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维基百科

MLL (基因)

一月 01, 1970

组蛋白-赖氨酸N-甲基转移酶HRX（英語：Histone-lysine N-methyltransferase HRX）是人体中由MLL（ALL1）基因编码的一种酶。MLL代表髓样/淋巴样，或混合世系白血病[1]。

髓样/淋巴样或混合世系白血病（三胸同源物，果蝇）
PDB rendering based on 2j2s.
有效结构
PDB 直系同源检索：PDBe, RCSB
标识
代号 MLL; ALL-1; CXXC7; HRX; HTRX1; KMT2A; MLL/GAS7; MLL1A; TET1-MLL; TRX1; WDSTS
扩展标识 遗传学：159555 鼠基因：96995 同源基因：4338 ChEMBL: 1293299 GeneCards: MLL Gene
EC編號 2.1.1.43
RNA表达模式
更多表达数据
直系同源体
物种 人类 小鼠
Entrez 4297 214162
Ensembl ENSG00000118058 ENSMUSG00000002028
UniProt Q03164 P55200
mRNA序列 NM_001197104 NM_001081049
蛋白序列 NP_001184033 NP_001074518
基因位置 Chr 11:
118.31 – 118.4 Mb		 Chr 9:
44.8 – 44.88 Mb
PubMed查询 [1] [2]

MLL是一种组蛋白甲基转移酶，被认为是影响基因转录的全局正向调控物。该蛋白属于组蛋白修饰酶类家族，包含了转活化结构域9aaTAD[2]，且参与了对转录记忆的表观遗传学维持。

MLL基因若发生重排（即染色体结构改变造成遗传物质的重新排列）则会导致严重的急性白血病，包括淋巴母细胞性及髓性[3]。该基因亦可能参与了精神分裂症中GAD67表达下调的过程[4]。

交互作用 编辑

现已显示MLL这个基因与HDAC1[5]、PPP1R15A[6]、宿主细胞因子C1[7]、MEN1[7] RBBP5,[7] ASH2L,[7]、CREB结合蛋白[8][9]、WDR5[7] CTBP1[5]及PPIE.[10]之间有着相互作用。

