Search Results

Overview

Uniprot IDQ15047
Protein NameHistone-lysine N-methyltransferase SETDB1
Gene NameSETDB1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1079 GLRRPPSKTSMHQSR
825 RCLDDIAKGSFVCIY

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)

Protein Sequence

10 MSSLPGCIGL 20 DAATATVESE 30 EIAELQQAVV 40 EELGISMEEL 50 RHFIDEELEK 60 MDCVQQRKKQ 70 LAELETWVIQ 80 KESEVAHVDQ 90 LFDDASRAVT 100 NCESLVKDFY 110 SKLGLQYRDS 120 SSEDESSRPT 130 EIIEIPDEDD 140 DVLSIDSGDA 150 GSRTPKDQKL 160 REAMAALRKS 170 AQDVQKFMDA 180 VNKKSSSQDL 190 HKGTLSQMSG 200 ELSKDGDLIV 210 SMRILGKKRT 220 KTWHKGTLIA 230 IQTVGPGKKY 240 KVKFDNKGKS 250 LLSGNHIAYD 260 YHPPADKLYV 270 GSRVVAKYKD 280 GNQVWLYAGI 290 VAETPNVKNK 300 LRFLIFFDDG 310 YASYVTQSEL 320 YPICRPLKKT 330 WEDIEDISCR 340 DFIEEYVTAY 350 PNRPMVLLKS 360 GQLIKTEWEG 370 TWWKSRVEEV 380 DGSLVRILFL 390 DDKRCEWIYR 400 GSTRLEPMFS 410 MKTSSASALE 420 KKQGQLRTRP 430 NMGAVRSKGP 440 VVQYTQDLTG 450 TGTQFKPVEP 460 PQPTAPPAPP 470 FPPAPPLSPQ 480 AGDSDLESQL 490 AQSRKQVAKK 500 STSFRPGSVG 510 SGHSSPTSPA 520 LSENVSGGKP 530 GINQTYRSPL 540 GSTASAPAPS 550 ALPAPPAPPV 560 FHGMLERAPA 570 EPSYRAPMEK 580 LFYLPHVCSY 590 TCLSRVRPMR 600 NEQYRGKNPL 610 LVPLLYDFRR 620 MTARRRVNRK 630 MGFHVIYKTP 640 CGLCLRTMQE 650 IERYLFETGC 660 DFLFLEMFCL 670 DPYVLVDRKF 680 QPYKPFYYIL 690 DITYGKEDVP 700 LSCVNEIDTT 710 PPPQVAYSKE 720 RIPGKGVFIN 730 TGPEFLVGCD 740 CKDGCRDKSK 750 CACHQLTIQA 760 TACTPGGQIN 770 PNSGYQYKRL 780 EECLPTGVYE 790 CNKRCKCDPN 800 MCTNRLVQHG 810 LQVRLQLFKT 820 QNKGWGIRCL 830 DDIAKGSFVC 840 IYAGKILTDD 850 FADKEGLEMG 860 DEYFANLDHI 870 ESVENFKEGY 880 ESDAPCSSDS 890 SGVDLKDQED 900 GNSGTEDPEE 910 SNDDSSDDNF 920 CKDEDFSTSS 930 VWRSYATRRQ 940 TRGQKENGLS 950 ETTSKDSHPP 960 DLGPPHIPVP 970 PSIPVGGCNP 980 PSSEETPKNK 990 VASWLSCNSV 1000 SEGGFADSDS 1010 HSSFKTNEGG 1020 EGRAGGSRME 1030 AEKASTSGLG 1040 IKDEGDIKQA 1050 KKEDTDDRNK 1060 MSVVTESSRN 1070 YGYNPSPVKP 1080 EGLRRPPSKT 1090 SMHQSRRLMA 1100 SAQSNPDDVL 1110 TLSSSTESEG 1120 ESGTSRKPTA 1130 GQTSATAVDS 1140 DDIQTISSGS 1150 EGDDFEDKKN 1160 MTGPMKRQVA 1170 VKSTRGFALK 1180 STHGIAIKST 1190 NMASVDKGES 1200 APVRKNTRQF 1210 YDGEESCYII 1220 DAKLEGNLGR 1230 YLNHSCSPNL 1240 FVQNVFVDTH 1250 DLRFPWVAFF 1260 ASKRIRAGTE 1270 LTWDYNYEVG 1280 SVEGKELLCC 1290 CGAIECRGRL L

Gene Ontology

Classification GO ID Description
Biological Process GO:0006351 DNA-templated transcription
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0003682 chromatin binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0140938 histone H3 methyltransferase activity
Molecular Function GO:0140015 histone H3K14ac reader activity
Molecular Function GO:0140942 histone H3K9 dimethyltransferase activity
Molecular Function GO:0046974 histone H3K9 methyltransferase activity
Molecular Function GO:0140948 histone H3K9 monomethyltransferase activity
Molecular Function GO:0140949 histone H3K9 trimethyltransferase activity
Molecular Function GO:0140947 histone H3K9me2 methyltransferase activity
Molecular Function GO:0062072 histone H3K9me2/3 reader activity
Molecular Function GO:1990841 promoter-specific chromatin binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0006346 DNA methylation-dependent constitutive heterochromatin formation
Biological Process GO:0070828 heterochromatin organization
Biological Process GO:0032259 methylation
Biological Process GO:0010629 negative regulation of gene expression
Biological Process GO:0141005 transposable element silencing by heterochromatin formation

Reference

[1] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.