CXA1_BOVIN
ID CXA1_BOVIN Reviewed; 383 AA.
AC P18246; Q2KJ91;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Gap junction alpha-1 protein;
DE AltName: Full=Connexin-43;
DE Short=Cx43;
DE AltName: Full=Vascular smooth muscle connexin-43;
GN Name=GJA1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1695901; DOI=10.1016/s0021-9258(19)38273-0;
RA Lash J.A., Critser E.S., Pressler M.L.;
RT "Cloning of a gap junctional protein from vascular smooth muscle and
RT expression in two-cell mouse embryos.";
RL J. Biol. Chem. 265:13113-13117(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thymus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
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. May play a role in cell
CC growth inhibition through the regulation of NOV expression and
CC localization. Plays an essential role in gap junction communication in
CC 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 with SGSM3 (By similarity). Interacts with RIC1/CIP150 (By similarity).
CC Interacts with CNST and CSNK1D (By similarity). Interacts (via C-
CC terminus) with TJP1. Interacts (via C-terminus) with SRC (via SH3
CC domain). Interacts (not ubiquitinated) with UBQLN4 (via UBA domain) (By
CC similarity). Interacts with NOV. Interacts with TMEM65 (By similarity).
CC {ECO:0000250|UniProtKB:P08050, ECO:0000250|UniProtKB:P17302,
CC ECO:0000250|UniProtKB:P23242}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P17302};
CC Multi-pass membrane protein {ECO:0000255}. Cell junction, gap junction
CC {ECO:0000250|UniProtKB:P17302}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P23242}. Note=Localizes at the intercalated disk
CC (ICD) in cardiomyocytes and proper localization at ICD is dependent on
CC TMEM65. {ECO:0000250|UniProtKB:P23242}.
CC -!- PTM: Phosphorylation at Ser-326, Ser-329 and Ser-331 by CK1 modulates
CC gap junction assembly. Phosphorylated at Ser-369 by PRKCG;
CC phosphorylation induces disassembly of gap junction plaques and
CC inhibition of gap junction activity. Phosphorylation at Ser-369 by
CC PRKCD triggers its internalization into small vesicles leading to
CC proteasome-mediated degradation (By similarity).
CC {ECO:0000250|UniProtKB:P08050, ECO:0000250|UniProtKB:P17302,
CC ECO:0000250|UniProtKB:Q6TYA7}.
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: 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; J05535; AAA30459.1; -; mRNA.
DR EMBL; BC105464; AAI05465.1; -; mRNA.
DR PIR; A36623; A36623.
DR RefSeq; NP_776493.1; NM_174068.2.
DR AlphaFoldDB; P18246; -.
DR SMR; P18246; -.
DR STRING; 9913.ENSBTAP00000002398; -.
DR iPTMnet; P18246; -.
DR PaxDb; P18246; -.
DR PeptideAtlas; P18246; -.
DR PRIDE; P18246; -.
DR Ensembl; ENSBTAT00000002398; ENSBTAP00000002398; ENSBTAG00000001835.
DR GeneID; 281193; -.
DR KEGG; bta:281193; -.
DR CTD; 2697; -.
DR VEuPathDB; HostDB:ENSBTAG00000001835; -.
DR VGNC; VGNC:29370; GJA1.
DR eggNOG; ENOG502QRAE; Eukaryota.
DR GeneTree; ENSGT01050000244914; -.
DR HOGENOM; CLU_037388_0_0_1; -.
DR InParanoid; P18246; -.
DR OMA; LIQWYMY; -.
DR OrthoDB; 823525at2759; -.
DR TreeFam; TF329606; -.
DR Reactome; R-BTA-190840; Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
DR Reactome; R-BTA-190861; Gap junction assembly.
DR Reactome; R-BTA-191650; Regulation of gap junction activity.
DR Reactome; R-BTA-9013406; RHOQ GTPase cycle.
DR Proteomes; UP000009136; Chromosome 9.
DR Bgee; ENSBTAG00000001835; Expressed in rumen papilla and 100 other tissues.
DR ExpressionAtlas; P18246; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0030054; C:cell junction; ISS:UniProtKB.
DR GO; GO:0005922; C:connexin complex; ISS:AgBase.
DR GO; GO:0005737; C:cytoplasm; ISS:AgBase.
DR GO; GO:0005769; C:early endosome; ISS:AgBase.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005916; C:fascia adherens; ISS:AgBase.
DR GO; GO:0005921; C:gap junction; ISS:AgBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0014704; C:intercalated disc; ISS:UniProtKB.
DR GO; GO:0005770; C:late endosome; ISS:AgBase.
DR GO; GO:0005764; C:lysosome; ISS:AgBase.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005771; C:multivesicular body; ISS:AgBase.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0070160; C:tight junction; IEA:Ensembl.