参考文献 编辑

  1. ^ Ziemin-van der Poel S. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci U S A. January 1992, 88 (23): 10735–9. PMC 53005  . PMID 1720549. doi:10.1073/pnas.88.23.10735. 
  2. ^ Piskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M. Nine-amino-acid transactivation domain: establishment and prediction utilities. Genomics. June 2007, 89 (6): 756–68. PMID 17467953. doi:10.1016/j.ygeno.2007.02.003. ; Piskacek M. Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300. Nature Precedings: Prepublication research and preliminary findings. November 2009. doi:10.1038/npre.2009.3488.2. ; Piskacek M. 9aaTADs mimic DNA to interact with a pseudo-DNA Binding Domain KIX of Med15 (Molecular Chameleons). Nature Preceedings: Prepublication research and preliminary findings. November 2009. doi:10.1038/npre.2009.3939.1. ; Goto NK, Zor T, Martinez-Yamout M, Dyson HJ, Wright PE. Cooperativity in transcription factor binding to the coactivator CREB-binding protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIX domain. J. Biol. Chem. November 2002, 277 (45): 43168–74. PMID 12205094. doi:10.1074/jbc.M207660200. ; Prasad R, Yano T, Sorio C, Nakamura T, Rallapalli R, Gu Y, Leshkowitz D, Croce CM, Canaani E. Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia. Proc. Natl. Acad. Sci. U.S.A. December 1995, 92 (26): 12160–4. PMC 40316  . PMID 8618864. doi:10.1073/pnas.92.26.12160. ; Ernst P, Wang J, Huang M, Goodman RH, Korsmeyer SJ. MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB-Binding Protein. Mol. Cell. Biol. April 2001, 21 (7): 2249–58. PMC 86859  . PMID 11259575. doi:10.1128/MCB.21.7.2249-2258.2001. 
  3. ^ Guenther MG, Jenner RG, Chevalier B, Nakamura T, Croce CM, Canaani E, Young RA. Global and Hox-specific roles for the MLL1 methyltransferase. Proc. Natl. Acad. Sci. U.S.A. June 2005, 102 (24): 8603–8. PMC 1150839  . PMID 15941828. doi:10.1073/pnas.0503072102. 
  4. ^ Huang HS, Matevossian A, Whittle C, Kim SY, Schumacher A, Baker SP, Akbarian S. Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters. J. Neurosci. October 2007, 27 (42): 11254–62. PMID 17942719. doi:10.1523/JNEUROSCI.3272-07.2007. 
  5. ^ 5.0 5.1 Xia, Zhen-Biao; Anderson Melanie; Diaz Manuel O; Zeleznik-Le Nancy J. MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein. Proc. Natl. Acad. Sci. U.S.A. (United States). July 2003, 100 (14): 8342–7. ISSN 0027-8424. PMC 166231  . PMID 12829790. doi:10.1073/pnas.1436338100. 
  6. ^ Adler, H T; Chinery R; Wu D Y; Kussick S J; Payne J M; Fornace A J; Tkachuk D C. Leukemic HRX Fusion Proteins Inhibit GADD34-Induced Apoptosis and Associate with the GADD34 and hSNF5/INI1 Proteins. Mol. Cell. Biol. (UNITED STATES). October 1999, 19 (10): 7050–60. ISSN 0270-7306. PMC 84700  . PMID 10490642. 
  7. ^ 7.0 7.1 7.2 7.3 7.4 Yokoyama, Akihiko; Wang Zhong; Wysocka Joanna; Sanyal Mrinmoy; Aufiero Deborah J; Kitabayashi Issay; Herr Winship; Cleary Michael L. Leukemia Proto-Oncoprotein MLL Forms a SET1-Like Histone Methyltransferase Complex with Menin To Regulate Hox Gene Expression. Mol. Cell. Biol. (United States). July 2004, 24 (13): 5639–49. ISSN 0270-7306. PMC 480881  . PMID 15199122. doi:10.1128/MCB.24.13.5639-5649.2004. 
  8. ^ Goto, Natalie K; Zor Tsaffrir; Martinez-Yamout Maria; Dyson H Jane; Wright Peter E. Cooperativity in transcription factor binding to the coactivator CREB-binding protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIX domain. J. Biol. Chem. (United States). November 2002, 277 (45): 43168–74. ISSN 0021-9258. PMID 12205094. doi:10.1074/jbc.M207660200. 
  9. ^ Ernst, P; Wang J; Huang M; Goodman R H; Korsmeyer S J. MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB-Binding Protein. Mol. Cell. Biol. (United States). April 2001, 21 (7): 2249–58. ISSN 0270-7306. PMC 86859  . PMID 11259575. doi:10.1128/MCB.21.7.2249-2258.2001. 
  10. ^ Fair, K; Anderson M; Bulanova E; Mi H; Tropschug M; Diaz M O. Protein Interactions of the MLL PHD Fingers Modulate MLL Target Gene Regulation in Human Cells. Mol. Cell. Biol. (United States). May 2001, 21 (10): 3589–97. ISSN 0270-7306. PMC 100280  . PMID 11313484. doi:10.1128/MCB.21.10.3589-3597.2001. 

