ID   SETB1_XENLA             Reviewed;        1269 AA.
AC   Q6INA9;
DT   03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 108.
DE   RecName: Full=Histone-lysine N-methyltransferase SETDB1;
DE            EC=2.1.1.366;
DE   AltName: Full=SET domain bifurcated 1;
GN   Name=setdb1;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Oocyte;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
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=N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-
CC         methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3]
CC         + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60288, Rhea:RHEA-
CC         COMP:15538, Rhea:RHEA-COMP:15541, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961,
CC         ChEBI:CHEBI:61976; EC=2.1.1.366; Evidence={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:PRU00906}.
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DR   EMBL; BC072374; AAH72374.1; -; mRNA.
DR   RefSeq; NP_001085076.2; NM_001091607.1.
DR   AlphaFoldDB; Q6INA9; -.
DR   SMR; Q6INA9; -.
DR   GeneID; 432147; -.
DR   KEGG; xla:432147; -.
DR   AGR; Xenbase:XB-GENE-866480; -.
DR   CTD; 432147; -.
DR   Xenbase; XB-GENE-866480; setdb1.L.
DR   OrthoDB; 2877903at2759; -.
DR   Proteomes; UP000186698; Chromosome 8L.
DR   Bgee; 432147; Expressed in ovary and 19 other cell types or tissues.
DR   GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR   GO; GO:0140948; F:histone H3K9 monomethyltransferase activity; IEA:RHEA.
DR   GO; GO:0140947; F:histone H3K9me2 methyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
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   CDD; cd20382; Tudor_SETDB1_rpt1; 1.
DR   CDD; cd21181; Tudor_SETDB1_rpt2; 1.
DR   Gene3D; 2.30.30.140; -; 3.
DR   Gene3D; 2.170.270.10; SET domain; 2.
DR   InterPro; IPR016177; DNA-bd_dom_sf.
DR   InterPro; IPR040880; DUF5604.
DR   InterPro; IPR025796; Hist-Lys_N-MeTrfase_SETDB1.
DR   InterPro; IPR001739; Methyl_CpG_DNA-bd.
DR   InterPro; IPR003616; Post-SET_dom.
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; IPR002999; Tudor.
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   SMART; SM00333; TUDOR; 2.
DR   SUPFAM; SSF54171; DNA-binding domain; 1.
DR   SUPFAM; SSF82199; SET domain; 1.
DR   PROSITE; PS50982; MBD; 1.
DR   PROSITE; PS50868; POST_SET; 1.
DR   PROSITE; PS50867; PRE_SET; 1.
DR   PROSITE; PS51573; SAM_MT43_SUVAR39_1; 1.
DR   PROSITE; PS50280; SET; 1.
PE   2: Evidence at transcript level;
KW   Chromatin regulator; Chromosome; Coiled coil; Metal-binding;
KW   Methyltransferase; Nucleus; Reference proteome; Repeat; Repressor;
KW   S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW   Transferase; Zinc.
FT   CHAIN           1..1269
FT                   /note="Histone-lysine N-methyltransferase SETDB1"
FT                   /id="PRO_0000281821"
FT   DOMAIN          250..312
FT                   /note="Tudor 1"
FT   DOMAIN          340..395
FT                   /note="Tudor 2"
FT   DOMAIN          620..691
FT                   /note="MBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00338"
FT   DOMAIN          753..826
FT                   /note="Pre-SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00157"
FT   DOMAIN          829..1244
FT                   /note="SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   DOMAIN          1253..1269
FT                   /note="Post-SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT   REGION          85..121
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          153..188
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          396..516
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          894..1139
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          9..63
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        153..186
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        396..417
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        453..493
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        894..918
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        937..963
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        964..987
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        990..1011
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1014..1036
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1065..1116
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         755
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         755
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         757
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         761
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         761
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         767
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         769
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         807
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         807
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         811
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         813
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         818
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         839..841
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         877
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   BINDING         879
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   BINDING         1198
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   BINDING         1201..1202
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         1204
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         1257
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         1259
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
FT   BINDING         1264
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   1269 AA;  141777 MW;  6241910CB4266FAC CRC64;
     MELEQMVVKE LGISMDDLRE LIDRELEKIE FVKQRKAQLL EMEQLVKQKE AEVDHVDKLF
     DNATRAVDDC ETLVKSLYDQ IGMTYKESSS EDEGSSKPTE VIEIPDEDDD DVMSVGSGEA
     VSKIPKEKHL LREAMAAMKR SRQDVQSIVE AIQKKSDGPQ TRFSSHPSSP TSSVGGSNQA
     SASNDMSKDG DLVVGMRILG KKRTKTWHKG TLISIQCVGT GKKFKVKFDN KGKSLLSGNH
     IAYDYHPPPE NLTVGSRVVA KYKDGNQVWL YAGIVAEPPS SKNKMRYLIF FDDGYASYVT
     HAELYPVCRP WSKSWEDIED VSCRDFIQEY VNAYPNRPMV LLKSGQLIKT EWEGTWWKSK
     VEEVDGSLVK ILFLDDKRCE WIYRGSTRLE PMFSMKTSNA STQEKQQAGQ QRTRPNVGAI
     RSKGPVVQFT HDLTGNEPEH NPAAPPSPQS MPSPQLIDTD SDSQQAQSKK QVAKKSTSFR
     PGSAGSGQSS PIPTESVPQP PAAPRPFQSN QSVQPVQSIQ PIQPIHNIQT IQTIQGIQTI
     QAIQPIQSIQ TLQPIQTIQP LQTIQTLQGN RIVTSIQQFQ IIRTENIPAE STYKAPKEKL
     FYLPHVCNYT CLSRIRPLSH RGKNPLLVPL LYDFRRMTAR RRVNRKMGFH VIYKSPCGLS
     LRTMPEIERY LFETQCKMLF LEMFCLDPYV LVDRKFQPQK PFYYIPDITY GKEDVMLSCV
     NEIDRTPPPQ VAYSKERIPG KGVFINTGAD YLVGCDCTDG CRDKSKCACH QLTIQATACT
     PGAQSNPMAG YQHKRLEECL PTGVYECNKR CKCSANMCNN RLVQHGLQVR LQLFKTQNKG
     WGIRGLDDIA KGSFVCIYAG KILTDDFADK EGLEMGDEYF ANLDHIESVE NFKEGYESDA
     KSSSDSSGVD LKEDHEENSG SEDQEESNDS SDDNFGKNED ITTSSVWRSY ATRRTTRGQK
     ENGTSETASK DSRTRDETTD CKLPEETSKN KVASWLSSNT MADSVMDSDS RSSLKMGEAL
     ETDKPKESEE ASKYPRFAEG NRAYGYNPTP TKKDGVRRPV TKTALHQIKR QSSSAQPTEE
     VLTLSSSSDS EVGSGTNGSK KPAAQATAND SDDIQTISSG SDEEEEKKNV AASAGPVKRQ
     VAVKSTRGFA LKSTHGITVK SNMASGEGGP GRRNTRQFFD GEESCYIIDA KLEGNLGRYL
     NHSCSPNLFV QNVFVDTHDL RFPWVAFFAS KRIRAGTELT WDYNYEVGSV EGKKLLCCCG
     STECRGRLL
//