KDM2A

KDM2A
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2YU1, 2YU2, 4BBQ
Identifikatori
Aliasi	KDM2A
Vanjski ID-jevi	OMIM: 605657 MGI: 1354736 HomoloGene: 56564 GeneCards: KDM2A
Lokacija gena (čovjek)
Hrom.	Hromosom 11 (čovjek)
Kraj	67,258,082 bp
Lokacija gena (miš)
Hrom.	Hromosom 19 (miš)
Kraj	4,448,313 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• vezivanje sa DNK; • oxidoreductase activity; • vezivanje iona cinka; • dioxygenase activity; • vezivanje iona metala; • histone demethylase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • histone H3-methyl-lysine-36 demethylase activity; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Ćelijska komponenta	• nukleoplazma; • jedro;
Biološki proces	• double-strand break repair via nonhomologous end joining; • GO:0009373 regulation of transcription, DNA-templated; • histone H3-K36 demethylation; • transcription, DNA-templated; • GO:0031497, GO:0006336, GO:0034724, GO:0001301, GO:0007580, GO:0034652, GO:0010847 chromatin organization; • GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II; • negative regulation of transcription by competitive promoter binding; • circadian regulation of gene expression; • regulation of circadian rhythm; • rhythmic process;
	Izvori:Amigo / QuickGO
Ortolozi
	22992
	225876
	ENSG00000173120
	ENSMUSG00000054611
	Q9Y2K7
	P59997
	NM_001256405; NM_012308
	NM_001001984
	NP_001243334; NP_036440
	NP_001001984
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

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

Dužina polipeptidnog lanca je 1.162 aminokiseline, a molekulska težina 132.793 Da.^[8].

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
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

Ovaj 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

^ ^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

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

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000173120 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000054611 - 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.

[pmid10231032-5] 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.

[pmid10531037-6] 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.

[entrez-7] "Entrez Gene: FBXL11 F-box and leucine-rich repeat protein 11".

[UniProt-8] "UniProt, Q9Y2K7". Pristupljeno 23. 8. 2021.

[pmid16362057-9] 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.

[pmid20417597-10] 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.

[doi.10.1371/journal.pgen.1002761-11] 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.

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p r u Oksidoreduktaze: dioksigenaze, uključujući steroidne hidroksilaze (EC 1.14)
1.14.11: 2-oxoglutarate	Prolyl hydroxylase HIF prolyl-hydroxylase EGLN1 EGLN2 EGLN3 P4HTM Lysyl hydroxylase
1.14.13: NADH or NADPH	Flavin-containing monooxygenase FMO1 FMO2 FMO3 FMO4 FMO5 Nitric oxide synthase NOS1 NOS2 NOS3 Cholesterol 7 alpha-hydroxylase Methane monooxygenase 3A4 14α-demethylase 24-hydroxycholesterol 7α-hydroxylase
1.14.14: reduced flavin or flavoprotein	19A1 2D6 2E1
1.14.15: reduced iron-sulfur protein	11B1 11B2 11A1
1.14.16: reduced pteridine (BH4 dependent)	Phenylalanine hydroxylase Tyrosine hydroxylase Tryptophan hydroxylase
1.14.17: reduced ascorbate	Dopamine beta-hydroxylase
1.14.18-19: other	Tyrosinase Stearoyl-CoA desaturase-1
1.14.99 - miscellaneous	Cyclooxygenase Heme oxygenase (HMOX1) Squalene monooxygenase 17A1 21A2 Ecdysone 20-monooxygenase Deoxyhypusine monooxygenase