深入阅读 编辑

  • Marschalek R; Nilson I; Löchner K; Greim, R; Siegler, G; Greil, J; Beck, JD; Fey, GH. The structure of the human ALL-1/MLL/HRX gene. Leuk. Lymphoma. 1998, 27 (5–6): 417–28. PMID 9477123. doi:10.3109/10428199709058308. 
  • Eguchi M, Eguchi-Ishimae M, Greaves M. The role of the MLL gene in infant leukemia. Int. J. Hematol. 2004, 78 (5): 390–401. PMID 14704031. doi:10.1007/BF02983811. 
  • Daser A, Rabbitts TH. Extending the repertoire of the mixed-lineage leukemia gene MLL in leukemogenesis. Genes Dev. 2004, 18 (9): 965–74. PMID 15132992. doi:10.1101/gad.1195504. 
  • Li ZY, Liu DP, Liang CC. New insight into the molecular mechanisms of MLL-associated leukemia. Leukemia. 2005, 19 (2): 183–90. PMID 15618964. doi:10.1038/sj.leu.2403602. 
  • Douet-Guilbert N; Morel F; Le Bris MJ; Sassolas, Bruno; Giroux, Jean-Dominique; De Braekeleer, Marc. Rearrangement of MLL in a patient with congenital acute monoblastic leukemia and granulocytic sarcoma associated with a t(1;11)(p36;q23) translocation. Leuk. Lymphoma. 2005, 46 (1): 143–6. PMID 15621793. doi:10.1080/104281904000010783. 

