ID CXA1_RAT Reviewed; 382 AA. AC P08050; Q53ZE1; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 223. 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=Cxn-43; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2826492; DOI=10.1083/jcb.105.6.2621; RA Beyer E.C., Paul D.L., Goodenough D.A.; RT "Connexin43: a protein from rat heart homologous to a gap junction protein RT from liver."; RL J. Cell Biol. 105:2621-2629(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Uterus; RX PubMed=1852114; DOI=10.1152/ajpendo.1991.260.5.e787; RA Lang L.M., Beyer E.C., Schwartz A.L., Gitlin J.D.; RT "Molecular cloning of a rat uterine gap junction protein and analysis of RT gene expression during gestation."; RL Am. J. Physiol. 260:E787-E793(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Sprague-Dawley; RA Ma L.X., Peng Y.W.; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Heart; 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 [5] RP PROTEIN SEQUENCE OF 2-33. RC TISSUE=Heart; RX PubMed=2987225; DOI=10.1016/s0021-9258(18)88810-x; RA Nicholson B.J., Gros D.B., Kent S.B.H., Hood L.E., Revel J.-P.; RT "The Mr 28,000 gap junction proteins from rat heart and liver are different RT but related."; RL J. Biol. Chem. 260:6514-6517(1985). RN [6] RP PROTEIN SEQUENCE OF 2-16. RC TISSUE=Brain; RX PubMed=1652440; DOI=10.1111/j.1432-1033.1991.tb21075.x; RA Dupont E., el Aoumari A., Fromaget C., Briand J.-C., Gros D.; RT "Affinity purification of a rat-brain junctional protein, connexin 43."; RL Eur. J. Biochem. 200:263-270(1991). RN [7] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND TOPOLOGY. RX PubMed=2472402; DOI=10.1083/jcb.108.6.2241; RA Yancey S.B., John S.A., Lal R., Austin B.J., Revel J.P.; RT "The 43-kD polypeptide of heart gap junctions: immunolocalization, RT topology, and functional domains."; RL J. Cell Biol. 108:2241-2254(1989). RN [8] RP DISULFIDE BONDS. RX PubMed=1651718; DOI=10.1016/0006-291x(91)91037-d; RA John S.A., Revel J.-P.; RT "Connexon integrity is maintained by non-covalent bonds: intramolecular RT disulfide bonds link the extracellular domains in rat connexin-43."; RL Biochem. Biophys. Res. Commun. 178:1312-1318(1991). RN [9] RP PHOSPHORYLATION AT SER-365; SER-368; SER-369 AND SER-373. RX PubMed=12417300; DOI=10.1016/s0014-5793(02)03441-5; RA Yogo K., Ogawa T., Akiyama M., Ishida N., Takeya T.; RT "Identification and functional analysis of novel phosphorylation sites in RT Cx43 in rat primary granulosa cells."; RL FEBS Lett. 531:132-136(2002). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, AND 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 SUBCELLULAR LOCATION, AND 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 INTERACTION WITH UBQLN4. RX PubMed=20127391; DOI=10.1007/s10858-010-9397-9; RA Kieken F., Spagnol G., Su V., Lau A.F., Sorgen P.L.; RT "NMR structure note: UBA domain of CIP75."; RL J. Biomol. NMR 46:245-250(2010). RN [13] RP INTERACTION WITH ANK3 AND PKP2, AND TISSUE SPECIFICITY. RX PubMed=21617128; DOI=10.1161/circresaha.111.247023; RA Sato P.Y., Coombs W., Lin X., Nekrasova O., Green K.J., Isom L.L., RA Taffet S.M., Delmar M.; RT "Interactions between ankyrin-G, Plakophilin-2, and Connexin43 at the RT cardiac intercalated disc."; RL Circ. Res. 109:193-201(2011). RN [14] RP INDUCTION. RX PubMed=22549838; DOI=10.1038/ncomms1812; RA Negoro H., Kanematsu A., Doi M., Suadicani S.O., Matsuo M., Imamura M., RA Okinami T., Nishikawa N., Oura T., Matsui S., Seo K., Tainaka M., Urabe S., RA Kiyokage E., Todo T., Okamura H., Tabata Y., Ogawa O.; RT "Involvement of urinary bladder Connexin43 and the circadian clock in RT coordination of diurnal micturition rhythm."; RL Nat. Commun. 3:809-809(2012). