DNMT3B

DNMT3B
Available structures
PDB	Pretraga ortologa: PDBe RCSB
List of PDB id codes
	3QKJ, 3FLG, 5CIU
Identifikatori
Alijasi	DNMT3B
Spoljašnji ID	OMIM: 602900 MGI: 1261819 HomoloGene: 56000 GeneCards: DNMT3B
Genska lokacija (miš)
Hr.	Chromosome 2 (mouse)
Kraj	153,529,650 bp
Obrazac RNK izražavanja
	More reference expression data
Genska ontologija
Molecular function	• GO:0102674, GO:0102675 methyltransferase activity; • transferase activity; • DNA binding; • GO:0001106 transcription corepressor activity; • DNA-methyltransferase activity; • chromatin binding; • metal ion binding; • GO:0001948, GO:0016582 везивање за протеине плазме; • DNA (cytosine-5-)-methyltransferase activity; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific; • histone deacetylase binding;
Cellular component	• цитоплазма; • intracellular membrane-bounded organelle; • Нуклеоплазма; • једро;
Biological process	• response to ionizing radiation; • C-5 methylation of cytosine; • response to estradiol; • реакција на хипоксију; • cellular response to hyperoxia; • GO:1901227 negative regulation of transcription by RNA polymerase II; • response to activity; • cellular response to dexamethasone stimulus; • response to vitamin A; • DNA methylation; • Metilacija; • GO:1901313 positive regulation of gene expression; • negative regulation of gene expression, epigenetic; • positive regulation of histone H3-K4 methylation; • positive regulation of neuron differentiation; • negative regulation of histone H3-K9 methylation; • Regulacija genske ekspresije; • response to caffeine; • одговор на отровну супстанцу; • реакција на кокаин;
	Sources:Amigo / QuickGO
Ortolozi
	1789
	13436
	ENSG00000088305
	ENSMUSG00000027478
	Q9UBC3
	O88509
NM_001207055; NM_001207056; NM_006892; NM_175848; NM_175849;
	NM_175850
NM_001003960; NM_001003961; NM_001003963; NM_001122997; NM_001271744;
	NM_001271745; NM_001271746; NM_001271747; NM_010068
NP_001193984; NP_001193985; NP_008823; NP_787044; NP_787045;
	NP_787046
NP_001003960; NP_001003961; NP_001003963; NP_001116469; NP_001258673;
	NP_001258674; NP_001258675; NP_001258676; NP_034198
	Wikidata
View/Edit Human	View/Edit Mouse

DNK (citozin-5)-metiltransferaza 3 beta, je enzim koji je kod ljudi kodiran DNMT3B genom.^[4] Mutacije ovog gena su asocirane sa imunodeficijencijom, nestabilnosti centromera i sindromom anomalija lica.^[5]

Funkcija

CpG metilacija je epigenetska modifikacija koja je važna za embrionalni razvoj, utiskivanje i inaktivaciju X-hromozoma. Studije na miševima su pokazale da je metilacija DNK potrebna za razvoj sisara. Ovaj gen kodira DNK metiltransferazu za koju se smatra da funkcioniše u de novo metilaciji, a ne u održavanju metilacije. Protein se prvenstveno lokalizuje u jedru i njegova ekspresija je razvojno regulisana. Opisano je osam alternativno spojenih varijanti transkripta. Sekvence pune dužine varijanti 4 i 5 nisu određene.^[4]

Klinički značaj

Sindrom imunodeficijencije-centromerne nestabilnosti-anomalije lica (ICF) je rezultat defekata u sazrevanju limfocita koji su rezultat aberantne metilacije DNK uzrokovane mutacijama u genu DNMT3B.^[5]

Varijante ovog gena takođe mogu doprineti zavisnosti od nikotina.^[6]

Interakcije

Pokazano je da DNMT3B formira interakcije sa:

