ID SETMR_MOUSE Reviewed; 309 AA. AC Q80UJ9; E9QLD6; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 125. DE RecName: Full=Histone-lysine N-methyltransferase SETMAR {ECO:0000305}; DE EC=2.1.1.357 {ECO:0000250|UniProtKB:Q53H47}; DE AltName: Full=SET domain without mariner transposase fusion protein {ECO:0000312|MGI:MGI:1921979}; GN Name=Setmar {ECO:0000312|MGI:MGI:1921979}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Czech II; TISSUE=Mammary tumor; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). CC -!- FUNCTION: Histone methyltransferase that methylates 'Lys-4' and 'Lys- CC 36' of histone H3, 2 specific tags for epigenetic transcriptional CC activation. Specifically mediates dimethylation of H3 'Lys-36'. CC {ECO:0000250|UniProtKB:Q53H47}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-methionine = 2 H(+) CC + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 S-adenosyl-L- CC homocysteine; Xref=Rhea:RHEA:60308, Rhea:RHEA-COMP:9785, Rhea:RHEA- CC COMP:9787, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61976; EC=2.1.1.357; CC Evidence={ECO:0000250|UniProtKB:Q53H47}; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q53H47}. CC Chromosome {ECO:0000250|UniProtKB:Q53H47}. 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. CC {ECO:0000250|UniProtKB:Q53H47}. CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}. 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; AC153916; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC045208; AAH45208.1; -; mRNA. DR CCDS; CCDS51867.1; -. DR RefSeq; NP_848478.2; NM_178391.4. DR AlphaFoldDB; Q80UJ9; -. DR SMR; Q80UJ9; -. DR STRING; 10090.ENSMUSP00000048225; -. DR iPTMnet; Q80UJ9; -. DR PhosphoSitePlus; Q80UJ9; -. DR EPD; Q80UJ9; -. DR PaxDb; 10090-ENSMUSP00000048225; -. DR ProteomicsDB; 256971; -. DR DNASU; 74729; -. DR Ensembl; ENSMUST00000049246.7; ENSMUSP00000048225.6; ENSMUSG00000034639.8. DR GeneID; 74729; -. DR KEGG; mmu:74729; -. DR UCSC; uc009dde.3; mouse. DR AGR; MGI:1921979; -. DR CTD; 6419; -. DR MGI; MGI:1921979; Setmar. DR VEuPathDB; HostDB:ENSMUSG00000034639; -. DR eggNOG; KOG1082; Eukaryota. DR GeneTree; ENSGT00940000162663; -. DR HOGENOM; CLU_020840_3_3_1; -. DR InParanoid; Q80UJ9; -. DR OMA; VDSMVPK; -. DR OrthoDB; 5481936at2759; -. DR PhylomeDB; Q80UJ9; -. DR TreeFam; TF316038; -. DR BioGRID-ORCS; 74729; 1 hit in 79 CRISPR screens. DR PRO; PR:Q80UJ9; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; Q80UJ9; Protein. DR Bgee; ENSMUSG00000034639; Expressed in ear vesicle and 215 other cell types or tissues. DR ExpressionAtlas; Q80UJ9; baseline and differential. DR GO; GO:0005730; C:nucleolus; ISO:MGI. DR GO; GO:0005634; C:nucleus; ISO:MGI. DR GO; GO:0035861; C:site of double-strand break; ISO:MGI. DR GO; GO:0003677; F:DNA binding; ISO:MGI. DR GO; GO:0044547; F:DNA topoisomerase binding; ISO:MGI. DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI. DR GO; GO:0004519; F:endonuclease activity; ISO:MGI. DR GO; GO:0140954; F:histone H3K36 dimethyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0046975; F:histone H3K36 methyltransferase activity; ISS:UniProtKB. DR GO; GO:0042800; F:histone H3K4 methyltransferase activity; ISS:UniProtKB. DR GO; GO:0042054; F:histone methyltransferase activity; IBA:GO_Central. DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI. DR GO; GO:0003697; F:single-stranded DNA binding; ISO:MGI. DR GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; ISO:MGI. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0008283; P:cell population proliferation; ISO:MGI. DR GO; GO:0006308; P:DNA catabolic process; ISO:MGI. DR GO; GO:0000729; P:DNA double-strand break processing; ISO:MGI. DR GO; GO:0015074; P:DNA integration; ISO:MGI. DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISO:MGI. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0044774; P:mitotic DNA integrity checkpoint signaling; ISO:MGI. DR GO; GO:2001251; P:negative regulation of chromosome organization; ISO:MGI. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IEA:UniProt. DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; ISO:MGI. DR GO; GO:0031297; P:replication fork processing; ISO:MGI. DR CDD; cd10544; SET_SETMAR; 1. DR Gene3D; 2.170.270.10; SET domain; 1. DR InterPro; IPR003616; Post-SET_dom. DR InterPro; IPR007728; Pre-SET_dom. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR046341; SET_dom_sf. DR PANTHER; PTHR46223:SF3; HISTONE H3 (LYS9) METHYLTRANSFERASE-RELATED; 1. DR PANTHER; PTHR46223; HISTONE-LYSINE N-METHYLTRANSFERASE SUV39H; 1. DR Pfam; PF05033; Pre-SET; 1. DR Pfam; PF00856; SET; 1. DR SMART; SM00468; PreSET; 1. DR SMART; SM00317; SET; 1. DR SUPFAM; SSF82199; SET domain; 1. DR PROSITE; PS50868; POST_SET; 1. DR PROSITE; PS50867; PRE_SET; 1. DR PROSITE; PS50280; SET; 1. DR Genevisible; Q80UJ9; MM. PE 2: Evidence at transcript level; KW Chromatin regulator; Chromosome; Metal-binding; Methyltransferase; Nucleus; KW Reference proteome; S-adenosyl-L-methionine; Transferase; Zinc. FT CHAIN 1..309 FT /note="Histone-lysine N-methyltransferase SETMAR" FT /id="PRO_0000259527" FT DOMAIN 74..137 FT /note="Pre-SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00157" FT DOMAIN 140..264 FT /note="SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT DOMAIN 284..300 FT /note="Post-SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155" FT BINDING 76 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 76 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 78 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 83 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 83 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 88 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 90 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 119 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 119 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 123 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 125 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 129 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 150..152 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 193 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT BINDING 221 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT BINDING 224..225 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 227 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 288 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 290 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT BINDING 295 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:Q53H47" FT CONFLICT 103 FT /note="L -> F (in Ref. 2; AAH45208)" FT /evidence="ECO:0000305" FT CONFLICT 273 FT /note="S -> R (in Ref. 2; AAH45208)" FT /evidence="ECO:0000305" SQ SEQUENCE 309 AA; 34417 MW; 38F60C1C5B13D80C CRC64; MSAEGVEKLS LEIAASEEES VAPTEQQDVA CGLENLPVSL WPLGAEPRPK PFQYTPDHVA GPGADIDPTQ ITFPGCACIE TPCVPGTCSC LRHENNYDDN LCLRDVGSEG KYAKPVFECN VLCQCGMRCR NRVVQNGLHF LLQVFQTEKK GWGLRTLEFI PKGRFVCEYA GEVLGFSEVQ RRIHLQTSHD SNYIIAVREH IYSGQIMETF VDPTYIGNIG RFLNHSCEPN LLMIPVRIDS MVPKLALFAA KDILPGEELS YDYSGRFLNQ VSSKDKEKID CSPPRKPCYC GAQSCTTFLP YDSSLYMAP //