UniProtKB - P18246 (CXA1_BOVIN)
Protein
Gap junction alpha-1 protein
Gene
GJA1
Organism
Bos taurus (Bovine)
Status
Functioni
Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract. May play a role in cell growth inhibition through the regulation of NOV expression and localization. Plays an essential role in gap junction communication in the ventricles (By similarity).By similarity
GO - Molecular functioni
- beta-catenin binding Source: Ensembl
- gap junction channel activity Source: AgBase
- gap junction channel activity involved in cell communication by electrical coupling Source: Ensembl
- gap junction hemi-channel activity Source: UniProtKB
- ion transmembrane transporter activity Source: Ensembl
- PDZ domain binding Source: AgBase
- SH3 domain binding Source: AgBase
- tubulin binding Source: UniProtKB
GO - Biological processi
- adult heart development Source: AgBase
- ATP transport Source: AgBase
- blood vessel morphogenesis Source: AgBase
- bone development Source: UniProtKB
- bone remodeling Source: UniProtKB
- cell-cell signaling Source: AgBase
- cell communication Source: AgBase
- cellular protein localization Source: Ensembl
- embryonic heart tube development Source: AgBase
- epithelial cell maturation Source: AgBase
- establishment of mitotic spindle orientation Source: Ensembl
- heart development Source: AgBase
- heart looping Source: AgBase
- in utero embryonic development Source: AgBase
- microtubule-based transport Source: UniProtKB
- negative regulation of cell growth Source: UniProtKB
- negative regulation of cell population proliferation Source: AgBase
- negative regulation of gonadotropin secretion Source: Ensembl
- negative regulation of trophoblast cell migration Source: Ensembl
- neuron migration Source: AgBase
- neuron projection morphogenesis Source: AgBase
- positive regulation of gene expression Source: Ensembl
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: AgBase
- positive regulation of mesodermal cell differentiation Source: Ensembl
- positive regulation of morphogenesis of an epithelium Source: Ensembl
- positive regulation of protein catabolic process Source: AgBase
- positive regulation of stem cell proliferation Source: Ensembl
- positive regulation of striated muscle tissue development Source: AgBase
- positive regulation of vascular associated smooth muscle cell proliferation Source: Ensembl
- protein complex oligomerization Source: AgBase
- regulation of apoptotic process Source: UniProtKB
- regulation of heart contraction Source: AgBase
- response to pH Source: AgBase
- signal transduction Source: Ensembl
- skeletal muscle tissue regeneration Source: AgBase
- spermatogenesis Source: UniProtKB
Enzyme and pathway databases
Reactomei | R-BTA-190840, Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane R-BTA-190861, Gap junction assembly R-BTA-191650, Regulation of gap junction activity |
Names & Taxonomyi
Protein namesi | Recommended name: Gap junction alpha-1 proteinAlternative name(s): Connexin-43 Short name: Cx43 Vascular smooth muscle connexin-43 |
Gene namesi | Name:GJA1 |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Organism-specific databases
VGNCi | VGNC:29370, GJA1 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum By similarity
Plasma membrane
- Cell membrane By similarity; Multi-pass membrane protein Sequence analysis
Other locations
- gap junction By similarity
Note: Localizes at the intercalated disk (ICD) in cardiomyocytes and proper localization at ICD is dependent on TMEM65.By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB-SubCell
Endosome
- early endosome Source: AgBase
- late endosome Source: AgBase
- multivesicular body Source: AgBase
Lysosome
- lysosome Source: AgBase
Mitochondrion
- mitochondrion Source: UniProtKB
Nucleus
- nucleoplasm Source: Ensembl
Plasma Membrane
- apical plasma membrane Source: UniProtKB
- connexin complex Source: AgBase
- plasma membrane Source: UniProtKB
Other locations
- cell junction Source: UniProtKB
