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Database: UniProt
Entry: P17302
LinkDB: P17302
Original site: P17302 
ID   CXA1_HUMAN              Reviewed;         382 AA.
AC   P17302; B2R5U9; Q6FHU1; Q9Y5I8;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 2.
DT   29-SEP-2021, entry version 248.
DE   RecName: Full=Gap junction alpha-1 protein;
DE   AltName: Full=Connexin-43;
DE            Short=Cx43;
DE   AltName: Full=Gap junction 43 kDa heart protein;
GN   Name=GJA1; Synonyms=GJAL;
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].
RC   TISSUE=Heart muscle;
RX   PubMed=1696265; DOI=10.1083/jcb.111.2.589;
RA   Fishman G.I., Spray D.C., Leinwand L.A.;
RT   "Molecular characterization and functional expression of the human cardiac
RT   gap junction channel.";
RL   J. Cell Biol. 111:589-598(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1646158; DOI=10.1016/0888-7543(91)90507-b;
RA   Fishman G.I., Eddy R.L., Shows T.B., Rosenthal L., Leinwand L.A.;
RT   "The human connexin gene family of gap junction proteins: distinct
RT   chromosomal locations but similar structures.";
RL   Genomics 10:250-256(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10581143; DOI=10.1053/euhj.1999.1718;
RA   Haefliger J.-A., Goy J.J., Waeber G.;
RT   "Sporadic cases of dilated cardiomyopathies associated with
RT   atrioventricular conduction defects are not linked to mutation within the
RT   connexins 40 and 43 genes.";
RL   Eur. Heart J. 20:1843-1843(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA   Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA   LaBaer J.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Cerebellum;
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 [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [7]
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   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [9]
RP   DISULFIDE BONDS.
RX   PubMed=9430691; DOI=10.1074/jbc.273.3.1519;
RA   Toyofuku T., Yabuki M., Otsu K., Kuzuya T., Hori M., Tada M.;
RT   "Intercellular calcium signaling via gap junction in connexin-43-
RT   transfected cells.";
RL   J. Biol. Chem. 273:1519-1528(1998).
RN   [10]
RP   INTERACTION WITH NOV.
RX   PubMed=15181016; DOI=10.1074/jbc.m404073200;
RA   Gellhaus A., Dong X., Propson S., Maass K., Klein-Hitpass L., Kibschull M.,
RA   Traub O., Willecke K., Perbal B., Lye S.J., Winterhager E.;
RT   "Connexin43 interacts with NOV: a possible mechanism for negative
RT   regulation of cell growth in choriocarcinoma cells.";
RL   J. Biol. Chem. 279:36931-36942(2004).
RN   [11]
RP   INTERACTION WITH NOV.
RX   PubMed=15213231; DOI=10.1074/jbc.m403952200;
RA   Fu C.T., Bechberger J.F., Ozog M.A., Perbal B., Naus C.C.;
RT   "CCN3 (NOV) interacts with connexin43 in C6 glioma cells: possible
RT   mechanism of connexin-mediated growth suppression.";
RL   J. Biol. Chem. 279:36943-36950(2004).
RN   [12]
RP   PHOSPHORYLATION AT SER-262.
RX   PubMed=14702389; DOI=10.1242/jcs.00889;
RA   Doble B.W., Dang X., Ping P., Fandrich R.R., Nickel B.E., Jin Y.,
RA   Cattini P.A., Kardami E.;
RT   "Phosphorylation of serine 262 in the gap junction protein connexin-43
RT   regulates DNA synthesis in cell-cell contact forming cardiomyocytes.";
RL   J. Cell Sci. 117:507-514(2004).
RN   [13]
RP   REVIEW.
RX   PubMed=10764404; DOI=10.1161/01.res.86.7.723;
RA   Saffitz J.E., Laing J.G., Yamada K.A.;
RT   "Connexin expression and turnover: implications for cardiac excitability.";
RL   Circ. Res. 86:723-728(2000).
RN   [14]
RP   SHOWS THAT HEART LATERALIZATION DEFECT ARE NOT DUE TO GJA1.
RX   PubMed=8873667; DOI=10.1161/01.cir.94.8.1909;
RA   Gebbia M., Towbin J.A., Casey B.;
RT   "Failure to detect connexin43 mutations in 38 cases of sporadic and
RT   familial heterotaxy.";
RL   Circulation 94:1909-1912(1996).
RN   [15]
RP   SHOWS THAT HEART LATERALIZATION DEFECTS ARE NOT DUE TO GJA1.
RX   PubMed=9155619; DOI=10.1136/hrt.77.4.369;
RA   Penman Splitt M., Tsai M.Y., Burn J., Goodship J.A.;
RT   "Absence of mutations in the regulatory domain of the gap junction protein
RT   connexin 43 in patients with visceroatrial heterotaxy.";
RL   Heart 77:369-370(1997).
RN   [16]
RP   SHOWS THAT HEART LATERALIZATION DEFECTS ARE NOT DUE TO GJA1.
RX   PubMed=9443444; DOI=10.1161/01.cir.97.1.117;
RA   Toth T., Hajdu J., Marton T., Nagy B., Papp Z.;
RT   "Connexin43 gene mutations and heterotaxy.";
RL   Circulation 97:117-118(1998).
RN   [17]
RP   ASSOCIATION WITH NON-SYNDROMIC AUTOSOMAL RECESSIVE DEAFNESS, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=11741837; DOI=10.1093/hmg/10.25.2945;
RA   Liu X.Z., Xia X.J., Adams J., Chen Z.Y., Welch K.O., Tekin M., Ouyang X.M.,
RA   Kristiansen A., Pandya A., Balkany T., Arnos K.S., Nance W.E.;
RT   "Mutations in GJA1 (connexin 43) are associated with non-syndromic
RT   autosomal recessive deafness.";
RL   Hum. Mol. Genet. 10:2945-2951(2001).
RN   [18]
RP   PHOSPHORYLATION AT SER-325; SER-328 AND SER-330 BY CSNK1D/CK1, AND
RP   INTERACTION WITH CSNK1D.
RX   PubMed=12270943; DOI=10.1074/jbc.m209427200;
RA   Cooper C.D., Lampe P.D.;
RT   "Casein kinase 1 regulates connexin-43 gap junction assembly.";
RL   J. Biol. Chem. 277:44962-44968(2002).
RN   [19]
RP   INTERACTION WITH RIC1.
RX   PubMed=16112082; DOI=10.1016/j.bbrc.2005.08.019;
RA   Akiyama M., Ishida N., Ogawa T., Yogo K., Takeya T.;
RT   "Molecular cloning and functional analysis of a novel Cx43 partner protein
RT   CIP150.";
RL   Biochem. Biophys. Res. Commun. 335:1264-1271(2005).
RN   [20]
RP   PHOSPHORYLATION AT SER-255 AND SER-262.
RX   PubMed=15605363; DOI=10.1002/mc.20072;
RA   Arnold J.M., Phipps M.W., Chen J., Phipps J.;
RT   "Cellular sublocalization of Cx43 and the establishment of functional
RT   coupling in IMR-32 neuroblastoma cells.";
RL   Mol. Carcinog. 42:159-169(2005).
RN   [21]
RP   INVOLVEMENT IN ODDD-AR.
RX   PubMed=16816024; DOI=10.1136/jmg.2005.037655;
RA   Richardson R.J., Joss S., Tomkin S., Ahmed M., Sheridan E., Dixon M.J.;
RT   "A nonsense mutation in the first transmembrane domain of connexin 43
RT   underlies autosomal recessive oculodentodigital syndrome.";
RL   J. Med. Genet. 43:E37-E37(2006).
