KDM2A
Lizin-specifična demetilaza 2A (KDM2A), znana i kao F-boksni i lucinlm bogati ponavljajući protein 11 (FBXL11) je enzim koji je kod ljudi kodiran genom KDM2A.[5][6][7] KDM2A je član natporodice alfa-ketoglutarat-zavisnih hidroksilaza, koje su proteini koji ne sadrže hem i sadrže gvožđe.
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 1.162 aminokiseline, a molekulska težina 132.793 Da.[8].
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MEPEEERIRY | SQRLRGTMRR | RYEDDGISDD | EIEGKRTFDL | EEKLHTNKYN | ||||
| ANFVTFMEGK | DFNVEYIQRG | GLRDPLIFKN | SDGLGIKMPD | PDFTVNDVKM | ||||
| CVGSRRMVDV | MDVNTQKGIE | MTMAQWTRYY | ETPEEEREKL | YNVISLEFSH | ||||
| TRLENMVQRP | STVDFIDWVD | NMWPRHLKES | QTESTNAILE | MQYPKVQKYC | ||||
| LMSVRGCYTD | FHVDFGGTSV | WYHIHQGGKV | FWLIPPTAHN | LELYENWLLS | ||||
| GKQGDIFLGD | RVSDCQRIEL | KQGYTFVIPS | GWIHAVYTPT | DTLVFGGNFL | ||||
| HSFNIPMQLK | IYNIEDRTRV | PNKFRYPFYY | EMCWYVLERY | VYCITNRSHL | ||||
| TKEFQKESLS | MDLELNGLES | GNGDEEAVDR | EPRRLSSRRS | VLTSPVANGV | ||||
| NLDYDGLGKT | CRSLPSLKKT | LAGDSSSDCS | RGSHNGQVWD | PQCAPRKDRQ | ||||
| VHLTHFELEG | LRCLVDKLES | LPLHKKCVPT | GIEDEDALIA | DVKILLEELA | ||||
| NSDPKLALTG | VPIVQWPKRD | KLKFPTRPKV | RVPTIPITKP | HTMKPAPRLT | ||||
| PVRPAAASPI | VSGARRRRVR | CRKCKACVQG | ECGVCHYCRD | MKKFGGPGRM | ||||
| KQSCVLRQCL | APRLPHSVTC | SLCGEVDQNE | ETQDFEKKLM | ECCICNEIVH | ||||
| PGCLQMDGEG | LLNEELPNCW | ECPKCYQEDS | SEKAQKRKME | ESDEEAVQAK | ||||
| VLRPLRSCDE | PLTPPPHSPT | SMLQLIHDPV | SPRGMVTRSS | PGAGPSDHHS | ||||
| ASRDERFKRR | QLLRLQATER | TMVREKENNP | SGKKELSEVE | KAKIRGSYLT | ||||
| VTLQRPTKEL | HGTSIVPKLQ | AITASSANLR | HSPRVLVQHC | PARTPQRGDE | ||||
| EGLGGEEEEE | EEEEEEDDSA | EEGGAARLNG | RGSWAQDGDE | SWMQREVWMS | ||||
| VFRYLSRREL | CECMRVCKTW | YKWCCDKRLW | TKIDLSRCKA | IVPQALSGII | ||||
| KRQPVSLDLS | WTNISKKQLT | WLVNRLPGLK | DLLLAGCSWS | AVSALSTSSC | ||||
| PLLRTLDLRW | AVGIKDPQIR | DLLTPPADKP | GQDNRSKLRN | MTDFRLAGLD | ||||
| ITDATLRLII | RHMPLLSRLD | LSHCSHLTDQ | SSNLLTAVGS | STRYSLTELN | ||||
| MAGCNKLTDQ | TLIYLRRIAN | VTLIDLRGCK | QITRKACEHF | ISDLSINSLY | ||||
| CLSDEKLIQK | IS |
Funkcija
urediOvaj gen kodira člana porodice proteinska F-kutija koju karakterizira približno 40 aminokiselinskih motiva, F-kutija. Proteini F-kutije čine jednu od četiri podjedinice kompleksa ubikvitin protein-ligaze pod nazivom SCF (SKP1-kulin-F-kutija), koji funkcioniraju u fosforilaciji-zavisnoj sveprisutnoj upotrebi. Proteini F-boksa su podijeljeni u tri klase: Fbws koji sadrže domene WD-40, Fbls koji sadrže ponavljanja bogata leucinom i Fbx koji sadrže ili različite module interakcije protein-protein ili bez prepoznatljivih motiva. Protein kodiran ovim genom pripada klasi Fbls i, osim F-boks-a, sadrži najmanje šest visoko degeneriranih ponavljanja bogatih leucinom.[7]
