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P08050

- CXA1_RAT

UniProt

P08050 - CXA1_RAT

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Protein

Gap junction alpha-1 protein

Gene

Gja1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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. 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 (By similarity).By similarity

GO - Molecular functioni

  1. connexin binding Source: RGD
  2. gap junction channel activity Source: RGD
  3. PDZ domain binding Source: RGD
  4. protein domain specific binding Source: RGD
  5. SH3 domain binding Source: RGD
  6. signal transducer activity Source: Ensembl

GO - Biological processi

  1. adult heart development Source: Ensembl
  2. apoptotic process Source: RGD
  3. ATP transport Source: RGD
  4. atrial ventricular junction remodeling Source: Ensembl
  5. blood vessel morphogenesis Source: Ensembl
  6. cardiac conduction Source: Ensembl
  7. cell-cell signaling Source: RGD
  8. cell communication Source: RGD
  9. cell communication by chemical coupling Source: Ensembl
  10. cell communication by electrical coupling Source: Ensembl
  11. cellular response to mechanical stimulus Source: RGD
  12. chronic inflammatory response Source: RGD
  13. embryonic digit morphogenesis Source: Ensembl
  14. endothelium development Source: RGD
  15. epithelial cell maturation Source: Ensembl
  16. gap junction assembly Source: UniProtKB
  17. heart development Source: RGD
  18. heart looping Source: Ensembl
  19. in utero embryonic development Source: Ensembl
  20. lens development in camera-type eye Source: Ensembl
  21. milk ejection Source: Ensembl
  22. negative regulation of cardiac muscle cell proliferation Source: RGD
  23. negative regulation of cell proliferation Source: RGD
  24. negative regulation of DNA biosynthetic process Source: RGD
  25. negative regulation of endothelial cell proliferation Source: RGD
  26. negative regulation of gene expression Source: Ensembl
  27. negative regulation of wound healing Source: RGD
  28. neuron migration Source: Ensembl
  29. neuron projection morphogenesis Source: RGD
  30. osteoblast differentiation Source: Ensembl
  31. positive regulation of behavioral fear response Source: RGD
  32. positive regulation of cell communication by chemical coupling Source: RGD
  33. positive regulation of cytosolic calcium ion concentration Source: RGD
  34. positive regulation of gene expression Source: Ensembl
  35. positive regulation of glomerular filtration Source: RGD
  36. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  37. positive regulation of insulin secretion Source: RGD
  38. positive regulation of protein catabolic process Source: RGD
  39. positive regulation of striated muscle tissue development Source: Ensembl
  40. positive regulation of vasoconstriction Source: RGD
  41. positive regulation of vasodilation Source: RGD
  42. protein oligomerization Source: RGD
  43. regulation of atrial cardiac muscle cell membrane depolarization Source: Ensembl
  44. regulation of bone mineralization Source: Ensembl
  45. regulation of bone remodeling Source: Ensembl
  46. regulation of calcium ion transport Source: RGD
  47. regulation of tight junction assembly Source: RGD
  48. regulation of ventricular cardiac muscle cell membrane depolarization Source: Ensembl
  49. regulation of ventricular cardiac muscle cell membrane repolarization Source: Ensembl
  50. response to fluid shear stress Source: RGD
  51. response to glucose Source: RGD
  52. response to peptide hormone Source: RGD
  53. response to pH Source: RGD
  54. skeletal muscle tissue regeneration Source: Ensembl
  55. transmembrane transport Source: RGD
  56. vascular transport Source: RGD
Complete GO annotation...

Protein family/group databases

TCDBi1.A.24.1.1. the gap junction-forming connexin (connexin) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Gap junction alpha-1 protein
Alternative name(s):
Connexin-43
Short name:
Cx43
Gap junction 43 kDa heart protein
Gene namesi
Name:Gja1
Synonyms:Cxn-43
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 20

Organism-specific databases

RGDi2690. Gja1.