RN   [22]
RP   NON-ASSOCIATION WITH NON-SYNDROMIC AUTOSOMAL RECESSIVE DEAFNESS, VARIANTS
RP   ODDD SER-17; PRO-18; ARG-21; GLU-22; THR-23; VAL-40; LYS-49; PHE-52 INS;
RP   SER-76; VAL-90; CYS-98; ASN-102; THR-130; GLU-134; ARG-138; HIS-202 AND
RP   LEU-216, AND VARIANT VAL-253.
RX   PubMed=12457340; DOI=10.1086/346090;
RA   Paznekas W.A., Boyadjiev S.A., Shapiro R.E., Daniels O., Wollnik B.,
RA   Keegan C.E., Innis J.W., Dinulos M.B., Christian C., Hannibal M.C.,
RA   Jabs E.W.;
RT   "Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of
RT   oculodentodigital dysplasia.";
RL   Am. J. Hum. Genet. 72:408-418(2003).
RN   [23]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-255; SER-314 AND SER-344, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [24]
RP   SUMOYLATION AT LYS-144 AND LYS-237, AND SUBCELLULAR LOCATION.
RX   PubMed=22411987; DOI=10.1074/jbc.m111.281832;
RA   Kjenseth A., Fykerud T.A., Sirnes S., Bruun J., Yohannes Z., Kolberg M.,
RA   Omori Y., Rivedal E., Leithe E.;
RT   "The gap junction channel protein connexin 43 is covalently modified and
RT   regulated by SUMOylation.";
RL   J. Biol. Chem. 287:15851-15861(2012).
RN   [25]
RP   INVOLVEMENT IN PPKCA1, VARIANT PPKCA1 VAL-8, AND CHARACTERIZATION OF
RP   VARIANT PPKCA1 VAL-8.
RX   PubMed=25168385; DOI=10.1093/hmg/ddu442;
RA   Wang H., Cao X., Lin Z., Lee M., Jia X., Ren Y., Dai L., Guan L., Zhang J.,
RA   Lin X., Zhang J., Chen Q., Feng C., Zhou E.Y., Yin J., Xu G., Yang Y.;
RT   "Exome sequencing reveals mutation in GJA1 as a cause of keratoderma-
RT   hypotrichosis-leukonychia totalis syndrome.";
RL   Hum. Mol. Genet. 24:243-250(2015).
RN   [26]
RP   INVOLVEMENT IN EKVP3, VARIANTS EKVP3 VAL-44 AND ASP-227, CHARACTERIZATION
RP   OF VARIANTS EKVP3 VAL-44 AND ASP-227, AND SUBCELLULAR LOCATION.
RX   PubMed=25398053; DOI=10.1038/jid.2014.485;
RG   Yale Center for Mendelian Genomics;
RA   Boyden L.M., Craiglow B.G., Zhou J., Hu R., Loring E.C., Morel K.D.,
RA   Lauren C.T., Lifton R.P., Bilguvar K., Paller A.S., Choate K.A.;
RT   "Dominant de novo mutations in GJA1 cause erythrokeratodermia variabilis et
RT   progressiva, without features of oculodentodigital dysplasia.";
RL   J. Invest. Dermatol. 135:1540-1547(2015).
RN   [27]
RP   VARIANTS HEART MALFORMATIONS GLY-352; PRO-364 AND ASN-365, VARIANTS ALA-326
RP   AND GLY-373, AND CHARACTERIZATION OF VARIANT HEART MALFORMATIONS PRO-364.
RX   PubMed=7715640; DOI=10.1056/nejm199505183322002;
RA   Britz-Cunningham S.H., Shah M.M., Zuppan C.W., Fletcher W.H.;
RT   "Mutations of the connexin43 gap-junction gene in patients with heart
RT   malformations and defects of laterality.";
RL   N. Engl. J. Med. 332:1323-1329(1995).
RN   [28]
RP   VARIANTS HLHS1 GLN-362 AND GLN-376, VARIANTS AVSD3 GLN-362 AND GLN-376, AND
RP   CHARACTERIZATION OF VARIANTS HLHS1 GLN-362 AND GLN-376.
RX   PubMed=11470490; DOI=10.1016/s0027-5107(01)00160-9;
RA   Dasgupta C., Martinez A.-M., Zuppan C.W., Shah M.M., Bailey L.L.,
RA   Fletcher W.H.;
RT   "Identification of connexin43 (alpha1) gap junction gene mutations in
RT   patients with hypoplastic left heart syndrome by denaturing gradient gel
RT   electrophoresis (DGGE).";
RL   Mutat. Res. 479:173-186(2001).
RN   [29]
RP   VARIANT ODDD MET-96.
RX   PubMed=15108203; DOI=10.1002/ajmg.a.20614;
RA   Kjaer K.W., Hansen L., Eiberg H., Leicht P., Opitz J.M., Tommerup N.;
RT   "Novel Connexin 43 (GJA1) mutation causes oculo-dento-digital dysplasia
RT   with curly hair.";
RL   Am. J. Med. Genet. A 127:152-157(2004).
RN   [30]
RP   VARIANT HSS HIS-76.
RX   PubMed=14974090; DOI=10.1002/humu.9220;
RA   Pizzuti A., Flex E., Mingarelli R., Salpietro C., Zelante L.,
RA   Dallapiccola B.;
RT   "A homozygous GJA1 gene mutation causes a Hallermann-Streiff/ODDD spectrum
RT   phenotype.";
RL   Hum. Mutat. 23:286-286(2004).
RN   [31]
RP   VARIANTS ODDD PRO-27; MET-31; VAL-40; TYR-69; PRO-113; ASN-134; GLN-148 AND
RP   HIS-202, AND VARIANT SDTY3 SER-143.
RX   PubMed=14729836; DOI=10.1136/jmg.2003.012005;
RA   Richardson R.R., Donnai D., Meire F., Dixon M.J.;
RT   "Expression of Gja1 correlates with the phenotype observed in
RT   oculodentodigital syndrome/type III syndactyly.";
RL   J. Med. Genet. 41:60-67(2004).
RN   [32]
RP   VARIANT ODDD PRO-194.
RX   PubMed=15637728; DOI=10.1002/ajmg.a.30554;
RA   Vitiello C., D'Adamo P., Gentile F., Vingolo E.M., Gasparini P., Banfi S.;
RT   "A novel GJA1 mutation causes oculodentodigital dysplasia without
RT   syndactyly.";
RL   Am. J. Med. Genet. A 133:58-60(2005).
RN   [33]
RP   VARIANT ODDD ARG-95.
RX   PubMed=16222672; DOI=10.1002/ajmg.a.30925;
RA   Honkaniemi J., Kalkkila J.P., Koivisto P., Kahara V., Latvala T.,
RA   Simola K.;
RT   "Letter to the editor: Novel GJA1 mutation in oculodentodigital
RT   dysplasia.";
RL   Am. J. Med. Genet. A 139:48-49(2005).
RN   [34]
RP   VARIANT ODDD HIS-59.
RX   PubMed=16219735; DOI=10.1001/archopht.123.10.1422;
RA   Vasconcellos J.P.C., Melo M.B., Schimiti R.B., Bressanim N.C., Costa F.F.,
RA   Costa V.P.;
RT   "A novel mutation in the GJA1 gene in a family with oculodentodigital
RT   dysplasia.";
RL   Arch. Ophthalmol. 123:1422-1426(2005).
RN   [35]
RP   VARIANTS CONGENITAL HEART MALFORMATIONS TRP-239; THR-251; PRO-253; LEU-283
RP   AND ASN-290.
RX   PubMed=15978203;
RA   Chen P., Xie L.-J., Huang G.-Y., Zhao X.-Q., Chang C.;
RT   "Mutations of connexin43 in fetuses with congenital heart malformations.";
RL   Chin. Med. J. 118:971-976(2005).