- cytoplasm Source: AgBase
- fascia adherens Source: AgBase
- gap junction Source: AgBase
- integral component of membrane Source: UniProtKB-KW
- intercalated disc Source: UniProtKB
- tight junction Source: Ensembl
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 2 – 23 | CytoplasmicBy similarityAdd BLAST | 22 | |
Transmembranei | 24 – 44 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 45 – 76 | ExtracellularBy similarityAdd BLAST | 32 | |
Transmembranei | 77 – 97 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 98 – 156 | CytoplasmicBy similarityAdd BLAST | 59 | |
Transmembranei | 157 – 177 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 178 – 208 | ExtracellularBy similarityAdd BLAST | 31 | |
Transmembranei | 209 – 229 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 230 – 383 | CytoplasmicBy similarityAdd BLAST | 154 |
Keywords - Cellular componenti
Cell junction, Cell membrane, Endoplasmic reticulum, Gap junction, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000057799 | 2 – 383 | Gap junction alpha-1 proteinAdd BLAST | 382 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 5 | PhosphoserineBy similarity | 1 | |
Disulfide bondi | 54 ↔ 193 | By similarity | ||
Cross-linki | 145 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity | ||
Disulfide bondi | 188 ↔ 199 | By similarity | ||
Cross-linki | 238 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity | ||
Modified residuei | 248 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 256 | PhosphoserineBy similarity | 1 | |
Modified residuei | 258 | PhosphoserineBy similarity | 1 | |
Modified residuei | 263 | PhosphoserineBy similarity | 1 | |
Modified residuei | 272 | S-nitrosocysteineBy similarity | 1 | |
Modified residuei | 276 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 307 | PhosphoserineBy similarity | 1 | |
Modified residuei | 315 | PhosphoserineBy similarity | 1 | |
Modified residuei | 326 | Phosphoserine; by CK1By similarity | 1 | |
Modified residuei | 327 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 329 | Phosphoserine; by CK1By similarity | 1 | |
Modified residuei | 331 | Phosphoserine; by CK1By similarity | 1 | |
Modified residuei | 345 | PhosphoserineBy similarity | 1 | |
Modified residuei | 366 | PhosphoserineBy similarity | 1 | |
Modified residuei | 369 | Phosphoserine; by PKC/PRKCG and PKC/PRKCDBy similarity | 1 | |
Modified residuei | 370 | PhosphoserineBy similarity | 1 | |
Modified residuei | 374 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Phosphorylation at Ser-326, Ser-329 and Ser-331 by CK1 modulates gap junction assembly. Phosphorylated at Ser-369 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of gap junction activity. Phosphorylation at Ser-369 by PRKCD triggers its internalization into small vesicles leading to proteasome-mediated degradation (By similarity).By similarity
Sumoylated with SUMO1, SUMO2 and SUMO3, which may regulate the level of functional Cx43 gap junctions at the plasma membrane. May be desumoylated by SENP1 or SENP2 (By similarity).By similarity
Acetylated in the developing cortex; leading to delocalization from the cell membrane.By similarity
Keywords - PTMi
Acetylation, Disulfide bond, Isopeptide bond, Phosphoprotein, S-nitrosylation, Ubl conjugationProteomic databases
PaxDbi | P18246 |
PeptideAtlasi | P18246 |
PRIDEi | P18246 |
PTM databases
iPTMneti | P18246 |
Expressioni
Gene expression databases
Bgeei | ENSBTAG00000001835, Expressed in prefrontal cortex and 18 other tissues |
Interactioni
Subunit structurei
A connexon is composed of a hexamer of connexins.
Interacts with SGSM3 (By similarity).
Interacts with RIC1/CIP150 (By similarity).
Interacts with CNST and CSNK1D (By similarity).
Interacts (via C-terminus) with TJP1.
Interacts (via C-terminus) with SRC (via SH3 domain).
Interacts (not ubiquitinated) with UBQLN4 (via UBA domain) (By similarity).
Interacts with NOV.
Interacts with TMEM65 (By similarity).