外部链接 编辑

一月 01, 1970
基因, 组蛋白, 赖氨酸n, 甲基转移酶hrx, 英語, histone, lysine, methyltransferase, 是人体中由mll, all1, 基因编码的一种酶, mll代表髓样, 淋巴样, 或混合世系白血病, 髓样, 淋巴样或混合世系白血病, 三胸同源物, 果蝇, rendering, based, 2j2s, 有效结构, 直系同源检索, pdbe, rcsb, pdb查询代码列表, 2agh, 2j2s, 2jyi, 2kkf, 2ku7, 2kyu, 2lxs, 2lxt, 2w5y, 2w. 组蛋白 赖氨酸N 甲基转移酶HRX 英語 Histone lysine N methyltransferase HRX 是人体中由MLL ALL1 基因编码的一种酶 MLL代表髓样 淋巴样 或混合世系白血病 1 髓样 淋巴样或混合世系白血病 三胸同源物 果蝇 PDB rendering based on 2j2s 有效结构 PDB 直系同源检索 PDBe RCSB PDB查询代码列表 2AGH 2J2S 2JYI 2KKF 2KU7 2KYU 2LXS 2LXT 2W5Y 2W5Z 3EG6 3EMH 3LQH 3LQI 3LQJ 3P4F 3U85 3U88 4ESG 4GQ6标识代号MLL ALL 1 CXXC7 HRX HTRX1 KMT2A MLL GAS7 MLL1A TET1 MLL TRX1 WDSTS扩展标识遗传学 159555 鼠基因 96995 同源基因 4338 ChEMBL 1293299 GeneCards MLL GeneEC編號2 1 1 43基因本体论描述 分子功能 AT DNA binding sequence specific DNA binding transcription factor activity protein binding zinc ion binding histone methyltransferase activity H3 K4 specific identical protein binding protein homodimerization activity transcription regulatory region DNA binding unmethylated CpG binding histone acetyl lysine binding 细胞成分 nucleus histone methyltransferase complex MLL1 complex 生物过程 transcription from RNA polymerase II promoter protein complex assembly apoptotic process positive regulation of transporter activity embryonic hemopoiesis histone H4 K16 acetylation positive regulation of transcription DNA dependent positive regulation of transcription from RNA polymerase II promoter histone H3 K4 methylation histone H3 K4 trimethylation positive regulation of cellular response to drug Sources Amigo QuickGORNA表达模式更多表达数据直系同源体物种人类小鼠Entrez4297214162EnsemblENSG00000118058ENSMUSG00000002028UniProtQ03164P55200mRNA序列NM 001197104NM 001081049蛋白序列NP 001184033NP 001074518基因位置Chr 11 118 31 118 4 MbChr 9 44 8 44 88 MbPubMed查询 1 2 查论编 MLL是一种组蛋白甲基转移酶 被认为是影响基因转录的全局正向调控物 该蛋白属于组蛋白修饰酶类家族 包含了转活化结构域9aaTAD 2 且参与了对转录记忆的表观遗传学维持 MLL基因若发生重排 即染色体结构改变造成遗传物质的重新排列 则会导致严重的急性白血病 包括淋巴母细胞性及髓性 3 该基因亦可能参与了精神分裂症中GAD67表达下调的过程 4 目录 1 交互作用 2 参考文献 3 深入阅读 4 外部链接交互作用 编辑现已显示MLL这个基因与HDAC1 5 PPP1R15A 6 宿主细胞因子C1 7 MEN1 7 RBBP5 7 ASH2L 7 CREB结合蛋白 8 9 WDR5 7 CTBP1 5 及PPIE 10 之间有着相互作用 参考文献 编辑 Ziemin van der Poel S Identification of a gene MLL that spans the breakpoint in 11q23 translocations associated with human leukemias Proc Natl Acad Sci U S A January 1992 88 23 10735 9 PMC 53005 nbsp PMID 1720549 doi 10 1073 pnas 88 23 10735 Piskacek S Gregor M Nemethova M Grabner M Kovarik P Piskacek M Nine amino acid transactivation domain establishment and prediction utilities Genomics June 2007 89 6 756 68 PMID 17467953 doi 10 1016 j ygeno 2007 02 003 Piskacek M Common Transactivation Motif 9aaTAD recruits multiple general co activators TAF9 MED15 CBP and p300 Nature Precedings Prepublication research and preliminary findings November 2009 doi 10 1038 npre 2009 3488 2 Piskacek M 9aaTADs mimic DNA to interact with a pseudo DNA Binding Domain KIX of Med15 Molecular Chameleons Nature Preceedings Prepublication research and preliminary findings November 2009 doi 10 1038 npre 2009 3939 1 Goto NK Zor T Martinez Yamout M Dyson HJ Wright PE Cooperativity in transcription factor binding to the coactivator CREB binding protein CBP The mixed lineage leukemia protein MLL activation domain binds to an allosteric site on the KIX domain J Biol Chem November 2002 277 45 43168 74 PMID 12205094 doi 10 1074 jbc M207660200 Prasad R Yano T Sorio C Nakamura T Rallapalli R Gu Y Leshkowitz D Croce CM Canaani E Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia Proc Natl Acad Sci U S A December 1995 92 26 12160 4 PMC 40316 nbsp PMID 8618864 doi 10 1073 pnas 92 26 12160 Ernst P Wang J Huang M Goodman RH Korsmeyer SJ MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB Binding Protein Mol Cell Biol April 2001 21 7 2249 58 PMC 86859 nbsp PMID 11259575 doi 10 1128 MCB 21 7 2249 2258 2001 Guenther