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Identification
HMDB Protein ID HMDBP00411
Secondary Accession Numbers
  • 5648
Name Histone-lysine N-methyltransferase SETDB1
Synonyms
  1. ERG-associated protein with SET domain
  2. ESET
  3. H3-K9-HMTase 4
  4. Histone H3-K9 methyltransferase 4
  5. Lysine N-methyltransferase 1E
  6. SET domain bifurcated 1
Gene Name SETDB1
Protein Type Unknown
Biological Properties
General Function Involved in DNA binding
Specific Function Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. Probably forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins.
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
inner cell mass cell proliferation
regulation of transcription, DNA-dependent
transcription, DNA-dependent
Cellular Component
chromosome
plasma membrane
Golgi apparatus
nucleus
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
transition metal ion binding
zinc ion binding
transferase activity
protein methyltransferase activity
protein-lysine n-methyltransferase activity
histone-lysine n-methyltransferase activity
nucleic acid binding
dna binding
transferase activity, transferring one-carbon groups
methyltransferase activity
Molecular Function
histone-lysine N-methyltransferase activity
zinc ion binding
DNA binding
Process
cellular process
cellular component organization at cellular level
organelle organization
chromosome organization
chromatin organization
chromatin modification
Cellular Location
  1. Nucleus
  2. Chromosome
Gene Properties
Chromosome Location 1
Locus 1q21
SNPs SETDB1
Gene Sequence
>3876 bp
ATGTCTTCCCTTCCTGGGTGCATTGGTTTGGATGCAGCAACAGCTACAGTGGAGTCTGAA
GAGATTGCAGAGCTGCAACAGGCAGTGGTTGAGGAACTGGGTATCTCTATGGAGGAACTT
CGGCATTTCATCGATGAGGAACTGGAGAAGATGGATTGTGTACAGCAACGCAAGAAGCAG
CTAGCAGAGTTAGAGACATGGGTAATACAGAAAGAATCTGAGGTGGCTCACGTTGACCAA
CTCTTTGATGATGCATCCAGGGCAGTGACTAATTGTGAGTCTTTGGTGAAGGACTTCTAC
TCCAAGCTGGGACTACAATACCGGGACAGTAGCTCTGAGGACGAATCTTCCCGGCCTACA
GAAATAATTGAGATTCCTGATGAAGATGATGATGTCCTCAGTATTGATTCAGGTGATGCT
GGGAGCAGAACTCCAAAAGACCAGAAGCTCCGTGAAGCTATGGCTGCCTTAAGAAAGTCA
GCTCAAGATGTTCAGAAGTTCATGGATGCTGTCAACAAGAAGAGCAGTTCCCAGGATCTG
CATAAAGGAACCTTGAGTCAGATGTCTGGAGAACTAAGCAAAGATGGTGACCTGATAGTC
AGCATGCGAATTCTGGGCAAGAAGAGAACTAAGACTTGGCACAAAGGCACCCTTATTGCC
ATCCAGACAGTTGGGCCAGGGAAGAAATACAAGGTGAAATTTGACAACAAAGGAAAGAGT
CTACTGTCGGGGAACCATATTGCCTATGATTACCACCCTCCTGCTGACAAGCTGTATGTG
GGCAGTCGGGTGGTCGCCAAATACAAAGATGGGAATCAGGTCTGGCTCTATGCTGGCATT
GTAGCTGAGACACCAAACGTCAAAAACAAGCTCAGGTTTCTCATTTTCTTTGATGATGGC
