CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-022020
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 N-lysine methyltransferase SETD8 
Protein Synonyms/Alias
 H4-K20-HMTase SETD8; Histone-lysine N-methyltransferase SETD8; Lysine N-methyltransferase 5A; PR/SET domain-containing protein 07; PR-Set7; PR/SET07; SET domain-containing protein 8 
Gene Name
 SETD8 
Gene Synonyms/Alias
 KMT5A; PRSET7; SET07; SET8 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
151NAVRSAMKSEEQKIKsumoylation[1]
172LVPFPNQKSEAAEPPsumoylation[1]
221GKTQQNRKLTDFYPVubiquitination[2]
234PVRRSSRKSKAELQSubiquitination[2, 3]
236RRSSRKSKAELQSEEubiquitination[2, 3, 4]
245ELQSEERKRIDELIEubiquitination[3]
255DELIESGKEEGMKIDubiquitination[3]
260SGKEEGMKIDLIDGKubiquitination[3]
267KIDLIDGKGRGVIATubiquitination[2, 3]
275GRGVIATKQFSRGDFubiquitination[2, 4]
349KCGNCQTKLHDIDGVubiquitination[2]
382YDYGDRSKASIEAHPubiquitination[2, 3]
392IEAHPWLKH******ubiquitination[2]
Reference
 [1] The UBC9 E2 SUMO conjugating enzyme binds the PR-Set7 histone methyltransferase to facilitate target gene repression.
 Spektor TM, Congdon LM, Veerappan CS, Rice JC.
 PLoS One. 2011;6(7):e22785. [PMID: 21829513]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 257 378 SET.
 REGION 267 269 S-adenosyl-L-methionine binding.
 REGION 339 340 S-adenosyl-L-methionine binding.
 BINDING 312 312 S-adenosyl-L-methionine.
 MOD_RES 100 100 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; Cell cycle; Cell division; Chromatin regulator; Chromosome; Coiled coil; Complete proteome; Direct protein sequencing; Methyltransferase; Mitosis; Nucleus; Phosphoprotein; Reference proteome; Repressor; S-adenosyl-L-methionine; Transcription; Transcription regulation; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 393 AA 
Protein Sequence
MGEGGAAAAL VAAAAAAAAA AAAVVAGQRR RRLGRRARCH GPGRAAGGKM SKPCAVEAAA 60
AAVAATAPGP EMVERRGPGR PRTDGENVFT GQSKIYSYMS PNKCSGMRFP LQEENSVTHH 120
EVKCQGKPLA GIYRKREEKR NAGNAVRSAM KSEEQKIKDA RKGPLVPFPN QKSEAAEPPK 180
TPPSSCDSTN AAIAKQALKK PIKGKQAPRK KAQGKTQQNR KLTDFYPVRR SSRKSKAELQ 240
SEERKRIDEL IESGKEEGMK IDLIDGKGRG VIATKQFSRG DFVVEYHGDL IEITDAKKRE 300
ALYAQDPSTG CYMYYFQYLS KTYCVDATRE TNRLGRLINH SKCGNCQTKL HDIDGVPHLI 360
LIASRDIAAG EELLYDYGDR SKASIEAHPW LKH 393 
Gene Ontology
 GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0018024; F:histone-lysine N-methyltransferase activity; IDA:UniProtKB.
 GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
 GO:0051301; P:cell division; IEA:UniProtKB-KW.
 GO:0007067; P:mitosis; IEA:UniProtKB-KW.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
 GO:0018026; P:peptidyl-lysine monomethylation; IDA:UniProtKB.
 GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR016858; Hist_H4-K20_MeTrfase.
 IPR001214; SET_dom. 
Pfam
 PF00856; SET 
SMART
 SM00317; SET 
PROSITE
 PS51571; SAM_MT43_PR_SET
 PS50280; SET 
PRINTS