RN   [36]
RP   VARIANT LEU-41.
RX   PubMed=15757815;
RA   Kellermayer R., Keller M., Ratajczak P., Richardson E., Harangi F.,
RA   Merei E., Melegh B., Kosztolanyi G., Richard G.;
RT   "Bigenic connexin mutations in a patient with hidrotic ectodermal
RT   dysplasia.";
RL   Eur. J. Dermatol. 15:75-79(2005).
RN   [37]
RP   VARIANTS ODDD VAL-40; ASP-110; THR-147 AND PHE-169 DEL.
RX   PubMed=16378922; DOI=10.1016/j.ejmg.2005.05.003;
RA   Debeer P., Van Esch H., Huysmans C., Pijkels E., De Smet L., Van de Ven W.,
RA   Devriendt K., Fryns J.-P.;
RT   "Novel GJA1 mutations in patients with oculo-dento-digital dysplasia
RT   (ODDD).";
RL   Eur. J. Med. Genet. 48:377-387(2005).
RN   [38]
RP   VARIANTS ODDD GLU-96; PRO-113; ASN-154 AND TYR-220.
RX   PubMed=16813608; DOI=10.1111/j.1399-0004.2006.00631.x;
RA   Wiest T., Herrmann O., Stoegbauer F., Grasshoff U., Enders H., Koch M.J.,
RA   Grond-Ginsbach C., Schwaninger M.;
RT   "Clinical and genetic variability of oculodentodigital dysplasia.";
RL   Clin. Genet. 70:71-72(2006).
RN   [39]
RP   VARIANT ODDD PRO-11.
RX   PubMed=16709485;
RA   Kelly S.C., Ratajczak P., Keller M., Purcell S.M., Griffin T., Richard G.;
RT   "A novel GJA 1 mutation in oculo-dento-digital dysplasia with curly hair
RT   and hyperkeratosis.";
RL   Eur. J. Dermatol. 16:241-245(2006).
RN   [40]
RP   VARIANT ODDD ALA-154.
RX   PubMed=17509830; DOI=10.1016/j.ijom.2007.03.004;
RA   van Es R.J.J., Wittebol-Post D., Beemer F.A.;
RT   "Oculodentodigital dysplasia with mandibular retrognathism and absence of
RT   syndactyly: a case report with a novel mutation in the connexin 43 gene.";
RL   Int. J. Oral Maxillofac. Surg. 36:858-860(2007).
RN   [41]
RP   VARIANT ODDD VAL-2.
RX   PubMed=18161618; DOI=10.1080/13816810701538620;
RA   de la Parra D.R., Zenteno J.C.;
RT   "A new GJA1 (connexin 43) mutation causing oculodentodigital dysplasia
RT   associated to uncommon features.";
RL   Ophthalmic Genet. 28:198-202(2007).
RN   [42]
RP   VARIANTS ODDD VAL-7; VAL-40; PRO-49; GLN-49 INS; ALA-96; PRO-106; ALA-154;
RP   PHE-201 AND HIS-202.
RX   PubMed=19338053; DOI=10.1002/humu.20958;
RA   Paznekas W.A., Karczeski B., Vermeer S., Lowry R.B., Delatycki M.,
RA   Laurence F., Koivisto P.A., Van Maldergem L., Boyadjiev S.A.,
RA   Bodurtha J.N., Jabs E.W.;
RT   "GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the
RT   oculodentodigital dysplasia phenotype.";
RL   Hum. Mutat. 30:724-733(2009).
RN   [43]
RP   VARIANTS ODDD PRO-11 AND 41-VAL--ALA-44 DEL.
RX   PubMed=21670345; DOI=10.1001/archophthalmol.2011.113;
RA   Gabriel L.A., Sachdeva R., Marcotty A., Rockwood E.J., Traboulsi E.I.;
RT   "Oculodentodigital dysplasia: new ocular findings and a novel connexin 43
RT   mutation.";
RL   Arch. Ophthalmol. 129:781-784(2011).
RN   [44]
RP   VARIANT ODDD ARG-206.
RX   PubMed=23550541; DOI=10.1111/cge.12158;
RA   Brice G., Ostergaard P., Jeffery S., Gordon K., Mortimer P.S., Mansour S.;
RT   "A novel mutation in GJA1 causing oculodentodigital syndrome and primary
RT   lymphoedema in a three generation family.";
RL   Clin. Genet. 84:378-381(2013).
RN   [45]
RP   VARIANT CMDR GLN-239.
RX   PubMed=23951358; DOI=10.1371/journal.pone.0073576;
RA   Hu Y., Chen I.P., de Almeida S., Tiziani V., Do Amaral C.M.,
RA   Gowrishankar K., Passos-Bueno M.R., Reichenberger E.J.;
RT   "A novel autosomal recessive GJA1 missense mutation linked to
RT   Craniometaphyseal dysplasia.";
RL   PLoS ONE 8:E73576-E73576(2013).
RN   [46]
RP   VARIANTS ODDD HIS-47; TYR-86 AND ARG-106.
RX   PubMed=24508941; DOI=10.1016/j.gene.2014.01.066;
RA   Jamsheer A., Sowinska-Seidler A., Socha M., Stembalska A., Kiraly-Borri C.,
RA   Latos-Bielenska A.;
RT   "Three novel GJA1 missense substitutions resulting in oculo-dento-digital
RT   dysplasia (ODDD) - further extension of the mutational spectrum.";
RL   Gene 539:157-161(2014).
RN   [47]
RP   VARIANT ODDD ILE-11.
RX   PubMed=28258662; DOI=10.1111/odi.12663;
RA   Porntaveetus T., Srichomthong C., Ohazama A., Suphapeetiporn K.,
RA   Shotelersuk V.;
RT   "A novel GJA1 mutation in oculodentodigitaldysplasia with extensive loss of
RT   enamel.";
RL   Oral Dis. 23:795-800(2017).
CC   -!- FUNCTION: Gap junction protein that acts as a regulator of bladder
CC       capacity. A gap junction consists of a cluster of closely packed pairs
CC       of transmembrane channels, the connexons, through which materials of
CC       low MW diffuse from one cell to a neighboring cell. May play a critical
CC       role in the physiology of hearing by participating in the recycling of
CC       potassium to the cochlear endolymph. Negative regulator of bladder
CC       functional capacity: acts by enhancing intercellular electrical and
CC       chemical transmission, thus sensitizing bladder muscles to cholinergic
CC       neural stimuli and causing them to contract (By similarity). May play a
CC       role in cell growth inhibition through the regulation of NOV expression
CC       and localization. Plays an essential role in gap junction communication
CC       in the ventricles (By similarity). {ECO:0000250|UniProtKB:P08050,
CC       ECO:0000250|UniProtKB:P23242}.
CC   -!- SUBUNIT: A connexon is composed of a hexamer of connexins. Interacts
CC       (via C-terminus) with TJP1 (By similarity). Interacts (via C-terminus)
CC       with SRC (via SH3 domain) (By similarity). Interacts (not
CC       ubiquitinated) with UBQLN4 (via UBA domain) (By similarity). Interacts
CC       with SGSM3 and CNST (By similarity). Interacts with RIC1/CIP150.
CC       Interacts with CSNK1D. Interacts with NOV (PubMed:15181016,
CC       PubMed:15213231). Interacts with TMEM65 (By similarity).
CC       {ECO:0000250|UniProtKB:P23242, ECO:0000269|PubMed:12270943,
CC       ECO:0000269|PubMed:15181016, ECO:0000269|PubMed:15213231,
CC       ECO:0000269|PubMed:16112082}.
