ID STB1A_DANRE Reviewed; 1436 AA.
AC Q1L8U8;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 1.
DT 27-MAR-2024, entry version 114.
DE RecName: Full=Histone-lysine N-methyltransferase SETDB1-A;
DE EC=2.1.1.354 {ECO:0000250|UniProtKB:Q15047};
DE AltName: Full=SET domain bifurcated 1A;
GN Name=setdb1a; ORFNames=si:ch211-81a5.6;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
CC -!- FUNCTION: Histone methyltransferase that specifically trimethylates
CC 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific
CC tag for epigenetic transcriptional repression by recruiting HP1 (CBX1,
CC CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in
CC euchromatin regions, thereby playing a central role in the silencing of
CC euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA
CC methylation. Plays a role in promoter hypermethylation and
CC transcriptional silencing of tumor suppressor genes (TSGs) or other
CC tumor-related genes. Also required to maintain a transcriptionally
CC repressive state of genes in undifferentiated embryonic stem cells
CC (ESCs). Associates at promoter regions of tumor suppressor genes (TSGs)
CC leading to their gene silencing (By similarity).
CC {ECO:0000250|UniProtKB:Q15047}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) +
CC N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60260, Rhea:RHEA-COMP:15537, Rhea:RHEA-
CC COMP:15547, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.354;
CC Evidence={ECO:0000250|UniProtKB:Q15047, ECO:0000255|PROSITE-
CC ProRule:PRU00906};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Chromosome {ECO:0000250}.
CC Note=Associated with non-pericentromeric regions of chromatin. Excluded
CC from nucleoli and islands of condensed chromatin (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: In the pre-SET domain, Cys residues bind 3 zinc ions that are
CC arranged in a triangular cluster; some of these Cys residues contribute
CC to the binding of two zinc ions within the cluster. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. Suvar3-9
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; CR626935; CAK04995.1; -; Genomic_DNA.
DR RefSeq; NP_001038232.1; NM_001044767.2.
DR AlphaFoldDB; Q1L8U8; -.
DR SMR; Q1L8U8; -.
DR STRING; 7955.ENSDARP00000082769; -.
DR PaxDb; 7955-ENSDARP00000060441; -.
DR GeneID; 553292; -.
DR KEGG; dre:553292; -.
DR AGR; ZFIN:ZDB-GENE-030131-2421; -.
DR CTD; 553292; -.
DR ZFIN; ZDB-GENE-030131-2421; setdb1a.
DR eggNOG; KOG1141; Eukaryota.
DR HOGENOM; CLU_252145_0_0_1; -.
DR InParanoid; Q1L8U8; -.
DR OMA; WHQGTIL; -.
DR OrthoDB; 4137399at2759; -.
DR PhylomeDB; Q1L8U8; -.
DR TreeFam; TF106411; -.
DR PRO; PR:Q1L8U8; -.
DR Proteomes; UP000000437; Chromosome 19.
DR Bgee; ENSDARG00000041243; Expressed in early embryo and 27 other cell types or tissues.
DR ExpressionAtlas; Q1L8U8; baseline.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0140999; F:histone H3K4 trimethyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046974; F:histone H3K9 methyltransferase activity; IBA:GO_Central.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0070828; P:heterochromatin organization; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0010629; P:negative regulation of gene expression; IBA:GO_Central.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin formation; ISS:UniProtKB.
DR CDD; cd01395; HMT_MBD; 1.
DR CDD; cd10517; SET_SETDB1; 1.
DR Gene3D; 2.30.30.140; -; 2.
DR Gene3D; 2.170.270.10; SET domain; 2.
DR InterPro; IPR016177; DNA-bd_dom_sf.
DR InterPro; IPR040880; DUF5604.
DR InterPro; IPR001739; Methyl_CpG_DNA-bd.
DR InterPro; IPR007728; Pre-SET_dom.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR047232; SETDB1/2-like_MBD.
DR InterPro; IPR041292; Tudor_4.
DR InterPro; IPR041291; TUDOR_5.
DR PANTHER; PTHR46024; HISTONE-LYSINE N-METHYLTRANSFERASE EGGLESS; 1.
DR PANTHER; PTHR46024:SF2; HISTONE-LYSINE N-METHYLTRANSFERASE SETDB1; 1.
DR Pfam; PF18300; DUF5604; 1.
DR Pfam; PF01429; MBD; 1.
DR Pfam; PF05033; Pre-SET; 1.
DR Pfam; PF00856; SET; 1.
DR Pfam; PF18358; Tudor_4; 1.
DR Pfam; PF18359; Tudor_5; 1.
DR SMART; SM00391; MBD; 1.
DR SMART; SM00468; PreSET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF54171; DNA-binding domain; 1.
DR SUPFAM; SSF82199; SET domain; 1.
DR PROSITE; PS50867; PRE_SET; 1.