TATGCTTCCTATGTCACACAGTCGGAACTGTATCCCATTTGCCGGCCACTGAAAAAGACT
TGGGAGGACATAGAAGACATCTCCTGCCGTGACTTCATAGAGGAGTATGTCACTGCCTAC
CCCAACCGCCCCATGGTACTGCTCAAGAGTGGCCAGCTTATCAAGACTGAGTGGGAAGGC
ACGTGGTGGAAGTCCCGAGTTGAGGAGGTGGATGGCAGCCTAGTCAGGATCCTCTTCCTG
GATGACAAAAGATGTGAGTGGATCTATCGAGGCTCTACACGGCTGGAGCCCATGTTCAGC
ATGAAAACATCCTCAGCCTCTGCACTGGAGAAGAAGCAAGGACAGCTCAGGACACGTCCA
AATATGGGTGCTGTGAGGAGCAAAGGCCCTGTTGTCCAGTACACACAGGATCTGACCGGT
ACTGGAACCCAGTTCAAGCCAGTGGAACCCCCACAGCCTACAGCTCCACCTGCCCCACCT
TTCCCACCTGCTCCACCTCTATCCCCCCAAGCAGGTGACAGTGACTTGGAAAGCCAGCTT
GCCCAGTCACGGAAGCAGGTAGCCAAAAAGAGCACGTCCTTTCGACCAGGATCTGTGGGC
TCTGGTCATTCCTCCCCTACATCTCCTGCACTCAGTGAAAATGTCTCTGGTGGGAAACCT
GGGATCAACCAGACATATAGATCACCTTTAGGCTCCACAGCCTCTGCCCCAGCACCCTCA
GCACTCCCGGCCCCTCCAGCACCCCCAGTCTTCCATGGCATGCTGGAGCGGGCCCCAGCA
GAGCCCTCCTACCGTGCTCCCATGGAGAAGCTTTTCTACTTACCTCATGTCTGCAGCTAT
ACCTGTCTGTCTCGAGTCAGACCTATGAGGAATGAGCAGTACCGGGGCAAGAACCCTCTG
CTGGTCCCGTTACTATATGACTTCCGGCGGATGACAGCCCGGCGTCGAGTTAACCGCAAG
ATGGGCTTTCATGTTATCTATAAGACACCTTGTGGTCTCTGCCTTCGGACAATGCAGGAG
ATAGAACGCTACCTTTTCGAGACTGGCTGTGACTTCCTCTTCCTGGAGATGTTCTGTTTG
GATCCATATGTTCTTGTGGACCGAAAGTTTCAGCCCTATAAGCCTTTTTACTATATTTTG
GACATCACTTATGGGAAGGAAGATGTTCCCCTATCCTGTGTCAATGAGATTGACACAACC
CCTCCACCCCAGGTGGCCTACAGCAAGGAACGTATCCCGGGCAAGGGTGTTTTCATTAAC
ACAGGCCCTGAATTTCTGGTTGGCTGTGACTGCAAGGATGGGTGTCGGGACAAGTCCAAG
TGTGCCTGCCATCAACTAACTATCCAGGCTACAGCCTGTACCCCAGGAGGCCAAATCAAC
CCTAACTCTGGCTACCAGTACAAGAGACTAGAAGAGTGTCTACCCACAGGGGTATATGAG
TGTAACAAACGCTGCAAATGTGACCCAAACATGTGCACAAACCGGTTGGTGCAACATGGA
CTACAAGTTCGGCTACAGCTATTCAAGACACAGAACAAGGGCTGGGGTATCCGCTGCTTG
GATGACATTGCCAAAGGCTCTTTTGTTTGTATTTATGCAGGCAAAATCCTGACAGATGAC
TTTGCAGACAAGGAGGGTCTGGAAATGGGTGATGAGTACTTTGCAAATCTGGACCATATC
GAGAGCGTGGAGAACTTCAAAGAAGGATATGAGAGTGATGCCCCCTGTTCCTCTGACAGC
AGTGGTGTAGACTTGAAGGACCAGGAAGATGGCAACAGCGGTACAGAGGACCCTGAAGAG
TCCAATGATGATAGCTCAGATGATAACTTCTGTAAGGATGAGGACTTCAGCACCAGTTCA
GTGTGGCGGAGCTATGCTACCCGGAGGCAGACCCGGGGCCAGAAAGAGAACGGACTCTCT
GAGACAACTTCCAAGGACTCCCACCCCCCAGATCTTGGACCCCCACATATTCCTGTTCCT
CCCTCAATCCCTGTAGGTGGCTGCAATCCACCTTCCTCCGAAGAGACACCCAAGAACAAG
GTGGCCTCATGGTTGAGCTGCAATAGTGTCAGTGAAGGTGGTTTTGCTGACTCTGATAGC
CATTCATCCTTCAAGACTAATGAAGGTGGGGAGGGCCGGGCTGGGGGAAGCCGAATGGAG
GCTGAGAAGGCCTCCACCTCAGGACTAGGCATCAAGGATGAGGGAGACATCAAACAGGCC
AAGAAAGAGGACACTGACGACCGAAACAAGATGTCAGTAGTTACTGAAAGCTCTCGAAAT
TACGGTTACAATCCTTCTCCTGTGAAGCCTGAAGGACTTCGCCGCCCACCTAGTAAGACT
AGTATGCATCAAAGCCGAAGACTCATGGCTTCTGCTCAGTCCAACCCTGATGATGTCCTG
ACACTGTCCAGCAGCACAGAAAGTGAGGGGGAAAGTGGGACCAGCCGAAAGCCCACTGCT
