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Identification
HMDB Protein ID HMDBP14555
Secondary Accession Numbers None
Name Histone-lysine N-methyltransferase MECOM
Synonyms
  1. Ecotropic virus integration site 1 protein homolog
  2. MDS1 and EVI1 complex locus protein
  3. Myelodysplasia syndrome 1 protein
  4. Myelodysplasia syndrome-associated protein 1
  5. EVI-1
Gene Name MECOM
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression. Oncogene which plays a role in development, cell proliferation and differentiation. May also play a role in apoptosis through regulation of the JNK and TGF-beta signaling. Involved in hematopoiesis.Displays histone methyltransferase activity and monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro. Probably catalyzes the monomethylation of free histone H3 in the cytoplasm which is then transported to the nucleus and incorporated into nucleosomes where SUV39H methyltransferases use it as a substrate to catalyze histone H3 'Lys-9' trimethylation. Likely to be one of the primary histone methyltransferases along with PRDM16 that direct cytoplasmic H3K9me1 methylation.
Pathways
  • Chronic myeloid leukemia
  • Lysine degradation
  • MAPK signaling pathway
Reactions Not Available
GO Classification
Biological Process
negative regulation of programmed cell death
apoptotic process
heterochromatin organization
regulation of transcription from RNA polymerase II promoter
negative regulation of transcription, DNA-dependent
positive regulation of transcription, DNA-dependent
cell differentiation
negative regulation of JNK cascade
hematopoietic stem cell proliferation
regulation of cell cycle
Cellular Component
cytosol
nucleus
nucleoplasm
nuclear speck
Molecular Function
histone methyltransferase activity (H3-K9 specific)
metal ion binding
sequence-specific DNA binding transcription factor activity
DNA-binding transcription activator activity, RNA polymerase II-specific
protein homodimerization activity
RNA polymerase II core promoter proximal region sequence-specific DNA binding
DNA binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 1230
Molecular Weight 138134.305
Theoretical pI 6.439
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q03112
UniProtKB/Swiss-Prot Entry Name MECOM_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  4. Chakraborty S, Senyuk V, Sitailo S, Chi Y, Nucifora G: Interaction of EVI1 with cAMP-responsive element-binding protein-binding protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of EVI1 and in co-localization in nuclear speckles. J Biol Chem. 2001 Nov 30;276(48):44936-43. Epub 2001 Sep 21. [PubMed:11568182 ]
  5. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  6. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [PubMed:18220336 ]
  7. Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Chen R, Chen Z, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang J, Wang J, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA: The DNA sequence, annotation and analysis of human chromosome 3. Nature. 2006 Apr 27;440(7088):1194-8. [PubMed:16641997 ]
  8. Kurokawa M, Mitani K, Yamagata T, Takahashi T, Izutsu K, Ogawa S, Moriguchi T, Nishida E, Yazaki Y, Hirai H: The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death. EMBO J. 2000 Jun 15;19(12):2958-68. [PubMed:10856240 ]
  9. Nitta E, Izutsu K, Yamaguchi Y, Imai Y, Ogawa S, Chiba S, Kurokawa M, Hirai H: Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP. Oncogene. 2005 Sep 8;24(40):6165-73. [PubMed:15897867 ]