DR PROSITE; PS50280; SET; 1.
PE 3: Inferred from homology;
KW Chromatin regulator; Chromosome; Metal-binding; Methyltransferase; Nucleus;
KW Reference proteome; Repeat; Repressor; S-adenosyl-L-methionine;
KW Transcription; Transcription regulation; Transferase; Zinc.
FT CHAIN 1..1436
FT /note="Histone-lysine N-methyltransferase SETDB1-A"
FT /id="PRO_0000281819"
FT DOMAIN 633..697
FT /note="Tudor 1"
FT DOMAIN 724..780
FT /note="Tudor 2"
FT DOMAIN 938..1009
FT /note="MBD"
FT DOMAIN 1075..1148
FT /note="Pre-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00157"
FT DOMAIN 1151..1411
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 1420..1436
FT /note="Post-SET"
FT REGION 170..200
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 250..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 344..570
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 781..849
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 869..894
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1247..1294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 270..327
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 357..401
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 417..444
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 455..471
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 472..514
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 524..538
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 539..570
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 797..849
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 869..887
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1251..1294
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1077
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1077
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1079
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1083
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1083
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 1089
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 1091
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1129
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1129
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 1133
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1135
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 1140
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 1161..1163
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1201
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 1365
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 1368..1369
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1371
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1424
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1426
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1431
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1436 AA; 160025 MW; 9C4174768AA95B5B CRC64;
MSREKDDENL LRMTKDDLQR WIQAEVERNP HLMQRREQLA QVEEWVKQKE RDSTCTRLLY
SNACESVLEC ESVMKGLYAL LGLDYRDEDS EEEGGGGQPH DVIQIADDEA ERRGNVICNG
EDDDNDDLVV IDLGATKETL EPMLEKVTVA IQKSSKLVQD LVQMVSKTSM GATSPLSTSS
SDINRPSSSS TPEIVRPESV TPKLEITNSI TIVKTESLSS VPKISSLFNS SEQCKSIADH
DSYFKPTIKT EPEWTPLTPW EDSESSPFEK LIKTESQSTD VTPSVMTPNK QPELLSFQST
TKIKPEPQST QANTELSSPP SNSKLLENHN SLSIAAIKNE SQLKASVSEV DLLESDSEQS
DNAATKTRFK PSEVTASSKL KSSGDHNSAS ASLNRTDPKV RPVTPSGTPP PSKSPPAVDN
TASVETNQTD SELPTETPVE ESTLPSNPKE AVIMSDAEST DKTEKPQTRK KSSKPSVTTT
SPESRLTSSK SPPVTKTSST QKETARAQSP SDSIDESADM EDSPDEPSNS PTESPTKTPD
KTTRNDAPAK PSKAKKSSKH SSSESSKTLK EIKLKVGAAV LGKKRHNHWS RGTVQEVETE
DDGNTYKVEF KKGKTIVLSA NHVAAYKPPS LKDLYIGCRV VASAKSENGK SLYNAGVMVE
LPERKNRMRF LVFFDDGLAT YLALPDLYFV CKQTKKVWRE IKDESSRKQV KDYLQVYPNP
IAVVLRLGQE TKAVRNGQFE DCTVLQLDGS LVQICYKNDK QKEWIYKGSD KLEHILTIKN
RHKQHSHKKH HSPEGKTQSS QPKTLHSSKS ASTSTSSANV SPVSSDSVSP ARVTRQSDKT
KTSISPQKIM SPAFQPKVVL QKISLPSSIS PAARVSNSNT NSSLISAKRP APDEEEDEYF
SEDEVEVLEQ EQNKSVYLHQ RCCPACLEEV RPHQVDIHHG KNPLLIPLLF KFRRMTARRR
IDGKLFFHIF YRSPCGRSLC DMQEVQDYLF ETRCDFLFLE MFCMDPFVLV NRARPPSTTT
GQPHLYLPDI SEGKEVMPVP CVNEVDNTLA PNVTYTKDRV PARGVFINTS SDFMVGCDCT
DGCRDRSKCA CHKLTIEATS LCTGGPVDVS AGYTHKRLPT SLPTGVYECN PLCRCDPRMC
SNRLVQHGMQ LRLELFMTQH KGWGIRCKDD VPKGTFVCVF TGKIVNEDKM NEDDTMSGNE
YLANLDFIEG VEKLKEGYES EAYCSDTEVE SSKKTITMKT GPLLKNSLYK EDSSSGEEPM
EVDTAKDKVK VHDKPLGERK LPNKPHETPK DTQKKISELR KNDGQESSGP KRCFAIKSFQ
RRVKPLESTE AQKEKTKTPK NTRGLFNDED ACYIIDARQE GNLGRYINHS CSPNLFVQNV
FVDTHDLRFP WVAFFASKRI KAGTELTWDY NYEVGSVEGK VLLCCCGSLR CTGRLL
//
