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Identification
HMDB Protein ID HMDBP01740
Secondary Accession Numbers
  • 7089
Name Gap junction alpha-1 protein
Synonyms
  1. Connexin-43
  2. Cx43
  3. Gap junction 43 kDa heart protein
Gene Name GJA1
Protein Type Enzyme
Biological Properties
General Function Involved in cell communication
Specific Function One 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
connexon complex
macromolecular complex
protein complex
Function
transmembrane transporter activity
transporter activity
Process
cellular process
developmental process
anatomical structure development
organ development
heart development
cell-cell signaling
cell communication
Cellular Location
  1. Cell membrane
  2. Multi-pass membrane protein
  3. Cell junction
  4. gap junction
Gene Properties
Chromosome Location Chromosome:6
Locus 6q21-q23.2
SNPs GJA1
Gene Sequence
>1149 bp
ATGGGTGACTGGAGCGCCTTAGGCAAACTCCTTGACAAGGTTCAAGCCTACTCAACTGCT
GGAGGGAAGGTGTGGCTGTCAGTACTTTTCATTTTCCGAATCCTGCTGCTGGGGACAGCG
GTTGAGTCAGCCTGGGGAGATGAGCAGTCTGCCTTTCGTTGTAACACTCAGCAACCTGGT
TGTGAAAATGTCTGCTATGACAAGTCTTTCCCAATCTCTCATGTGCGCTTCTGGGTCCTG
CAGATCATATTTGTGTCTGTACCCACACTCTTGTACCTGGCTCATGTGTTCTATGTGATG
CGAAAGGAAGAGAAACTGAACAAGAAAGAGGAAGAACTCAAGGTTGCCCAAACTGATGGT
GTCAATGTGGACATGCACTTGAAGCAGATTGAGATAAAGAAGTTCAAGTACGGTATTGAA
GAGCATGGTAAGGTGAAAATGCGAGGGGGGTTGCTGCGAACCTACATCATCAGTATCCTC
TTCAAGTCTATCTTTGAGGTGGCCTTCTTGCTGATCCAGTGGTACATCTATGGATTCAGC
TTGAGTGCTGTTTACACTTGCAAAAGAGATCCCTGCCCACATCAGGTGGACTGTTTCCTC
TCTCGCCCCACGGAGAAAACCATCTTCATCATCTTCATGCTGGTGGTGTCCTTGGTGTCC
CTGGCCTTGAATATCATTGAACTCTTCTATGTTTTCTTCAAGGGCGTTAAGGATCGGGTT
AAGGGAAAGAGCGACCCTTACCATGCGACCAGTGGTGCGCTGAGCCCTGCCAAAGACTGT
GGGTCTCAAAAATATGCTTATTTCAATGGCTGCTCCTCACCAACCGCTCCCCTCTCGCCT
ATGTCTCCTCCTGGGTACAAGCTGGTTACTGGCGACAGAAACAATTCTTCTTGCCGCAAT
TACAACAAGCAAGCAAGTGAGCAAAACTGGGCTAATTACAGTGCAGAACAAAATCGAATG
GGGCAGGCGGGAAGCACCATCTCTAACTCCCATGCACAGCCTTTTGATTTCCCCGATGAT
AACCAGAATTCTAAAAAACTAGCTGCTGGACATGAATTACAGCCACTAGCCATTGTGGAC
CAGCGACCTTCAAGCAGAGCCAGCAGTCGTGCCAGCAGCAGACCTCGGCCTGATGACCTG
GAGATCTAG
Protein Properties
Number of Residues 382
Molecular Weight 43008.0
Theoretical pI 8.98
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 14-36
  • 77-99
  • 155-177
  • 209-231
Protein Sequence
>Gap junction alpha-1 protein
MGDWSALGKLLDKVQAYSTAGGKVWLSVLFIFRILLLGTAVESAWGDEQSAFRCNTQQPG
CENVCYDKSFPISHVRFWVLQIIFVSVPTLLYLAHVFYVMRKEEKLNKKEEELKVAQTDG
VNVDMHLKQIEIKKFKYGIEEHGKVKMRGGLLRTYIISILFKSIFEVAFLLIQWYIYGFS
LSAVYTCKRDPCPHQVDCFLSRPTEKTIFIIFMLVVSLVSLALNIIELFYVFFKGVKDRV
KGKSDPYHATSGALSPAKDCGSQKYAYFNGCSSPTAPLSPMSPPGYKLVTGDRNNSSCRN
YNKQASEQNWANYSAEQNRMGQAGSTISNSHAQPFDFPDDNQNSKKLAAGHELQPLAIVD
QRPSSRASSRASSRPRPDDLEI
GenBank ID Protein 29917
UniProtKB/Swiss-Prot ID P17302
UniProtKB/Swiss-Prot Entry Name CXA1_HUMAN
PDB IDs
GenBank Gene ID X52947
GeneCard ID GJA1
GenAtlas ID GJA1
HGNC ID HGNC:4274
References
General References
