SETDB1
entrez
9869
canonical
uniprot
Q15047
canonical
ensembl
ENSG00000143379
resolver
ensp
ENSP00000271640
resolver
ensp
ENSP00000357958
resolver
ensp
ENSP00000357959
resolver
ensp
ENSP00000357965
resolver
ensp
ENSP00000432348
resolver
ensp
ENSP00000436148
resolver
ensp
ENSP00000508664
resolver
ensp
ENSP00000509425
resolver
ensp
ENSP00000554798
resolver
ensp
ENSP00000554799
resolver
ensp
ENSP00000554800
resolver
ensp
ENSP00000554802
resolver
ensp
ENSP00000593233
resolver
ensp
ENSP00000593234
resolver
ensp
ENSP00000659519
resolver
ensp
ENSP00000725366
resolver
enst
ENST00000368963
resolver
enst
ENST00000692314
resolver
enst
ENST00000692827
resolver
enst
ENST00000884739
resolver
enst
ENST00000884743
resolver
enst
ENST00000923174
resolver
enst
ENST00000923175
resolver
genesymbol
SETDB1
resolver
genesymbol_syn
ESET
resolver
genesymbol_syn
KIAA0067
resolver
genesymbol_syn
KMT1E
resolver
hgnc
HGNC:10761
resolver
uniprot
A0A8I5KT93
resolver
uniprot
A6NEW2
resolver
uniprot
Q5SZD8
resolver
uniprot
Q5SZD9
resolver
uniprot
Q5SZE0
resolver
uniprot
Q5SZE7
resolver
uniprot
Q96GM9
resolver
uniprot
X6R732
resolver
uniprot_entry
A0A8I5KT93_HUMAN
resolver
uniprot_entry
SETB1_HUMAN
resolver
uniprot_entry
X6R732_HUMAN
resolver
uniprot_sec
A6NEW2
resolver
uniprot_sec
Q5SZD8
resolver
uniprot_sec
Q5SZD9
resolver
uniprot_sec
Q5SZE0
resolver
uniprot_sec
Q5SZE7
resolver
uniprot_sec
Q96GM9
resolver
amino_acid_sequence
MSSLPGCIGLDAATATVESEEIAELQQAVVEELGISMEELRHFIDEELEKMDCVQQRKKQLAELETWVIQKESEVAHVDQLFDDASRAVTNCESLVKDFYSKLGLQYRDSSSEDESSRPTEIIEIPDEDDDVLSIDSGDAGSRTPKDQKLREAMAALRKSAQDVQKFMDAVNKKSSSQDLHKGTLSQMSGELSKDGDLIVSMRILGKKRTKTWHKGTLIAIQTVGPGKKYKVKFDNKGKSLLSGNHIAYDYHPPADKLYVGSRVVAKYKDGNQVWLYAGIVAETPNVKNKLRFLIFFDDGYASYVTQSELYPICRPLKKTWEDIEDISCRDFIEEYVTAYPNRPMVLLKSGQLIKTEWEGTWWKSRVEEVDGSLVRILFLDDKRCEWIYRGSTRLEPMFSMKTSSASALEKKQGQLRTRPNMGAVRSKGPVVQYTQDLTGTGTQFKPVEPPQPTAPPAPPFPPAPPLSPQAGDSDLESQLAQSRKQVAKKSTSFRPGSVGSGHSSPTSPALSENVSGGKPGINQTYRSPLGSTASAPAPSALPAPPAPPVFHGMLERAPAEPSYRAPMEKLFYLPHVCSYTCLSRVRPMRNEQYRGKNPLLVPLLYDFRRMTARRRVNRKMGFHVIYKTPCGLCLRTMQEIERYLFETGCDFLFLEMFCLDPYVLVDRKFQPYKPFYYILDITYGKEDVPLSCVNEIDTTPPPQVAYSKERIPGKGVFINTGPEFLVGCDCKDGCRDKSKCACHQLTIQATACTPGGQINPNSGYQYKRLEECLPTGVYECNKRCKCDPNMCTNRLVQHGLQVRLQLFKTQNKGWGIRCLDDIAKGSFVCIYAGKILTDDFADKEGLEMGDEYFANLDHIESVENFKEGYESDAPCSSDSSGVDLKDQEDGNSGTEDPEESNDDSSDDNFCKDEDFSTSSVWRSYATRRQTRGQKENGLSETTSKDSHPPDLGPPHIPVPPSIPVGGCNPPSSEETPKNKVASWLSCNSVSEGGFADSDSHSSFKTNEGGEGRAGGSRMEAEKASTSGLGIKDEGDIKQAKKEDTDDRNKMSVVTESSRNYGYNPSPVKPEGLRRPPSKTSMHQSRRLMASAQSNPDDVLTLSSSTESEGESGTSRKPTAGQTSATAVDSDDIQTISSGSEGDDFEDKKNMTGPMKRQVAVKSTRGFALKSTHGIAIKSTNMASVDKGESAPVRKNTRQFYDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVAFFASKRIRAGTELTWDYNYEVGSVEGKELLCCCGAIECRGRLL
uniprot
proteins
ec_number
2.1.1.366
uniprot
proteins
function
FUNCTION: Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3) (PubMed:11959841, PubMed:12869583, PubMed:14536086, PubMed:27237050, PubMed:39096901). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones (PubMed:11959841, PubMed:12869583, PubMed:14536086, PubMed:27237050, PubMed:39096901). Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes (PubMed:12869583, PubMed:14536086, PubMed:27237050, PubMed:39096901). H3 'Lys-9' trimethylation is coordinated with DNA methylation (PubMed:12869583, PubMed:14536086, PubMed:27237050, PubMed:39096901). Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation (PubMed:14536086). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 (PubMed:14536086). SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins (PubMed:24623306). Required for HUSH-mediated heterochromatin formation and gene silencing (PubMed:27732843). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (PubMed:37938770). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). Also catalyzes mono- and dimethylation of 'Lys-9' of free histone H3 (H3K9me1 and H3K9me2) during translation in the cytoplasm, which is then transported to the nucleus and incorporated into nucleosomes (PubMed:26405197). {ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:12869583, ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:26405197, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:27237050, ECO:0000269|PubMed:27732843, ECO:0000269|PubMed:37938770, ECO:0000269|PubMed:39096901}.; FUNCTION: [Isoform 2]: Lacks all domains required for histone methyltransferase activity. {ECO:0000305}.
