CXA1_RABIT
ID CXA1_RABIT Reviewed; 382 AA.
AC Q6TYA7;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Gap junction alpha-1 protein;
DE AltName: Full=Connexin-43;
DE Short=Cx43;
GN Name=GJA1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15083360; DOI=10.1007/s00427-004-0403-7;
RA van der Heyden M.A., van Eijk M., Wilders R., de Bakker J.M., Opthof T.;
RT "Connexin43 orthologues in vertebrates: phylogeny from fish to man.";
RL Dev. Genes Evol. 214:261-266(2004).
RN [2]
RP PHOSPHORYLATION AT SER-368, AND MUTAGENESIS OF SER-368.
RX PubMed=15642736; DOI=10.1074/jbc.m407762200;
RA Lin D., Takemoto D.J.;
RT "Oxidative activation of protein kinase Cgamma through the C1 domain.
RT Effects on gap junctions.";
RL J. Biol. Chem. 280:13682-13693(2005).
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-325, Ser-328 and Ser-330 by CK1 modulates
CC gap junction assembly (By similarity). Phosphorylated at Ser-368 by
CC PRKCG; phosphorylation induces disassembly of gap junction plaques and
CC inhibition of gap junction activity. Phosphorylation at Ser-368 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:0000269|PubMed:15642736}.
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; AY382590; AAR33084.1; -; Genomic_DNA.
DR RefSeq; NP_001185877.1; NM_001198948.1.
DR RefSeq; XP_008261519.1; XM_008263297.2.
DR AlphaFoldDB; Q6TYA7; -.
DR BMRB; Q6TYA7; -.
DR SMR; Q6TYA7; -.
DR BioGRID; 1171958; 1.
DR STRING; 9986.ENSOCUP00000019547; -.
DR iPTMnet; Q6TYA7; -.
DR GeneID; 100008935; -.
DR KEGG; ocu:100008935; -.
DR CTD; 2697; -.
DR eggNOG; ENOG502QRAE; Eukaryota.
DR HOGENOM; CLU_037388_0_0_1; -.
DR InParanoid; Q6TYA7; -.
DR OMA; LIQWYMY; -.
DR OrthoDB; 823525at2759; -.
DR TreeFam; TF329606; -.
DR Proteomes; UP000001811; Unplaced.
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:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0014704; C:intercalated disc; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
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: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:0015631; F:tubulin binding; ISS:UniProtKB.
DR GO; GO:0060348; P:bone development; ISS:UniProtKB.
DR GO; GO:0046849; P:bone remodeling; ISS:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; IEA:Ensembl.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:InterPro.
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: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:0010628; P:positive regulation of gene expression; IEA:Ensembl.
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:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IEA:Ensembl.
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 1: Evidence at protein 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..382
FT /note="Gap junction alpha-1 protein"
FT /id="PRO_0000313001"
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:0000250|UniProtKB:P17302"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08050"
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:0000250|UniProtKB:P23242"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT MOD_RES 325
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:P17302"
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:0000250|UniProtKB:P17302"
FT MOD_RES 330
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:P17302"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17302"
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:0000269|PubMed:15642736"
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: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."
FT /evidence="ECO:0000269|PubMed:15642736"
SQ SEQUENCE 382 AA; 43033 MW; CAFEF68793025077 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
KGKSDPYHAT TGPLSPSKDC GSPKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN
YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNSKKLAAG HELQPLAIVD
QRPSSRASSR ASSRPRPDDL EI
