Defects in this gene lead to the most common form of congenital deafness in developed countries, called DFNB1 (also known as connexin 26 deafness or GJB2-related deafness).[5] One fairly common mutation is the deletion of one guanine from a string of six, resulting in a frameshift and termination of the protein at amino acid number 13. Having two copies of this mutation results in deafness.[6]
Connexin 26 also plays a role in tumor suppression through mediation of the cell cycle.[7] The abnormal expression of Cx26, correlated with several types of human cancers, may serve as a prognostic factor for cancers such as colorectal cancer,[8] breast cancer,[9] and bladder cancer.[10] Furthermore, Cx26 over-expression is suggested to promote cancer development by facilitating cell migration and invasion[11] and by stimulating the self-perpetuation ability of cancer stem cells.[12]
Functionedit
Gap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells. These structures were shown to consist of cell-to-cell channels. Proteins, called connexins, purified from fractions of enriched gap junctions from different tissues differ. The connexins are designated by their molecular mass. Another system of nomenclature divides gap junction proteins into two categories, alpha and beta, according to sequence similarities at the nucleotide and amino acid levels. For example, CX43 (GJA1) is designated alpha-1 gap junction protein, whereas GJB1 (CX32), and GJB2 (CX26; this protein) are called beta-1 and beta-2 gap junction proteins, respectively. This nomenclature emphasizes that GJB1 and GJB2 are more homologous to each other than either of them is to gap junction protein, alpha GJA1.[13]
^Zytsar MV, Barashkov NA, Bady-Khoo MS, Shubina-Olejnik OA, Danilenko NG, Bondar AA, et al. (August 2018). "Updated carrier rates for c.35delG (GJB2) associated with hearing loss in Russia and common c.35delG haplotypes in Siberia". BMC Medical Genetics. 19 (1): 138. doi:10.1186/s12881-018-0650-5. PMC6081885. PMID 30086704.
^Tanaka M, Grossman HB (February 2004). "Connexin 26 induces growth suppression, apoptosis and increased efficacy of doxorubicin in prostate cancer cells". Oncology Reports. 11 (2): 537–41. PMID 14719096.
^Nomura S, Maeda K, Noda E, Inoue T, Fukunaga S, Nagahara H, Hirakawa K (June 2010). "Clinical significance of the expression of connexin26 in colorectal cancer". Journal of Experimental & Clinical Cancer Research. 29: 79. doi:10.1186/1756-9966-29-79. PMC2907868. PMID 20565955.
^Teleki I, Krenacs T, Szasz MA, Kulka J, Wichmann B, Leo C, Papassotiropoulos B, Riemenschnitter C, Moch H, Varga Z (February 2013). "The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer". BMC Cancer. 13: 50. doi:10.1186/1471-2407-13-50. PMC3583680. PMID 23374644.
^Gee J, Tanaka M, Grossman HB (March 2003). "Connexin 26 is abnormally expressed in bladder cancer". The Journal of Urology. 169 (3): 1135–7. doi:10.1097/01.ju.0000041954.91331.df. PMID 12576868.
^Kotini M, Mayor R (May 2015). "Connexins in migration during development and cancer". Developmental Biology. 401 (1): 143–51. doi:10.1016/j.ydbio.2014.12.023. PMID 25553982.
^Thiagarajan PS, Sinyuk M, Turaga SM, Mulkearns-Hubert EE, Hale JS, Rao V, et al. (February 2018). "Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase". Nature Communications. 9 (1): 578. Bibcode:2018NatCo...9..578T. doi:10.1038/s41467-018-02938-1. PMC5805730. PMID 29422613.
^"Entrez Gene: GJB2 gap junction protein, beta 2, 26kDa".
Further readingedit
Kenneson A, Van Naarden Braun K, Boyle C (2002). "GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review". Genetics in Medicine. 4 (4): 258–74. doi:10.1097/00125817-200207000-00004. PMID 12172392.