CC   -!- INTERACTION:
CC       P17302; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-1103439, EBI-2875816;
CC       P17302; Q8TAB5: C1orf216; NbExp=3; IntAct=EBI-1103439, EBI-747505;
CC       P17302; O43889-2: CREB3; NbExp=4; IntAct=EBI-1103439, EBI-625022;
CC       P17302; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-1103439, EBI-9087876;
CC       P17302; Q02487-1: DSC2; NbExp=2; IntAct=EBI-1103439, EBI-6900677;
CC       P17302; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-1103439, EBI-10317425;
CC       P17302; Q5VZY2: PLPP4; NbExp=3; IntAct=EBI-1103439, EBI-10485931;
CC       P17302; Q07157: TJP1; NbExp=3; IntAct=EBI-1103439, EBI-79553;
CC       P17302; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-1103439, EBI-10694905;
CC       P17302; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-1103439, EBI-2548832;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22411987,
CC       ECO:0000269|PubMed:25398053}; Multi-pass membrane protein
CC       {ECO:0000255}. Cell junction, gap junction
CC       {ECO:0000269|PubMed:22411987, ECO:0000269|PubMed:25398053}. Endoplasmic
CC       reticulum {ECO:0000250|UniProtKB:P23242}. Note=Localizes at the
CC       intercalated disk (ICD) in cardiomyocytes and the proper localization
CC       at ICD is dependent on TMEM65. {ECO:0000250|UniProtKB:P23242}.
CC   -!- TISSUE SPECIFICITY: Expressed in the heart and fetal cochlea.
CC       {ECO:0000269|PubMed:11741837}.
CC   -!- PTM: Phosphorylated at Ser-368 by PRKCG; phosphorylation induces
CC       disassembly of gap junction plaques and inhibition of gap junction
CC       activity (By similarity). Phosphorylation at Ser-325, Ser-328 and Ser-
CC       330 by CK1 modulates gap junction assembly. Phosphorylation at Ser-368
CC       by PRKCD triggers its internalization into small vesicles leading to
CC       proteasome-mediated degradation (By similarity).
CC       {ECO:0000250|UniProtKB:P08050, ECO:0000250|UniProtKB:Q6TYA7,
CC       ECO:0000269|PubMed:12270943, ECO:0000269|PubMed:14702389,
CC       ECO:0000269|PubMed:15605363}.
CC   -!- PTM: Sumoylated with SUMO1, SUMO2 and SUMO3, which may regulate the
CC       level of functional Cx43 gap junctions at the plasma membrane. May be
CC       desumoylated by SENP1 or SENP2. {ECO:0000269|PubMed:22411987}.
CC   -!- PTM: S-nitrosylation at Cys-271 is enriched at the muscle endothelial
CC       gap junction in arteries, it augments channel permeability and may
CC       regulate of smooth muscle cell to endothelial cell communication.
CC       {ECO:0000250|UniProtKB:P23242}.
CC   -!- PTM: Acetylated in the developing cortex; leading to delocalization
CC       from the cell membrane. {ECO:0000250|UniProtKB:P23242}.
CC   -!- DISEASE: Oculodentodigital dysplasia (ODDD) [MIM:164200]: A disease
CC       characterized by a typical facial appearance and variable involvement
CC       of the eyes, dentition, and fingers. Characteristic facial features
CC       include a narrow, pinched nose with hypoplastic alae nasi, prominent
CC       columella and thin anteverted nares together with a narrow nasal
CC       bridge, and prominent epicanthic folds giving the impression of
CC       hypertelorism. The teeth are usually small and carious. Typical eye
CC       findings include microphthalmia and microcornea. The characteristic
CC       digital malformation is complete syndactyly of the fourth and fifth
CC       fingers (syndactyly type III) but the third finger may be involved and
CC       associated camptodactyly is a common finding. Cardiac abnormalities are
CC       observed in rare instances. {ECO:0000269|PubMed:12457340,
CC       ECO:0000269|PubMed:14729836, ECO:0000269|PubMed:15108203,
CC       ECO:0000269|PubMed:15637728, ECO:0000269|PubMed:16219735,
CC       ECO:0000269|PubMed:16222672, ECO:0000269|PubMed:16378922,
CC       ECO:0000269|PubMed:16709485, ECO:0000269|PubMed:16813608,
CC       ECO:0000269|PubMed:16816024, ECO:0000269|PubMed:17509830,
CC       ECO:0000269|PubMed:18161618, ECO:0000269|PubMed:19338053,
CC       ECO:0000269|PubMed:21670345, ECO:0000269|PubMed:23550541,
CC       ECO:0000269|PubMed:24508941, ECO:0000269|PubMed:28258662}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Oculodentodigital dysplasia, autosomal recessive (ODDD-AR)
CC       [MIM:257850]: A disease characterized by a typical facial appearance
CC       and variable involvement of the eyes, dentition, and fingers.
CC       Characteristic facial features include a narrow, pinched nose with
CC       hypoplastic alae nasi, prominent columella and thin anteverted nares
CC       together with a narrow nasal bridge, and prominent epicanthic folds
CC       giving the impression of hypertelorism. The teeth are usually small and
CC       carious. Typical eye findings include microphthalmia and microcornea.
CC       The characteristic digital malformation is complete syndactyly of the
CC       fourth and fifth fingers (syndactyly type III) but the third finger may
CC       be involved and associated camptodactyly is a common finding. Cardiac
CC       abnormalities are observed in rare instances.
CC       {ECO:0000269|PubMed:16816024}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Syndactyly 3 (SDTY3) [MIM:186100]: A form of syndactyly, a
CC       congenital anomaly of the hand or foot marked by persistence of the
CC       webbing between adjacent digits that are more or less completely
CC       attached. In SDTY3, there is usually complete and bilateral syndactyly
CC       between the fourth and fifth fingers. Usually it is soft tissue
CC       syndactyly but occasionally the distal phalanges are fused. The fifth
CC       finger is short with absent or rudimentary middle phalanx. The feet are
CC       not affected. {ECO:0000269|PubMed:14729836}. Note=The disease may be
CC       caused by variants affecting the gene represented in this entry.
CC   -!- DISEASE: Hypoplastic left heart syndrome 1 (HLHS1) [MIM:241550]: A
CC       syndrome due to defective development of the aorta proximal to the
CC       entrance of the ductus arteriosus, and hypoplasia of the left ventricle
CC       and mitral valve. As a result of the abnormal circulation, the ductus
CC       arteriosus and foramen ovale are patent and the right atrium, right
CC       ventricle, and pulmonary artery are enlarged.
CC       {ECO:0000269|PubMed:11470490}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Hallermann-Streiff syndrome (HSS) [MIM:234100]: A disorder
CC       characterized by a typical skull shape (brachycephaly with frontal
CC       bossing), hypotrichosis, microphthalmia, cataracts, beaked nose,
CC       micrognathia, skin atrophy, dental anomalies and proportionate short
CC       stature. Mental retardation is present in a minority of cases.
CC       {ECO:0000269|PubMed:14974090}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Atrioventricular septal defect 3 (AVSD3) [MIM:600309]: A
CC       congenital heart malformation characterized by a common
CC       atrioventricular junction coexisting with deficient atrioventricular
CC       septation. The complete form involves underdevelopment of the lower
CC       part of the atrial septum and the upper part of the ventricular septum;
CC       the valve itself is also shared. A less severe form, known as ostium
CC       primum atrial septal defect, is characterized by separate
CC       atrioventricular valvar orifices despite a common junction.
CC       {ECO:0000269|PubMed:11470490}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Craniometaphyseal dysplasia, autosomal recessive (CMDR)
CC       [MIM:218400]: An osteochondrodysplasia characterized by hyperostosis
CC       and sclerosis of the craniofacial bones associated with abnormal
CC       modeling of the metaphyses. Sclerosis of the skull may lead to
CC       asymmetry of the mandible, as well as to cranial nerve compression,
CC       that may finally result in hearing loss and facial palsy.