GGTCAGACTTCGGCTACAGCGGTTGACAGTGATGATATCCAGACCATATCCTCTGGCTCT
GAAGGGGATGACTTTGAGGACAAGAAGAACATGACTGGTCCAATGAAGCGTCAAGTGGCA
GTAAAATCAACCCGAGGCTTTGCTCTTAAATCAACCCATGGGATTGCAATTAAATCAACC
AACATGGCCTCTGTGGACAAGGGGGAGAGCGCACCTGTTCGTAAGAACACACGCCAATTC
TATGATGGCGAGGAGTCTTGCTACATCATTGATGCCAAGCTTGAAGGCAACCTGGGCCGC
TACCTCAACCACAGTTGCAGCCCCAACCTGTTTGTCCAGAATGTCTTCGTGGATACCCAT
GATCTTCGCTTCCCCTGGGTGGCCTTCTTTGCCAGCAAAAGAATCCGGGCTGGGACAGAA
CTTACTTGGGACTACAACTACGAGGTGGGCAGTGTGGAAGGCAAGGAGCTACTCTGTTGC
TGTGGGGCCATTGAATGCAGAGGACGTCTTCTTTAG
Protein Properties
Number of Residues 1291
Molecular Weight 143155.6
Theoretical pI 6.028
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Histone-lysine N-methyltransferase SETDB1
MSSLPGCIGLDAATATVESEEIAELQQAVVEELGISMEELRHFIDEELEKMDCVQQRKKQ
LAELETWVIQKESEVAHVDQLFDDASRAVTNCESLVKDFYSKLGLQYRDSSSEDESSRPT
EIIEIPDEDDDVLSIDSGDAGSRTPKDQKLREAMAALRKSAQDVQKFMDAVNKKSSSQDL
HKGTLSQMSGELSKDGDLIVSMRILGKKRTKTWHKGTLIAIQTVGPGKKYKVKFDNKGKS
LLSGNHIAYDYHPPADKLYVGSRVVAKYKDGNQVWLYAGIVAETPNVKNKLRFLIFFDDG
YASYVTQSELYPICRPLKKTWEDIEDISCRDFIEEYVTAYPNRPMVLLKSGQLIKTEWEG
TWWKSRVEEVDGSLVRILFLDDKRCEWIYRGSTRLEPMFSMKTSSASALEKKQGQLRTRP
NMGAVRSKGPVVQYTQDLTGTGTQFKPVEPPQPTAPPAPPFPPAPPLSPQAGDSDLESQL
AQSRKQVAKKSTSFRPGSVGSGHSSPTSPALSENVSGGKPGINQTYRSPLGSTASAPAPS
ALPAPPAPPVFHGMLERAPAEPSYRAPMEKLFYLPHVCSYTCLSRVRPMRNEQYRGKNPL
LVPLLYDFRRMTARRRVNRKMGFHVIYKTPCGLCLRTMQEIERYLFETGCDFLFLEMFCL
DPYVLVDRKFQPYKPFYYILDITYGKEDVPLSCVNEIDTTPPPQVAYSKERIPGKGVFIN
TGPEFLVGCDCKDGCRDKSKCACHQLTIQATACTPGGQINPNSGYQYKRLEECLPTGVYE
CNKRCKCDPNMCTNRLVQHGLQVRLQLFKTQNKGWGIRCLDDIAKGSFVCIYAGKILTDD
FADKEGLEMGDEYFANLDHIESVENFKEGYESDAPCSSDSSGVDLKDQEDGNSGTEDPEE
SNDDSSDDNFCKDEDFSTSSVWRSYATRRQTRGQKENGLSETTSKDSHPPDLGPPHIPVP
PSIPVGGCNPPSSEETPKNKVASWLSCNSVSEGGFADSDSHSSFKTNEGGEGRAGGSRME
AEKASTSGLGIKDEGDIKQAKKEDTDDRNKMSVVTESSRNYGYNPSPVKPEGLRRPPSKT
SMHQSRRLMASAQSNPDDVLTLSSSTESEGESGTSRKPTAGQTSATAVDSDDIQTISSGS
EGDDFEDKKNMTGPMKRQVAVKSTRGFALKSTHGIAIKSTNMASVDKGESAPVRKNTRQF
YDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVAFFASKRIRAGTE
LTWDYNYEVGSVEGKELLCCCGAIECRGRLL
GenBank ID Protein 55960634
UniProtKB/Swiss-Prot ID Q15047
UniProtKB/Swiss-Prot Entry Name SETB1_HUMAN
PDB IDs
GenBank Gene ID AL590133
GeneCard ID SETDB1
GenAtlas ID SETDB1
HGNC ID HGNC:10761
References
General References
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  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. 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 ]
  5. Molina H, Horn DM, Tang N, Mathivanan S, Pandey A: Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2199-204. Epub 2007 Feb 7. [PubMed:17287340 ]
