SETB1_XENLA
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 03-AUG-2022, entry version 101.
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 CTD; 432147; -.
DR Xenbase; XB-GENE-866480; setdb1.L.
DR OrthoDB; 183716at2759; -.
DR Proteomes; UP000186698; Chromosome 8L.
DR Bgee; 432147; Expressed in ovary and 19 other 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:0018024; F:histone-lysine N-methyltransferase activity; IEA:InterPro.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0034968; P:histone lysine methylation; IEA:InterPro.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; ISS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; ISS:UniProtKB.
DR Gene3D; 2.170.270.10; -; 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; IPR002999; Tudor.
DR InterPro; IPR041292; Tudor_4.
DR InterPro; IPR041291; TUDOR_5.
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; SSF54171; 1.
DR SUPFAM; SSF82199; SSF82199; 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
