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CACNA2D3
Identifikatori
Aliasi	CACNA2D3
Vanjski ID-jevi	OMIM: 606399 MGI: 1338890 HomoloGene: 74929 GeneCards: CACNA2D3
Lokacija gena (čovjek)
Hrom.	Hromosom 3 (čovjek)
Kraj	55,074,557 bp
Lokacija gena (miš)
Hrom.	Hromosom 14 (miš)
Kraj	29,443,821 bp
Ontologija gena
Molekularna funkcija	• vezivanje iona metala; • voltage-gated ion channel activity; • calcium channel activity; • voltage-gated calcium channel activity;
Ćelijska komponenta	• integral component of membrane; • ćelijska membrana; • membrana; • Naponom kontrolirani kalcijev kanal;
Biološki proces	• regulation of ion transmembrane transport; • ion transport; • calcium ion transport; • calcium ion transmembrane transport; • cardiac conduction;
	Izvori:Amigo / QuickGO
Ortolozi
	55799
	12294
	ENSG00000157445
	ENSMUSG00000021991
	Q8IZS8
	Q9Z1L5
	NM_018398
	NM_009785
	NP_060868
	NP_033915
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Naponski ovisna podjedinica 3 kalcijevog kanala alfa2/delta jest protein koji je kod ljudi kodiran genom CACNA2D3 sa hromosoma 3, lokus 3p21.1.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.091 aminokiselina, а molekulska težina 123.011 Da.^[6]

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
MAGPGSPRRA	SRGASALLAA	ALLYAALGDV	VRSEQQIPLS	VVKLWASAFG
GEIKSIAAKY	SGSQLLQKKY	KEYEKDVAIE	EIDGLQLVKK	LAKNMEEMFH
KKSEAVRRLV	EAAEEAHLKH	EFDADLQYEY	FNAVLINERD	KDGNFLELGK
EFILAPNDHF	NNLPVNISLS	DVQVPTNMYN	KDPAIVNGVY	WSESLNKVFV
DNFDRDPSLI	WQYFGSAKGF	FRQYPGIKWE	PDENGVIAFD	CRNRKWYIQA
ATSPKDVVIL	VDVSGSMKGL	RLTIAKQTVS	SILDTLGDDD	FFNIIAYNEE
LHYVEPCLNG	TLVQADRTNK	EHFREHLDKL	FAKGIGMLDI	ALNEAFNILS
DFNHTGQGSI	CSQAIMLITD	GAVDTYDTIF	AKYNWPDRKV	RIFTYLIGRE
AAFADNLKWM	ACANKGFFTQ	ISTLADVQEN	VMEYLHVLSR	PKVIDQEHDV
VWTEAYIDST	LPQAQKLTDD	QGPVLMTTVA	MPVFSKQNET	RSKGILLGVV
GTDVPVKELL	KTIPKYKLGI	HGYAFAITNN	GYILTHPELR	LLYEEGKKRR
KPNYSSVDLS	EVEWEDRDDV	LRNAMVNRKT	GKFSMEVKKT	VDKGKRVLVM
TNDYYYTDIK	GTPFSLGVAL	SRGHGKYFFR	GNVTIEEGLH	DLEHPDVSLA
DEWSYCNTDL	HPEHRHLSQL	EAIKLYLKGK	EPLLQCDKEL	IQEVLFDAVV
SAPIEAYWTS	LALNKSENSD	KGVEVAFLGT	RTGLSRINLF	VGAEQLTNQD
FLKAGDKENI	FNADHFPLWY	RRAAEQIPGS	FVYSIPFSTG	PVNKSNVVTA
STSIQLLDER	KSPVVAAVGI	QMKLEFFQRK	FWTASRQCAS	LDGKCSISCD
DETVNCYLID	NNGFILVSED	YTQTGDFFGE	IEGAVMNKLL	TMGSFKRITL
YDYQAMCRAN	KESSDGAHGL	LDPYNAFLSA	VKWIMTELVL	FLVEFNLCSW
WHSDMTAKAQ	KLKQTLEPCD	TEYPAFVSER	TIKETTGNIA	CEDCSKSFVI
QQIPSSNLFM	VVVDSSCLCE	SVAPITMAPI	EIRYNESLKC	ERLKAQKIRR
RPESCHGFHP	EENARECGGA	PSLQAQTVLL	LLPLLLMLFS	R

