Histone-lysine N-methyltransferase SETD7

Details

Name
Histone-lysine N-methyltransferase SETD7
Synonyms
  • 2.1.1.43
  • H3-K4-HMTase SETD7
  • Histone H3-K4 methyltransferase SETD7
  • KIAA1717
  • KMT7
  • Lysine N-methyltransferase 7
  • SET domain-containing protein 7
  • SET7
  • SET7/9
  • SET9
Gene Name
SETD7
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004957|Histone-lysine N-methyltransferase SETD7
MDSDDEMVEEAVEGHLDDDGLPHGFCTVTYSSTDRFEGNFVHGEKNGRGKFFFFDGSTLE
GYYVDDALQGQGVYTYEDGGVLQGTYVDGELNGPAQEYDTDGRLIFKGQYKDNIRHGVCW
IYYPDGGSLVGEVNEDGEMTGEKIAYVYPDERTALYGKFIDGEMIEGKLATLMSTEEGRP
HFELMPGNSVYHFDKSTSSCISTNALLPDPYESERVYVAESLISSAGEGLFSKVAVGPNT
VMSFYNGVRITHQEVDSRDWALNGNTLSLDEETVIDVPEPYNHVSKYCASLGHKANHSFT
PNCIYDMFVHPRFGPIKCIRTLRAVEADEELTVAYGYDHSPPGKSGPEAPEWYQVELKAF
QATQQK
Number of residues
366
Molecular Weight
40720.595
Theoretical pI
4.25
GO Classification
Functions
chromatin binding / histone-lysine N-methyltransferase activity / p53 binding / protein-lysine N-methyltransferase activity
Processes
cellular response to DNA damage stimulus / chromatin modification / chromatin organization / heterochromatin organization / peptidyl-lysine dimethylation / peptidyl-lysine monomethylation / positive regulation of transcription, DNA-templated / regulation of histone H3-K9 methylation / response to ethanol / transcription, DNA-templated
Components
chromosome / nucleolus / nucleoplasm
General Function
Protein-lysine n-methyltransferase activity
Specific Function
Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. Has also methyltransferase activity toward non-histone proteins such as p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins. Monomethylates 'Lys-189' of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II. Monomethylates 'Lys-372' of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0011800|Histone-lysine N-methyltransferase SETD7 (SETD7)
ATGGATAGCGACGACGAGATGGTGGAGGAGGCGGTGGAAGGGCACCTGGACGATGACGGA
TTACCGCACGGGTTCTGCACAGTCACCTACTCCTCCACAGACAGATTTGAGGGGAACTTT
GTTCACGGAGAAAAGAACGGACGGGGGAAGTTCTTCTTCTTTGATGGCAGCACCCTGGAG
GGGTATTATGTGGATGATGCCTTGCAGGGCCAGGGAGTTTACACTTACGAAGATGGGGGA
GTTCTCCAGGGCACGTATGTAGACGGAGAGCTGAACGGTCCAGCCCAGGAATATGACACA
GATGGGAGACTGATCTTCAAGGGGCAGTATAAAGATAACATTCGTCATGGAGTGTGCTGG
ATATATTACCCAGATGGAGGAAGCCTTGTAGGAGAAGTAAATGAAGATGGGGAGATGACT
GGAGAGAAGATAGCCTATGTGTACCCTGATGAGAGGACCGCACTTTATGGGAAATTTATT
GATGGAGAGATGATAGAAGGCAAACTGGCTACCCTTATGTCCACTGAAGAAGGGAGGCCT
CACTTTGAACTGATGCCTGGAAATTCAGTGTACCACTTTGATAAGTCGACTTCATCTTGC
ATTTCTACCAATGCTCTTCTTCCAGATCCTTATGAATCAGAAAGGGTTTATGTTGCTGAA
TCTCTTATTTCCAGTGCTGGAGAAGGACTTTTTTCAAAGGTAGCTGTGGGACCTAATACT
GTTATGTCTTTTTATAATGGAGTTCGAATTACACACCAAGAGGTTGACAGCAGGGACTGG
GCCCTTAATGGGAACACCCTCTCCCTTGATGAAGAAACGGTCATTGATGTGCCTGAGCCC
TATAACCACGTATCCAAGTACTGTGCCTCCTTGGGACACAAGGCAAATCACTCCTTCACT
CCAAACTGCATCTACGATATTGGCCAGAAGAATCACCTGGGAACGTGTAAAAGAAGCAGA
TTTGGGGCTCCACTCCCAAAGATCCCACATCTGGATCAAGCGCCCTGGGTAGAACACAGA
AAAGCTGGCATTCCTCTTTATAGTGCAGCCCAAGGACTGATGCTCATAATGATGTTCGTG
AGTAATTAA
Chromosome Location
4
Locus
4q28
External Identifiers
ResourceLink
UniProtKB IDQ8WTS6
UniProtKB Entry NameSETD7_HUMAN
GenBank Gene IDAF448510
GenAtlas IDSETD7
HGNC IDHGNC:30412
General References