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; SER-257; SER-306; SER-314; RP SER-325; THR-326; SER-328 AND SER-330, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [16] RP PHOSPHORYLATION AT SER-368, AND MUTAGENESIS OF SER-368. RX PubMed=24500718; DOI=10.1074/jbc.m113.533265; RA Cone A.C., Cavin G., Ambrosi C., Hakozaki H., Wu-Zhang A.X., Kunkel M.T., RA Newton A.C., Sosinsky G.E.; RT "Protein kinase Cdelta-mediated phosphorylation of Connexin43 gap junction RT channels causes movement within gap junctions followed by vesicle RT internalization and protein degradation."; RL J. Biol. Chem. 289:8781-8798(2014). RN [17] RP STRUCTURE BY ELECTRON MICROSCOPY (17.0 ANGSTROMS), SUBUNIT, AND TOPOLOGY. RX PubMed=1371548; DOI=10.1016/0022-2836(92)90253-g; RA Yeager M., Gilula N.B.; RT "Membrane topology and quaternary structure of cardiac gap junction ion RT channels."; RL J. Mol. Biol. 223:929-948(1992). RN [18] RP STRUCTURE BY NMR OF 255-381, AND INTERACTION WITH TJP1 AND SRC. RX PubMed=15492000; DOI=10.1074/jbc.m409552200; RA Sorgen P.L., Duffy H.S., Sahoo P., Coombs W., Delmar M., Spray D.C.; RT "Structural changes in the carboxyl terminus of the gap junction protein RT connexin43 indicates signaling between binding domains for c-Src and zonula RT occludens-1."; RL J. Biol. Chem. 279:54695-54701(2004). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 374-382 IN COMPLEX WITH TJP1, RP SUBCELLULAR LOCATION, AND INTERACTION WITH TJP1. RX PubMed=18636092; DOI=10.1038/emboj.2008.138; RA Chen J., Pan L., Wei Z., Zhao Y., Zhang M.; RT "Domain-swapped dimerization of ZO-1 PDZ2 generates specific and regulatory RT connexin43-binding sites."; RL EMBO J. 27:2113-2123(2008). 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. Negative regulator CC of bladder functional capacity: acts by enhancing intercellular CC electrical and chemical transmission, thus sensitizing bladder muscles CC to cholinergic neural stimuli and causing them to contract (By CC similarity). May play a role in cell growth inhibition through the CC regulation of NOV expression and localization (PubMed:15181016). Plays CC an essential role in gap junction communication in the ventricles (By CC similarity). {ECO:0000250|UniProtKB:P23242, CC ECO:0000269|PubMed:15181016}. CC -!- SUBUNIT: A connexon is composed of a hexamer of connexins CC (PubMed:1371548). Interacts with SGSM3 (By similarity). Interacts with CC RIC1/CIP150 (By similarity). Interacts with CNST and CSNK1D (By CC similarity). Interacts (via C-terminus) with TJP1 (PubMed:15492000, CC PubMed:18636092). Interacts (via C-terminus) with SRC (via SH3 domain) CC (PubMed:15492000). Interacts (not ubiquitinated) with UBQLN4 (via UBA CC domain) (PubMed:20127391). Interacts with NOV (PubMed:15181016, CC PubMed:15213231). Interacts with TMEM65 (By similarity). Interacts with CC ANK3/ANKG and PKP2 (PubMed:21617128). {ECO:0000250|UniProtKB:P17302, CC ECO:0000250|UniProtKB:P23242, ECO:0000269|PubMed:1371548, CC ECO:0000269|PubMed:15181016, ECO:0000269|PubMed:15213231, CC ECO:0000269|PubMed:15492000, ECO:0000269|PubMed:18636092, CC ECO:0000269|PubMed:20127391, ECO:0000269|PubMed:21617128}. CC -!- INTERACTION: CC P08050; Q63664: Kcnj8; NbExp=4; IntAct=EBI-476947, EBI-6991142; CC P08050; Q8VCZ6: Sgsm3; Xeno; NbExp=4; IntAct=EBI-476947, EBI-525155; CC P08050; Q9NRR5: UBQLN4; Xeno; NbExp=2; IntAct=EBI-476947, EBI-711226; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18636092}; CC Multi-pass membrane protein {ECO:0000255}. Cell junction, gap junction CC {ECO:0000269|PubMed:15213231, ECO:0000269|PubMed:18636092, CC ECO:0000269|PubMed:2472402}. Endoplasmic reticulum CC {ECO:0000250|UniProtKB:P23242}. Note=Localizes at the intercalated disk CC (ICD) in cardiomyocytes and the proper localization at ICD is dependent CC on TMEM65. {ECO:0000250|UniProtKB:P23242}. CC -!- TISSUE SPECIFICITY: Detected in ventricle and atrium (at protein CC level). {ECO:0000269|PubMed:21617128, ECO:0000269|PubMed:2472402}. CC -!