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  5. Fishman GI, Spray DC, Leinwand LA: Molecular characterization and functional expression of the human cardiac gap junction channel. J Cell Biol. 1990 Aug;111(2):589-98. [PubMed:1696265 ]
  6. Fishman GI, Eddy RL, Shows TB, Rosenthal L, Leinwand LA: The human connexin gene family of gap junction proteins: distinct chromosomal locations but similar structures. Genomics. 1991 May;10(1):250-6. [PubMed:1646158 ]
  7. Haefliger JA, Goy JJ, Waeber G: Sporadic cases of dilated cardiomyopathies associated with atrioventricular conduction defects are not linked to mutation within the connexins 40 and 43 genes. Eur Heart J. 1999 Dec;20(24):1843. [PubMed:10581143 ]
  8. Toyofuku T, Yabuki M, Otsu K, Kuzuya T, Hori M, Tada M: Intercellular calcium signaling via gap junction in connexin-43-transfected cells. J Biol Chem. 1998 Jan 16;273(3):1519-28. [PubMed:9430691 ]
  9. Doble BW, Dang X, Ping P, Fandrich RR, Nickel BE, Jin Y, Cattini PA, Kardami E: Phosphorylation of serine 262 in the gap junction protein connexin-43 regulates DNA synthesis in cell-cell contact forming cardiomyocytes. J Cell Sci. 2004 Jan 26;117(Pt 3):507-14. [PubMed:14702389 ]
  10. Saffitz JE, Laing JG, Yamada KA: Connexin expression and turnover : implications for cardiac excitability. Circ Res. 2000 Apr 14;86(7):723-8. [PubMed:10764404 ]
  11. Gebbia M, Towbin JA, Casey B: Failure to detect connexin43 mutations in 38 cases of sporadic and familial heterotaxy. Circulation. 1996 Oct 15;94(8):1909-12. [PubMed:8873667 ]
  12. Penman Splitt M, Tsai MY, Burn J, Goodship JA: Absence of mutations in the regulatory domain of the gap junction protein connexin 43 in patients with visceroatrial heterotaxy. Heart. 1997 Apr;77(4):369-70. [PubMed:9155619 ]
  13. Toth T, Hajdu J, Marton T, Nagy B, Papp Z: connexin43 gene mutations and heterotaxy. Circulation. 1998 Jan 6-13;97(1):117-8. [PubMed:9443444 ]
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  15. Akiyama M, Ishida N, Ogawa T, Yogo K, Takeya T: Molecular cloning and functional analysis of a novel Cx43 partner protein CIP150. Biochem Biophys Res Commun. 2005 Oct 7;335(4):1264-71. [PubMed:16112082 ]
  16. Richardson RJ, Joss S, Tomkin S, Ahmed M, Sheridan E, Dixon MJ: A nonsense mutation in the first transmembrane domain of connexin 43 underlies autosomal recessive oculodentodigital syndrome. J Med Genet. 2006 Jul;43(7):e37. [PubMed:16816024 ]
  17. Paznekas WA, Boyadjiev SA, Shapiro RE, Daniels O, Wollnik B, Keegan CE, Innis JW, Dinulos MB, Christian C, Hannibal MC, Jabs EW: Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am J Hum Genet. 2003 Feb;72(2):408-18. Epub 2002 Nov 27. [PubMed:12457340 ]
  18. Britz-Cunningham SH, Shah MM, Zuppan CW, Fletcher WH: Mutations of the Connexin43 gap-junction gene in patients with heart malformations and defects of laterality. N Engl J Med. 1995 May 18;332(20):1323-9. [PubMed:7715640 ]