Thalmann R, Henzl MT, Killick R, Ignatova EG, Thalmann I (January 2003). "Toward an understanding of cochlear homeostasis: the impact of location and the role of OCP1 and OCP2". Acta Oto-Laryngologica. 123 (2): 203–8. doi:10.1080/0036554021000028100. PMID 12701741. S2CID 2048758.
Yotsumoto S, Hashiguchi T, Chen X, Ohtake N, Tomitaka A, Akamatsu H, Matsunaga K, Shiraishi S, Miura H, Adachi J, Kanzaki T (April 2003). "Novel mutations in GJB2 encoding connexin-26 in Japanese patients with keratitis-ichthyosis-deafness syndrome". The British Journal of Dermatology. 148 (4): 649–53. doi:10.1046/j.1365-2133.2003.05245.x. PMID 12752120. S2CID 20748122.
Apps SA, Rankin WA, Kurmis AP (February 2007). "Connexin 26 mutations in autosomal recessive deafness disorders: a review". International Journal of Audiology. 46 (2): 75–81. doi:10.1080/14992020600582190. PMID 17365058. S2CID 30841401.
Welch KO, Marin RS, Pandya A, Arnos KS (July 2007). "Compound heterozygosity for dominant and recessive GJB2 mutations: effect on phenotype and review of the literature". American Journal of Medical Genetics. Part A. 143A (14): 1567–73. doi:10.1002/ajmg.a.31701. PMID 17431919. S2CID 34944902.
Harris A, Locke D (2009). Connexins, A Guide. New York: Springer. p. 574. ISBN978-1-934115-46-6.
Smith RJ, Shearer AE, Hildebrand MS, Van Camp G (January 2014). "Hereditary Hearing Loss and Deafness Overview". Deafness and Hereditary Hearing Loss Overview. University of Washington, Seattle. PMID 20301607. NBK1434. In Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A (1993). Pagon RA, Bird TD, Dolan CR, et al. (eds.). GeneReviews [Internet]. Seattle WA: University of Washington, Seattle. PMID 20301295.
Smith RJ, Sheffield AM, Van Camp G (2012-04-19). Nonsyndromic Hearing Loss and Deafness, DFNA3. University of Washington, Seattle. PMID 20301708. NBK1536. In GeneReviews
Smith RJ, Van Camp G (2014-01-02). Nonsyndromic Hearing Loss and Deafness, DFNB1. University of Washington, Seattle. PMID 20301449. NBK1272. In GeneReviews
This article on a gene on human chromosome 13 is a stub. You can help Wikipedia by expanding it.
gjb2, junction, beta, protein, also, known, connexin, cx26, protein, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes2zw3, 3iz1, 3iz2, 5era, 5er7identifiersaliases, cx26, dfna3, dfna3a, dfnb1, dfnb1a, nsrd1, junction. Gap junction beta 2 protein GJB2 also known as connexin 26 Cx26 is a protein that in humans is encoded by the GJB2 gene GJB2Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes2ZW3 3IZ1 3IZ2 5ERA 5ER7IdentifiersAliasesGJB2 CX26 DFNA3 DFNA3A DFNB1 DFNB1A HID KID NSRD1 PPK gap junction protein beta 2 BAPSExternal IDsOMIM 121011 MGI 95720 HomoloGene 2975 GeneCards GJB2Gene location Human Chr Chromosome 13 human 1 Band13q12 11Start20 187 463 bp 1 End20 192 938 bp 1 Gene location Mouse Chr Chromosome 14 mouse 2 Band14 C3 14 30 1 cMStart57 336 057 bp 2 End57 342 159 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inhuman penisbody of tonguecavity of mouthvulvapancreatic ductal cellskin of abdomentrigeminal ganglionparotid glandthymussuperior surface of tongueTop expressed instria vascularishair folliclemeningessuperior surface of tongueutricleleft lobe of livercervixlipesophaguscorneal stromaMore reference expression dataBioGPSn aGene ontologyMolecular functionidentical protein binding gap junction channel activity calcium ion binding metal ion bindingCellular componentintegral component of membrane connexin complex membrane plasma membrane cell junction gap junction endoplasmic reticulum Golgi intermediate compartment cytoplasm cytosol lateral plasma membrane cell body