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1.A.24.1.1
Connexin 43 (gap junction α-1 protein), CX43 (transports ATP, ADP and AMP better than CX32 does; Goldberg et al., 2002). Hemichannels mediate efflux of glutathione, glutamate and other amino acids as well as ATP (Stridh et al., 2008; Kang et al., 2008). CX43 has a half life of ~3 h due to ubiquitination and lysosomal and proteasomal degradation (Leithe and Rivedal, 2007). Cx43 and Cx46 regulate each other's expression and turnover in a reciprocal manner in addition to their conventional roles as gap junction proteins in lens cells (Banerjee et al., 2011). A mutant form of Connexin 43 causes Oculodentodigital dysplasia (Gabriel et al., 2011).  Suppressing the function of Cx43 promotes expression of wound healing-associated genes and hibitits scarring (Tarzemany et al. 2015).  Channel conductance and size selectivity are largely determined by pore diameter, whereas charge selectivity results from the amino-terminal domains; transitions between fully open and (multiple) closed states involves global changes in structure of the pore-forming domains (Ek Vitorín et al. 2016). The human Cx43 orthologue is almost identical to the rat protein.  It may mediate resistance against the parkinsonian toxin, 1-methyl-4-phenylpyridine (MPP+) which induces apoptosis in neuroblastoma cells by modulating mitochondrial apoptosis (Kim et al. 2016).  Dopamine neurons may be the target of MPP+ and play a role in Parkinson's disease. In humans, Cx43 plays roles in the development of the central nervous system and in the progression of glioma (Wang et al. 2017).  It interacts with and is regulated by many proteins including NOV (CCN3, IGFBP9; P48745) (Giepmans 2006). Cx43 plays roles in intercellular communication mediated by extracellular vesicles, tunnelling nanotubes and gap junctions (Ribeiro-Rodrigues et al. 2017). Phosphorylation of Cx43 leads to astrocytic coupling and apoptosis, and ultimately, to vascular regeneration in retinal ischemia (Slavi et al. 2018).

Accession Number:P08050
Protein Name:CXA1 aka CX43 aka GJA1 aka CXN-43
Length:382
Molecular Weight:43031.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:4
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate glutamate, Amino acids, ATP, small molecules

Cross database links:

Genevestigator: P08050
eggNOG: maNOG05724
RefSeq: NP_036699.1   
Entrez Gene ID: 24392   
Pfam: PF00029    PF03508    PF10582   
KEGG: rno:24392   

Gene Ontology

GO:0005922 C:connexon complex
GO:0005769 C:early endosome
GO:0005789 C:endoplasmic reticulum membrane
GO:0005916 C:fascia adherens
GO:0030660 C:Golgi-associated vesicle membrane
GO:0005887 C:integral to plasma membrane
GO:0005764 C:lysosome
GO:0045121 C:membrane raft
GO:0005741 C:mitochondrial outer membrane
GO:0005771 C:multivesicular body
GO:0005243 F:gap junction channel activity
GO:0030165 F:PDZ domain binding
GO:0017124 F:SH3 domain binding
GO:0006915 P:apoptosis
GO:0015867 P:ATP transport
GO:0007267 P:cell-cell signaling
GO:0016264 P:gap junction assembly
GO:0008285 P:negative regulation of cell proliferation
GO:0048812 P:neuron projection morphogenesis
GO:0045732 P:positive regulation of protein catabolic pr...
GO:0051259 P:protein oligomerization
GO:0051924 P:regulation of calcium ion transport
GO:0043434 P:response to peptide hormone stimulus
GO:0009268 P:response to pH
GO:0010232 P:vascular transport

References (8)

[1] “Connexin43: a protein from rat heart homologous to a gap junction protein from liver.”  Beyer E.C.et.al.   2826492
[2] “Molecular cloning of a rat uterine gap junction protein and analysis of gene expression during gestation.”  Lang L.M.et.al.   1852114
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “The Mr 28,000 gap junction proteins from rat heart and liver are different but related.”  Nicholson B.J.et.al.   2987225
[5] “Affinity purification of a rat-brain junctional protein, connexin 43.”  Dupont E.et.al.   1652440
[6] “Connexon integrity is maintained by non-covalent bonds: intramolecular disulfide bonds link the extracellular domains in rat connexin-43.”  John S.A.et.al.   1651718
[7] “Membrane topology and quaternary structure of cardiac gap junction ion channels.”  Yeager M.et.al.   1371548
[8] “Identification and functional analysis of novel phosphorylation sites in Cx43 in rat primary granulosa cells.”  Yogo K.et.al.   12417300
Structure:
1R5S   3CYY     

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS AFRCNTQQPG 
61:	CENVCYDKSF PISHVRFWVL QIIFVSVPTL LYLAHVFYVM RKEEKLNKKE EELKVAQTDG 
121:	VNVEMHLKQI EIKKFKYGIE EHGKVKMRGG LLRTYIISIL FKSVFEVAFL LIQWYIYGFS 
181:	LSAVYTCKRD PCPHQVDCFL SRPTEKTIFI IFMLVVSLVS LALNIIELFY VFFKGVKDRV 
241:	KGRSDPYHAT TGPLSPSKDC GSPKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN 
301:	YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNAKKVAAG HELQPLAIVD 
361:	QRPSSRASSR ASSRPRPDDL EI