By similarityGO - Molecular functioni
- beta-catenin binding Source: Ensembl
- PDZ domain binding Source: AgBase
- SH3 domain binding Source: AgBase
- tubulin binding Source: UniProtKB
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000002398 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 245 – 383 | Interaction with NOVBy similarityAdd BLAST | 139 | |
Regioni | 265 – 383 | Interaction with UBQLN4By similarityAdd BLAST | 119 |
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QRAE, Eukaryota |
GeneTreei | ENSGT00990000203503 |
HOGENOMi | CLU_037388_0_0_1 |
InParanoidi | P18246 |
OMAi | LVIQWYM |
OrthoDBi | 823525at2759 |
TreeFami | TF329606 |
Family and domain databases
Gene3Di | 1.20.1440.80, 1 hit 1.20.5.1130, 1 hit |
InterProi | View protein in InterPro IPR035091, Alpha_helix_dom_sf IPR000500, Connexin IPR002261, Connexin43 IPR013124, Connexin43_C IPR034634, Connexin_C IPR019570, Connexin_CCC IPR017990, Connexin_CS IPR013092, Connexin_N IPR038359, Connexin_N_sf |
PANTHERi | PTHR11984, PTHR11984, 1 hit PTHR11984:SF33, PTHR11984:SF33, 1 hit |
Pfami | View protein in Pfam PF00029, Connexin, 1 hit PF03508, Connexin43, 1 hit |
PRINTSi | PR00206, CONNEXIN PR01132, CONNEXINA1 |
SMARTi | View protein in SMART SM00037, CNX, 1 hit SM01089, Connexin_CCC, 1 hit |
SUPFAMi | SSF118220, SSF118220, 1 hit |
PROSITEi | View protein in PROSITE PS00407, CONNEXINS_1, 1 hit PS00408, CONNEXINS_2, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P18246-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS
60 70 80 90 100
AFRCNTQQPG CENVCYDKSF PISHVRFWVL QIIFVSVPTL LYLAHVFYVM
110 120 130 140 150
RKEEKLNKKE EELKVVAQTD GANVDMHLKQ IEIKKFKYGI EEHGKVKMRG
160 170 180 190 200
GLLRTYIISI LFKSVFEVAF LLIQWYIYGF SLSAVYTCKR DPCPHQVDCF
210 220 230 240 250
LSRPTEKTIF IIFMLVVSLV SLALNIIELF YVFFKGVKDR VKGKSDPYHT
260 270 280 290 300
TTGPLSPSKD CGSPKYAYFN GCSSPTAPLS PMSPPGYKLV TGDRNNSSCR
310 320 330 340 350
NYNKQASEQN WANYSAEQNR MGQAGSTISN SHAQPFDFPD DHQNSKKLDA
360 370 380
GHELQPLAIV DQRPSSRASS RASSRPRPDD LEI
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J05535 mRNA Translation: AAA30459.1 BC105464 mRNA Translation: AAI05465.1 |
PIRi | A36623 |
RefSeqi | NP_776493.1, NM_174068.2 |
Genome annotation databases
Ensembli | ENSBTAT00000002398; ENSBTAP00000002398; ENSBTAG00000001835 |
GeneIDi | 281193 |
KEGGi | bta:281193 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J05535 mRNA Translation: AAA30459.1 BC105464 mRNA Translation: AAI05465.1 |
PIRi | A36623 |
RefSeqi | NP_776493.1, NM_174068.2 |
3D structure databases
SMRi | P18246 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000002398 |
PTM databases
iPTMneti | P18246 |
Proteomic databases
PaxDbi | P18246 |
PeptideAtlasi | P18246 |
PRIDEi | P18246 |
Genome annotation databases
Ensembli | ENSBTAT00000002398; ENSBTAP00000002398; ENSBTAG00000001835 |
GeneIDi | 281193 |
KEGGi | bta:281193 |
Organism-specific databases
CTDi | 2697 |
VGNCi | VGNC:29370, GJA1 |
Phylogenomic databases
eggNOGi | ENOG502QRAE, Eukaryota |
GeneTreei | ENSGT00990000203503 |
HOGENOMi | CLU_037388_0_0_1 |
InParanoidi | P18246 |
OMAi | LVIQWYM |
OrthoDBi | 823525at2759 |
TreeFami | TF329606 |
Enzyme and pathway databases
Reactomei | R-BTA-190840, Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane R-BTA-190861, Gap junction assembly R-BTA-191650, Regulation of gap junction activity |
Gene expression databases
Bgeei | ENSBTAG00000001835, Expressed in prefrontal cortex and 18 other tissues |
Family and domain databases
Gene3Di | 1.20.1440.80, 1 hit 1.20.5.1130, 1 hit |
InterProi | View protein in InterPro IPR035091, Alpha_helix_dom_sf IPR000500, Connexin IPR002261, Connexin43 IPR013124, Connexin43_C IPR034634, Connexin_C IPR019570, Connexin_CCC IPR017990, Connexin_CS IPR013092, Connexin_N IPR038359, Connexin_N_sf |
PANTHERi | PTHR11984, PTHR11984, 1 hit PTHR11984:SF33, PTHR11984:SF33, 1 hit |
Pfami | View protein in Pfam PF00029, Connexin, 1 hit PF03508, Connexin43, 1 hit |
PRINTSi | PR00206, CONNEXIN PR01132, CONNEXINA1 |
SMARTi | View protein in SMART SM00037, CNX, 1 hit SM01089, Connexin_CCC, 1 hit |
SUPFAMi | SSF118220, SSF118220, 1 hit |
PROSITEi | View protein in PROSITE PS00407, CONNEXINS_1, 1 hit PS00408, CONNEXINS_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CXA1_BOVIN | |
Accessioni | P18246Primary (citable) accession number: P18246 Secondary accession number(s): Q2KJ91 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1990 |
Last sequence update: | January 23, 2007 | |
Last modified: | December 2, 2020 | |
This is version 170 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families