CC       {ECO:0000269|PubMed:23951358}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Erythrokeratodermia variabilis et progressiva 3 (EKVP3)
CC       [MIM:617525]: A form of erythrokeratodermia variabilis et progressiva,
CC       a genodermatosis characterized by the coexistence of two independent
CC       skin lesions: transient erythema and hyperkeratosis that is usually
CC       localized but occasionally occurs in its generalized form. Clinical
CC       presentation varies significantly within a family and from one family
CC       to another. Palmoplantar keratoderma is present in around 50% of cases.
CC       {ECO:0000269|PubMed:25398053}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Palmoplantar keratoderma and congenital alopecia 1 (PPKCA1)
CC       [MIM:104100]: A rare autosomal dominant disorder characterized by
CC       severe hyperkeratosis of the palms and soles, and congenital
CC       hypotrichosis or alopecia. Dystrophic nail changes occur in some
CC       patients. {ECO:0000269|PubMed:25168385}. Note=The disease is caused by
CC       variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the connexin family. Alpha-type (group II)
CC       subfamily. {ECO:0000305}.
CC   -!- CAUTION: PubMed:7715640 reported a mutation Pro-364 linked to
CC       congenital heart diseases. PubMed:8873667 later shown that it is an
CC       artifact. {ECO:0000305}.
CC   -!- CAUTION: PubMed:11741837 reported 2 mutations (Phe-11 and Ala-24)
CC       linked to non-syndromic autosomal recessive deafness (DFNBG). These
CC       mutations have subsequently been shown (PubMed:12457340) to involve the
CC       pseudogene of connexin-43 located on chromosome 5.
CC       {ECO:0000305|PubMed:12457340}.
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DR   EMBL; X52947; CAA37122.1; -; mRNA.
DR   EMBL; M65188; AAA52131.1; -; mRNA.
DR   EMBL; AF151980; AAD37802.2; -; Genomic_DNA.
DR   EMBL; CR541660; CAG46461.1; -; mRNA.
DR   EMBL; AK312324; BAG35246.1; -; mRNA.
DR   EMBL; AL139098; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471051; EAW48178.1; -; Genomic_DNA.
DR   EMBL; BC026329; AAH26329.1; -; mRNA.
DR   CCDS; CCDS5123.1; -.
DR   PIR; A35853; A35853.
DR   RefSeq; NP_000156.1; NM_000165.4.
DR   PDB; 2LL2; NMR; -; A=234-259.
DR   PDBsum; 2LL2; -.
DR   BMRB; P17302; -.
DR   SMR; P17302; -.
DR   BioGRID; 108964; 104.
DR   IntAct; P17302; 46.
DR   MINT; P17302; -.
DR   STRING; 9606.ENSP00000282561; -.
DR   DrugBank; DB01136; Carvedilol.
DR   iPTMnet; P17302; -.
DR   PhosphoSitePlus; P17302; -.
DR   BioMuta; GJA1; -.
DR   DMDM; 117706; -.
DR   EPD; P17302; -.
DR   jPOST; P17302; -.
DR   MassIVE; P17302; -.
DR   MaxQB; P17302; -.
DR   PaxDb; P17302; -.
DR   PeptideAtlas; P17302; -.
DR   PRIDE; P17302; -.
DR   ProteomicsDB; 53467; -.
DR   TopDownProteomics; P17302; -.
DR   ABCD; P17302; 3 sequenced antibodies.
DR   Antibodypedia; 4382; 1228 antibodies.
DR   DNASU; 2697; -.
DR   Ensembl; ENST00000282561; ENSP00000282561; ENSG00000152661.
DR   Ensembl; ENST00000647564; ENSP00000497565; ENSG00000152661.
DR   Ensembl; ENST00000649003; ENSP00000497283; ENSG00000152661.
DR   Ensembl; ENST00000650427; ENSP00000497367; ENSG00000152661.
DR   GeneID; 2697; -.
DR   KEGG; hsa:2697; -.
DR   UCSC; uc003pyr.4; human.
DR   CTD; 2697; -.
DR   DisGeNET; 2697; -.
DR   GeneCards; GJA1; -.
DR   HGNC; HGNC:4274; GJA1.
DR   HPA; ENSG00000152661; Low tissue specificity.
DR   MalaCards; GJA1; -.
DR   MIM; 104100; phenotype.
DR   MIM; 121014; gene.
DR   MIM; 164200; phenotype.
DR   MIM; 186100; phenotype.
DR   MIM; 218400; phenotype.
DR   MIM; 234100; phenotype.
DR   MIM; 241550; phenotype.
DR   MIM; 257850; phenotype.
DR   MIM; 600309; phenotype.
DR   MIM; 617525; phenotype.
DR   neXtProt; NX_P17302; -.
DR   OpenTargets; ENSG00000152661; -.
DR   Orphanet; 1010; Autosomal dominant palmoplantar keratoderma and congenital alopecia.
DR   Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR   Orphanet; 1522; Craniometaphyseal dysplasia.
DR   Orphanet; 317; Erythrokeratodermia variabilis.
DR   Orphanet; 2248; Hypoplastic left heart syndrome.
DR   Orphanet; 2710; Oculodentodigital dysplasia.
DR   Orphanet; 93404; Syndactyly type 3.
DR   PharmGKB; PA28685; -.
DR   VEuPathDB; HostDB:ENSG00000152661; -.
DR   eggNOG; ENOG502QRAE; Eukaryota.
DR   GeneTree; ENSGT01040000240437; -.
DR   HOGENOM; CLU_037388_0_0_1; -.
DR   InParanoid; P17302; -.
DR   OMA; LVIQWYM; -.
DR   OrthoDB; 519426at2759; -.
DR   PhylomeDB; P17302; -.
DR   TreeFam; TF329606; -.
DR   PathwayCommons; P17302; -.
DR   Reactome; R-HSA-190704; Oligomerization of connexins into connexons.
DR   Reactome; R-HSA-190827; Transport of connexins along the secretory pathway.
DR   Reactome; R-HSA-190840; Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
DR   Reactome; R-HSA-190861; Gap junction assembly.
DR   Reactome; R-HSA-190873; Gap junction degradation.
DR   Reactome; R-HSA-191650; Regulation of gap junction activity.
DR   Reactome; R-HSA-196025; Formation of annular gap junctions.
DR   Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR   Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR   SignaLink; P17302; -.
DR   SIGNOR; P17302; -.
DR   BioGRID-ORCS; 2697; 26 hits in 980 CRISPR screens.
DR   ChiTaRS; GJA1; human.
DR   GeneWiki; GJA1; -.
DR   GenomeRNAi; 2697; -.
DR   Pharos; P17302; Tbio.
DR   PRO; PR:P17302; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; P17302; protein.
DR   Bgee; ENSG00000152661; Expressed in pigmented layer of retina and 246 other tissues.
DR   Genevisible; P17302; HS.
DR   GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR   GO; GO:0030054; C:cell junction; IDA:UniProtKB.
DR   GO; GO:0044291; C:cell-cell contact zone; IDA:ARUK-UCL.
DR   GO; GO:0005922; C:connexin complex; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL.
DR   GO; GO:0005769; C:early endosome; IEA:Ensembl.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0005916; C:fascia adherens; IEA:Ensembl.
DR   GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR   GO; GO:0005921; C:gap junction; IDA:BHF-UCL.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:BHF-UCL.
DR   GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR   GO; GO:0030660; C:Golgi-associated vesicle membrane; TAS:Reactome.
DR   GO; GO:0005887; C:integral component of plasma membrane; TAS:UniProtKB.
DR   GO; GO:0014704; C:intercalated disc; IDA:BHF-UCL.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0005764; C:lysosome; IEA:Ensembl.
