ID CXA4_HUMAN Reviewed; 333 AA. AC P35212; A8K698; D3DPR4; Q9P106; Q9UBL1; Q9UNA9; Q9UNB0; Q9UNB1; Q9Y5N7; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 24-JAN-2024, entry version 191. DE RecName: Full=Gap junction alpha-4 protein; DE AltName: Full=Connexin-37; DE Short=Cx37; GN Name=GJA4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=7680674; DOI=10.1172/jci116321; RA Reed K.E., Westphale E.M., Larson D.M., Wang H.-Z., Veenstra R.D., RA Beyer E.C.; RT "Molecular cloning and functional expression of human connexin37, an RT endothelial cell gap junction protein."; RL J. Clin. Invest. 91:997-1004(1993). RN [2] RP SEQUENCE REVISION. RA Beyer E.C.; RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-71; VAL-128; ILE-130 RP AND SER-319. RA van Zeijl L., Cotgreave I.A.; RT "A connexin 37 genotypic variant in atherosclerosis."; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ILE-130 AND SER-319. RA Kumari S., Varadaraj K., Valiunas V., Ramanan S.V., Beyer E.C., Brink P.R.; RT "Functional expression and biophysical properties of two polymorphic forms RT of human connexin37."; RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Lench N.J., Williams G., Williams E., Gharani N., Franks S.; RT "Connexin 37 mutation screening in anovulatory polycystic ovary syndrome."; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary, Pancreas, and Spleen; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP VARIANT ILE-130. RX PubMed=8761439; DOI=10.1093/carcin/17.8.1761; RA Krutovskikh V., Mironov N., Yamasaki H.; RT "Human connexin 37 is polymorphic but not mutated in tumours."; RL Carcinogenesis 17:1761-1763(1996). RN [11] RP VARIANT SER-319. RX PubMed=10447790; DOI=10.1046/j.1365-2796.1999.00564.x; RA Boerma M., Forsberg L., Van Zeijl L., Morgenstern R., De Faire U., RA Lemne C., Erlinge D., Thulin T., Hong Y., Cotgreave I.A.; RT "A genetic polymorphism in connexin 37 as a prognostic marker for RT atherosclerotic plaque development."; RL J. Intern. Med. 246:211-218(1999). RN [12] RP VARIANT SER-319. RX PubMed=10728596; RX DOI=10.1002/(sici)1097-0215(20000401)86:1<67::aid-ijc10>3.0.co;2-1; RA Saito T., Krutovskikh V., Marion M.J., Ishak K.G., Bennett W.P., RA Yamasaki H.; RT "Human hemangiosarcomas have a common polymorphism but no mutations in the RT connexin37 gene."; RL Int. J. Cancer 86:67-70(2000). CC -!- FUNCTION: One gap junction consists of a cluster of closely packed CC pairs of transmembrane channels, the connexons, through which materials CC of low MW diffuse from one cell to a neighboring cell. CC -!- SUBUNIT: A connexon is composed of a hexamer of connexins. CC -!- INTERACTION: CC P35212; P60033: CD81; NbExp=3; IntAct=EBI-6918707, EBI-712921; CC P35212; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-6918707, EBI-12070086; CC P35212; P35372: OPRM1; NbExp=3; IntAct=EBI-6918707, EBI-2624570; CC P35212; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-6918707, EBI-2548832; CC P35212; Q96FB2; NbExp=3; IntAct=EBI-6918707, EBI-2857623; CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Cell CC junction, gap junction. CC -!- TISSUE SPECIFICITY: Expressed in multiple organs and tissues, including CC heart, uterus, ovary, and blood vessel endothelium. CC -!- SIMILARITY: Belongs to the connexin family. Alpha-type (group II) CC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M96789; AAA52558.2; -; mRNA. DR EMBL; AF139100; AAD31869.1; -; Genomic_DNA. DR EMBL; AF139101; AAD31870.1; -; Genomic_DNA. DR EMBL; AF139102; AAD31871.1; -; Genomic_DNA. DR EMBL; AF139103; AAD31872.1; -; Genomic_DNA. DR EMBL; AF139104; AAD31873.1; -; Genomic_DNA. DR EMBL; AF139105; AAD31874.1; -; Genomic_DNA. DR EMBL; AF181620; AAD56940.1; -; mRNA. DR EMBL; AF132674; AAF62342.1; -; Genomic_DNA. DR EMBL; AK291563; BAF84252.1; -; mRNA. DR EMBL; AL121988; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07440.