DR GO; GO:0008013; F:beta-catenin binding; IEA:Ensembl.
DR GO; GO:0005243; F:gap junction channel activity; ISS:AgBase.
DR GO; GO:1903763; F:gap junction channel activity involved in cell communication by electrical coupling; IEA:Ensembl.
DR GO; GO:0055077; F:gap junction hemi-channel activity; ISS:UniProtKB.
DR GO; GO:0015075; F:ion transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0030165; F:PDZ domain binding; ISS:AgBase.
DR GO; GO:0017124; F:SH3 domain binding; ISS:AgBase.
DR GO; GO:0015631; F:tubulin binding; ISS:UniProtKB.
DR GO; GO:0007512; P:adult heart development; ISS:AgBase.
DR GO; GO:0015867; P:ATP transport; ISS:AgBase.
DR GO; GO:0048514; P:blood vessel morphogenesis; ISS:AgBase.
DR GO; GO:0060348; P:bone development; ISS:UniProtKB.
DR GO; GO:0046849; P:bone remodeling; ISS:UniProtKB.
DR GO; GO:0007154; P:cell communication; ISS:AgBase.
DR GO; GO:0007267; P:cell-cell signaling; ISS:AgBase.
DR GO; GO:0035050; P:embryonic heart tube development; ISS:AgBase.
DR GO; GO:0002070; P:epithelial cell maturation; ISS:AgBase.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; ISS:AgBase.
DR GO; GO:0001947; P:heart looping; ISS:AgBase.
DR GO; GO:0001701; P:in utero embryonic development; ISS:AgBase.
DR GO; GO:0099111; P:microtubule-based transport; ISS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:AgBase.
DR GO; GO:0032277; P:negative regulation of gonadotropin secretion; IEA:Ensembl.
DR GO; GO:1901164; P:negative regulation of trophoblast cell migration; IEA:Ensembl.
DR GO; GO:0001764; P:neuron migration; ISS:AgBase.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:AgBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:AgBase.
DR GO; GO:1905772; P:positive regulation of mesodermal cell differentiation; IEA:Ensembl.
DR GO; GO:1905332; P:positive regulation of morphogenesis of an epithelium; IEA:Ensembl.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:AgBase.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0045844; P:positive regulation of striated muscle tissue development; ISS:AgBase.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0051259; P:protein complex oligomerization; ISS:AgBase.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0008016; P:regulation of heart contraction; ISS:AgBase.
DR GO; GO:0009268; P:response to pH; ISS:AgBase.
DR GO; GO:0007165; P:signal transduction; IEA:Ensembl.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; ISS:AgBase.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Acetylation; Cell junction; Cell membrane; Disulfide bond;
KW Endoplasmic reticulum; Gap junction; Isopeptide bond; Membrane;
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..383
FT /note="Gap junction alpha-1 protein"
FT /id="PRO_0000057799"
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..156
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT TRANSMEM 157..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 178..208
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT TRANSMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..383
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT REGION 245..383
FT /note="Interaction with NOV"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT REGION 265..383
FT /note="Interaction with UBQLN4"
FT /evidence="ECO:0000250|UniProtKB:P23242"
FT REGION 318..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 318..338
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 248
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P23242"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT MOD_RES 272
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P23242"
FT MOD_RES 276
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P23242"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23242"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT MOD_RES 326
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT MOD_RES 327
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P23242"
FT MOD_RES 329
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT MOD_RES 331
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23242"
FT MOD_RES 369
FT /note="Phosphoserine; by PKC/PRKCG and PKC/PRKCD"
FT /evidence="ECO:0000250|UniProtKB:P23242"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23242"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08050"
FT DISULFID 54..193
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT DISULFID 188..199
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT CROSSLNK 145
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT CROSSLNK 238
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P17302"
SQ SEQUENCE 383 AA; 43188 MW; B77459AAD14142D8 CRC64;
MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS AFRCNTQQPG
CENVCYDKSF PISHVRFWVL QIIFVSVPTL LYLAHVFYVM RKEEKLNKKE EELKVVAQTD
GANVDMHLKQ IEIKKFKYGI EEHGKVKMRG GLLRTYIISI LFKSVFEVAF LLIQWYIYGF
SLSAVYTCKR DPCPHQVDCF LSRPTEKTIF IIFMLVVSLV SLALNIIELF YVFFKGVKDR
VKGKSDPYHT TTGPLSPSKD CGSPKYAYFN GCSSPTAPLS PMSPPGYKLV TGDRNNSSCR
NYNKQASEQN WANYSAEQNR MGQAGSTISN SHAQPFDFPD DHQNSKKLDA GHELQPLAIV
DQRPSSRASS RASSRPRPDD LEI