  6. Meierhofer D, Wang X, Huang L, Kaiser P: Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry. J Proteome Res. 2008 Oct;7(10):4566-76. doi: 10.1021/pr800468j. Epub 2008 Sep 10. [PubMed:18781797 ]
  7. Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, Seki N, Kawarabayasi Y, Ishikawa K, Tabata S: Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 1994;1(5):223-9. [PubMed:7584044 ]
  8. Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ 3rd: SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev. 2002 Apr 15;16(8):919-32. [PubMed:11959841 ]
  9. Ayyanathan K, Lechner MS, Bell P, Maul GG, Schultz DC, Yamada Y, Tanaka K, Torigoe K, Rauscher FJ 3rd: Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation. Genes Dev. 2003 Aug 1;17(15):1855-69. Epub 2003 Jul 17. [PubMed:12869583 ]
  10. Wang H, An W, Cao R, Xia L, Erdjument-Bromage H, Chatton B, Tempst P, Roeder RG, Zhang Y: mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression. Mol Cell. 2003 Aug;12(2):475-87. [PubMed:14536086 ]
  11. Sarraf SA, Stancheva I: Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol Cell. 2004 Aug 27;15(4):595-605. [PubMed:15327775 ]
  12. Verschure PJ, van der Kraan I, de Leeuw W, van der Vlag J, Carpenter AE, Belmont AS, van Driel R: In vivo HP1 targeting causes large-scale chromatin condensation and enhanced histone lysine methylation. Mol Cell Biol. 2005 Jun;25(11):4552-64. [PubMed:15899859 ]
  13. Gevaert K, Staes A, Van Damme J, De Groot S, Hugelier K, Demol H, Martens L, Goethals M, Vandekerckhove J: Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC. Proteomics. 2005 Sep;5(14):3589-99. [PubMed:16097034 ]
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  15. Ichimura T, Watanabe S, Sakamoto Y, Aoto T, Fujita N, Nakao M: Transcriptional repression and heterochromatin formation by MBD1 and MCAF/AM family proteins. J Biol Chem. 2005 Apr 8;280(14):13928-35. Epub 2005 Feb 2. [PubMed:15691849 ]
  16. Li H, Rauch T, Chen ZX, Szabo PE, Riggs AD, Pfeifer GP: The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem. 2006 Jul 14;281(28):19489-500. Epub 2006 May 8. [PubMed:16682412 ]
  17. Rosendorff A, Sakakibara S, Lu S, Kieff E, Xuan Y, DiBacco A, Shi Y, Shi Y, Gill G: NXP-2 association with SUMO-2 depends on lysines required for transcriptional repression. Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5308-13. Epub 2006 Mar 27. [PubMed:16567619 ]
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