DR   GO; GO:0045121; C:membrane raft; ISS:BHF-UCL.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IEA:Ensembl.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0005771; C:multivesicular body; IEA:Ensembl.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR   GO; GO:0070160; C:tight junction; IDA:ARUK-UCL.
DR   GO; GO:0043014; F:alpha-tubulin binding; IDA:UniProtKB.
DR   GO; GO:0008013; F:beta-catenin binding; IPI:ARUK-UCL.
DR   GO; GO:0071253; F:connexin binding; IEA:Ensembl.
DR   GO; GO:0097718; F:disordered domain specific binding; IEA:Ensembl.
DR   GO; GO:0015562; F:efflux transmembrane transporter activity; ISS:ARUK-UCL.
DR   GO; GO:0005243; F:gap junction channel activity; IDA:BHF-UCL.
DR   GO; GO:0086075; F:gap junction channel activity involved in cardiac conduction electrical coupling; NAS:BHF-UCL.
DR   GO; GO:1903763; F:gap junction channel activity involved in cell communication by electrical coupling; IDA:BHF-UCL.
DR   GO; GO:0055077; F:gap junction hemi-channel activity; IMP:UniProtKB.
DR   GO; GO:0034634; F:glutathione transmembrane transporter activity; ISS:ARUK-UCL.
DR   GO; GO:0015075; F:ion transmembrane transporter activity; IDA:BHF-UCL.
DR   GO; GO:0030165; F:PDZ domain binding; IEA:Ensembl.
DR   GO; GO:0017124; F:SH3 domain binding; IEA:Ensembl.
DR   GO; GO:0015631; F:tubulin binding; IDA:UniProtKB.
DR   GO; GO:0006915; P:apoptotic process; IEA:Ensembl.
DR   GO; GO:0015867; P:ATP transport; IEA:Ensembl.
DR   GO; GO:0086014; P:atrial cardiac muscle cell action potential; TAS:BHF-UCL.
DR   GO; GO:0060348; P:bone development; ISS:UniProtKB.
DR   GO; GO:0046849; P:bone remodeling; ISS:UniProtKB.
DR   GO; GO:0003161; P:cardiac conduction system development; NAS:BHF-UCL.
DR   GO; GO:0010644; P:cell communication by electrical coupling; IDA:BHF-UCL.
DR   GO; GO:0086064; P:cell communication by electrical coupling involved in cardiac conduction; NAS:BHF-UCL.
DR   GO; GO:0007267; P:cell-cell signaling; IDA:BHF-UCL.
DR   GO; GO:0034613; P:cellular protein localization; IMP:ARUK-UCL.
DR   GO; GO:1904646; P:cellular response to amyloid-beta; ISS:ARUK-UCL.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR   GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Ensembl.
DR   GO; GO:0002544; P:chronic inflammatory response; IEA:Ensembl.
DR   GO; GO:0046697; P:decidualization; IEA:Ensembl.
DR   GO; GO:0003158; P:endothelium development; IEA:Ensembl.
DR   GO; GO:1905867; P:epididymis development; IEA:Ensembl.
DR   GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:ARUK-UCL.
DR   GO; GO:0140115; P:export across plasma membrane; ISS:ARUK-UCL.
DR   GO; GO:0016264; P:gap junction assembly; TAS:UniProtKB.
DR   GO; GO:0014047; P:glutamate secretion; ISS:ARUK-UCL.
DR   GO; GO:0034220; P:ion transmembrane transport; IDA:BHF-UCL.
DR   GO; GO:0035633; P:maintenance of blood-brain barrier; NAS:ARUK-UCL.
DR   GO; GO:0035437; P:maintenance of protein localization in endoplasmic reticulum; IEA:Ensembl.
DR   GO; GO:0099111; P:microtubule-based transport; IMP:UniProtKB.
DR   GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; IEA:Ensembl.
DR   GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR   GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IEA:Ensembl.
DR   GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IEA:Ensembl.
DR   GO; GO:0032277; P:negative regulation of gonadotropin secretion; IMP:ARUK-UCL.
DR   GO; GO:1901164; P:negative regulation of trophoblast cell migration; IMP:ARUK-UCL.
DR   GO; GO:0061045; P:negative regulation of wound healing; IEA:Ensembl.
DR   GO; GO:0048812; P:neuron projection morphogenesis; IEA:Ensembl.
DR   GO; GO:2000987; P:positive regulation of behavioral fear response; IEA:Ensembl.
DR   GO; GO:0010652; P:positive regulation of cell communication by chemical coupling; IEA:Ensembl.
DR   GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR   GO; GO:0003104; P:positive regulation of glomerular filtration; IEA:Ensembl.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; HMP:UniProtKB.
DR   GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR   GO; GO:1905772; P:positive regulation of mesodermal cell differentiation; IMP:ARUK-UCL.
DR   GO; GO:1905332; P:positive regulation of morphogenesis of an epithelium; IMP:ARUK-UCL.
DR   GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR   GO; GO:2000648; P:positive regulation of stem cell proliferation; IMP:ARUK-UCL.
DR   GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:ARUK-UCL.
DR   GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl.
DR   GO; GO:0042981; P:regulation of apoptotic process; IEA:Ensembl.
DR   GO; GO:2000810; P:regulation of bicellular tight junction assembly; IEA:Ensembl.
DR   GO; GO:0051924; P:regulation of calcium ion transport; IEA:Ensembl.
DR   GO; GO:0010649; P:regulation of cell communication by electrical coupling; IEA:Ensembl.
DR   GO; GO:0022898; P:regulation of transmembrane transporter activity; IEA:Ensembl.
DR   GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR   GO; GO:0034405; P:response to fluid shear stress; IEA:Ensembl.
DR   GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR   GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR   GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR   GO; GO:0009268; P:response to pH; IEA:Ensembl.
DR   GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; IDA:BHF-UCL.
DR   GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR   GO; GO:0010232; P:vascular transport; IEA:Ensembl.
DR   GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR   GO; GO:0042908; P:xenobiotic transport; ISS:ARUK-UCL.
DR   Gene3D; 1.20.1440.80; -; 1.
DR   Gene3D; 1.20.5.1130; -; 1.
DR   InterPro; IPR035091; Alpha_helix_dom_sf.
DR   InterPro; IPR000500; Connexin.
DR   InterPro; IPR002261; Connexin43.
DR   InterPro; IPR013124; Connexin43_C.
DR   InterPro; IPR034634; Connexin_C.
DR   InterPro; IPR019570; Connexin_CCC.
DR   InterPro; IPR017990; Connexin_CS.
DR   InterPro; IPR013092; Connexin_N.
DR   InterPro; IPR038359; Connexin_N_sf.
DR   PANTHER; PTHR11984; PTHR11984; 1.
DR   PANTHER; PTHR11984:SF33; PTHR11984:SF33; 1.
DR   Pfam; PF00029; Connexin; 1.
DR   Pfam; PF03508; Connexin43; 1.
DR   PRINTS; PR00206; CONNEXIN.
DR   PRINTS; PR01132; CONNEXINA1.
DR   SMART; SM00037; CNX; 1.
DR   SMART; SM01089; Connexin_CCC; 1.
DR   SUPFAM; SSF118220; SSF118220; 1.
DR   PROSITE; PS00407; CONNEXINS_1; 1.