Funkcija

Ovaj gen kodira člana porodice alfa-2/delta podjedinica, proteina u kompleksu kalcijski kanal zavisnom od napona. Kalcijski kanali posreduju u dotoku iona kalcija u ćeliju nakon polarizacije membrane i sastoje se od kompleksa alfa-1, alfa-2/delta, beta i gama podjedinica u omjeru 1:1:1:1. Postoje različite verzije svake od ovih podjedinica, ili eksprimirane iz sličnih gena ili rezultat alternativne prerade. Istraživanja na vrlo sličnom proteinu kod kunića sugeriraju da se opisani protein cijepa na alfa-2 i delta podjedinicu. Uočene su alternativne transkripcijske varijante transkripta ovog gena, ali nisu detaljno okarakterisane.

Klinički značaj

Brojne studije prijavile su povezanost između metilacija gena CACNA2D3 i kancera.

Rak dojke

Utišavanje transkripcije gena CACNA2D3 ovisno o metilaciji može doprinijeti metastatskom fenotipu karcinom dojke. Analiza metilacije u CACNA2D3 CpG otoka može imati potencijal kao biomarker za rizik od razvoja metastatske bolesti.^[7]

Rak želuca

Gubitak ekspresije gena CACNA2D3 preko aberantne hipermetilacije promotora može doprinijeti karcinogenezi želuca, a metilacija CACNA2D3 je koristan prognostički marker za pacijente s uznapredovalim rakom želuca.^[8] Fizičko vježbanje korelirano je sa nižom učestalošću metilacija CACNA2D3-a.^[9]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000157445 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021991 - 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.
^ "Entrez Gene: Calcium channel, voltage-dependent, alpha 2/delta subunit 3".
^ "UniProt, Q8IZS8" (jezik: engleski). Pristupljeno 2. 11. 2021.
^ Palmieri C, Rudraraju B, Monteverde M, Lattanzio L, Gojis O, Brizio R, Garrone O, Merlano M, Syed N, Lo Nigro C, Crook T (2012). "Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas". Br. J. Cancer. 107 (2): 375–81. doi:10.1038/bjc.2012.231. PMC 3394973. PMID 22644305.
^ Wanajo A, Sasaki A, Nagasaki H, Shimada S, Otsubo T, Owaki S, Shimizu Y, Eishi Y, Kojima K, Nakajima Y, Kawano T, Yuasa Y, Akiyama Y (2008). "Methylation of the calcium channel-related gene, CACNA2D3, is frequent and a poor prognostic factor in gastric cancer". Gastroenterology. 135 (2): 580–90. doi:10.1053/j.gastro.2008.05.041. PMID 18588891.
^ Yuasa Y, Nagasaki H, Akiyama Y, Hashimoto Y, Takizawa T, Kojima K, Kawano T, Sugihara K, Imai K, Nakachi K (2009). "DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients". Int. J. Cancer. 124 (11): 2677–82. doi:10.1002/ijc.24231. PMID 19170207. S2CID 46627170.

