; Potential
	Topological domain	41 – 76	36	Extracellular Potential
	Transmembrane	77 – 97	21	Helical; Potential
	Topological domain	98 – 164	67	Cytoplasmic Potential
	Transmembrane	165 – 185	21	Helical; Potential
	Topological domain	186 – 205	20	Extracellular Potential
	Transmembrane	206 – 226	21	Helical; Potential
	Topological domain	227 – 358	132	Cytoplasmic Potential
Natural variations
	Natural variant	85	1	V → I in ATFB11. Ref.9		VAR_066249
	Natural variant	88	1	P → S in FAS; somatic. Ref.8		VAR_035013
	Natural variant	96	1	A → S in FAS. Ref.8		VAR_035014
	Natural variant	221	1	L → I in ATFB11. Ref.9		VAR_066250
	Natural variant	229	1	L → M in ATFB11. Ref.9		VAR_066251

Sequences

	Sequence		Length	Mass (Da)
	P36382 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: DE9DD863C130229A	FASTA	358	40,380
	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

References

	« Hide 'large scale' referencesShow '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. , 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 FAS 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

GeneReviews

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.
IPI	IPI00217262.
PIR	I38429.
RefSeq	NP_005257.2. NM_005266.5. NP_859054.1. NM_181703.2. XP_003960235.1. XM_003960186.1. XP_003960236.1. XM_003960187.1.
UniGene	Hs.447968.
3D structure databases
ProteinModelPortal	P36382.
ModBase	Search...
Protein-protein interaction databases
IntAct	P36382. 3 interactions.
MINT	MINT-1454178.
STRING	9606.ENSP00000271348.
PTM databases
PhosphoSite	P36382.
Polymorphism databases
DMDM	8928556.
Proteomic databases
PaxDb	P36382.
PRIDE	P36382.
Protocols and materials databases
DNASU	2702.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000271348; ENSP00000271348; ENSG00000143140. ENST00000369237; ENSP00000358240; ENSG00000143140. ENST00000430508; ENSP00000407645; ENSG00000143140.
GeneID	101060613. 2702.
KEGG	hsa:101060613. hsa:2702.
UCSC	uc001eps.1. human.
Organism-specific databases
CTD	2702.
GeneCards	GC01M147228.
HGNC	HGNC:4279. GJA5.
HPA	CAB013080.
MIM	108770. phenotype. 121013. gene. 614049. phenotype.
neXtProt	NX_P36382.
Orphanet	1344. Atrial cardiomyopathy with heart block. 334. Familial atrial fibrillation.
PharmGKB	PA28690.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG45265.
HOGENOM	HOG000231127.
HOVERGEN	HBG009576.
InParanoid	P36382.
KO	K07614.
OMA	DWSFLGE.
OrthoDB	EOG4MSCZF.
PhylomeDB	P36382.
Enzyme and pathway databases
Reactome	REACT_11123. Membrane Trafficking.
Gene expression databases
Bgee	P36382.
CleanEx	HS_GJA5.
Genevestigator	P36382.
GermOnline	ENSG00000143140. Homo sapiens.
Family and domain databases
InterPro	IPR000500. Connexin. IPR002264. Connexin40. IPR019570. Connexin_CCC. IPR017990. Connexin_CS. IPR013092. Connexin_N. [Graphical view]
PANTHER	PTHR11984. PTHR11984. 1 hit. PTHR11984:SF13. PTHR11984:SF13. 1 hit.
Pfam	PF00029. Connexin. 1 hit. PF10582. Connexin_CCC. 1 hit. [Graphical view]
PRINTS	PR00206. CONNEXIN. PR01135. CONNEXINA5.
SMART	SM00037. CNX. 1 hit. SM01089. Connexin_CCC. 1 hit. [Graphical view]
PROSITE	PS00407. CONNEXINS_1. 1 hit. PS00408. CONNEXINS_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	10682.
SOURCE	Search...

Entry information

Entry name

CXA5_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 120 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.