DR   PROSITE; PS00408; CONNEXINS_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cataract; Cell junction; Cell membrane;
KW   Disease variant; Disulfide bond; Endoplasmic reticulum; Gap junction;
KW   Hypotrichosis; Isopeptide bond; Membrane; Palmoplantar keratoderma;
KW   Phosphoprotein; Reference proteome; S-nitrosylation; Transmembrane;
KW   Transmembrane helix; Ubl conjugation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P08050"
FT   CHAIN           2..382
FT                   /note="Gap junction alpha-1 protein"
FT                   /id="PRO_0000057801"
FT   TOPO_DOM        2..23
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P08050"
FT   TRANSMEM        24..44
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        45..76
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P08050"
FT   TRANSMEM        77..97
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        98..155
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P08050"
FT   TRANSMEM        156..176
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        177..207
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P08050"
FT   TRANSMEM        208..228
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        229..382
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P08050"
FT   REGION          244..382
FT                   /note="Interaction with NOV"
FT                   /evidence="ECO:0000250|UniProtKB:P08050"
FT   REGION          264..382
FT                   /note="Interaction with UBQLN4"
FT                   /evidence="ECO:0000250|UniProtKB:P23242"
FT   REGION          317..382
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        317..340
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         5
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P08050"
FT   MOD_RES         247
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P23242"
FT   MOD_RES         255
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:15605363,
FT                   ECO:0007744|PubMed:21406692"
FT   MOD_RES         262
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:14702389,
FT                   ECO:0000269|PubMed:15605363"
FT   MOD_RES         271
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P23242"
FT   MOD_RES         275
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P23242"
FT   MOD_RES         306
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P23242"
FT   MOD_RES         314
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21406692"
FT   MOD_RES         325
FT                   /note="Phosphoserine; by CK1"
FT                   /evidence="ECO:0000269|PubMed:12270943"
FT   MOD_RES         326
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P23242"
FT   MOD_RES         328
FT                   /note="Phosphoserine; by CK1"
FT                   /evidence="ECO:0000269|PubMed:12270943"
FT   MOD_RES         330
FT                   /note="Phosphoserine; by CK1"
FT                   /evidence="ECO:0000269|PubMed:12270943"
FT   MOD_RES         344
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21406692"
FT   MOD_RES         365
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P23242"
FT   MOD_RES         368
FT                   /note="Phosphoserine; by PKC/PRKCG and PKC/PRKCD"
FT                   /evidence="ECO:0000250|UniProtKB:P23242"
FT   MOD_RES         369
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P23242"
FT   MOD_RES         373
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P08050"
FT   DISULFID        54..192
FT                   /evidence="ECO:0000269|PubMed:9430691"
FT   DISULFID        187..198
FT                   /evidence="ECO:0000269|PubMed:9430691"
FT   CROSSLNK        144
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO)"
FT                   /evidence="ECO:0000269|PubMed:22411987"
FT   CROSSLNK        237
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO)"
FT                   /evidence="ECO:0000269|PubMed:22411987"
FT   VARIANT         2
FT                   /note="G -> V (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:18161618"
FT                   /id="VAR_058990"
FT   VARIANT         7
FT                   /note="L -> V (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:19338053"
FT                   /id="VAR_058991"
FT   VARIANT         8
FT                   /note="G -> V (in PPKCA1; can form functional gap
FT                   junctions; results in enhanced hemichannel activity that
FT                   causes increased cell death; dbSNP:rs864309644)"
FT                   /evidence="ECO:0000269|PubMed:25168385"
FT                   /id="VAR_075754"
FT   VARIANT         11
FT                   /note="L -> I (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:28258662"
FT                   /id="VAR_078238"
FT   VARIANT         11
FT                   /note="L -> P (in ODDD; dbSNP:rs121912969)"
FT                   /evidence="ECO:0000269|PubMed:16709485,
FT                   ECO:0000269|PubMed:21670345"
FT                   /id="VAR_058992"
FT   VARIANT         17
FT                   /note="Y -> S (in ODDD; dbSNP:rs104893961)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015747"
FT   VARIANT         18
FT                   /note="S -> P (in ODDD; dbSNP:rs104893962)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015748"
FT   VARIANT         21
FT                   /note="G -> R (in ODDD; dbSNP:rs104893963)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015749"
FT   VARIANT         22
FT                   /note="G -> E (in ODDD; dbSNP:rs104893964)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015750"
FT   VARIANT         23
FT                   /note="K -> T (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015751"
FT   VARIANT         27
FT                   /note="S -> P (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:14729836"
FT                   /id="VAR_038356"
FT   VARIANT         31
FT                   /note="I -> M (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:14729836"
FT                   /id="VAR_038357"
FT   VARIANT         40
FT                   /note="A -> V (in ODDD; dbSNP:rs1554200992)"
FT                   /evidence="ECO:0000269|PubMed:12457340,
FT                   ECO:0000269|PubMed:14729836, ECO:0000269|PubMed:16378922,
FT                   ECO:0000269|PubMed:19338053"
FT                   /id="VAR_015752"
FT   VARIANT         41..44
FT                   /note="Missing (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:21670345"
FT                   /id="VAR_070439"
FT   VARIANT         41
FT                   /note="V -> L (found in a patient with hidrotic ectodermal
FT                   dysplasia, abortive features of oculodentodigital dysplasia
FT                   and extensive hyperkeratosis of the skin; unknown
FT                   pathological significance; the patient also carries GJB2
FT                   variant H-127)"
FT                   /evidence="ECO:0000269|PubMed:15757815"
FT                   /id="VAR_058993"
FT   VARIANT         44
FT                   /note="A -> V (in EKVP3; loss of localization to the plasma
FT                   membrane, retention in the Golgi apparatus;
FT                   dbSNP:rs794729675)"
FT                   /evidence="ECO:0000269|PubMed:25398053"
FT                   /id="VAR_075755"
FT   VARIANT         47
FT                   /note="D -> H (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:24508941"
FT                   /id="VAR_071009"
FT   VARIANT         49
FT                   /note="Q -> K (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015753"
FT   VARIANT         49
FT                   /note="Q -> P (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:19338053"
FT                   /id="VAR_058994"
FT   VARIANT         49
FT                   /note="Q -> QQ (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:19338053"
FT                   /id="VAR_058995"
FT   VARIANT         52
FT                   /note="F -> FF (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015754"
FT   VARIANT         59
FT                   /note="P -> H (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:16219735"
FT                   /id="VAR_058996"
FT   VARIANT         69
FT                   /note="S -> Y (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:14729836"
FT                   /id="VAR_038358"
FT   VARIANT         76
FT                   /note="R -> H (in HSS; overlapping features with
FT                   oculodentodigital dysplasia; dbSNP:rs267606844)"
FT                   /evidence="ECO:0000269|PubMed:14974090"
FT                   /id="VAR_058997"
FT   VARIANT         76
FT                   /note="R -> S (in ODDD; dbSNP:rs267606845)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015755"
FT   VARIANT         86
FT                   /note="S -> Y (in ODDD; de novo mutation found in a
FT                   sporadic case)"
FT                   /evidence="ECO:0000269|PubMed:24508941"
FT                   /id="VAR_071010"
FT   VARIANT         90
FT                   /note="L -> V (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015756"
