Biology:GJB2
 Generic protein structure example |
Gap junction beta-2 protein (GJB2), also known as connexin 26 (Cx26) — is a protein that in humans is encoded by the GJB2 gene.
Function
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.[1]
Gap junction beta-2 protein is a member of the connexin protein family and plays a crucial role in forming gap junctions, which are channels that allow the transport of nutrients, ions, and signaling molecules between adjacent cells.[2] GJB2 is widely expressed throughout the body, with particularly important functions in the inner ear and skin. In the cochlea, GJB2 is believed to be essential for maintaining proper potassium ion levels and for the maturation of certain cochlear cells, both of which are critical for the process of converting sound waves into electrical nerve impulses.[2] In the skin, GJB2 contributes to the growth, maturation, and stability of the epidermis.[2]
Clinical significance
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).[3] 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.[4]
Connexin 26 also plays a role in tumor suppression through mediation of the cell cycle.[5] The abnormal expression of Cx26, correlated with several types of human cancers, may serve as a prognostic factor for cancers such as colorectal cancer,[6] breast cancer,[7] and bladder cancer.[8] Furthermore, Cx26 over-expression is suggested to promote cancer development by facilitating cell migration and invasion[9] and by stimulating the self-perpetuation ability of cancer stem cells.[10]
See also
- Connexin
- Gap junction
- Vohwinkel syndrome
- Bart–Pumphrey syndrome
References
- ↑ "Entrez Gene: GJB2 gap junction protein, beta 2, 26kDa". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2706.
- ↑ 2.0 2.1 2.2 "GJB2 gene". MedlinePlus. U.S. National Library of Medicine. https://medlineplus.gov/genetics/gene/gjb2/.
- ↑ "Connexin 26 mutations in hereditary non-syndromic sensorineural deafness". Nature 387 (6628): 80–83. May 1997. doi:10.1038/387080a0. PMID 9139825. Bibcode: 1997Natur.387...80K.
- ↑ "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. August 2018. doi:10.1186/s12881-018-0650-5. PMID 30086704.
- ↑ "Connexin 26 induces growth suppression, apoptosis and increased efficacy of doxorubicin in prostate cancer cells". Oncology Reports 11 (2): 537–541. February 2004. PMID 14719096. https://www.spandidos-publications.com/or/11/2/537. Retrieved 2018-02-18.
- ↑ "Clinical significance of the expression of connexin26 in colorectal cancer". Journal of Experimental & Clinical Cancer Research 29 (1): 79. June 2010. doi:10.1186/1756-9966-29-79. PMID 20565955.
- ↑ "The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer". BMC Cancer 13: 50. February 2013. doi:10.1186/1471-2407-13-50. PMID 23374644.
- ↑ "Connexin 26 is abnormally expressed in bladder cancer" (in English). The Journal of Urology 169 (3): 1135–1137. March 2003. doi:10.1097/01.ju.0000041954.91331.df. PMID 12576868.
- ↑ "Connexins in migration during development and cancer". Developmental Biology 401 (1): 143–151. May 2015. doi:10.1016/j.ydbio.2014.12.023. PMID 25553982.
- ↑ "Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase" (in En). Nature Communications 9 (1): 578. February 2018. doi:10.1038/s41467-018-02938-1. PMID 29422613. Bibcode: 2018NatCo...9..578T.
Further reading
- "GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review". Genetics in Medicine 4 (4): 258–274. 2002. doi:10.1097/00125817-200207000-00004. PMID 12172392.
- "Toward an understanding of cochlear homeostasis: the impact of location and the role of OCP1 and OCP2". Acta Oto-Laryngologica 123 (2): 203–208. January 2003. doi:10.1080/0036554021000028100. PMID 12701741.
- "Novel mutations in GJB2 encoding connexin-26 in Japanese patients with keratitis-ichthyosis-deafness syndrome". The British Journal of Dermatology 148 (4): 649–653. April 2003. doi:10.1046/j.1365-2133.2003.05245.x. PMID 12752120.
- "Connexin 26 mutations in autosomal recessive deafness disorders: a review". International Journal of Audiology 46 (2): 75–81. February 2007. doi:10.1080/14992020600582190. PMID 17365058.
- "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): 1567–1573. July 2007. doi:10.1002/ajmg.a.31701. PMID 17431919.
- Connexins, A Guide. New York: Springer. 2009. pp. 574. ISBN 978-1-934115-46-6. https://www.springer.com/978-1-934115-46-6.
- "Deafness and Hereditary Hearing Loss Overview". GeneReviews. University of Washington, Seattle. January 2014. NBK1434. https://www.ncbi.nlm.nih.gov/books/NBK1434/.
- "Nonsyndromic Hearing Loss and Deafness, DFNA3". GeneReviews. University of Washington, Seattle. 2012-04-19. NBK1536. https://www.ncbi.nlm.nih.gov/books/NBK1536/.
- "GJB2-Related Autosomal Recessive Nonsyndromic Hearing Loss". GeneReviews. University of Washington, Seattle. 2014-01-02. NBK1272. https://www.ncbi.nlm.nih.gov/books/NBK1272/.
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