P35212 (CXA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gap junction alpha-4 protein

Alternative name(s):
Connexin-37
Short name=Cx37

Gene names

Name:

GJA4

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	333 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.
Tissue specificity	Expressed in multiple organs and tissues, including heart, uterus, ovary, and blood vessel endothelium.
Sequence similarities	Belongs to the connexin family. Alpha-type (group II) subfamily.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Gap junction Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood vessel development Inferred from electronic annotation. Source: Compara calcium ion transport Inferred from electronic annotation. Source: Compara cell-cell junction assembly Traceable author statement Ref.1. Source: ProtInc cell-cell signaling Inferred from electronic annotation. Source: Compara response to pain Inferred from electronic annotation. Source: Compara transport Traceable author statement Ref.1. Source: ProtInc
Cellular_component	connexon complex Inferred from electronic annotation. Source: Compara gap junction Traceable author statement Ref.1. Source: ProtInc integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 333	333	Gap junction alpha-4 protein		PRO_0000057814
Regions
	Topological domain	1 – 20	20	Cytoplasmic Potential
	Transmembrane	21 – 40	20	Helical; Potential
	Topological domain	41 – 76	36	Extracellular Potential
	Transmembrane	77 – 99	23	Helical; Potential
	Topological domain	100 – 148	49	Cytoplasmic Potential
	Transmembrane	149 – 165	17	Helical; Potential
	Topological domain	166 – 207	42	Extracellular Potential
	Transmembrane	208 – 230	23	Helical; Potential
	Topological domain	231 – 333	103	Cytoplasmic Potential
Natural variations
	Natural variant	71	1	P → S. Ref.3		VAR_009159
	Natural variant	128	1	A → V. Ref.3		VAR_009160
	Natural variant	130	1	V → I. Ref.3 Ref.4 Ref.10 Corresponds to variant rs41266431 [ dbSNP | Ensembl ].		VAR_009161
	Natural variant	319	1	P → S in allele CX37*2. Ref.3 Ref.4 Ref.11 Ref.12 Corresponds to variant rs1764391 [ dbSNP | Ensembl ].		VAR_009162