  10. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231 ]
  11. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [PubMed:23186163 ]
  12. Hendriks IA, Lyon D, Young C, Jensen LJ, Vertegaal AC, Nielsen ML: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat Struct Mol Biol. 2017 Mar;24(3):325-336. doi: 10.1038/nsmb.3366. Epub 2017 Jan 23. [PubMed:28112733 ]
  13. Hendriks IA, D'Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC: Uncovering global SUMOylation signaling networks in a site-specific manner. Nat Struct Mol Biol. 2014 Oct;21(10):927-36. doi: 10.1038/nsmb.2890. Epub 2014 Sep 14. [PubMed:25218447 ]
  14. Hendriks IA, Treffers LW, Verlaan-de Vries M, Olsen JV, Vertegaal ACO: SUMO-2 Orchestrates Chromatin Modifiers in Response to DNA Damage. Cell Rep. 2015 Mar 17;10(10):1778-1791. doi: 10.1016/j.celrep.2015.02.033. Epub 2015 Mar 12. [PubMed:25772364 ]
  15. Mochizuki N, Shimizu S, Nagasawa T, Tanaka H, Taniwaki M, Yokota J, Morishita K: A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells. Blood. 2000 Nov 1;96(9):3209-14. [PubMed:11050005 ]
  16. Morishita K, Parganas E, Douglass EC, Ihle JN: Unique expression of the human Evi-1 gene in an endometrial carcinoma cell line: sequence of cDNAs and structure of alternatively spliced transcripts. Oncogene. 1990 Jul;5(7):963-71. [PubMed:2115646 ]
  17. Fears S, Mathieu C, Zeleznik-Le N, Huang S, Rowley JD, Nucifora G: Intergenic splicing of MDS1 and EVI1 occurs in normal tissues as well as in myeloid leukemia and produces a new member of the PR domain family. Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1642-7. doi: 10.1073/pnas.93.4.1642. [PubMed:8643684 ]
  18. Mitani K, Ogawa S, Tanaka T, Miyoshi H, Kurokawa M, Mano H, Yazaki Y, Ohki M, Hirai H: Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. EMBO J. 1994 Feb 1;13(3):504-10. [PubMed:8313895 ]
  19. Ogawa S, Kurokawa M, Tanaka T, Mitani K, Inazawa J, Hangaishi A, Tanaka K, Matsuo Y, Minowada J, Tsubota T, Yazaki Y, Hirai H: Structurally altered Evi-1 protein generated in the 3q21q26 syndrome. Oncogene. 1996 Jul 4;13(1):183-91. [PubMed:8700545 ]
  20. Kurokawa M, Mitani K, Irie K, Matsuyama T, Takahashi T, Chiba S, Yazaki Y, Matsumoto K, Hirai H: The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting Smad3. Nature. 1998 Jul 2;394(6688):92-6. doi: 10.1038/27945. [PubMed:9665135 ]
  21. Liu Y, Chen L, Ko TC, Fields AP, Thompson EA: Evi1 is a survival factor which conveys resistance to both TGFbeta- and taxol-mediated cell death via PI3K/AKT. Oncogene. 2006 Jun 15;25(25):3565-75. doi: 10.1038/sj.onc.1209403. Epub 2006 Feb 6. [PubMed:16462766 ]
  22. Shimabe M, Goyama S, Watanabe-Okochi N, Yoshimi A, Ichikawa M, Imai Y, Kurokawa M: Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells. Oncogene. 2009 Dec 10;28(49):4364-74. doi: 10.1038/onc.2009.288. [PubMed:19767769 ]
  23. Pinheiro I, Margueron R, Shukeir N, Eisold M, Fritzsch C, Richter FM, Mittler G, Genoud C, Goyama S, Kurokawa M, Son J, Reinberg D, Lachner M, Jenuwein T: Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell. 2012 Aug 31;150(5):948-60. doi: 10.1016/j.cell.2012.06.048. [PubMed:22939622 ]
  24. Niihori T, Ouchi-Uchiyama M, Sasahara Y, Kaneko T, Hashii Y, Irie M, Sato A, Saito-Nanjo Y, Funayama R, Nagashima T, Inoue S, Nakayama K, Ozono K, Kure S, Matsubara Y, Imaizumi M, Aoki Y: Mutations in MECOM, Encoding Oncoprotein EVI1, Cause Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia. Am J Hum Genet. 2015 Dec 3;97(6):848-54. doi: 10.1016/j.ajhg.2015.10.010. Epub 2015 Nov 12. [PubMed:26581901 ]