Subcellular locationi

Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication. Cell junctiongap junction 1 Publication

GO - Cellular componenti

  1. apical plasma membrane Source: Ensembl
  2. connexon complex Source: RGD
  3. contractile fiber Source: Ensembl
  4. cytoplasm Source: RGD
  5. cytosol Source: Ensembl
  6. early endosome Source: RGD
  7. endoplasmic reticulum membrane Source: Reactome
  8. endosome Source: RGD
  9. extracellular vesicular exosome Source: Ensembl
  10. fascia adherens Source: RGD
  11. gap junction Source: UniProtKB
  12. Golgi apparatus Source: BHF-UCL
  13. Golgi-associated vesicle membrane Source: Reactome
  14. Golgi membrane Source: Reactome
  15. integral component of plasma membrane Source: UniProtKB
  16. intermediate filament Source: Ensembl
  17. late endosome Source: RGD
  18. lateral plasma membrane Source: Ensembl
  19. lysosome Source: RGD
  20. membrane Source: MGI
  21. membrane raft Source: BHF-UCL
  22. mitochondrial outer membrane Source: RGD
  23. multivesicular body Source: RGD
  24. plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Gap junction, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed2 Publications
Chaini2 – 382381Gap junction alpha-1 proteinPRO_0000057804Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi54 ↔ 192By similarity
Cross-linki144 – 144Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Disulfide bondi187 ↔ 198By similarity
Cross-linki237 – 237Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei247 – 2471PhosphotyrosineBy similarity
Modified residuei255 – 2551PhosphoserineBy similarity
Modified residuei262 – 2621PhosphoserineBy similarity
Modified residuei271 – 2711S-nitrosocysteineBy similarity
Modified residuei306 – 3061PhosphoserineBy similarity
Modified residuei314 – 3141PhosphoserineBy similarity
Modified residuei325 – 3251Phosphoserine; by CK1By similarity
Modified residuei328 – 3281Phosphoserine; by CK1By similarity
Modified residuei330 – 3301Phosphoserine; by CK1By similarity
Modified residuei365 – 3651Phosphoserine1 Publication
Modified residuei368 – 3681Phosphoserine; by PKC/PRKCG1 Publication
Modified residuei369 – 3691Phosphoserine1 Publication
Modified residuei373 – 3731Phosphoserine1 Publication

Post-translational modificationi

Contains at least one intramolecular disulfide bond.
Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly. Phosphorylated at Ser-368 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of gap junction activity (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
S-nitrosylation at Cys-271 is enriched at the muscle endothelial gap junction in arteries, it augments channel permeability and may regulate of smooth muscle cell to endothelial cell communication.

Keywords - PTMi

Disulfide bond, Isopeptide bond, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

PaxDbiP08050.
PRIDEiP08050.

PTM databases

PhosphoSiteiP08050.

Expressioni

Inductioni

In bladder smooth muscle cells, exhibits night/day variations with low levels during the sleep phase, at circadian time (CT) 4-8 (at protein level). Expression starts to increase around CT12 and forms a plateau during the active phase (CT16-24) (at protein level).1 Publication

Gene expression databases

ExpressionAtlasiP08050. baseline and differential.
GenevestigatoriP08050.

Interactioni

Subunit structurei

A connexon is composed of a hexamer of connexins. Interacts with SGSM3. Interacts with RIC1/CIP150. Interacts with CNST and CSNK1D (By similarity). Interacts (via C-terminus) with TJP1. Interacts (via C-terminus) with SRC (via SH3 domain). Interacts with UBQLN4.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Sgsm3Q8VCZ64EBI-476947,EBI-525155From a different organism.

Protein-protein interaction databases

BioGridi246562. 116 interactions.
DIPiDIP-34793N.
IntActiP08050. 8 interactions.
MINTiMINT-1791096.

Structurei

Secondary structure

1
382
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni256 – 2594
Beta strandi263 – 2653
Beta strandi297 – 3004
Helixi317 – 3259
Helixi342 – 3487
Turni349 – 3524
Beta strandi360 – 3623
Turni366 – 3705
Beta strandi379 – 3813

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1R5SNMR-A255-382[»]
3CYYX-ray2.40C/D374-382[»]
DisProtiDP00278.
ProteinModelPortaliP08050.
SMRiP08050. Positions 252-382.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08050.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 1312Cytoplasmic1 PublicationAdd
BLAST
Topological domaini37 – 7640Extracellular1 PublicationAdd
BLAST
Topological domaini100 – 15455Cytoplasmic1 PublicationAdd
BLAST
Topological domaini178 – 20831Extracellular1 PublicationAdd
BLAST
Topological domaini232 – 382151Cytoplasmic1 PublicationAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei14 – 3623HelicalCuratedAdd
BLAST
Transmembranei77 – 9923HelicalCuratedAdd
BLAST
Transmembranei155 – 17723HelicalCuratedAdd
BLAST
Transmembranei209 – 23123HelicalCuratedAdd
BLAST