FT   VARIANT         95
FT                   /note="H -> R (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:16222672"
FT                   /id="VAR_058998"
FT   VARIANT         96
FT                   /note="V -> A (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:19338053"
FT                   /id="VAR_058999"
FT   VARIANT         96
FT                   /note="V -> E (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:16813608"
FT                   /id="VAR_059000"
FT   VARIANT         96
FT                   /note="V -> M (in ODDD; dbSNP:rs28931601)"
FT                   /evidence="ECO:0000269|PubMed:15108203"
FT                   /id="VAR_059001"
FT   VARIANT         98
FT                   /note="Y -> C (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015757"
FT   VARIANT         102
FT                   /note="K -> N (in ODDD; dbSNP:rs1554201011)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015758"
FT   VARIANT         106
FT                   /note="L -> P (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:19338053"
FT                   /id="VAR_059002"
FT   VARIANT         106
FT                   /note="L -> R (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:24508941"
FT                   /id="VAR_071011"
FT   VARIANT         110
FT                   /note="E -> D (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:16378922"
FT                   /id="VAR_059003"
FT   VARIANT         113
FT                   /note="L -> P (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:14729836,
FT                   ECO:0000269|PubMed:16813608"
FT                   /id="VAR_038359"
FT   VARIANT         130
FT                   /note="I -> T (in ODDD; dbSNP:rs1554201017)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015759"
FT   VARIANT         134
FT                   /note="K -> E (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015760"
FT   VARIANT         134
FT                   /note="K -> N (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:14729836"
FT                   /id="VAR_038360"
FT   VARIANT         138
FT                   /note="G -> R (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015761"
FT   VARIANT         143
FT                   /note="G -> S (in SDTY3; dbSNP:rs28931600)"
FT                   /evidence="ECO:0000269|PubMed:14729836"
FT                   /id="VAR_038361"
FT   VARIANT         147
FT                   /note="M -> T (in ODDD; dbSNP:rs1057518872)"
FT                   /evidence="ECO:0000269|PubMed:16378922"
FT                   /id="VAR_059004"
FT   VARIANT         148
FT                   /note="R -> Q (in ODDD; dbSNP:rs962041031)"
FT                   /evidence="ECO:0000269|PubMed:14729836"
FT                   /id="VAR_014095"
FT   VARIANT         154
FT                   /note="T -> A (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:17509830,
FT                   ECO:0000269|PubMed:19338053"
FT                   /id="VAR_059005"
FT   VARIANT         154
FT                   /note="T -> N (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:16813608"
FT                   /id="VAR_059006"
FT   VARIANT         168
FT                   /note="A -> T (in dbSNP:rs2228961)"
FT                   /id="VAR_014096"
FT   VARIANT         169
FT                   /note="Missing (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:16378922"
FT                   /id="VAR_059007"
FT   VARIANT         194
FT                   /note="H -> P (in ODDD; atypical form of ODDD characterized
FT                   by the predominance of the ocular involvement and by the
FT                   absence of hand and/or foot syndactyly and absence of any
FT                   neurologic signs; dbSNP:rs104893966)"
FT                   /evidence="ECO:0000269|PubMed:15637728"
FT                   /id="VAR_059008"
FT   VARIANT         201
FT                   /note="S -> F (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:19338053"
FT                   /id="VAR_059009"
FT   VARIANT         202
FT                   /note="R -> H (in ODDD; dbSNP:rs750294638)"
FT                   /evidence="ECO:0000269|PubMed:12457340,
FT                   ECO:0000269|PubMed:14729836, ECO:0000269|PubMed:19338053"
FT                   /id="VAR_015762"
FT   VARIANT         206
FT                   /note="K -> R (in ODDD; dbSNP:rs397518464)"
FT                   /evidence="ECO:0000269|PubMed:23550541"
FT                   /id="VAR_070440"
FT   VARIANT         216
FT                   /note="V -> L (in ODDD; dbSNP:rs1554201043)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015763"
FT   VARIANT         220
FT                   /note="S -> Y (in ODDD)"
FT                   /evidence="ECO:0000269|PubMed:16813608"
FT                   /id="VAR_059010"
FT   VARIANT         227
FT                   /note="E -> D (in EKVP3; loss of localization to the plasma
FT                   membrane, retention in the Golgi apparatus;
FT                   dbSNP:rs875989815)"
FT                   /evidence="ECO:0000269|PubMed:25398053"
FT                   /id="VAR_075756"
FT   VARIANT         239
FT                   /note="R -> Q (in CMDR; dbSNP:rs764670582)"
FT                   /evidence="ECO:0000269|PubMed:23951358"
FT                   /id="VAR_070441"
FT   VARIANT         239
FT                   /note="R -> W (in congenital heart malformations)"
FT                   /evidence="ECO:0000269|PubMed:15978203"
FT                   /id="VAR_014100"
FT   VARIANT         251
FT                   /note="S -> T (in congenital heart malformations)"
FT                   /evidence="ECO:0000269|PubMed:15978203"
FT                   /id="VAR_059011"
FT   VARIANT         253
FT                   /note="A -> P (in congenital heart malformations)"
FT                   /evidence="ECO:0000269|PubMed:15978203"
FT                   /id="VAR_059012"
FT   VARIANT         253
FT                   /note="A -> V (in dbSNP:rs17653265)"
FT                   /evidence="ECO:0000269|PubMed:12457340"
FT                   /id="VAR_015764"
FT   VARIANT         283
FT                   /note="P -> L (in congenital heart malformations)"
FT                   /evidence="ECO:0000269|PubMed:15978203"
FT                   /id="VAR_014101"
FT   VARIANT         290
FT                   /note="T -> N (in congenital heart malformations)"
FT                   /evidence="ECO:0000269|PubMed:15978203"
FT                   /id="VAR_014102"
FT   VARIANT         326
FT                   /note="T -> A"
FT                   /evidence="ECO:0000269|PubMed:7715640"
FT                   /id="VAR_059013"
FT   VARIANT         352
FT                   /note="E -> G (in heart malformations)"
FT                   /evidence="ECO:0000269|PubMed:7715640"
FT                   /id="VAR_059014"
FT   VARIANT         362
FT                   /note="R -> Q (in HLHS1 and AVSD3; unknown pathological
FT                   significance; associated with Q-376 in one individual with
FT                   atrioventricular septal defect; abolishes phosphorylation
FT                   by PKA and PKC; dbSNP:rs2227885)"
FT                   /evidence="ECO:0000269|PubMed:11470490"
FT                   /id="VAR_032924"
FT   VARIANT         364
FT                   /note="S -> P (in heart malformations; shows abnormalities
FT                   in the regulation of cell-cell communication as compared
FT                   with cells expressing normal GJA1)"
FT                   /evidence="ECO:0000269|PubMed:7715640"
FT                   /id="VAR_059015"
FT   VARIANT         365
FT                   /note="S -> N (in heart malformations)"
FT                   /evidence="ECO:0000269|PubMed:7715640"
FT                   /id="VAR_059016"
FT   VARIANT         373
FT                   /note="S -> G"
FT                   /evidence="ECO:0000269|PubMed:7715640"
FT                   /id="VAR_059017"
FT   VARIANT         376
FT                   /note="R -> Q (in HLHS1 and AVSD3; unknown pathological
FT                   significance; associated with Q-362 in one individual with
FT                   atrioventricular septal defect; abolishes phosphorylation
FT                   by PKA and PKC; dbSNP:rs104893965)"
FT                   /evidence="ECO:0000269|PubMed:11470490"
FT                   /id="VAR_032925"
FT   HELIX           240..242
FT                   /evidence="ECO:0007829|PDB:2LL2"
FT   HELIX           246..253
FT                   /evidence="ECO:0007829|PDB:2LL2"
FT   HELIX           255..257
FT                   /evidence="ECO:0007829|PDB:2LL2"
SQ   SEQUENCE   382 AA;  43008 MW;  7DDDAD8040284176 CRC64;
     MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS AFRCNTQQPG
     CENVCYDKSF PISHVRFWVL QIIFVSVPTL LYLAHVFYVM RKEEKLNKKE EELKVAQTDG
     VNVDMHLKQI EIKKFKYGIE EHGKVKMRGG LLRTYIISIL FKSIFEVAFL LIQWYIYGFS
     LSAVYTCKRD PCPHQVDCFL SRPTEKTIFI IFMLVVSLVS LALNIIELFY VFFKGVKDRV
     KGKSDPYHAT SGALSPAKDC GSQKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN
     YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNSKKLAAG HELQPLAIVD
     QRPSSRASSR ASSRPRPDDL EI
//
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