Sequences

	Sequence		Length	Mass (Da)
	P35212 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 93AD224531E5EAD2	FASTA	333	37,414
	10 20 30 40 50 60 MGDWGFLEKL LDQVQEHSTV VGKIWLTVLF IFRILILGLA GESVWGDEQS DFECNTAQPG 70 80 90 100 110 120 CTNVCYDQAF PISHIRYWVL QFLFVSTPTL VYLGHVIYLS RREERLRQKE GELRALPAKD 130 140 150 160 170 180 PQVERALAAV ERQMAKISVA EDGRLRIRGA LMGTYVASVL CKSVLEAGFL YGQWRLYGWT 190 200 210 220 230 240 MEPVFVCQRA PCPYLVDCFV SRPTEKTIFI IFMLVVGLIS LVLNLLELVH LLCRCLSRGM 250 260 270 280 290 300 RARQGQDAPP TQGTSSDPYT DQVFFYLPVG QGPSSPPCPT YNGLSSSEQN WANLTTEERL 310 320 330 ASSRPPLFLD PPPQNGQKPP SRPSSSASKK QYV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression of human connexin37, an endothelial cell gap junction protein." Reed K.E., Westphale E.M., Larson D.M., Wang H.-Z., Veenstra R.D., Beyer E.C. J. Clin. Invest. 91:997-1004(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Beyer E.C. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"A connexin 37 genotypic variant in atherosclerosis." van Zeijl L., Cotgreave I.A. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-71; VAL-128; ILE-130 AND SER-319.
[4]	"Functional expression and biophysical properties of two polymorphic forms of human connexin37." Kumari S., Varadaraj K., Valiunas V., Ramanan S.V., Beyer E.C., Brink P.R. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ILE-130 AND SER-319.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[6]	"Connexin 37 mutation screening in anovulatory polycystic ovary syndrome." Lench N.J., Williams G., Williams E., Gharani N., Franks S. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"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].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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: Ovary, Pancreas and Spleen.
[10]	"Human connexin 37 is polymorphic but not mutated in tumours." Krutovskikh V., Mironov N., Yamasaki H. Carcinogenesis 17:1761-1763(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ILE-130.
[11]	"A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development." Boerma M., Forsberg L., Van Zeijl L., Morgenstern R., De Faire U., Lemne C., Erlinge D., Thulin T., Hong Y., Cotgreave I.A. J. Intern. Med. 246:211-218(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SER-319.
[12]	"Human hemangiosarcomas have a common polymorphism but no mutations in the connexin37 gene." Saito T., Krutovskikh V., Marion M.J., Ishak K.G., Bennett W.P., Yamasaki H. Int. J. Cancer 86:67-70(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SER-319.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M96789 mRNA. Translation: AAA52558.2. AF139100 Genomic DNA. Translation: AAD31869.1. AF139101 Genomic DNA. Translation: AAD31870.1. AF139102 Genomic DNA. Translation: AAD31871.1. AF139103 Genomic DNA. Translation: AAD31872.1. AF139104 Genomic DNA. Translation: AAD31873.1. AF139105 Genomic DNA. Translation: AAD31874.1. AF181620 mRNA. Translation: AAD56940.1. AF132674 Genomic DNA. Translation: AAF62342.1. AK291563 mRNA. Translation: BAF84252.1. AL121988 Genomic DNA. Translation: CAB90268.1. CH471059 Genomic DNA. Translation: EAX07440.1. CH471059 Genomic DNA. Translation: EAX07441.1. BC027889 mRNA. Translation: AAH27889.1. BC072389 mRNA. Translation: AAH72389.1.
IPI	IPI00219023.
PIR	I55593.
RefSeq	NP_002051.2. NM_002060.2.
UniGene	Hs.296310.
3D structure databases
ProteinModelPortal	P35212.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000343676.
Protein family/group databases
TCDB	1.A.24.1.6. gap junction-forming connexin family.
PTM databases
PhosphoSite	P35212.
Polymorphism databases
DMDM	8928555.
Proteomic databases
PaxDb	P35212.
PRIDE	P35212.
Protocols and materials databases
DNASU	2701.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000342280; ENSP00000343676; ENSG00000187513.
GeneID	2701.
KEGG	hsa:2701.
UCSC	uc001bya.3. human.
Organism-specific databases
CTD	2701.
GeneCards	GC01P035258.
HGNC	HGNC:4278. GJA4.
HPA	CAB013247.
MIM	121012. gene.
neXtProt	NX_P35212.
PharmGKB	PA28689.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG39708.
HOVERGEN	HBG009576.
InParanoid	P35212.
KO	K07613.
OMA	RGALMGT.
OrthoDB	EOG4PC9SJ.
PhylomeDB	P35212.
Enzyme and pathway databases
Reactome	REACT_11123. Membrane Trafficking.
Gene expression databases
ArrayExpress	P35212.
Bgee	P35212.
CleanEx	HS_GJA4.
Genevestigator	P35212.
GermOnline	ENSG00000187513. Homo sapiens.
Family and domain databases
InterPro	IPR000500. Connexin. IPR002263. Connexin37. IPR019570. Connexin_CCC. IPR017990. Connexin_CS. IPR013092. Connexin_N. [Graphical view]
PANTHER	PTHR11984. PTHR11984. 1 hit. PTHR11984:SF17. PTHR11984:SF17. 1 hit.
Pfam	PF00029. Connexin. 1 hit. PF10582. Connexin_CCC. 1 hit. [Graphical view]
PRINTS	PR00206. CONNEXIN. PR01134. CONNEXINA4.
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
ChiTaRS	GJA4. human.
GenomeRNAi	2701.
NextBio	10678.
SOURCE	Search...

Entry information

Entry name

CXA4_HUMAN

Accession

Primary (citable) accession number: P35212
Secondary accession number(s): A8K698 , D3DPR4, Q9P106, Q9UBL1, Q9UNA9, Q9UNB0, Q9UNB1, Q9Y5N7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 121 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.