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG45368.
GeneTreeiENSGT00760000118780.
HOGENOMiHOG000231127.
HOVERGENiHBG009576.
InParanoidiP08050.
KOiK07372.
OMAiGANVDMH.
OrthoDBiEOG7P2XSS.
PhylomeDBiP08050.
TreeFamiTF329606.

Family and domain databases

InterProiIPR000500. Connexin.
IPR002261. Connexin43.
IPR013124. Connexin43_C.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERiPTHR11984. PTHR11984. 1 hit.
PfamiPF00029. Connexin. 1 hit.
PF03508. Connexin43. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]
PRINTSiPR00206. CONNEXIN.
PR01132. CONNEXINA1.
SMARTiSM00037. CNX. 1 hit.
SM01089. Connexin_CCC. 1 hit.
[Graphical view]
PROSITEiPS00407. CONNEXINS_1. 1 hit.
PS00408. CONNEXINS_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P08050-1 [UniParc]FASTAAdd to Basket

« Hide

        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 EELKVAQTDG VNVEMHLKQI EIKKFKYGIE EHGKVKMRGG
160 170 180 190 200
LLRTYIISIL FKSVFEVAFL LIQWYIYGFS LSAVYTCKRD PCPHQVDCFL
210 220 230 240 250
SRPTEKTIFI IFMLVVSLVS LALNIIELFY VFFKGVKDRV KGRSDPYHAT
260 270 280 290 300
TGPLSPSKDC GSPKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN
310 320 330 340 350
YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNAKKVAAG
360 370 380
HELQPLAIVD QRPSSRASSR ASSRPRPDDL EI
Length:382
Mass (Da):43,031
Last modified:January 23, 2007 - v2
Checksum:i0196416EA6A69490
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti2 – 21G → A AA sequence (PubMed:2987225)Curated
Sequence conflicti16 – 161A → T no nucleotide entry (PubMed:1852114)Curated
Sequence conflicti28 – 281V → I AA sequence (PubMed:2987225)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X06656 mRNA. Translation: CAA29855.1.
AY324140 mRNA. Translation: AAP88589.1.
BC081842 mRNA. Translation: AAH81842.1.
PIRiA24047.
S00532.
RefSeqiNP_036699.1. NM_012567.2.
XP_006256565.1. XM_006256503.2.
UniGeneiRn.10346.

Genome annotation databases

EnsembliENSRNOT00000001054; ENSRNOP00000001054; ENSRNOG00000000805.
GeneIDi24392.
KEGGirno:24392.
UCSCiRGD:2690. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X06656 mRNA. Translation: CAA29855.1 .
AY324140 mRNA. Translation: AAP88589.1 .
BC081842 mRNA. Translation: AAH81842.1 .
PIRi A24047.
S00532.
RefSeqi NP_036699.1. NM_012567.2.
XP_006256565.1. XM_006256503.2.
UniGenei Rn.10346.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1R5S NMR - A 255-382 [» ]
3CYY X-ray 2.40 C/D 374-382 [» ]
DisProti DP00278.
ProteinModelPortali P08050.
SMRi P08050. Positions 252-382.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 246562. 116 interactions.
DIPi DIP-34793N.
IntActi P08050. 8 interactions.
MINTi MINT-1791096.

Protein family/group databases

TCDBi 1.A.24.1.1. the gap junction-forming connexin (connexin) family.

PTM databases

PhosphoSitei P08050.

Proteomic databases

PaxDbi P08050.
PRIDEi P08050.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000001054 ; ENSRNOP00000001054 ; ENSRNOG00000000805 .
GeneIDi 24392.
KEGGi rno:24392.
UCSCi RGD:2690. rat.

Organism-specific databases

CTDi 2697.
RGDi 2690. Gja1.