  1. Wang H, Cao R, Xia L, Erdjument-Bromage H, Borchers C, Tempst P, Zhang Y: Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase. Mol Cell. 2001 Dec;8(6):1207-17. [PubMed:11779497]
  2. Nishioka K, Chuikov S, Sarma K, Erdjument-Bromage H, Allis CD, Tempst P, Reinberg D: Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev. 2002 Feb 15;16(4):479-89. [PubMed:11850410]
  3. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed:15815621]
  4. Nagase T, Kikuno R, Hattori A, Kondo Y, Okumura K, Ohara O: Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 2000 Dec 31;7(6):347-55. [PubMed:11214970]
  5. 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]
  6. Martens JH, Verlaan M, Kalkhoven E, Zantema A: Cascade of distinct histone modifications during collagenase gene activation. Mol Cell Biol. 2003 Mar;23(5):1808-16. [PubMed:12588998]
  7. Kouskouti A, Scheer E, Staub A, Tora L, Talianidis I: Gene-specific modulation of TAF10 function by SET9-mediated methylation. Mol Cell. 2004 Apr 23;14(2):175-82. [PubMed:15099517]
  8. Francis J, Chakrabarti SK, Garmey JC, Mirmira RG: Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II elongation during activation of insulin transcription. J Biol Chem. 2005 Oct 28;280(43):36244-53. Epub 2005 Sep 1. [PubMed:16141209]
  9. Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T, Berger SL: Repression of p53 activity by Smyd2-mediated methylation. Nature. 2006 Nov 30;444(7119):629-32. Epub 2006 Nov 15. [PubMed:17108971]
  10. Hu P, Zhang Y: Catalytic mechanism and product specificity of the histone lysine methyltransferase SET7/9: an ab initio QM/MM-FE study with multiple initial structures. J Am Chem Soc. 2006 Feb 1;128(4):1272-8. [PubMed:16433545]
  11. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  12. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  13. Wilson JR, Jing C, Walker PA, Martin SR, Howell SA, Blackburn GM, Gamblin SJ, Xiao B: Crystal structure and functional analysis of the histone methyltransferase SET7/9. Cell. 2002 Oct 4;111(1):105-15. [PubMed:12372304]
  14. Jacobs SA, Harp JM, Devarakonda S, Kim Y, Rastinejad F, Khorasanizadeh S: The active site of the SET domain is constructed on a knot. Nat Struct Biol. 2002 Nov;9(11):833-8. [PubMed:12389038]
  15. Xiao B, Jing C, Wilson JR, Walker PA, Vasisht N, Kelly G, Howell S, Taylor IA, Blackburn GM, Gamblin SJ: Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature. 2003 Feb 6;421(6923):652-6. Epub 2003 Jan 22. [PubMed:12540855]
  16. Kwon T, Chang JH, Kwak E, Lee CW, Joachimiak A, Kim YC, Lee J, Cho Y: Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9-AdoMet. EMBO J. 2003 Jan 15;22(2):292-303. [PubMed:12514135]
  17. Chuikov S, Kurash JK, Wilson JR, Xiao B, Justin N, Ivanov GS, McKinney K, Tempst P, Prives C, Gamblin SJ, Barlev NA, Reinberg D: Regulation of p53 activity through lysine methylation. Nature. 2004 Nov 18;432(7015):353-60. Epub 2004 Nov 3. [PubMed:15525938]
  18. Couture JF, Collazo E, Hauk G, Trievel RC: Structural basis for the methylation site specificity of SET7/9. Nat Struct Mol Biol. 2006 Feb;13(2):140-6. Epub 2006 Jan 15. [PubMed:16415881]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01752S-adenosyl-L-homocysteineexperimentalunknownDetails