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Identification
HMDB Protein ID HMDBP03103
Secondary Accession Numbers
  • 8641
Name N-lysine methyltransferase SETD8
Synonyms
  1. H4-K20-HMTase SETD8
  2. Lysine N-methyltransferase 5A
  3. PR-Set7
  4. PR/SET domain-containing protein 07
  5. PR/SET07
  6. SET domain-containing protein 8
  7. Histone-lysine N-methyltransferase SETD8
Gene Name SETD8
Protein Type Unknown
Biological Properties
General Function Involved in histone-lysine N-methyltransferase activity
Specific Function Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes.
Pathways
  • Lysine degradation
Reactions
S-Adenosylmethionine + L-lysine-[histone] → S-Adenosylhomocysteine + N(6)-methyl-L-lysine-[histone] details
Protein lysine + S-Adenosylmethionine → Protein N6-methyl-L-lysine + S-Adenosylhomocysteine details
S-Adenosylmethionine + Protein N6-methyl-L-lysine → S-Adenosylhomocysteine + Protein N6,N6-dimethyl-L-lysine details
S-Adenosylmethionine + Protein N6,N6-dimethyl-L-lysine → S-Adenosylhomocysteine + Protein N6,N6,N6-trimethyl-L-lysine details
GO Classification
Biological Process
cell division
peptidyl-lysine monomethylation
negative regulation of transcription from RNA polymerase II promoter
regulation of DNA damage response, signal transduction by p53 class mediator
transcription, DNA-dependent
mitosis
Cellular Component
chromosome
nucleus
Molecular Function
histone-lysine N-methyltransferase activity
transcription corepressor activity
Cellular Location
  1. Nucleus
  2. Chromosome
Gene Properties
Chromosome Location 12
Locus 12q24.31
SNPs SETD8
Gene Sequence
>1182 bp
ATGGGGGAAGGGGGCGCCGCGGCGGCGCTGGTGGCGGCGGCAGCAGCAGCAGCAGCGGCA
GCGGCAGCGGTGGTGGCCGGGCAGCGGCGGCGGCGGCTAGGGCGCAGGGCGCGCTGCCAT
GGGCCTGGCCGGGCTGCAGGCGGGAAGATGTCCAAGCCCTGCGCGGTGGAGGCGGCGGCG
GCGGCGGTGGCAGCGACGGCCCCGGGCCCGGAGATGGTGGAGCGGAGGGGCCCGGGGAGG
CCCCGCACCGACGGGGAGAACGTATTTACCGGGCAGTCAAAGATCTATTCCTACATGAGC
CCGAACAAATGCTCTGGAATGCGTTTCCCCCTTCAGGAAGAGAACTCAGTTACACATCAC
GAAGTCAAATGCCAGGGGAAACCATTAGCTGGAATCTACAGGAAACGAGAAGAGAAAAGA
AATGCTGGGAACGCAGTACGGAGCGCCATGAAGTCCGAGGAACAGAAGATCAAAGACGCC
AGGAGACGTCCCCTGGTACCTTTTCCAAACCAAAAATCTGAAGCAGCAGAACCTCCAAAA
ACTCCACCCTCATCTTGTGATTCCACCAATGCAGCCATCGCCAAGCAAGCCCTGAAAAAG
CCCATCAAGGGCAAACAGGCCCCCCGAAAAAAAGCTCAAGGAAAAACGCAACAGAATCGC
AAACTTACGGATTTCTACCCTGTCCGAAGGAGCTCCAGGAAGAGCAAAGCCGAGCTGCAG
TCTGAAGAAAGGAAAAGAATAGATGAATTGATTGAAAGTGGGAAGGAAGAAGGAATGAAG
ATCGACCTCATCGATGGCAAAGGCAGGGGTGTGATTGCCACCAAGCAGTTCTCCCGGGGT
GCCTTTGTGGTGGAATACCACGGGGACCTCATCGAGATCACCGACGCCAAGAAACGGGAG
GCTCTGTACGCACAGGACCCTTCCACGGGCTGCTACATGTACTATTTTCAGTATCTGAGC
AAAACCTACTGCGTGGATGCAACTAGAGAGACAAATCGCCTAGGAAGACTGATCAATCAC
AGCAAACGTGGGAACTGCCAAACCAAACTGCACGACATCGACGGCGTACCTCACCTCATC
CTCATCGCCTCCCGAGACATCGCGGCTGGGGAGGAGCCCCTGTATGACTATGGGGACCGC