FBXL11/KDM2A je histon H3 lizin 36 demetilazni enzim. Enzimska aktivnost FBXL11/KDM2A oslanja se na konzervirani domen JmjC u N-kraju proteina koji koordinira gvožđe i alfaketoglutarat, kako bi katalizirao demetilaciju putem mehanizam zasnovanog na hidroksilaciji.[9] Nedavno je pokazano da domen koji veže ZF-CxxC DNK unutar FBXL11/KDM2A ima sposobnost interakcije s nemetiliranom DNK i taj domen cilja FBXL11/KDM2A na otočnim regijama genoma CpG-a, gdje posebno uklanja metilacija histon H3-lizin 36.[10] Ovaj mehanizam djeluje tako da stvara hromatinsko okruženje na CpG otocima koji ističe ove regulatorne elemente i razlikuje ih od neregulativnih regija u velikim složenim genomima sisara. U istraživanju na mišjim hepatocitima pokazalo se da ovaj gen regulira jetrenu glukoneogenezu.[11]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000173120 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000054611 - 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.
- ^ Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Jul 1999). "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (1): 63–70. doi:10.1093/dnares/6.1.63. PMID 10231032.
- ^ Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW (Dec 1999). "A family of mammalian F-box proteins". Curr Biol. 9 (20): 1180–2. doi:10.1016/S0960-9822(00)80021-4. PMID 10531037. S2CID 14341845.
- ^ a b "Entrez Gene: FBXL11 F-box and leucine-rich repeat protein 11".
- ^ "UniProt, Q9Y2K7". Pristupljeno 23. 8. 2021.
- ^ Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (februar 2006). "Histone demethylation by a family of JmjC domain-containing proteins". Nature. 439 (7078): 811–6. doi:10.1038/nature04433. PMID 16362057. S2CID 4415889.
- ^ Blackledge NP, Zhou JC, Tolstorukov MY, Farcas AM, Park PJ, Klose RJ (Apr 2010). "CpG islands recruit a histone H3 lysine 36 demethylase". Molecular Cell. 38 (2): 179–90. doi:10.1016/j.molcel.2010.04.009. PMC 3098377. PMID 20417597.
- ^ Pan D, Mao C, Zou T, Yao AY, Cooper MP, Boyartchuk V, Wang YX (2012). "The Histone Demethylase Jhdm1a Regulates Hepatic Gluconeogenesis". PLOS Genetics. 8 (6): e1002761. doi:10.1371/journal.pgen.1002761. PMC 3375226. PMID 22719268.
Dopunska literatura
uredi- Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
- Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M (1999). "Identification of a family of human F-box proteins". Curr. Biol. 9 (20): 1177–9. doi:10.1016/S0960-9822(00)80020-2. PMID 10531035. S2CID 7467493.
- Ilyin GP, Rialland M, Pigeon C, Guguen-Guillouzo C (2001). "cDNA cloning and expression analysis of new members of the mammalian F-box protein family". Genomics. 67 (1): 40–7. doi:10.1006/geno.2000.6211. PMID 10945468.
- Hattori A, Okumura K, Nagase T, Kikuno R, Hirosawa M, Ohara O (2001). "Characterization of long cDNA clones from human adult spleen". DNA Res. 7 (6): 357–66. doi:10.1093/dnares/7.6.357. PMID 11214971.
- Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, Osada H (2004). "M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP". Proc. Natl. Acad. Sci. U.S.A. 101 (13): 4419–24. doi:10.1073/pnas.0307700101. PMC 384762. PMID 15070733.
- Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (2004). "Functional proteomics mapping of a human signaling pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
- Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M (2005). "Nucleolar proteome dynamics". Nature. 433 (7021): 77–83. doi:10.1038/nature03207. PMID 15635413. S2CID 4344740.
- Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (2006). "Histone demethylation by a family of JmjC domain-containing proteins". Nature. 439 (7078): 811–6. doi:10.1038/nature04433. PMID 16362057. S2CID 4415889.
- Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
Vanjski linkovi
uredi