- INDUCTION: In bladder smooth muscle cells, exhibits night/day CC variations with low levels during the sleep phase, at circadian time CC (CT) 4-8 (at protein level). Expression starts to increase around CT12 CC and forms a plateau during the active phase (CT16-24) (at protein CC level). {ECO:0000269|PubMed:22549838}. CC -!- PTM: Contains at least one intramolecular disulfide bond. CC -!- PTM: Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates CC gap junction assembly. Phosphorylated at Ser-368 by PRKCG; CC phosphorylation induces disassembly of gap junction plaques and CC inhibition of gap junction activity (By similarity). Phosphorylation at CC Ser-368 by PRKCD triggers its internalization into small vesicles CC leading to proteasome-mediated degradation (PubMed:24500718). CC {ECO:0000250|UniProtKB:P17302, ECO:0000250|UniProtKB:Q6TYA7, CC ECO:0000269|PubMed:24500718}. 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 (By similarity). CC {ECO:0000250|UniProtKB:P17302}. 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 -!- 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; X06656; CAA29855.1; -; mRNA. DR EMBL; AY324140; AAP88589.1; -; mRNA. DR EMBL; BC081842; AAH81842.1; -; mRNA. DR PIR; A24047; A24047. DR PIR; S00532; S00532. DR RefSeq; NP_036699.1; NM_012567.2. DR PDB; 1R5S; NMR; -; A=255-382. DR PDB; 2N8T; NMR; -; B=276-289. DR PDB; 3CYY; X-ray; 2.40 A; C/D=374-382. DR PDBsum; 1R5S; -. DR PDBsum; 2N8T; -. DR PDBsum; 3CYY; -. DR AlphaFoldDB; P08050; -. DR BMRB; P08050; -. DR SMR; P08050; -. DR BioGRID; 246562; 302. DR CORUM; P08050; -. DR DIP; DIP-34793N; -. DR IntAct; P08050; 20. DR MINT; P08050; -. DR STRING; 10116.ENSRNOP00000001054; -. DR TCDB; 1.A.24.1.1; the gap junction-forming connexin (connexin) family. DR iPTMnet; P08050; -. DR PhosphoSitePlus; P08050; -. DR SwissPalm; P08050; -. DR PaxDb; 10116-ENSRNOP00000001054; -. DR DNASU; 24392; -. DR Ensembl; ENSRNOT00000100494.1; ENSRNOP00000093256.1; ENSRNOG00000000805.7. DR Ensembl; ENSRNOT00055026181; ENSRNOP00055021299; ENSRNOG00055015329. DR Ensembl; ENSRNOT00060013216; ENSRNOP00060010026; ENSRNOG00060008013. DR Ensembl; ENSRNOT00065004734; ENSRNOP00065003381; ENSRNOG00065003322. DR GeneID; 24392; -. DR KEGG; rno:24392; -. DR UCSC; RGD:2690; rat. DR AGR; RGD:2690; -. DR CTD; 2697; -. DR RGD; 2690; Gja1. DR eggNOG; ENOG502QRAE; Eukaryota. DR GeneTree; ENSGT01090000260070; -. DR HOGENOM; CLU_037388_0_0_1; -. DR InParanoid; P08050; -. DR OMA; WYMYGFT; -. DR OrthoDB; 5301774at2759; -. DR PhylomeDB; P08050; -. DR TreeFam; TF329606; -. DR Reactome; R-RNO-190840; Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane. DR Reactome; R-RNO-190861; Gap junction assembly. DR Reactome; R-RNO-190873; Gap junction degradation. DR Reactome; R-RNO-191650; Regulation of gap junction activity. DR Reactome; R-RNO-196025; Formation of annular gap junctions. DR Reactome; R-RNO-9013406; RHOQ GTPase cycle. DR EvolutionaryTrace; P08050; -. DR PRO; PR:P08050; -. DR Proteomes; UP000002494; Chromosome 20. DR Bgee; ENSRNOG00000000805; Expressed in ovary and 20 other cell types or tissues. DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB. DR GO; GO:0030054; C:cell junction; ISO:RGD. DR GO; GO:0044291; C:cell-cell contact zone; ISO:RGD. DR GO; GO:0005911; C:cell-cell junction; ISO:RGD. DR GO; GO:0005922; C:connexin complex; IDA:UniProtKB. DR GO; GO:0043292; C:contractile fiber; ISO:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0005769; C:early endosome; IDA:RGD. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0005768; C:endosome; IDA:RGD. DR GO; GO:0005916; C:fascia adherens; IDA:RGD. DR GO; GO:0005921; C:gap junction; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA: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:0014704; C:intercalated disc; IDA:RGD. DR GO; GO:0005882; C:intermediate filament; ISO:RGD. DR GO; GO:0005770; C:late endosome; IDA:RGD. DR GO; GO:0016328; C:lateral plasma membrane; ISO:RGD. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL. DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:RGD. DR GO; GO:0005739; C:mitochondrion; ISO:RGD. DR GO; GO:0005771; C:multivesicular body; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA. DR GO; GO:0070160; C:tight junction; ISO:RGD. DR GO; GO:0008013; F:beta-catenin binding; ISO:RGD. DR GO; GO:0048487; F:beta-tubulin binding; ISO:RGD. DR GO; GO:0071253; F:connexin binding; IPI:RGD. DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA. DR GO; GO:0015562; F:efflux transmembrane transporter activity; ISO:RGD. DR GO; GO:0005243; F:gap junction channel activity; IDA:CAFA. DR GO; GO:1903763; F:gap junction channel activity involved in cell communication by electrical coupling; ISO:RGD. DR GO; GO:0055077; F:gap junction hemi-channel activity; ISS:UniProtKB. DR GO; GO:0034634; F:glutathione transmembrane transporter activity; ISO:RGD. DR GO; GO:0015075; F:monoatomic ion transmembrane transporter activity; ISO:RGD. DR GO; GO:0030165; F:PDZ domain binding; IPI:CAFA. DR GO; GO:0019904; F:protein domain specific binding; IDA:RGD. DR GO; GO:1990782; F:protein tyrosine kinase binding; ISO:RGD. DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD. DR GO; GO:0017124; F:SH3 domain binding; IDA:RGD. DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD. DR GO; GO:0015631; F:tubulin binding; ISS:UniProtKB. DR GO; GO:0007512; P:adult heart development; ISO:RGD. DR GO; GO:0015867; P:ATP transport; IMP:RGD. DR GO; GO:0003294; P:atrial ventricular junction remodeling; ISO:RGD. DR GO; GO:0048514; P:blood vessel morphogenesis; ISO:RGD. DR GO; GO:0060348; P:bone development; ISS:UniProtKB. DR GO; GO:0046849; P:bone remodeling; ISS:UniProtKB. DR GO; GO:0061337; P:cardiac conduction; ISO:RGD. DR GO; GO:0010643; P:cell communication by chemical coupling; ISO:RGD. DR GO; GO:0010644; P:cell communication by electrical coupling; ISO:RGD. DR GO; GO:0045216; P:cell-cell junction organization; ISO:RGD. DR GO; GO:0007267; P:cell-cell signaling; IDA:RGD. DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:RGD. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD. DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEP:RGD. DR GO; GO:0071467; P:cellular response to pH; ISO:RGD. DR GO; GO:0002544; P:chronic inflammatory response; IMP:RGD. DR GO; GO:0002069; P:columnar/cuboidal epithelial cell maturation; ISO:RGD. DR GO; GO:0046697; P:decidualization; IEP:RGD. DR GO; GO:0042733; P:embryonic digit morphogenesis; ISO:RGD. DR GO; GO:0035050; P:embryonic heart tube development; ISO:RGD. DR GO; GO:0003158; P:endothelium development; IEP:RGD. DR GO; GO:1905867; P:epididymis development; IEP:RGD. DR GO; GO:0000132; P:establishment of mitotic spindle orientation; ISO:RGD. DR GO; GO:0140115; P:export across plasma membrane; ISO:RGD. DR GO; GO:0016264; P:gap junction assembly; TAS:UniProtKB. DR GO; GO:0014047; P:glutamate secretion; ISO:RGD. DR GO; GO:0007507; P:heart development; IEP:RGD. DR GO; GO:0001947; P:heart looping; ISO:RGD. DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD. DR GO; GO:0002088; P:lens development in camera-type eye; ISO:RGD. DR GO; GO:0035437; P:maintenance of protein localization in endoplasmic reticulum; IDA:RGD. DR GO; GO:0008584; P:male gonad development; ISO:RGD. DR GO; GO:0099111; P:microtubule-based transport; ISS:UniProtKB. DR GO; GO:0060156; P:milk ejection reflex; ISO:RGD. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; ISO:RGD. DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; IMP:RGD. DR GO; GO:0030308; P:negative regulation of cell growth; IMP:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD. DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IDA:RGD. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:RGD. DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD. DR GO; GO:0032277; P:negative regulation of gonadotropin secretion; ISO:RGD. DR GO; GO:1901164; P:negative regulation of trophoblast cell migration; ISO:RGD. DR GO; GO:0097402; P:neuroblast migration; ISO:RGD. DR GO; GO:0001764; P:neuron migration; ISO:RGD. DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:RGD. DR GO; GO:0001649; P:osteoblast differentiation; ISO:RGD. DR GO; GO:2000987; P:positive regulation of behavioral fear response; IMP:RGD. DR GO; GO:0010652; P:positive regulation of cell communication by chemical coupling; IMP:RGD. 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; IMP:RGD. DR GO; GO:1904446; P:positive regulation of establishment of Sertoli cell barrier; IMP:RGD. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD. DR GO; GO:0003104; P:positive regulation of glomerular filtration; IMP:RGD. DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:RGD. DR GO; GO:0045836; P:positive regulation of meiotic nuclear division; IMP:RGD. DR GO; GO:1905772; P:positive regulation of mesodermal cell differentiation; ISO:RGD. DR GO; GO:1905332; P:positive regulation of morphogenesis of an epithelium; ISO:RGD. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:RGD. DR GO; GO:2000648; P:positive regulation of stem cell proliferation; ISO:RGD. DR GO; GO:0045844; P:positive regulation of striated muscle tissue development; ISO:RGD. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:RGD. DR GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD. DR GO; GO:0008104; P:protein localization; ISO:RGD. DR GO; GO:0110053; P:regulation of actin filament organization; IMP:RGD. DR GO; GO:0042981; P:regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0060371; P:regulation of atrial cardiac muscle cell membrane depolarization; ISO:RGD. DR GO; GO:2000810; P:regulation of bicellular tight junction assembly; IMP:RGD. DR GO; GO:0030500; P:regulation of bone mineralization; ISO:RGD. DR GO; GO:0046850; P:regulation of bone remodeling; ISO:RGD. DR GO; GO:0051924; P:regulation of calcium ion transport; IMP:RGD. DR GO; GO:0010649; P:regulation of cell communication by electrical coupling; IDA:RGD. DR GO; GO:0008016; P:regulation of heart contraction; ISO:RGD. DR GO; GO:0022898; P:regulation of transmembrane transporter activity; IMP:CAFA. DR GO; GO:0060373; P:regulation of ventricular cardiac muscle cell membrane depolarization; ISO:RGD. DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; ISO:RGD. DR GO; GO:0032355; P:response to estradiol; IEP:RGD. DR GO; GO:0034405; P:response to fluid shear stress; IEP:RGD. DR GO; GO:0009749; P:response to glucose; IEP:RGD. DR GO; GO:0002931; P:response to ischemia; IEP:RGD. DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD. DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD. DR GO; GO:0009268; P:response to pH; IDA:RGD. DR GO; GO:0032526; P:response to retinoic acid; IEP:RGD. DR GO; GO:0007165; P:signal transduction; ISO:RGD. DR GO; GO:0043403; P:skeletal muscle tissue regeneration; ISO:RGD. DR GO; GO:0007283; P:spermatogenesis; IMP:RGD. DR GO; GO:0042110; P:T cell activation; ISO:RGD. DR GO; GO:0042098; P:T cell proliferation; ISO:RGD. DR GO; GO:0055085; P:transmembrane transport; IDA:CAFA. DR GO; GO:0010232; P:vascular transport; IMP:RGD. DR GO; GO:0042311; P:vasodilation; IMP:RGD. DR GO; GO:0042908; P:xenobiotic transport; ISO:RGD. DR DisProt; DP00278; -. DR Gene3D; 1.20.5.1130; Connexin43; 1. DR Gene3D; 1.20.1440.80; Gap junction channel protein cysteine-rich domain; 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; CONNEXIN; 1. DR PANTHER; PTHR11984:SF33; GAP JUNCTION ALPHA-1 PROTEIN; 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; Connexin43; 1. DR PROSITE; PS00407; CONNEXINS_1; 1. DR PROSITE; PS00408; CONNEXINS_2; 1. DR Genevisible; P08050; RN. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cell junction; Cell membrane; KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; KW Gap junction; Isopeptide bond; Membrane; Phosphoprotein; KW Reference proteome; S-nitrosylation; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:1652440, FT ECO:0000269|PubMed:2987225" FT CHAIN 2..382 FT /note="Gap junction alpha-1 protein" FT /id="PRO_0000057804" FT TOPO_DOM 2..23 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:1371548, FT ECO:0000305|PubMed:2472402" FT TRANSMEM 24..44 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 45..76 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:1371548, FT ECO:0000305|PubMed:2472402" FT TRANSMEM 77..97 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 98..155 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:1371548, FT ECO:0000305|PubMed:2472402" FT TRANSMEM 156..176 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 177..207 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:1371548, FT ECO:0000305|PubMed:2472402" FT TRANSMEM 208..228 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 229..382 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:1371548, FT ECO:0000305|PubMed:2472402" FT REGION 244..382 FT /note="Interaction with NOV" FT /evidence="ECO:0000269|PubMed:15181016, FT ECO:0000269|PubMed:15213231" 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..337 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 5 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 247 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P23242" FT MOD_RES 255 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P17302" FT MOD_RES 257 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 262 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P17302" 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:0007744|PubMed:22673903" FT MOD_RES 314 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 325 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 326 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 328 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 330 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 365 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12417300" FT MOD_RES 368 FT /note="Phosphoserine; by PKC/PRKCG and PKC/PRKCD" FT /evidence="ECO:0000269|PubMed:24500718, FT ECO:0000305|PubMed:12417300" FT MOD_RES 369 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12417300" FT MOD_RES 373 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12417300" FT DISULFID 54..192 FT /evidence="ECO:0000250|UniProtKB:P17302" FT DISULFID 187..198 FT /evidence="ECO:0000250|UniProtKB:P17302" FT CROSSLNK 144 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250|UniProtKB:P17302" FT CROSSLNK 237 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250|UniProtKB:P17302" FT MUTAGEN 368 FT /note="S->A: Loss of phosphorylation by PKC/PRKCD." FT /evidence="ECO:0000269|PubMed:24500718" FT CONFLICT 2 FT /note="G -> A (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 16 FT /note="A -> T (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 28 FT /note="V -> I (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT TURN 256..259 FT /evidence="ECO:0007829|PDB:1R5S" FT STRAND 263..265 FT /evidence="ECO:0007829|PDB:1R5S" FT STRAND 283..285 FT /evidence="ECO:0007829|PDB:2N8T" FT STRAND 297..300 FT /evidence="ECO:0007829|PDB:1R5S" FT HELIX 317..325 FT /evidence="ECO:0007829|PDB:1R5S" FT HELIX 342..348 FT /evidence="ECO:0007829|PDB:1R5S" FT TURN 349..352 FT /evidence="ECO:0007829|PDB:1R5S" FT STRAND 360..362 FT /evidence="ECO:0007829|PDB:1R5S" FT TURN 366..370 FT /evidence="ECO:0007829|PDB:1R5S" FT STRAND 379..381 FT /evidence="ECO:0007829|PDB:3CYY" SQ SEQUENCE 382 AA; 43031 MW; 0196416EA6A69490 CRC64; MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS AFRCNTQQPG CENVCYDKSF PISHVRFWVL QIIFVSVPTL LYLAHVFYVM RKEEKLNKKE EELKVAQTDG VNVEMHLKQI EIKKFKYGIE EHGKVKMRGG LLRTYIISIL FKSVFEVAFL LIQWYIYGFS LSAVYTCKRD PCPHQVDCFL SRPTEKTIFI IFMLVVSLVS LALNIIELFY VFFKGVKDRV KGRSDPYHAT TGPLSPSKDC GSPKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNAKKVAAG HELQPLAIVD QRPSSRASSR ASSRPRPDDL EI //