CXA1_RAT
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 03-AUG-2022, entry version 214.
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 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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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).
CC {ECO:0000250|UniProtKB:P17302, ECO:0000250|UniProtKB:P23242,
CC ECO:0000269|PubMed:1371548, ECO:0000269|PubMed:15181016,
CC ECO:0000269|PubMed:15213231, ECO:0000269|PubMed:15492000,
CC ECO:0000269|PubMed:18636092, ECO:0000269|PubMed:20127391}.
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: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}.
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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; 19.
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 PaxDb; P08050; -.
DR PRIDE; P08050; -.
DR DNASU; 24392; -.
DR Ensembl; ENSRNOT00000100494; ENSRNOP00000093256; ENSRNOG00000000805.
DR GeneID; 24392; -.
DR KEGG; rno:24392; -.
DR UCSC; RGD:2690; rat.
DR CTD; 2697; -.
DR RGD; 2690; Gja1.
DR eggNOG; ENOG502QRAE; Eukaryota.
DR GeneTree; ENSGT01050000244914; -.
DR HOGENOM; CLU_037388_0_0_1; -.
DR InParanoid; P08050; -.
DR OMA; LIQWYMY; -.
DR OrthoDB; 823525at2759; -.
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 Reactome; R-RNO-9013409; RHOJ GTPase cycle.
DR EvolutionaryTrace; P08050; -.
DR PRO; PR:P08050; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000000805; Expressed in ovary and 20 other tissues.
DR Genevisible; P08050; RN.
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; IDA: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:0005887; C:integral component of plasma membrane; TAS:UniProtKB.
DR GO; GO:0014704; C:intercalated disc; ISO: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:0005764; C:lysosome; IDA: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: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:0006915; P:apoptotic process; IMP: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:0007154; P:cell communication; IMP: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; IEA:Ensembl.
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:0002070; P:epithelial cell maturation; ISO: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:0034220; P:ion transmembrane transport; 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: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:0061045; P:negative regulation of wound healing; IMP:RGD.
DR GO; GO:0097402; P:neuroblast migration; IEA:Ensembl.
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: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: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: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; ISS:UniProtKB.
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; 1.20.1440.80; -; 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; 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