Phylogenomic databases

eggNOGi NOG45368.
GeneTreei ENSGT00760000118780.
HOGENOMi HOG000231127.
HOVERGENi HBG009576.
InParanoidi P08050.
KOi K07372.
OMAi GANVDMH.
OrthoDBi EOG7P2XSS.
PhylomeDBi P08050.
TreeFami TF329606.

Miscellaneous databases

EvolutionaryTracei P08050.
NextBioi 603181.
PROi P08050.

Gene expression databases

ExpressionAtlasi P08050. baseline and differential.
Genevestigatori P08050.

Family and domain databases

InterProi IPR000500. Connexin.
IPR002261. Connexin43.
IPR013124. Connexin43_C.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view ]
PANTHERi PTHR11984. PTHR11984. 1 hit.
Pfami PF00029. Connexin. 1 hit.
PF03508. Connexin43. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view ]
PRINTSi PR00206. CONNEXIN.
PR01132. CONNEXINA1.
SMARTi SM00037. CNX. 1 hit.
SM01089. Connexin_CCC. 1 hit.
[Graphical view ]
PROSITEi PS00407. CONNEXINS_1. 1 hit.
PS00408. CONNEXINS_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Connexin43: a protein from rat heart homologous to a gap junction protein from liver."
    Beyer E.C., Paul D.L., Goodenough D.A.
    J. Cell Biol. 105:2621-2629(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Molecular cloning of a rat uterine gap junction protein and analysis of gene expression during gestation."
    Lang L.M., Beyer E.C., Schwartz A.L., Gitlin J.D.
    Am. J. Physiol. 260:E787-E793(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Uterus.
  3. Ma L.X., Peng Y.W.
    Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Heart.
  5. "The Mr 28,000 gap junction proteins from rat heart and liver are different but related."
    Nicholson B.J., Gros D.B., Kent S.B.H., Hood L.E., Revel J.-P.
    J. Biol. Chem. 260:6514-6517(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-33.
    Tissue: Heart.
  6. "Affinity purification of a rat-brain junctional protein, connexin 43."
    Dupont E., el Aoumari A., Fromaget C., Briand J.-C., Gros D.
    Eur. J. Biochem. 200:263-270(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-16.
    Tissue: Brain.
  7. "Connexon integrity is maintained by non-covalent bonds: intramolecular disulfide bonds link the extracellular domains in rat connexin-43."
    John S.A., Revel J.-P.
    Biochem. Biophys. Res. Commun. 178:1312-1318(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.
  8. "Membrane topology and quaternary structure of cardiac gap junction ion channels."
    Yeager M., Gilula N.B.
    J. Mol. Biol. 223:929-948(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY.
  9. "Identification and functional analysis of novel phosphorylation sites in Cx43 in rat primary granulosa cells."
    Yogo K., Ogawa T., Akiyama M., Ishida N., Takeya T.
    FEBS Lett. 531:132-136(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-365; SER-368; SER-369 AND SER-373.
  10. Cited for: INTERACTION WITH UBQLN4.
  11. "Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm."
    Negoro H., Kanematsu A., Doi M., Suadicani S.O., Matsuo M., Imamura M., Okinami T., Nishikawa N., Oura T., Matsui S., Seo K., Tainaka M., Urabe S., Kiyokage E., Todo T., Okamura H., Tabata Y., Ogawa O.
    Nat. Commun. 3:809-809(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  12. "Structural changes in the carboxyl terminus of the gap junction protein connexin43 indicates signaling between binding domains for c-Src and zonula occludens-1."
    Sorgen P.L., Duffy H.S., Sahoo P., Coombs W., Delmar M., Spray D.C.
    J. Biol. Chem. 279:54695-54701(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 255-381, INTERACTION WITH TJP1 AND SRC.
  13. "Domain-swapped dimerization of ZO-1 PDZ2 generates specific and regulatory connexin43-binding sites."
    Chen J., Pan L., Wei Z., Zhao Y., Zhang M.
    EMBO J. 27:2113-2123(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 374-382 IN COMPLEX WITH TJP1, SUBCELLULAR LOCATION, INTERACTION WITH TJP1.

Entry informationi

Entry nameiCXA1_RAT
AccessioniPrimary (citable) accession number: P08050
Secondary accession number(s): Q53ZE1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: October 29, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3