ID SETB2_XENLA Reviewed; 703 AA. AC Q6YI93; B7ZRV6; DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot. DT 05-OCT-2010, sequence version 2. DT 27-MAR-2024, entry version 98. DE RecName: Full=Histone-lysine N-methyltransferase SETDB2; DE EC=2.1.1.366 {ECO:0000250|UniProtKB:Q96T68}; DE AltName: Full=Chronic lymphocytic leukemia deletion region gene 8 protein homolog; DE AltName: Full=SET domain bifurcated 2; GN Name=setdb2; Synonyms=clld8; 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 [MRNA]. RA Ruzov A., Meehan R.; RT "Molecular cloning and analysis of the expression of SET-domain putative RT histone methyltransferase CLLD8 in Xenopus laevis."; RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Oocyte; RG NIH - Xenopus Gene Collection (XGC) project; RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Histone methyltransferase involved in left-right axis CC specification in early development and mitosis. Specifically CC trimethylates 'Lys-9' of histone H3 (H3K9me3). H3K9me3 is a specific CC tag for epigenetic transcriptional repression that recruits HP1 (CBX1, CC CBX3 and/or CBX5) proteins to methylated histones. Contributes to CC H3K9me3 in both the interspersed repetitive elements and centromere- CC associated repeats. Plays a role in chromosome condensation and CC segregation during mitosis (By similarity). {ECO:0000250}. 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; CC Evidence={ECO:0000250|UniProtKB:Q96T68}; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Chromosome {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. {ECO:0000255|PROSITE-ProRule:PRU00190}. CC -!- SEQUENCE CAUTION: CC Sequence=AAN61106.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY145835; AAN61106.1; ALT_FRAME; mRNA. DR EMBL; BC170303; AAI70303.1; -; mRNA. DR RefSeq; NP_001082765.1; NM_001089296.1. DR AlphaFoldDB; Q6YI93; -. DR MaxQB; Q6YI93; -. DR GeneID; 398711; -. DR KEGG; xla:398711; -. DR AGR; Xenbase:XB-GENE-1219036; -. DR CTD; 398711; -. DR Xenbase; XB-GENE-1219036; setdb2.S. DR OrthoDB; 2877903at2759; -. DR Proteomes; UP000186698; Chromosome 2S. DR Bgee; 398711; Expressed in blastula and 18 other cell types or tissues. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0046974; F:histone H3K9 methyltransferase activity; ISS:UniProtKB. DR GO; GO:0140948; F:histone H3K9 monomethyltransferase activity; IEA:RHEA. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0007059; P:chromosome segregation; ISS:UniProtKB. DR GO; GO:0001947; P:heart looping; ISS:UniProtKB. DR GO; GO:0070986; P:left/right axis specification; ISS:UniProtKB. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0000278; P:mitotic cell cycle; ISS:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB. DR CDD; cd01395; HMT_MBD; 1. DR CDD; cd10523; SET_SETDB2; 1. DR Gene3D; 2.170.270.10; SET domain; 2. DR InterPro; IPR016177; DNA-bd_dom_sf. 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 PANTHER; PTHR46024; HISTONE-LYSINE N-METHYLTRANSFERASE EGGLESS; 1. DR PANTHER; PTHR46024:SF3; HISTONE-LYSINE N-METHYLTRANSFERASE SETDB2; 1. DR Pfam; PF01429; MBD; 1. DR Pfam; PF05033; Pre-SET; 1. DR Pfam; PF00856; SET; 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; PS50868; POST_SET; 1. DR PROSITE; PS50867; PRE_SET; 1. DR PROSITE; PS50280; SET; 1. PE 2: Evidence at transcript level; KW Cell cycle; Cell division; Chromatin regulator; Chromosome; KW Developmental protein; Metal-binding; Methyltransferase; Mitosis; Nucleus; KW Reference proteome; S-adenosyl-L-methionine; Transferase; Zinc. FT CHAIN 1..703 FT /note="Histone-lysine N-methyltransferase SETDB2" FT /id="PRO_0000281825" FT DOMAIN 178..248 FT /note="MBD" FT DOMAIN 310..384 FT /note="Pre-SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00157" FT DOMAIN 387..678 FT /note="SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT REGION 492..588 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 531..585 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 312 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 312 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 314 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 318 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 318 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 324 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 326 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 365 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 365 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 369 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 371 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 376 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 397..399 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250" FT BINDING 632 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT BINDING 635..636 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250" FT BINDING 638 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 691 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 693 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 698 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250" FT CONFLICT 97 FT /note="K -> Q (in Ref. 1; AAN61106)" FT /evidence="ECO:0000305" FT CONFLICT 175 FT /note="S -> P (in Ref. 1; AAN61106)" FT /evidence="ECO:0000305" SQ SEQUENCE 703 AA; 78698 MW; 12D86C32892B5325 CRC64; MEQSANARQS TLRSRTQELN TLSVLSKDVS LEDAKKYWKD RQADGKVDWI FEKVLNKLKI LWQKIKDGSA TNLEYVRAVI LVNEAGNLEE DLEEDLKEDT DTIHIDIHKE NEVQENTDCS PERKEDTCLN LNTDCGTDVS GSEPECNSTV SPPAAERVYF GNHSCGPSCL SGINSFLFTK GNPLQLPISC DFQRCHLKIN SPDDLSHILY KAPCGRSLRD YDEVHSYLTE TGCHFLAVDN FSFNNHVRLD SNSSFNQGIV QDCDISNDVE SVPVAFSNEI DNTRPSNFIY RKTSWPPGYS LNNFTDIFVK CCNCTDGCLD ILTCSCLQLT AQAFTKCMES SLGIGPLGYK HKRLQEPIPT GLYECNVSCK CDRMLCQNRV VQHGLKLRLQ VFKTNTKGWG VRCLDDVDKG TFVCIYAGRI LIRTADCTVK STPDDSVACG NEDHEDSTST CALILSKRKR KTSHSDSEVT VMHTNPYSMR SHGLSVHRLS NTFSPRQARS GEREFSLQPL RRPKTKTSML QKRRRQLIEE GACTVQNSSE EEGPTPPQSP EQKSSAGTKI QRNENSDETA SGYVSEESSS SVISGGHPLE KPISKFKSKL NKTTVYLSTS PEQTCEENLH FLDASKEGNV GRFLNHSCCP NLFVQQVFVD THQKCFPWVA FFTNSVVKAG TELTWDYSYD IGTAADQEIQ CLCGQKTCKN KVV //