perinuclear region of cytoplasm astrocyte projection integral component of plasma membraneBiological processsensory perception of sound cell communication cell cell signaling gap junction assembly response to ischemia female pregnancy human ageing response to estradiol response to lipopolysaccharide response to retinoic acid response to progesterone cellular response to oxidative stress response to human chorionic gonadotropin response to antibiotic decidualization inner ear development transmembrane transport cellular response to glucagon stimulus cellular response to dexamethasone stimulus epididymis development gap junction mediated intercellular transportSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez270614619EnsemblENSG00000165474ENSMUSG00000046352UniProtP29033Q00977RefSeq mRNA NM 004004NM 008125RefSeq protein NP 003995NP 032151Location UCSC Chr 13 20 19 20 19 MbChr 14 57 34 57 34 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Clinical significance 2 Function 3 See also 4 References 5 Further readingClinical significance editDefects in this gene lead to the most common form of congenital deafness in developed countries called DFNB1 also known as connexin 26 deafness or GJB2 related deafness 5 One fairly common mutation is the deletion of one guanine from a string of six resulting in a frameshift and termination of the protein at amino acid number 13 Having two copies of this mutation results in deafness 6 Connexin 26 also plays a role in tumor suppression through mediation of the cell cycle 7 The abnormal expression of Cx26 correlated with several types of human cancers may serve as a prognostic factor for cancers such as colorectal cancer 8 breast cancer 9 and bladder cancer 10 Furthermore Cx26 over expression is suggested to promote cancer development by facilitating cell migration and invasion 11 and by stimulating the self perpetuation ability of cancer stem cells 12 Function editGap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells These structures were shown to consist of cell to cell channels Proteins called connexins purified from fractions of enriched gap junctions from different tissues differ The connexins are designated by their molecular mass Another system of nomenclature divides gap junction proteins into two categories alpha and beta according to sequence similarities at the nucleotide and amino acid levels For example CX43 GJA1 is designated alpha 1 gap junction protein whereas GJB1 CX32 and GJB2 CX26 this protein are called beta 1 and beta 2 gap junction proteins respectively This nomenclature emphasizes that GJB1 and GJB2 are more homologous to each other than either of them is to gap junction protein alpha GJA1 13 See also editConnexin Gap junction Vohwinkel syndrome Bart Pumphrey syndromeReferences edit a b c GRCh38 Ensembl release 89 ENSG00000165474 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000046352 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Kelsell DP Dunlop J Stevens HP Lench NJ Liang JN Parry G Mueller RF Leigh IM May 1997 Connexin 26 mutations in hereditary non syndromic sensorineural deafness Nature 387 6628 80 3 Bibcode 1997Natur 387 80K doi 10 1038 387080a0 PMID 9139825 S2CID 4311728 Zytsar MV Barashkov NA Bady Khoo MS Shubina Olejnik OA Danilenko NG Bondar AA et al August 2018 Updated carrier rates for c 35delG GJB2 associated with hearing loss in Russia and common c 35delG haplotypes in Siberia BMC Medical Genetics 19 1 138 doi 10 1186 s12881 018 0650 5 PMC 6081885 PMID 30086704 Tanaka M Grossman HB February 2004 Connexin 26 induces growth suppression apoptosis and increased efficacy of doxorubicin