uniprot
proteins
mass_dalton
143157
uniprot
proteins
mutagenesis
MUTAGEN 268; /note="Y->A: Decreased binding to H3K9me3 and H3K14ac without affecting binding to H3K9me1."; /evidence="ECO:0000269|PubMed:29234025"; MUTAGEN 332; /note="F->A: Decreased binding to H3K9me2 and H3K14ac."; /evidence="ECO:0000269|PubMed:29234025"; MUTAGEN 358; /note="W->A: Decreased binding to H3K9me2 and abolished binding to H3K9me1."; /evidence="ECO:0000269|PubMed:29234025"; MUTAGEN 363; /note="W->A: Decreased binding to H3K9me2 and abolished binding to H3K9me1."; /evidence="ECO:0000269|PubMed:29234025"; MUTAGEN 382; /note="D->A: Decreased binding to H3K9me1 without affecting binding to H3K9me2, H3K9me3 or H3K14ac."; /evidence="ECO:0000269|PubMed:29234025"; MUTAGEN 388; /note="I->A: Abolished binding to H3K9me2 and H3K14ac."; /evidence="ECO:0000269|PubMed:29234025"; MUTAGEN 729..731; /note="CDC->LDP: Abolishes methyltransferase activity."; /evidence="ECO:0000269|PubMed:11959841"; MUTAGEN 866; /note="F->K: No effect on K-867 ubiquitination."; /evidence="ECO:0000269|PubMed:27237050"; MUTAGEN 867; /note="K->R: Not monoubiquitinated by UBE2E. Loss of methyltransferase activity."; /evidence="ECO:0000269|PubMed:27237050, ECO:0000269|PubMed:39096901"; MUTAGEN 868; /note="E->K: No effect on K-867 ubiquitination."; /evidence="ECO:0000269|PubMed:27237050"; MUTAGEN 1224; /note="H->K: Abolishes methyltransferase activity."; /evidence="ECO:0000269|PubMed:11959841"; MUTAGEN 1226; /note="C->A: Abolishes methyltransferase activity."; /evidence="ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:39096901"; MUTAGEN 1279; /note="C->Y: Abolishes methyltransferase activity."; /evidence="ECO:0000269|PubMed:11959841
uniprot
proteins
post_translational_modification
PTM: Degraded by the proteasome, shielded by interaction with ATF7IP. {ECO:0000269|PubMed:27732843}.; PTM: Monoubiquitinated at Lys-867 by E2 enzymes of the UBE2E family. The conjugated-Ub is protected from deubiquitination by the SET domain. Monoubiquitination at Lys-867 is required for catalytic activity, H3K9 methylation and endogenous retrovirus silencing. {ECO:0000269|PubMed:27237050}.
uniprot
proteins
protein_family
Class V-like SAM-binding methyltransferase superfamily
uniprot
proteins
protein_family
Histone-lysine methyltransferase family
uniprot
proteins
protein_family
Suvar3-9 subfamily
uniprot
proteins
pubmed
11959841
uniprot
proteins
pubmed
12869583
uniprot
proteins
pubmed
14536086
uniprot
proteins
pubmed
15327775
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15691849
uniprot
proteins
pubmed
15899859
uniprot
proteins
pubmed
16567619
uniprot
proteins
pubmed
16682412
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17066076
uniprot
proteins
pubmed
17142323
uniprot
proteins
pubmed
17952062
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19061646
uniprot
proteins
pubmed
20871592
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22939622
uniprot
proteins
pubmed
23034801
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24623306
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25358353
uniprot
proteins
pubmed
25755297
uniprot
proteins
pubmed
25772364
uniprot
proteins
pubmed
26405197
uniprot
proteins
pubmed
27029610
uniprot
proteins
pubmed
27237050
uniprot
proteins
pubmed
27732843
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
29234025
uniprot
proteins
pubmed
30487602
uniprot
proteins
pubmed
30849389
uniprot
proteins
pubmed
31612521
uniprot
proteins
pubmed
32051553
uniprot
proteins
pubmed
32890405
uniprot
proteins
pubmed
37179361
uniprot
proteins
pubmed
37938770
uniprot
proteins
pubmed
39096901
uniprot
proteins
pubmed
7584044
uniprot
proteins
sequence_length
1291
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27732843}. Cytoplasm {ECO:0000269|PubMed:26405197, ECO:0000269|PubMed:27732843}. Chromosome {ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:29234025}. Note=Associated with non-pericentromeric regions of chromatin (PubMed:27029610). Recruited to H3K9me and H3K19ac marks on chromatin (PubMed:29234025). Excluded from nucleoli and islands of condensed chromatin (PubMed:27732843). {ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:27732843, ECO:0000269|PubMed:29234025}.
uniprot
proteins