Setdb1

Histone-lysine N-methyltransferase SETDB1

1307 amino acids

Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (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. 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. 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:29728365). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. 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).

Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.

144.549 kDa

MSSLPGCMSLAAAPAAADSAEIAELQQAVVEELGISMEELRQYIDEELEKMDCIQQRKKQLAELETWVLQKESEVAYVDRLFDDASREVTNCESLVKDFYSKLGLQYHDSSSEDEASRPTEIIEIPDEDDDVLSIDSGDAGSRTPKDQKLREAMAALRKSAQDVQKFMDAVNKKSSSQDLHKGTLGQVSGELSKDGDLIVSMRILGKKRTKTWHKGTLIAIQTVGLGKKYKVKFDNKGKSLLSGNHIAYDYHPPADKLFVGSRVVAKYKDGNQVWLYAGIVAETPNVKNKLRFLIFFDDGYASYVTQSELYPICRPLKKTWEDIEDSSCRDFIEEYITAYPNRPMVLLKSGQLIKTEWEGTWWKSRVEEVDGSLVRILFLDDKRCEWIYRGSTRLEPMFSMKTSSASAMEKKQGGQLRTRPNMGAVRSKGPVVQYTQDLTGTGIQFKPMEPLQPIAPPAPLPIPPLSPQAADTDLESQLAQSRKQVAKKSTSFRPGSVGSGHSSPTSSTLSENVSAGKLGINQTYRSPLASVTSTPASAAPPVPPVPPGPPTPPGPPAPPGPLAPPAFHGMLERAPAEPSYRAPMEKLFYLPHVCSYTCLSRIRPMRNEQYRGKNPLLVPLLYDFRRMTARRRVNRKMGFHVIYKTPCGLCLRTMQEIERYLFETGCDFLFLEMFCLDPYVLVDRKFQPFKPFYYILDITYGKEDVPLSCVNEIDTTPPPQVAYSKERIPGKGVFINTGPEFLVGCDCKDGCRDKSKCACHQLTIQATACTPGGQVNPNSGYQYKRLEECLPTGVYECNKRCNCDPNMCTNRLVQHGLQVRLQLFKTQNKGWGIRCLDDIAKGSFVCIYAGKILTDDFADKEGLEMGDEYFANLDHIESVENFKEGYESDVPTSSDSSGVDMKDQEDGNSGSEDPEESNDDSSDDNFCKDEDFSTSSVWRSYATRRQTRGQKENELSEMTSKDSRPPDLGPPHVPIPSSVSVGGCNPPSSEETPKNKVASWLSCNSVSEGGFADSDSRSSFKTSEGGDGRAGGGRGEAERASTSGLSFKDEGDNKQPKKEDPENRNKMPVVTEGSQNHGHNPPMKSEGLRRPASKMSVLQSQRVVTSTQSNPDDILTLSSSTESEGESGTSRKPTAGHTSATAVDSDDIQTISSGSDGDDFEDKKNLSGPTKRQVAVKSTRGFALKSTHGIAIKSTNMASVDKGESAPVRKNTRQFYDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVAFFASKRIRAGTELTWDYNYEVGSVEGKELLCCCGAIECRGRLL

SETDB1

Histone-lysine N-methyltransferase SETDB1

1291 amino acids

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 (PubMed:12869583, PubMed:17952062). Required for HUSH-mediated heterochromatin formation and gene silencing. Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation (PubMed:27732843, PubMed:14536086). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 (PubMed:14536086, PubMed:15327775). SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. 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 (By similarity). 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).

Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.

