GJB2

GJB2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2ZW3, 3IZ1, 3IZ2, 5ERA, 5ER7
Identifikatori
Aliasi	GJB2
Vanjski ID-jevi	OMIM: 121011 MGI: 95720 HomoloGene: 2975 GeneCards: GJB2
Lokacija gena (čovjek)
Hrom.	Hromosom 13 (čovjek)
Kraj	20,192,938 bp
Lokacija gena (miš)
Hrom.	Hromosom 14 (miš)
Kraj	57,342,159 bp
Ontologija gena
Molekularna funkcija	• vezivanje identičnih proteina; • gap junction channel activity; • calcium ion binding; • vezivanje iona metala;
Ćelijska komponenta	• integral component of membrane; • connexin complex; • membrana; • ćelijska membrana; • međućelijske veze; • gap junction; • endoplasmic reticulum-Golgi intermediate compartment; • citoplazma; • citosol; • lateral plasma membrane; • cell body; • perinuklearno područje citoplazme; • astrocyte projection; • integral component of plasma membrane;
Biološki proces	• sluh; • cell communication; • cell-cell signaling; • gap junction assembly; • response to ischemia; • female pregnancy; • GO:0010260 starenje; • response to estradiol; • response to lipopolysaccharide; • response to retinoic acid; • response to progesterone; • cellular response to oxidative stress; • response to human chorionic gonadotropin; • GO:1904576 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 transport;
	Izvori:Amigo / QuickGO
Ortolozi
	2706
	14619
	ENSG00000165474
	ENSMUSG00000046352
	P29033
	Q00977
	NM_004004
	NM_008125
	NP_003995
	NP_032151
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Međuprostorni vezni protein beta-2 (GJB2), popznatiji koneksin 26 (Cx26) — je protein koji je kod ljudi kodiran genom GJB2.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 226 aminokiselina, a molekulska težina 26.215 Da,^[5]

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin

P: Prolin
Q: Glutamin
R: Arginin

S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

10	20	30	40	50
MDWGTLQTIL	GGVNKHSTSI	GKIWLTVLFI	FRIMILVVAA	KEVWGDEQAD
FVCNTLQPGC	KNVCYDHYFP	ISHIRLWALQ	LIFVSTPALL	VAMHVAYRRH
EKKRKFIKGE	IKSEFKDIEE	IKTQKVRIEG	SLWWTYTSSI	FFRVIFEAAF
MYVFYVMYDG	FSMQRLVKCN	AWPCPNTVDC	FVSRPTEKTV	FTVFMIAVSG
ICILLNVTEL	CYLLIRYCSG	KSKKPV

Funkcija

Pukotinske (lijevo, sa koneksinom) i neki primjeri ostallih međućelijdkih veza

Pukotinske veze su prvo okarakterizirane elektronskom mikroskopijom, kao regionalno specijalizirane strukture na plazmamembrani koje dolaze u dodir s adherentnim (susjednim) ćelijama, odnosno u ostvarivanju međućelijskih veza.

Pokazalo se da se ove strukture sastoje od ćelije do ćelije. Proteini, zvani koneksini, prečišćeni iz frakcija obogaćenih presjeka iz različitih tkiva razlikuju se. Koneksini su okarakterizirani njihovom molekulskom masom. Drugi sistem nomenklature dijeli vezne proteine u dvije kategorije, alfa i beta, prema sličnostima sekvenci na nivou nukleotida i aminokiselina. Naprimjer, CX43 (GJA1) je označen spojni međuprpstorni protein alfa-1, dok se GJB1 (CX32) i GJB2 (CX26; ovaj protein) nazivaju beta-1 i beta-2 spojni proteini. Ova nomenklatura naglašava da su GJB1 i GJB2 međusobno homologniji nego što je to jedno od njih sa spojnim proteinom alfa GJA1.^[6]

Klinički značaj

Greške ovog gena dovode do najčešćeg oblika kongenitalne gluhoće u razvijenim zemljama, koji se naziva DFNB1 (poznat i kao koneksinska gluhoća 26 ili GJB2).^[7] Jedna od prilično uobičajenih mutacija je delecija jednog guanina, od šest u sekvenci, što rezultira okvirnom mutacijom i prekidom proteina na aminokiselini broj 13. U dvije kopije, ova mutacija rezultira gluhoćom.^[8]

Koneksin 26 također ima ulogu u supresija tumora posredstvom ćelijskog ciklusa.^[9] Nenormalna ekspresija Cx26, u korelacijama s nekoliko tipova ljudskih karcinoma, može poslužiti kao prognostički faktor za malignome, kao što je kolorektumski karcinom,^[10]rak dojke,^[11] i rak mokraćne bešike.^[12] Nadalje, predlpženo je da prekomjerna ekspresija Cx26 podstiče razvoj raka, olakšavajući migraciju i invaziju ćelija ^[13] i stimuliranjem sposobnosti samoodržavanja matičnih ćelija raka.^[14]

