MLL (基因)

MLL
已知的结构
PDB	直系同源搜索：PDBe RCSB
PDBID列表
	2AGH、2J2S、2JYI、2KKF、2KU7、2KYU、2LXS、2LXT、2MTN、2W5Y、2W5Z、3EG6、3EMH、3LQI、3LQJ、3P4F、3U85、3U88、4ESG、4GQ6、4NW3、5F6L、5F5E
标识符
代号	KMT2A
扩展标识	MGI：96995；HomoloGene：4338；GeneCards：KMT2A；OMA：KMT2A - orthologs
基因位置（人类）
染色体	11號染色體
终止	118,526,832 bp
基因位置（小鼠）
染色体	小鼠9号染色体
终止	44,792,594 bp
RNA表达模式
	Top expressed in
	ventricular zone; ; epithelium of colon; ; ganglionic eminence; ; Brodmann area 23; ; lateral nuclear group of thalamus;
	Top expressed in
	tail of embryo; ; Rostral migratory stream; ; CA3 field; ; central gray substance of midbrain; ; neural layer of retina;
	查阅更多表达数据
	; ; ; ;
	查阅更多表达数据
基因本體
分子功能	methyltransferase activity; 轉移酶活性; DNA结合; protein homodimerization activity; minor groove of adenine-thymine-rich DNA binding; DNA结合转录因子活性; 鋅離子結合; chromatin binding; 金屬離子結合; core promoter sequence-specific DNA binding; 血浆蛋白结合; unmethylated CpG binding; lysine-acetylated histone binding; 相同蛋白质结合; histone-lysine N-methyltransferase activity; histone methyltransferase activity (H3-K4 specific); DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding;
細胞組分	核质; 细胞核; histone methyltransferase complex; 细胞质基质; MLL1 complex;
生物學過程	visual learning; response to potassium ion; regulation of transcription, DNA-templated; 認知; positive regulation of transporter activity; positive regulation of cellular response to drug; response to light stimulus; rhythmic process; regulation of short-term neuronal synaptic plasticity; histone H3-K4 trimethylation; membrane depolarization; regulation of histone H3-K4 methylation; regulation of histone H3-K9 acetylation; transcription by RNA polymerase II; post-embryonic development; peptidyl-lysine monomethylation; 脾的发生; circadian regulation of gene expression; regulation of histone H3-K14 acetylation; transcription, DNA-templated; regulation of histone H3-K27 acetylation; positive regulation of transcription, DNA-templated; DNA甲基化; histone H3-K4 methylation; 甲基化; positive regulation of histone H3-K4 methylation; 探究行为; embryonic hemopoiesis; histone H3-K4 dimethylation; 基因調節; homeostasis of number of cells within a tissue; histone H4-K16 acetylation; definitive hemopoiesis; anterior/posterior pattern specification; negative regulation of cell population proliferation; 细胞凋亡; regulation of megakaryocyte differentiation; regulation of hematopoietic stem cell differentiation; chromatin organization; positive regulation of transcription by RNA polymerase II; protein-containing complex assembly; negative regulation of DNA methylation;
	来源：Amigo / QuickGO
直系同源
	4297
	214162
	ENSG00000118058
	ENSMUSG00000002028
	Q03164
	P55200
	NM_001197104; NM_005933; NM_024891
	NM_001081049; NM_001357549
	NP_001184033; NP_005924
	NP_001344478
	维基数据
檢視/編輯人類	檢視/編輯小鼠

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^[5]。

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^[6]，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^[7]。该基因亦可能参与了精神分裂症中GAD67表达下调的过程^[8]。

交互作用

现已显示MLL这个基因与HDAC1^[9]、PPP1R15A^[10]、宿主细胞因子C1^[11]、MEN1^[11]RBBP5,^[11]ASH2L,^[11]、CREB结合蛋白^[12]^[13]、WDR5^[11]CTBP1^[9]及PPIE.^[14]之间有着相互作用。

参考文献

^ ^1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000118058 – Ensembl, May 2017
^ ^2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000002028 – Ensembl, 2017年5月
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^9.0 ^9.1 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.
^ 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.
^ ^11.0 ^11.1 ^11.2 ^11.3 ^11.4 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.
^ 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 . 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 . PMID 11313484. doi:10.1128/MCB.21.10.3589-3597.2001.

深入阅读

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

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

[refGRCh38Ensembl-1] 1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000118058 – Ensembl, May 2017

[refGRCm38Ensembl-2] 2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000002028 – Ensembl, 2017年5月

[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.

[pmid1720549-5] 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.

[9aaTAD-6] 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.

[pmid15941828-7] 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.

[pmid17942719-8] 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.

[pmid12829790-9] 9.0 ^9.1 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.

[pmid10490642-10] 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.

[pmid15199122-11] 11.0 ^11.1 ^11.2 ^11.3 ^11.4 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.

[pmid12205094-12] 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.

[pmid11259575-13] 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.

[pmid11313484-14] 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.

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