143.157 kDa

MSSLPGCIGLDAATATVESEEIAELQQAVVEELGISMEELRHFIDEELEKMDCVQQRKKQLAELETWVIQKESEVAHVDQLFDDASRAVTNCESLVKDFYSKLGLQYRDSSSEDESSRPTEIIEIPDEDDDVLSIDSGDAGSRTPKDQKLREAMAALRKSAQDVQKFMDAVNKKSSSQDLHKGTLSQMSGELSKDGDLIVSMRILGKKRTKTWHKGTLIAIQTVGPGKKYKVKFDNKGKSLLSGNHIAYDYHPPADKLYVGSRVVAKYKDGNQVWLYAGIVAETPNVKNKLRFLIFFDDGYASYVTQSELYPICRPLKKTWEDIEDISCRDFIEEYVTAYPNRPMVLLKSGQLIKTEWEGTWWKSRVEEVDGSLVRILFLDDKRCEWIYRGSTRLEPMFSMKTSSASALEKKQGQLRTRPNMGAVRSKGPVVQYTQDLTGTGTQFKPVEPPQPTAPPAPPFPPAPPLSPQAGDSDLESQLAQSRKQVAKKSTSFRPGSVGSGHSSPTSPALSENVSGGKPGINQTYRSPLGSTASAPAPSALPAPPAPPVFHGMLERAPAEPSYRAPMEKLFYLPHVCSYTCLSRVRPMRNEQYRGKNPLLVPLLYDFRRMTARRRVNRKMGFHVIYKTPCGLCLRTMQEIERYLFETGCDFLFLEMFCLDPYVLVDRKFQPYKPFYYILDITYGKEDVPLSCVNEIDTTPPPQVAYSKERIPGKGVFINTGPEFLVGCDCKDGCRDKSKCACHQLTIQATACTPGGQINPNSGYQYKRLEECLPTGVYECNKRCKCDPNMCTNRLVQHGLQVRLQLFKTQNKGWGIRCLDDIAKGSFVCIYAGKILTDDFADKEGLEMGDEYFANLDHIESVENFKEGYESDAPCSSDSSGVDLKDQEDGNSGTEDPEESNDDSSDDNFCKDEDFSTSSVWRSYATRRQTRGQKENGLSETTSKDSHPPDLGPPHIPVPPSIPVGGCNPPSSEETPKNKVASWLSCNSVSEGGFADSDSHSSFKTNEGGEGRAGGSRMEAEKASTSGLGIKDEGDIKQAKKEDTDDRNKMSVVTESSRNYGYNPSPVKPEGLRRPPSKTSMHQSRRLMASAQSNPDDVLTLSSSTESEGESGTSRKPTAGQTSATAVDSDDIQTISSGSEGDDFEDKKNMTGPMKRQVAVKSTRGFALKSTHGIAIKSTNMASVDKGESAPVRKNTRQFYDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVAFFASKRIRAGTELTWDYNYEVGSVEGKELLCCCGAIECRGRLL

setdb1

Histone-lysine N-methyltransferase SETDB1

1269 amino acids

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. Plays a role in promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes. Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (By similarity).

Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.

141.777 kDa

MELEQMVVKELGISMDDLRELIDRELEKIEFVKQRKAQLLEMEQLVKQKEAEVDHVDKLFDNATRAVDDCETLVKSLYDQIGMTYKESSSEDEGSSKPTEVIEIPDEDDDDVMSVGSGEAVSKIPKEKHLLREAMAAMKRSRQDVQSIVEAIQKKSDGPQTRFSSHPSSPTSSVGGSNQASASNDMSKDGDLVVGMRILGKKRTKTWHKGTLISIQCVGTGKKFKVKFDNKGKSLLSGNHIAYDYHPPPENLTVGSRVVAKYKDGNQVWLYAGIVAEPPSSKNKMRYLIFFDDGYASYVTHAELYPVCRPWSKSWEDIEDVSCRDFIQEYVNAYPNRPMVLLKSGQLIKTEWEGTWWKSKVEEVDGSLVKILFLDDKRCEWIYRGSTRLEPMFSMKTSNASTQEKQQAGQQRTRPNVGAIRSKGPVVQFTHDLTGNEPEHNPAAPPSPQSMPSPQLIDTDSDSQQAQSKKQVAKKSTSFRPGSAGSGQSSPIPTESVPQPPAAPRPFQSNQSVQPVQSIQPIQPIHNIQTIQTIQGIQTIQAIQPIQSIQTLQPIQTIQPLQTIQTLQGNRIVTSIQQFQIIRTENIPAESTYKAPKEKLFYLPHVCNYTCLSRIRPLSHRGKNPLLVPLLYDFRRMTARRRVNRKMGFHVIYKSPCGLSLRTMPEIERYLFETQCKMLFLEMFCLDPYVLVDRKFQPQKPFYYIPDITYGKEDVMLSCVNEIDRTPPPQVAYSKERIPGKGVFINTGADYLVGCDCTDGCRDKSKCACHQLTIQATACTPGAQSNPMAGYQHKRLEECLPTGVYECNKRCKCSANMCNNRLVQHGLQVRLQLFKTQNKGWGIRGLDDIAKGSFVCIYAGKILTDDFADKEGLEMGDEYFANLDHIESVENFKEGYESDAKSSSDSSGVDLKEDHEENSGSEDQEESNDSSDDNFGKNEDITTSSVWRSYATRRTTRGQKENGTSETASKDSRTRDETTDCKLPEETSKNKVASWLSSNTMADSVMDSDSRSSLKMGEALETDKPKESEEASKYPRFAEGNRAYGYNPTPTKKDGVRRPVTKTALHQIKRQSSSAQPTEEVLTLSSSSDSEVGSGTNGSKKPAAQATANDSDDIQTISSGSDEEEEKKNVAASAGPVKRQVAVKSTRGFALKSTHGITVKSNMASGEGGPGRRNTRQFFDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVAFFASKRIRAGTELTWDYNYEVGSVEGKKLLCCCGSTECRGRLL