MG Jenner RG Chevalier B Nakamura T Croce CM Canaani E Young RA Global and Hox specific roles for the MLL1 methyltransferase Proc Natl Acad Sci U S A June 2005 102 24 8603 8 PMC 1150839 nbsp PMID 15941828 doi 10 1073 pnas 0503072102 Huang HS Matevossian A Whittle C Kim SY Schumacher A Baker SP Akbarian S Prefrontal dysfunction in schizophrenia involves mixed lineage leukemia 1 regulated histone methylation at GABAergic gene promoters J Neurosci October 2007 27 42 11254 62 PMID 17942719 doi 10 1523 JNEUROSCI 3272 07 2007 5 0 5 1 Xia Zhen Biao Anderson Melanie Diaz Manuel O Zeleznik Le Nancy J MLL repression domain interacts with histone deacetylases the polycomb group proteins HPC2 and BMI 1 and the corepressor C terminal binding protein Proc Natl Acad Sci U S A United States July 2003 100 14 8342 7 ISSN 0027 8424 PMC 166231 nbsp PMID 12829790 doi 10 1073 pnas 1436338100 Adler H T Chinery R Wu D Y Kussick S J Payne J M Fornace A J Tkachuk D C Leukemic HRX Fusion Proteins Inhibit GADD34 Induced Apoptosis and Associate with the GADD34 and hSNF5 INI1 Proteins Mol Cell Biol UNITED STATES October 1999 19 10 7050 60 ISSN 0270 7306 PMC 84700 nbsp PMID 10490642 7 0 7 1 7 2 7 3 7 4 Yokoyama Akihiko Wang Zhong Wysocka Joanna Sanyal Mrinmoy Aufiero Deborah J Kitabayashi Issay Herr Winship Cleary Michael L Leukemia Proto Oncoprotein MLL Forms a SET1 Like Histone Methyltransferase Complex with Menin To Regulate Hox Gene Expression Mol Cell Biol United States July 2004 24 13 5639 49 ISSN 0270 7306 PMC 480881 nbsp PMID 15199122 doi 10 1128 MCB 24 13 5639 5649 2004 Goto Natalie K Zor Tsaffrir Martinez Yamout Maria Dyson H Jane Wright Peter E Cooperativity in transcription factor binding to the coactivator CREB binding protein CBP The mixed lineage leukemia protein MLL activation domain binds to an allosteric site on the KIX domain J Biol Chem United States November 2002 277 45 43168 74 ISSN 0021 9258 PMID 12205094 doi 10 1074 jbc M207660200 Ernst P Wang J Huang M Goodman R H Korsmeyer S J MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB Binding Protein Mol Cell Biol United States April 2001 21 7 2249 58 ISSN 0270 7306 PMC 86859 nbsp PMID 11259575 doi 10 1128 MCB 21 7 2249 2258 2001 Fair K Anderson M Bulanova E Mi H Tropschug M Diaz M O Protein Interactions of the MLL PHD Fingers Modulate MLL Target Gene Regulation in Human Cells Mol Cell Biol United States May 2001 21 10 3589 97 ISSN 0270 7306 PMC 100280 nbsp PMID 11313484 doi 10 1128 MCB 21 10 3589 3597 2001 深入阅读 编辑Marschalek R Nilson I Lochner K Greim R Siegler G Greil J Beck JD Fey GH The structure of the human ALL 1 MLL HRX gene Leuk Lymphoma 1998 27 5 6 417 28 PMID 9477123 doi 10 3109 10428199709058308 Eguchi M Eguchi Ishimae M Greaves M The role of the MLL gene in infant leukemia Int J Hematol 2004 78 5 390 401 PMID 14704031 doi 10 1007 BF02983811 Daser A Rabbitts TH Extending the repertoire of the mixed lineage leukemia gene MLL in leukemogenesis Genes Dev 2004 18 9 965 74 PMID 15132992 doi 10 1101 gad 1195504 Li ZY Liu DP Liang CC New insight into the molecular mechanisms of MLL associated leukemia Leukemia 2005 19 2 183 90 PMID 15618964 doi 10 1038 sj leu 2403602 Douet Guilbert N Morel F Le Bris MJ Sassolas Bruno Giroux Jean Dominique De Braekeleer Marc Rearrangement of MLL in a patient with congenital acute monoblastic leukemia and granulocytic sarcoma associated with a t 1 11 p36 q23 translocation Leuk Lymphoma 2005 46 1 143 6 PMID 15621793 doi 10 1080 104281904000010783 外部链接 编辑MLL OMIM Entry 页面存档备份 存于互联网档案馆 MYELOID LYMPHOID OR MIXED LINEAGE LEUKEMIA GENE MLL 醫學主題詞表 MeSH MLL protein human Gene MLL on the Atlas of Genetics and Oncology 取自 https zh wikipedia org w index php title MLL 基因 amp oldid 79616671, 维基百科，wiki，书籍，书籍，图书馆，

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