AGCAAGGCTTCCATTGAAGCCCACCCATGGCTGAAGCATTAA
Protein Properties
Number of Residues 393
Molecular Weight 39222.325
Theoretical pI 9.567
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Histone-lysine N-methyltransferase SETD8
MGEGGAAAALVAAAAAAAAAAAAVVAGQRRRRLGRRARCHGPGRAAGGKMSKPCAVEAAA
AAVAATAPGPEMVERRGPGRPRTDGENVFTGQSKIYSYMSPNKCSGMRFPLQEENSVTHH
EVKCQGKPLAGIYRKREEKRNAGNAVRSAMKSEEQKIKDARKGPLVPFPNQKSEAAEPPK
TPPSSCDSTNAAIAKQALKKPIKGKQAPRKKAQGKTQQNRKLTDFYPVRRSSRKSKAELQ
SEERKRIDELIESGKEEGMKIDLIDGKGRGVIATKQFSRGDFVVEYHGDLIEITDAKKRE
ALYAQDPSTGCYMYYFQYLSKTYCVDATRETNRLGRLINHSKCGNCQTKLHDIDGVPHLI
LIASRDIAAGEELLYDYGDRSKASIEAHPWLKH
GenBank ID Protein 15029567
UniProtKB/Swiss-Prot ID Q9NQR1
UniProtKB/Swiss-Prot Entry Name SETD8_HUMAN
PDB IDs
GenBank Gene ID AF287261
GeneCard ID SETD8
GenAtlas ID SETD8
HGNC ID HGNC:29489
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  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. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  4. Nishioka K, Rice JC, Sarma K, Erdjument-Bromage H, Werner J, Wang Y, Chuikov S, Valenzuela P, Tempst P, Steward R, Lis JT, Allis CD, Reinberg D: PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Mol Cell. 2002 Jun;9(6):1201-13. [PubMed:12086618 ]
  5. Yin Y, Liu C, Tsai SN, Zhou B, Ngai SM, Zhu G: SET8 recognizes the sequence RHRK20VLRDN within the N terminus of histone H4 and mono-methylates lysine 20. J Biol Chem. 2005 Aug 26;280(34):30025-31. Epub 2005 Jun 17. [PubMed:15964846 ]
  6. Fang J, Feng Q, Ketel CS, Wang H, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Simon JA, Zhang Y: Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase. Curr Biol. 2002 Jul 9;12(13):1086-99. [PubMed:12121615 ]
  7. Rice JC, Nishioka K, Sarma K, Steward R, Reinberg D, Allis CD: Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7 expression and its localization to mitotic chromosomes. Genes Dev. 2002 Sep 1;16(17):2225-30. [PubMed:12208845 ]
  8. Julien E, Herr W: A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1. Mol Cell. 2004 Jun 18;14(6):713-25. [PubMed:15200950 ]
  9. Sims JK, Houston SI, Magazinnik T, Rice JC: A trans-tail histone code defined by monomethylated H4 Lys-20 and H3 Lys-9 demarcates distinct regions of silent chromatin. J Biol Chem. 2006 May 5;281(18):12760-6. Epub 2006 Mar 3. [PubMed:16517599 ]
  10. Xiao B, Jing C, Kelly G, Walker PA, Muskett FW, Frenkiel TA, Martin SR, Sarma K, Reinberg D, Gamblin SJ, Wilson JR: Specificity and mechanism of the histone methyltransferase Pr-Set7. Genes Dev. 2005 Jun 15;19(12):1444-54. Epub 2005 Jun 2. [PubMed:15933069 ]
  11. Couture JF, Collazo E, Brunzelle JS, Trievel RC: Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase. Genes Dev. 2005 Jun 15;19(12):1455-65. Epub 2005 Jun 2. [PubMed:15933070 ]