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Protein

Gap junction alpha-4 protein

Gene

GJA4

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 - Biological processi

  1. blood vessel development Source: Ensembl
  2. calcium ion transport Source: Ensembl
  3. cell-cell junction assembly Source: ProtInc
  4. cell-cell signaling Source: Ensembl
  5. endothelium development Source: Ensembl
  6. response to pain Source: Ensembl
  7. transport Source: ProtInc
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_9509. Gap junction assembly.

Protein family/group databases

TCDBi1.A.24.1.6. the gap junction-forming connexin (connexin) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Gap junction alpha-4 protein
Alternative name(s):
Connexin-37
Short name:
Cx37
Gene namesi
Name:GJA4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:4278. GJA4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2020CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei21 – 4020HelicalSequence AnalysisAdd
BLAST
Topological domaini41 – 7636ExtracellularSequence AnalysisAdd
BLAST
Transmembranei77 – 9923HelicalSequence AnalysisAdd
BLAST
Topological domaini100 – 14849CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei149 – 16517HelicalSequence AnalysisAdd
BLAST
Topological domaini166 – 20742ExtracellularSequence AnalysisAdd
BLAST
Transmembranei208 – 23023HelicalSequence AnalysisAdd
BLAST
Topological domaini231 – 333103CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. connexon complex Source: Ensembl
  2. gap junction Source: ProtInc
  3. integral component of plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Gap junction, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28689.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 333333Gap junction alpha-4 proteinPRO_0000057814Add
BLAST

Proteomic databases

PaxDbiP35212.
PRIDEiP35212.

PTM databases

PhosphoSiteiP35212.

Expressioni

Tissue specificityi

Expressed in multiple organs and tissues, including heart, uterus, ovary, and blood vessel endothelium.

Gene expression databases

BgeeiP35212.
CleanExiHS_GJA4.
ExpressionAtlasiP35212. baseline and differential.
GenevestigatoriP35212.

Organism-specific databases

HPAiCAB013247.

Interactioni

Subunit structurei

A connexon is composed of a hexamer of connexins.

Binary interactionsi

WithEntry#Exp.IntActNotes
OPRM1P353722EBI-6918707,EBI-2624570

Protein-protein interaction databases

IntActiP35212. 3 interactions.
STRINGi9606.ENSP00000343676.

Structurei

3D structure databases

ProteinModelPortaliP35212.
SMRiP35212. Positions 3-234.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG39708.
GeneTreeiENSGT00760000118780.
HOVERGENiHBG009576.
InParanoidiP35212.
KOiK07613.
OMAiQNWANLT.
OrthoDBiEOG7P2XSS.
PhylomeDBiP35212.
TreeFamiTF329606.

Family and domain databases

InterProiIPR000500. Connexin.
IPR002263. Connexin37.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERiPTHR11984. PTHR11984. 1 hit.
PfamiPF00029. Connexin. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]
PRINTSiPR00206. CONNEXIN.
PR01134. CONNEXINA4.
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.

P35212-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MGDWGFLEKL LDQVQEHSTV VGKIWLTVLF IFRILILGLA GESVWGDEQS
60 70 80 90 100
DFECNTAQPG CTNVCYDQAF PISHIRYWVL QFLFVSTPTL VYLGHVIYLS
110 120 130 140 150
RREERLRQKE GELRALPAKD PQVERALAAV ERQMAKISVA EDGRLRIRGA
160 170 180 190 200
LMGTYVASVL CKSVLEAGFL YGQWRLYGWT MEPVFVCQRA PCPYLVDCFV
210 220 230 240 250
SRPTEKTIFI IFMLVVGLIS LVLNLLELVH LLCRCLSRGM RARQGQDAPP
260 270 280 290 300
TQGTSSDPYT DQVFFYLPVG QGPSSPPCPT YNGLSSSEQN WANLTTEERL
310 320 330
ASSRPPLFLD PPPQNGQKPP SRPSSSASKK QYV
Length:333
Mass (Da):37,414
Last modified:January 23, 2007 - v3
Checksum:i93AD224531E5EAD2
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti71 – 711P → S.1 Publication
VAR_009159
Natural varianti128 – 1281A → V.1 Publication
VAR_009160
Natural varianti130 – 1301V → I.3 Publications
Corresponds to variant rs41266431 [ dbSNP | Ensembl ].
VAR_009161
Natural varianti319 – 3191P → S in allele CX37*2. 4 Publications
Corresponds to variant rs1764391 [ dbSNP | Ensembl ].
VAR_009162

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS30669.1.
PIRiI55593.
RefSeqiNP_002051.2. NM_002060.2.
XP_005270807.1. XM_005270750.1.
UniGeneiHs.296310.

Genome annotation databases

EnsembliENST00000342280; ENSP00000343676; ENSG00000187513.
GeneIDi2701.
KEGGihsa:2701.
UCSCiuc001bya.3. human.

Polymorphism databases

DMDMi8928555.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS30669.1.
PIRiI55593.
RefSeqiNP_002051.2. NM_002060.2.
XP_005270807.1. XM_005270750.1.
UniGeneiHs.296310.

3D structure databases

ProteinModelPortaliP35212.
SMRiP35212. Positions 3-234.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP35212. 3 interactions.
STRINGi9606.ENSP00000343676.

Chemistry

GuidetoPHARMACOLOGYi725.

Protein family/group databases

TCDBi1.A.24.1.6. the gap junction-forming connexin (connexin) family.

PTM databases

PhosphoSiteiP35212.

Polymorphism databases

DMDMi8928555.

Proteomic databases

PaxDbiP35212.
PRIDEiP35212.

Protocols and materials databases

DNASUi2701.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000342280; ENSP00000343676; ENSG00000187513.
GeneIDi2701.
KEGGihsa:2701.
UCSCiuc001bya.3. human.

Organism-specific databases

CTDi2701.
GeneCardsiGC01P035258.
HGNCiHGNC:4278. GJA4.
HPAiCAB013247.
MIMi121012. gene.
neXtProtiNX_P35212.
PharmGKBiPA28689.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG39708.
GeneTreeiENSGT00760000118780.
HOVERGENiHBG009576.
InParanoidiP35212.
KOiK07613.
OMAiQNWANLT.
OrthoDBiEOG7P2XSS.
PhylomeDBiP35212.
TreeFamiTF329606.

Enzyme and pathway databases

ReactomeiREACT_9509. Gap junction assembly.

Miscellaneous databases

ChiTaRSiGJA4. human.
GeneWikiiGJA4.
GenomeRNAii2701.
NextBioi10678.
PROiP35212.
SOURCEiSearch...

Gene expression databases

BgeeiP35212.
CleanExiHS_GJA4.
ExpressionAtlasiP35212. baseline and differential.
GenevestigatoriP35212.

Family and domain databases

InterProiIPR000500. Connexin.
IPR002263. Connexin37.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERiPTHR11984. PTHR11984. 1 hit.
PfamiPF00029. Connexin. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]
PRINTSiPR00206. CONNEXIN.
PR01134. CONNEXINA4.
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 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. 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.

Entry informationi

Entry nameiCXA4_HUMAN
AccessioniPrimary (citable) accession number: P35212
Secondary accession number(s): A8K698
, D3DPR4, Q9P106, Q9UBL1, Q9UNA9, Q9UNB0, Q9UNB1, Q9Y5N7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: January 23, 2007
Last modified: January 7, 2015
This is version 135 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.