Također pogledajte

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000165474 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000046352 - Ensembl, maj 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.
^ "UniProt, P29033". Pristupljeno 11. 9. 2017.
^ "Entrez Gene: GJB2 gap junction protein, beta 2, 26kDa".
^ Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, Mueller RF, Leigh IM (maj 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.
^ 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 (februar 2004). "Connexin 26 induces growth suppression, apoptosis and increased efficacy of doxorubicin in prostate cancer cells". Oncology Reports. 11 (2): 537–41. PMID 14719096. Arhivirano s originala, 1. 8. 2021. Pristupljeno 1. 8. 2021.
^ Nomura S, Maeda K, Noda E, Inoue T, Fukunaga S, Nagahara H, Hirakawa K (juni 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. PMC 2907868. PMID 20565955.
^ Teleki I, Krenacs T, Szasz MA, Kulka J, Wichmann B, Leo C, Papassotiropoulos B, Riemenschnitter C, Moch H, Varga Z (februar 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 (mart 2003). "Connexin 26 is abnormally expressed in bladder cancer". The Journal of Urology (jezik: English). 169 (3): 1135–7. doi:10.1097/01.ju.0000041954.91331.df. PMID 12576868.CS1 održavanje: nepoznati jezik (link)
^ Kotini M, Mayor R (maj 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. (februar 2018). "Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase". Nature Communications (jezik: engleski). 9 (1): 578. Bibcode:2018NatCo...9..578T. doi:10.1038/s41467-018-02938-1. PMC 5805730. PMID 29422613.

Dopunska literatura

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 (januar 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.
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.
Apps SA, Rankin WA, Kurmis AP (februar 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.
Welch KO, Marin RS, Pandya A, Arnos KS (juli 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.
Harris A, Locke D (2009). Connexins, A Guide. New York: Springer. str. 574. ISBN 978-1-934115-46-6.
Smith RJ, Shearer AE, Hildebrand MS, Van Camp G (januar 2014). "Hereditary Hearing Loss and Deafness Overview". Deafness and Hereditary Hearing Loss Overview. University of Washington, Seattle. NBK1434. In Pagon RA, Bird TD, Dolan CR, et al., ured. (1993). GeneReviews [Internet]. Seattle WA: University of Washington, Seattle.
Smith RJ, Sheffield AM, Van Camp G (19. 4. 2012). Nonsyndromic Hearing Loss and Deafness, DFNA3. University of Washington, Seattle. NBK1536. In GeneReviews
Smith RJ, Van Camp G (2. 1. 2014). Nonsyndromic Hearing Loss and Deafness, DFNB1. University of Washington, Seattle. NBK1272. In GeneReviews

Vanjski linkovi

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000165474 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000046352 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[UniProt-5] "UniProt, P29033". Pristupljeno 11. 9. 2017.

[6] "Entrez Gene: GJB2 gap junction protein, beta 2, 26kDa".

[7] Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, Mueller RF, Leigh IM (maj 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.

[8] 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.

[9] Tanaka M, Grossman HB (februar 2004). "Connexin 26 induces growth suppression, apoptosis and increased efficacy of doxorubicin in prostate cancer cells". Oncology Reports. 11 (2): 537–41. PMID 14719096. Arhivirano s originala, 1. 8. 2021. Pristupljeno 1. 8. 2021.

[10] Nomura S, Maeda K, Noda E, Inoue T, Fukunaga S, Nagahara H, Hirakawa K (juni 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. PMC 2907868. PMID 20565955.

[11] Teleki I, Krenacs T, Szasz MA, Kulka J, Wichmann B, Leo C, Papassotiropoulos B, Riemenschnitter C, Moch H, Varga Z (februar 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.

[12] Gee J, Tanaka M, Grossman HB (mart 2003). "Connexin 26 is abnormally expressed in bladder cancer". The Journal of Urology (jezik: English). 169 (3): 1135–7. doi:10.1097/01.ju.0000041954.91331.df. PMID 12576868.CS1 održavanje: nepoznati jezik (link)

[13] Kotini M, Mayor R (maj 2015). "Connexins in migration during development and cancer". Developmental Biology. 401 (1): 143–51. doi:10.1016/j.ydbio.2014.12.023. PMID 25553982.

[14] Thiagarajan PS, Sinyuk M, Turaga SM, Mulkearns-Hubert EE, Hale JS, Rao V, et al. (februar 2018). "Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase". Nature Communications (jezik: engleski). 9 (1): 578. Bibcode:2018NatCo...9..578T. doi:10.1038/s41467-018-02938-1. PMC 5805730. PMID 29422613.

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