in prostate cancer cells Oncology Reports 11 2 537 41 PMID 14719096 Nomura S Maeda K Noda E Inoue T Fukunaga S Nagahara H Hirakawa K June 2010 Clinical significance of the expression of connexin26 in colorectal cancer Journal of Experimental amp Clinical Cancer Research 29 79 doi 10 1186 1756 9966 29 79 PMC 2907868 PMID 20565955 Teleki I Krenacs T Szasz MA Kulka J Wichmann B Leo C Papassotiropoulos B Riemenschnitter C Moch H Varga Z February 2013 The potential prognostic value of connexin 26 and 46 expression in neoadjuvant treated breast cancer BMC Cancer 13 50 doi 10 1186 1471 2407 13 50 PMC 3583680 PMID 23374644 Gee J Tanaka M Grossman HB March 2003 Connexin 26 is abnormally expressed in bladder cancer The Journal of Urology 169 3 1135 7 doi 10 1097 01 ju 0000041954 91331 df PMID 12576868 Kotini M Mayor R May 2015 Connexins in migration during development and cancer Developmental Biology 401 1 143 51 doi 10 1016 j ydbio 2014 12 023 PMID 25553982 Thiagarajan PS Sinyuk M Turaga SM Mulkearns Hubert EE Hale JS Rao V et al February 2018 Cx26 drives self renewal in triple negative breast cancer via interaction with NANOG and focal adhesion kinase Nature Communications 9 1 578 Bibcode 2018NatCo 9 578T doi 10 1038 s41467 018 02938 1 PMC 5805730 PMID 29422613 Entrez Gene GJB2 gap junction protein beta 2 26kDa Further reading editKenneson A Van Naarden Braun K Boyle C 2002 GJB2 connexin 26 variants and nonsyndromic sensorineural hearing loss a HuGE review Genetics in Medicine 4 4 258 74 doi 10 1097 00125817 200207000 00004 PMID 12172392 Thalmann R Henzl MT Killick R Ignatova EG Thalmann I January 2003 Toward an understanding of cochlear homeostasis the impact of location and the role of OCP1 and OCP2 Acta Oto Laryngologica 123 2 203 8 doi 10 1080 0036554021000028100 PMID 12701741 S2CID 2048758 Yotsumoto S Hashiguchi T Chen X Ohtake N Tomitaka A Akamatsu H Matsunaga K Shiraishi S Miura H Adachi J Kanzaki T April 2003 Novel mutations in GJB2 encoding connexin 26 in Japanese patients with keratitis ichthyosis deafness syndrome The British Journal of Dermatology 148 4 649 53 doi 10 1046 j 1365 2133 2003 05245 x PMID 12752120 S2CID 20748122 Apps SA Rankin WA Kurmis AP February 2007 Connexin 26 mutations in autosomal recessive deafness disorders a review International Journal of Audiology 46 2 75 81 doi 10 1080 14992020600582190 PMID 17365058 S2CID 30841401 Welch KO Marin RS Pandya A Arnos KS July 2007 Compound heterozygosity for dominant and recessive GJB2 mutations effect on phenotype and review of the literature American Journal of Medical Genetics Part A 143A 14 1567 73 doi 10 1002 ajmg a 31701 PMID 17431919 S2CID 34944902 Harris A Locke D 2009 Connexins A Guide New York Springer p 574 ISBN 978 1 934115 46 6 Smith RJ Shearer AE Hildebrand MS Van Camp G January 2014 Hereditary Hearing Loss and Deafness Overview Deafness and Hereditary Hearing Loss Overview University of Washington Seattle PMID 20301607 NBK1434 In Adam MP Everman DB Mirzaa GM Pagon RA Wallace SE Bean LJH Gripp KW Amemiya A 1993 Pagon RA Bird TD Dolan CR et al eds GeneReviews Internet Seattle WA University of Washington Seattle PMID 20301295 Smith RJ Sheffield AM Van Camp G 2012 04 19 Nonsyndromic Hearing Loss and Deafness DFNA3 University of Washington Seattle PMID 20301708 NBK1536 In GeneReviews Smith RJ Van Camp G 2014 01 02 Nonsyndromic Hearing Loss and Deafness DFNB1 University of Washington Seattle PMID 20301449 NBK1272 In GeneReviews nbsp This article on a gene on human chromosome 13 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title GJB2 amp oldid 1114129077, wikipedia, wiki, book, books, library,