Reference

^ ^а ^б ^в GRCm38: Ensembl release 89: ENSMUSG00000027478 - Ensembl, May 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.
^ ^а ^б „Entrez Gene: DNMT3B DNA (cytosine-5-)-methyltransferase 3 beta”.
^ ^а ^б Ehrlich M (октобар 2003). „The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease”. Clinical Immunology. 109 (1): 17—28. PMID 14585272. doi:10.1016/S1521-6616(03)00201-8.
^ Hancock DB, Guo Y, Reginsson GW, Gaddis NC, Lutz SM, Sherva R, et al. (октобар 2017). „Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence”. Molecular Psychiatry. 23 (9): 1911—1919. PMC 5882602 . PMID 28972577. doi:10.1038/mp.2017.193.
^ ^а ^б ^в Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E, Jenuwein T, Peters AH (јул 2003). „Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin”. Current Biology. 13 (14): 1192—200. PMID 12867029. S2CID 2320997. doi:10.1016/s0960-9822(03)00432-9 .
^ ^а ^б Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S (август 2002). „Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases”. The EMBO Journal. 21 (15): 4183—95. PMC 126147 . PMID 12145218. doi:10.1093/emboj/cdf401.
^ Ling Y, Sankpal UT, Robertson AK, McNally JG, Karpova T, Robertson KD (2004). „Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription”. Nucleic Acids Research. 32 (2): 598—610. PMC 373322 . PMID 14752048. doi:10.1093/nar/gkh195.
^ ^а ^б ^в Geiman TM, Sankpal UT, Robertson AK, Chen Y, Mazumdar M, Heale JT, Schmiesing JA, Kim W, Yokomori K, Zhao Y, Robertson KD (2004). „Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery”. Nucleic Acids Research. 32 (9): 2716—29. PMC 419596 . PMID 15148359. doi:10.1093/nar/gkh589.
^ ^а ^б Kang ES, Park CW, Chung JH (децембар 2001). „Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1”. Biochemical and Biophysical Research Communications. 289 (4): 862—8. PMID 11735126. doi:10.1006/bbrc.2001.6057.

Literatura

Wijmenga C, Hansen RS, Gimelli G, Björck EJ, Davies EG, Valentine D, Belohradsky BH, van Dongen JJ, Smeets DF, van den Heuvel LP, Luyten JA, Strengman E, Weemaes C, Pearson PL (децембар 2000). „Genetic variation in ICF syndrome: evidence for genetic heterogeneity”. Human Mutation. 16 (6): 509—17. PMID 11102980. S2CID 6746943. doi:10.1002/1098-1004(200012)16:6<509::AID-HUMU8>3.0.CO;2-V .
Okano M, Xie S, Li E (јул 1998). „Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases”. Nature Genetics. 19 (3): 219—20. PMID 9662389. S2CID 256263. doi:10.1038/890.
Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA (јун 1999). „The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors”. Nucleic Acids Research. 27 (11): 2291—8. PMC 148793 . PMID 10325416. doi:10.1093/nar/27.11.2291.
Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E (август 1999). „Cloning, expression and chromosome locations of the human DNMT3 gene family”. Gene. 236 (1): 87—95. PMID 10433969. doi:10.1016/S0378-1119(99)00252-8.
Okano M, Bell DW, Haber DA, Li E (октобар 1999). „DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development”. Cell. 99 (3): 247—57. PMID 10555141. S2CID 15122892. doi:10.1016/S0092-8674(00)81656-6 .
Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK, Weemaes CM, Gartler SM (децембар 1999). „The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome”. Proceedings of the National Academy of Sciences of the United States of America. 96 (25): 14412—7. PMC 24450 . PMID 10588719. doi:10.1073/pnas.96.25.14412 .
Xu GL, Bestor TH, Bourc'his D, Hsieh CL, Tommerup N, Bugge M, Hulten M, Qu X, Russo JJ, Viegas-Péquignot E (новембар 1999). „Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene”. Nature. 402 (6758): 187—91. PMID 10647011. S2CID 4338524. doi:10.1038/46052.
Hartley JL, Temple GF, Brasch MA (новембар 2000). „DNA cloning using in vitro site-specific recombination”. Genome Research. 10 (11): 1788—95. PMC 310948 . PMID 11076863. doi:10.1101/gr.143000.
Fuks F, Burgers WA, Godin N, Kasai M, Kouzarides T (мај 2001). „Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription”. The EMBO Journal. 20 (10): 2536—44. PMC 125250 . PMID 11350943. doi:10.1093/emboj/20.10.2536.
Kang ES, Park CW, Chung JH (децембар 2001). „Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1”. Biochemical and Biophysical Research Communications. 289 (4): 862—8. PMID 11735126. doi:10.1006/bbrc.2001.6057.
Rhee I, Bachman KE, Park BH, Jair KW, Yen RW, Schuebel KE, Cui H, Feinberg AP, Lengauer C, Kinzler KW, Baylin SB, Vogelstein B (април 2002). „DNMT1 and DNMT3b cooperate to silence genes in human cancer cells”. Nature. 416 (6880): 552—6. PMID 11932749. S2CID 4397868. doi:10.1038/416552a.
Hata K, Okano M, Lei H, Li E (април 2002). „Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice”. Development. 129 (8): 1983—93. PMID 11934864. doi:10.1242/dev.129.8.1983.
Beaulieu N, Morin S, Chute IC, Robert MF, Nguyen H, MacLeod AR (август 2002). „An essential role for DNA methyltransferase DNMT3B in cancer cell survival”. The Journal of Biological Chemistry. 277 (31): 28176—81. PMID 12015329. doi:10.1074/jbc.M204734200 .
Saito Y, Kanai Y, Sakamoto M, Saito H, Ishii H, Hirohashi S (јул 2002). „Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis”. Proceedings of the National Academy of Sciences of the United States of America. 99 (15): 10060—5. PMC 126624 . PMID 12110732. doi:10.1073/pnas.152121799 .
Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S (август 2002). „Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases”. The EMBO Journal. 21 (15): 4183—95. PMC 126147 . PMID 12145218. doi:10.1093/emboj/cdf401.
Deplus R, Brenner C, Burgers WA, Putmans P, Kouzarides T, de Launoit Y, Fuks F (септембар 2002). „Dnmt3L is a transcriptional repressor that recruits histone deacetylase”. Nucleic Acids Research. 30 (17): 3831—8. PMC 137431 . PMID 12202768. doi:10.1093/nar/gkf509.
Shen H, Wang L, Spitz MR, Hong WK, Mao L, Wei Q (септембар 2002). „A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer”. Cancer Research. 62 (17): 4992—5. PMID 12208751.
Shirohzu H, Kubota T, Kumazawa A, Sado T, Chijiwa T, Inagaki K, Suetake I, Tajima S, Wakui K, Miki Y, Hayashi M, Fukushima Y, Sasaki H (септембар 2002). „Three novel DNMT3B mutations in Japanese patients with ICF syndrome”. American Journal of Medical Genetics. 112 (1): 31—7. PMID 12239717. doi:10.1002/ajmg.10658.