  19. Dasgupta C, Martinez AM, Zuppan CW, Shah MM, Bailey LL, Fletcher WH: Identification of connexin43 (alpha1) gap junction gene mutations in patients with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis (DGGE). Mutat Res. 2001 Aug 8;479(1-2):173-86. [PubMed:11470490 ]
  20. Kjaer KW, Hansen L, Eiberg H, Leicht P, Opitz JM, Tommerup N: Novel Connexin 43 (GJA1) mutation causes oculo-dento-digital dysplasia with curly hair. Am J Med Genet A. 2004 Jun 1;127A(2):152-7. [PubMed:15108203 ]
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  22. Richardson R, Donnai D, Meire F, Dixon MJ: Expression of Gja1 correlates with the phenotype observed in oculodentodigital syndrome/type III syndactyly. J Med Genet. 2004 Jan;41(1):60-7. [PubMed:14729836 ]
  23. Vitiello C, D'Adamo P, Gentile F, Vingolo EM, Gasparini P, Banfi S: A novel GJA1 mutation causes oculodentodigital dysplasia without syndactyly. Am J Med Genet A. 2005 Feb 15;133A(1):58-60. [PubMed:15637728 ]
  24. Honkaniemi J, Kalkkila JP, Koivisto P, Kahara V, Latvala T, Simola K: Letter to the editor: Novel GJA1 mutation in oculodentodigital dysplasia. Am J Med Genet A. 2005 Nov 15;139(1):48-9. [PubMed:16222672 ]
  25. Vasconcellos JP, Melo MB, Schimiti RB, Bressanim NC, Costa FF, Costa VP: A novel mutation in the GJA1 gene in a family with oculodentodigital dysplasia. Arch Ophthalmol. 2005 Oct;123(10):1422-6. [PubMed:16219735 ]
  26. Chen P, Xie LJ, Huang GY, Zhao XQ, Chang C: Mutations of connexin43 in fetuses with congenital heart malformations. Chin Med J (Engl). 2005 Jun 20;118(12):971-6. [PubMed:15978203 ]
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  28. Debeer P, Van Esch H, Huysmans C, Pijkels E, De Smet L, Van de Ven W, Devriendt K, Fryns JP: Novel GJA1 mutations in patients with oculo-dento-digital dysplasia (ODDD). Eur J Med Genet. 2005 Oct-Dec;48(4):377-87. [PubMed:16378922 ]
  29. Wiest T, Herrmann O, Stogbauer F, Grasshoff U, Enders H, Koch MJ, Grond-Ginsbach C, Schwaninger M: Clinical and genetic variability of oculodentodigital dysplasia. Clin Genet. 2006 Jul;70(1):71-2. [PubMed:16813608 ]
  30. Kelly SC, Ratajczak P, Keller M, Purcell SM, Griffin T, Richard G: A novel GJA 1 mutation in oculo-dento-digital dysplasia with curly hair and hyperkeratosis. Eur J Dermatol. 2006 May-Jun;16(3):241-5. [PubMed:16709485 ]
  31. van Es RJ, Wittebol-Post D, Beemer FA: Oculodentodigital dysplasia with mandibular retrognathism and absence of syndactyly: a case report with a novel mutation in the connexin 43 gene. Int J Oral Maxillofac Surg. 2007 Sep;36(9):858-60. Epub 2007 May 16. [PubMed:17509830 ]
  32. de la Parra DR, Zenteno JC: A new GJA1 (connexin 43) mutation causing oculodentodigital dysplasia associated to uncommon features. Ophthalmic Genet. 2007 Dec;28(4):198-202. [PubMed:18161618 ]
  33. Paznekas WA, Karczeski B, Vermeer S, Lowry RB, Delatycki M, Laurence F, Koivisto PA, Van Maldergem L, Boyadjiev SA, Bodurtha JN, Jabs EW: GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype. Hum Mutat. 2009 May;30(5):724-33. doi: 10.1002/humu.20958. [PubMed:19338053 ]