O88974
uniprot
O88974
canonical
amino_acid_sequence
MSSLPGCMSLAAAPAAADSAEIAELQQAVVEELGISMEELRQYIDEELEKMDCIQQRKKQLAELETWVLQKESEVAYVDRLFDDASREVTNCESLVKDFYSKLGLQYHDSSSEDEASRPTEIIEIPDEDDDVLSIDSGDAGSRTPKDQKLREAMAALRKSAQDVQKFMDAVNKKSSSQDLHKGTLGQVSGELSKDGDLIVSMRILGKKRTKTWHKGTLIAIQTVGLGKKYKVKFDNKGKSLLSGNHIAYDYHPPADKLFVGSRVVAKYKDGNQVWLYAGIVAETPNVKNKLRFLIFFDDGYASYVTQSELYPICRPLKKTWEDIEDSSCRDFIEEYITAYPNRPMVLLKSGQLIKTEWEGTWWKSRVEEVDGSLVRILFLDDKRCEWIYRGSTRLEPMFSMKTSSASAMEKKQGGQLRTRPNMGAVRSKGPVVQYTQDLTGTGIQFKPMEPLQPIAPPAPLPIPPLSPQAADTDLESQLAQSRKQVAKKSTSFRPGSVGSGHSSPTSSTLSENVSAGKLGINQTYRSPLASVTSTPASAAPPVPPVPPGPPTPPGPPAPPGPLAPPAFHGMLERAPAEPSYRAPMEKLFYLPHVCSYTCLSRIRPMRNEQYRGKNPLLVPLLYDFRRMTARRRVNRKMGFHVIYKTPCGLCLRTMQEIERYLFETGCDFLFLEMFCLDPYVLVDRKFQPFKPFYYILDITYGKEDVPLSCVNEIDTTPPPQVAYSKERIPGKGVFINTGPEFLVGCDCKDGCRDKSKCACHQLTIQATACTPGGQVNPNSGYQYKRLEECLPTGVYECNKRCNCDPNMCTNRLVQHGLQVRLQLFKTQNKGWGIRCLDDIAKGSFVCIYAGKILTDDFADKEGLEMGDEYFANLDHIESVENFKEGYESDVPTSSDSSGVDMKDQEDGNSGSEDPEESNDDSSDDNFCKDEDFSTSSVWRSYATRRQTRGQKENELSEMTSKDSRPPDLGPPHVPIPSSVSVGGCNPPSSEETPKNKVASWLSCNSVSEGGFADSDSRSSFKTSEGGDGRAGGGRGEAERASTSGLSFKDEGDNKQPKKEDPENRNKMPVVTEGSQNHGHNPPMKSEGLRRPASKMSVLQSQRVVTSTQSNPDDILTLSSSTESEGESGTSRKPTAGHTSATAVDSDDIQTISSGSDGDDFEDKKNLSGPTKRQVAVKSTRGFALKSTHGIAIKSTNMASVDKGESAPVRKNTRQFYDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVAFFASKRIRAGTELTWDYNYEVGSVEGKELLCCCGAIECRGRLL
uniprot
proteins
ec_number
2.1.1.366
uniprot
proteins
function
FUNCTION: Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3) (PubMed:11791185, PubMed:22939622). 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:11791185, PubMed:22939622). Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes (PubMed:27237050, PubMed:39096901). H3 'Lys-9' trimethylation is coordinated with DNA methylation (By similarity). Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation (By similarity). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 (By similarity). SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins (By similarity). Required for HUSH-mediated heterochromatin formation and gene silencing (By similarity). 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 (By similarity). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (By similarity). 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:20164836, PubMed:27237050, PubMed:29728365). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (By similarity). 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:Q15047, ECO:0000269|PubMed:11791185, ECO:0000269|PubMed:20164836, ECO:0000269|PubMed:22939622, ECO:0000269|PubMed:27237050, ECO:0000269|PubMed:29728365, ECO:0000269|PubMed:39096901}.
uniprot
proteins
mass_dalton
144549
uniprot
proteins
mutagenesis
MUTAGEN 798; /note="C->T: Abolishes methyltransferase activity."; /evidence="ECO:0000269|PubMed:11791185"; MUTAGEN 1242; /note="C->A: Decreases endogenous retroviruses silencing and cell growth."; /evidence="ECO:0000269|PubMed:20164836"; MUTAGEN 1242; /note="C->T: Abolishes methyltransferase activity."; /evidence="ECO:0000269|PubMed:11791185
uniprot
proteins
post_translational_modification
PTM: Degraded by the proteasome, shielded by interaction with ATF7IP. {ECO:0000250|UniProtKB:Q15047}.; PTM: Monoubiquitinated at Lys-884 by E2 enzymes UBE2E family. The conjugated-Ub is protected from deubiquitination through the SET domain. Monoubiquitination at Lys-884 is required for catalytic activity and 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
11791185
uniprot
proteins
pubmed
12398767
uniprot
proteins
pubmed
12693553
uniprot
proteins
pubmed
14522075
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
20164836
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22939622
uniprot
proteins
pubmed
27237050
uniprot
proteins
pubmed
29728365
uniprot
proteins
pubmed
31112734
uniprot
proteins
pubmed
34272044
uniprot
proteins
pubmed
39096901
uniprot
proteins
sequence_length
1307
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29728365}. Cytoplasm {ECO:0000250|UniProtKB:Q15047}. Chromosome {ECO:0000269|PubMed:29728365}. Note=Associated with non-pericentromeric regions of chromatin. Recruited to H3K9me and H3K19ac marks on chromatin. Excluded from nucleoli and islands of condensed chromatin. {ECO:0000250|UniProtKB:Q15047}.
uniprot
proteins