Dopunska literatura

Palmieri C, Rudraraju B, Monteverde M, Lattanzio L, Gojis O, Brizio R, Garrone O, Merlano M, Syed N, Lo Nigro C, Crook T (2012). "Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas". British Journal of Cancer. 107 (2): 375–81. doi:10.1038/bjc.2012.231. PMC 3394973. PMID 22644305.
Leone PE, González MB, Elosua C, Gómez-Moreta JA, Lumbreras E, Robledo C, Santos-Briz A, Valero JM, de la Guardia RD, Gutiérrez NC, Hernández JM, García JL (2012). "Integration of global spectral karyotyping, CGH arrays, and expression arrays reveals important genes in the pathogenesis of glioblastoma multiforme". Annals of Surgical Oncology. 19 (7): 2367–79. doi:10.1245/s10434-011-2202-5. PMID 22395973. S2CID 1687472.
Abo-Dalo B, Kim HG, Roes M, Stefanova M, Higgins A, Shen Y, Mundlos S, Quade BJ, Gusella JF, Kutsche K (2007). "Extensive molecular genetic analysis of the 3p14.3 region in patients with Zimmermann-Laband syndrome". American Journal of Medical Genetics Part A. 143A (22): 2668–74. doi:10.1002/ajmg.a.32034. PMID 17937436. S2CID 22798244.
Wang KS, Liu XF, Aragam N (2010). "A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder". Schizophrenia Research. 124 (1–3): 192–9. doi:10.1016/j.schres.2010.09.002. PMID 20889312. S2CID 21402201.
Ovsyannikova IG, Kennedy RB, O'Byrne M, Jacobson RM, Pankratz VS, Poland GA (2012). "Genome-wide association study of antibody response to smallpox vaccine". Vaccine. 30 (28): 4182–9. doi:10.1016/j.vaccine.2012.04.055. PMC 3367131. PMID 22542470.
Hanke S, Bugert P, Chudek J, Kovacs G (2001). "Cloning a calcium channel alpha2delta-3 subunit gene from a putative tumor suppressor gene region at chromosome 3p21.1 in conventional renal cell carcinoma". Gene. 264 (1): 69–75. doi:10.1016/s0378-1119(00)00600-4. PMID 11245980.
Neely GG, Hess A, Costigan M, Keene AC, Goulas S, Langeslag M, Griffin RS, Belfer I, Dai F, Smith SB, Diatchenko L, Gupta V, Xia CP, Amann S, Kreitz S, Heindl-Erdmann C, Wolz S, Ly CV, Arora S, Sarangi R, Dan D, Novatchkova M, Rosenzweig M, Gibson DG, Truong D, Schramek D, Zoranovic T, Cronin SJ, Angjeli B, Brune K, Dietzl G, Maixner W, Meixner A, Thomas W, Pospisilik JA, Alenius M, Kress M, Subramaniam S, Garrity PA, Bellen HJ, Woolf CJ, Penninger JM (2010). "A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene". Cell. 143 (4): 628–38. doi:10.1016/j.cell.2010.09.047. PMC 3040441. PMID 21074052.
Qin N, Yagel S, Momplaisir ML, Codd EE, D'Andrea MR (2002). "Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit". Molecular Pharmacology. 62 (3): 485–96. doi:10.1124/mol.62.3.485. PMID 12181424.

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

Vanjski linkovi

Lokacija ljudskog genoma CACNA2D3 i stranica sa detaljima o genu CACNA2D3 u UCSC Genome Browseru.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000157445 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021991 - 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.

[entrez-5] "Entrez Gene: Calcium channel, voltage-dependent, alpha 2/delta subunit 3".

[UniProt-6] "UniProt, Q8IZS8" (jezik: engleski). Pristupljeno 2. 11. 2021.

[pmid22644305-7] Palmieri C, Rudraraju B, Monteverde M, Lattanzio L, Gojis O, Brizio R, Garrone O, Merlano M, Syed N, Lo Nigro C, Crook T (2012). "Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas". Br. J. Cancer. 107 (2): 375–81. doi:10.1038/bjc.2012.231. PMC 3394973. PMID 22644305.

[pmid18588891-8] Wanajo A, Sasaki A, Nagasaki H, Shimada S, Otsubo T, Owaki S, Shimizu Y, Eishi Y, Kojima K, Nakajima Y, Kawano T, Yuasa Y, Akiyama Y (2008). "Methylation of the calcium channel-related gene, CACNA2D3, is frequent and a poor prognostic factor in gastric cancer". Gastroenterology. 135 (2): 580–90. doi:10.1053/j.gastro.2008.05.041. PMID 18588891.

[pmid19170207-9] Yuasa Y, Nagasaki H, Akiyama Y, Hashimoto Y, Takizawa T, Kojima K, Kawano T, Sugihara K, Imai K, Nakachi K (2009). "DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients". Int. J. Cancer. 124 (11): 2677–82. doi:10.1002/ijc.24231. PMID 19170207. S2CID 46627170.

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