Spoljašnje veze

DNMT3b на US National Library of Medicine Medical Subject Headings (MeSH)
EC 2.1.1.37

[refGRCm38Ensembl-1] а ^б ^в GRCm38: Ensembl release 89: ENSMUSG00000027478 - Ensembl, May 2017

[2] „Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] „Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-4] а ^б „Entrez Gene: DNMT3B DNA (cytosine-5-)-methyltransferase 3 beta”.

[Ehrlich_2003-5] а ^б Ehrlich M (октобар 2003). „The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease”. Clinical Immunology. 109 (1): 17—28. PMID 14585272. doi:10.1016/S1521-6616(03)00201-8.

[HancockGuo2017-6] Hancock DB, Guo Y, Reginsson GW, Gaddis NC, Lutz SM, Sherva R, et al. (октобар 2017). „Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence”. Molecular Psychiatry. 23 (9): 1911—1919. PMC 5882602 . PMID 28972577. doi:10.1038/mp.2017.193.

[pmid12867029-7] а ^б ^в Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E, Jenuwein T, Peters AH (јул 2003). „Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin”. Current Biology. 13 (14): 1192—200. PMID 12867029. S2CID 2320997. doi:10.1016/s0960-9822(03)00432-9 .

[pmid12145218-8] а ^б Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S (август 2002). „Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases”. The EMBO Journal. 21 (15): 4183—95. PMC 126147 . PMID 12145218. doi:10.1093/emboj/cdf401.

[pmid14752048-9] Ling Y, Sankpal UT, Robertson AK, McNally JG, Karpova T, Robertson KD (2004). „Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription”. Nucleic Acids Research. 32 (2): 598—610. PMC 373322 . PMID 14752048. doi:10.1093/nar/gkh195.

[pmid15148359-10] а ^б ^в Geiman TM, Sankpal UT, Robertson AK, Chen Y, Mazumdar M, Heale JT, Schmiesing JA, Kim W, Yokomori K, Zhao Y, Robertson KD (2004). „Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery”. Nucleic Acids Research. 32 (9): 2716—29. PMC 419596 . PMID 15148359. doi:10.1093/nar/gkh589.

[pmid11735126-11] а ^б Kang ES, Park CW, Chung JH (децембар 2001). „Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1”. Biochemical and Biophysical Research Communications. 289 (4): 862—8. PMID 11735126. doi:10.1006/bbrc.2001.6057.

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