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07441.1; -; Genomic_DNA. DR EMBL; BC027889; AAH27889.1; -; mRNA. DR EMBL; BC072389; AAH72389.1; -; mRNA. DR CCDS; CCDS30669.1; -. DR PIR; I55593; I55593. DR RefSeq; NP_002051.2; NM_002060.2. DR RefSeq; XP_005270807.1; XM_005270750.2. DR RefSeq; XP_016856532.1; XM_017001043.1. DR AlphaFoldDB; P35212; -. DR SMR; P35212; -. DR BioGRID; 108968; 8. DR IntAct; P35212; 7. DR MINT; P35212; -. DR STRING; 9606.ENSP00000343676; -. DR TCDB; 1.A.24.1.6; the gap junction-forming connexin (connexin) family. DR iPTMnet; P35212; -. DR PhosphoSitePlus; P35212; -. DR BioMuta; GJA4; -. DR DMDM; 8928555; -. DR MassIVE; P35212; -. DR PaxDb; 9606-ENSP00000343676; -. DR PeptideAtlas; P35212; -. DR Antibodypedia; 4590; 341 antibodies from 31 providers. DR DNASU; 2701; -. DR Ensembl; ENST00000342280.5; ENSP00000343676.4; ENSG00000187513.9. DR GeneID; 2701; -. DR KEGG; hsa:2701; -. DR MANE-Select; ENST00000342280.5; ENSP00000343676.4; NM_002060.3; NP_002051.2. DR UCSC; uc001bya.3; human. DR AGR; HGNC:4278; -. DR CTD; 2701; -. DR DisGeNET; 2701; -. DR GeneCards; GJA4; -. DR HGNC; HGNC:4278; GJA4. DR HPA; ENSG00000187513; Low tissue specificity. DR MalaCards; GJA4; -. DR MIM; 121012; gene. DR neXtProt; NX_P35212; -. DR OpenTargets; ENSG00000187513; -. DR PharmGKB; PA28689; -. DR VEuPathDB; HostDB:ENSG00000187513; -. DR eggNOG; ENOG502QU20; Eukaryota. DR GeneTree; ENSGT01090000260070; -. DR InParanoid; P35212; -. DR OMA; FHLCCKN; -. DR OrthoDB; 5301774at2759; -. DR PhylomeDB; P35212; -. DR TreeFam; TF329606; -. DR PathwayCommons; P35212; -. DR Reactome; R-HSA-190861; Gap junction assembly. DR SignaLink; P35212; -. DR BioGRID-ORCS; 2701; 11 hits in 1149 CRISPR screens. DR GeneWiki; GJA4; -. DR GenomeRNAi; 2701; -. DR Pharos; P35212; Tbio. DR PRO; PR:P35212; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P35212; Protein. DR Bgee; ENSG00000187513; Expressed in tibial artery and 144 other cell types or tissues. DR ExpressionAtlas; P35212; baseline and differential. DR GO; GO:0005922; C:connexin complex; IBA:GO_Central. DR GO; GO:0005921; C:gap junction; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc. DR GO; GO:0005243; F:gap junction channel activity; IBA:GO_Central. DR GO; GO:0001568; P:blood vessel development; IEA:Ensembl. DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl. DR GO; GO:0007043; P:cell-cell junction assembly; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; IBA:GO_Central. DR GO; GO:0003158; P:endothelium development; IEA:Ensembl. DR GO; GO:0048265; P:response to pain; IEA:Ensembl. DR Gene3D; 1.20.1440.80; Gap junction channel protein cysteine-rich domain; 1. DR InterPro; IPR000500; Connexin. DR InterPro; IPR002263; Connexin37. DR InterPro; IPR019570; Connexin_CCC. DR InterPro; IPR017990; Connexin_CS. DR InterPro; IPR013092; Connexin_N. DR InterPro; IPR038359; Connexin_N_sf. DR PANTHER; PTHR11984; CONNEXIN; 1. DR PANTHER; PTHR11984:SF54; GAP JUNCTION ALPHA-4 PROTEIN; 1. DR Pfam; PF00029; Connexin; 1. DR PRINTS; PR00206; CONNEXIN. DR PRINTS; PR01134; CONNEXINA4. DR SMART; SM00037; CNX; 1. DR SMART; SM01089; Connexin_CCC; 1. DR PROSITE; PS00407; CONNEXINS_1; 1. DR PROSITE; PS00408; CONNEXINS_2; 1. DR Genevisible; P35212; HS. PE 1: Evidence at protein level; KW Cell junction; Cell membrane; Gap junction; Membrane; Reference proteome; KW Transmembrane; Transmembrane helix. FT CHAIN 1..333 FT /note="Gap junction alpha-4 protein" FT /id="PRO_0000057814" FT TOPO_DOM 1..20 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 21..40 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 41..76 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 77..99 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 100..148 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 149..165 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 166..207 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 208..230 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 231..333 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 292..333 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VARIANT 71 FT /note="P -> S" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_009159" FT VARIANT 128 FT /note="A -> V (in dbSNP:rs147128480)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_009160" FT VARIANT 130 FT /note="V -> I (in dbSNP:rs41266431)" FT /evidence="ECO:0000269|PubMed:8761439, ECO:0000269|Ref.3, FT ECO:0000269|Ref.4" FT /id="VAR_009161" FT VARIANT 319 FT /note="P -> S (in allele CX37*2; dbSNP:rs1764391)" FT /evidence="ECO:0000269|PubMed:10447790, FT ECO:0000269|PubMed:10728596, ECO:0000269|Ref.3, FT ECO:0000269|Ref.4" FT /id="VAR_009162" SQ SEQUENCE 333 AA; 37414 MW; 93AD224531E5EAD2 CRC64; MGDWGFLEKL LDQVQEHSTV VGKIWLTVLF IFRILILGLA GESVWGDEQS DFECNTAQPG CTNVCYDQAF PISHIRYWVL QFLFVSTPTL VYLGHVIYLS RREERLRQKE GELRALPAKD PQVERALAAV ERQMAKISVA EDGRLRIRGA LMGTYVASVL CKSVLEAGFL YGQWRLYGWT MEPVFVCQRA PCPYLVDCFV SRPTEKTIFI IFMLVVGLIS LVLNLLELVH LLCRCLSRGM RARQGQDAPP TQGTSSDPYT DQVFFYLPVG QGPSSPPCPT YNGLSSSEQN WANLTTEERL ASSRPPLFLD PPPQNGQKPP SRPSSSASKK QYV //