ID SMYD2_HUMAN Reviewed; 433 AA. AC Q9NRG4; B2R9P9; I6L9H7; Q4V765; Q5VSH9; Q96AI4; DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot. DT 13-SEP-2005, sequence version 2. DT 24-JAN-2024, entry version 179. DE RecName: Full=N-lysine methyltransferase SMYD2; DE EC=2.1.1.- {ECO:0000269|PubMed:18065756, ECO:0000269|PubMed:21782458, ECO:0000269|PubMed:21880715}; DE AltName: Full=HSKM-B; DE AltName: Full=Histone methyltransferase SMYD2; DE EC=2.1.1.354 {ECO:0000269|PubMed:18065756, ECO:0000269|PubMed:21782458, ECO:0000269|PubMed:21880715}; DE AltName: Full=Lysine N-methyltransferase 3C; DE AltName: Full=SET and MYND domain-containing protein 2; GN Name=SMYD2; Synonyms=KMT3C; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-165. RC TISSUE=Liver cancer; RA Li Y., Wu T., Xu S., Ren S., Chen Z., Han Z.; RT "A novel gene expressed in human liver cancer tissue."; RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-165. RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP GLU-165. RC TISSUE=Colon; 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). RN [5] RP FUNCTION, INTERACTION WITH TP53, AND MUTAGENESIS OF HIS-207. RX PubMed=17108971; DOI=10.1038/nature05287; RA Huang J., Perez-Burgos L., Placek B.J., Sengupta R., Richter M., RA Dorsey J.A., Kubicek S., Opravil S., Jenuwein T., Berger S.L.; RT "Repression of p53 activity by Smyd2-mediated methylation."; RL Nature 444:629-632(2006). RN [6] RP INDUCTION. RX PubMed=17242690; DOI=10.1038/sj.cr.7310121; RA Wang C., Chen X., Wang Y., Gong J., Hu G.; RT "C/EBPalphap30 plays transcriptional regulatory roles distinct from RT C/EBPalphap42."; RL Cell Res. 17:374-383(2007). RN [7] RP FUNCTION. RX PubMed=17805299; DOI=10.1038/nature06092; RA Huang J., Sengupta R., Espejo A.B., Lee M.G., Dorsey J.A., Richter M., RA Opravil S., Shiekhattar R., Bedford M.T., Jenuwein T., Berger S.L.; RT "p53 is regulated by the lysine demethylase LSD1."; RL Nature 449:105-108(2007). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH EPB41L3; HSP90AA1 AND RP TP53. RX PubMed=18065756; DOI=10.1074/mcp.m700271-mcp200; RA Abu-Farha M., Lambert J.P., Al-Madhoun A.S., Elisma F., Skerjanc I.S., RA Figeys D.; RT "The tale of two domains: proteomics and genomics analysis of SMYD2, a new RT histone methyltransferase."; RL Mol. Cell. Proteomics 7:560-572(2008). RN [9] RP FUNCTION, INTERACTION WITH RB, AND MUTAGENESIS OF TYR-240. RX PubMed=20870719; DOI=10.1074/jbc.m110.137612; RA Saddic L.A., West L.E., Aslanian A., Yates J.R. III, Rubin S.M., Gozani O., RA Sage J.; RT "Methylation of the retinoblastoma tumor suppressor by SMYD2."; RL J. Biol. Chem. 285:37733-37740(2010). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) IN COMPLEX WITH RP S-ADENOSYL-L-METHIONINE AND ZINC IONS. RX PubMed=21724641; DOI=10.1093/jmcb/mjr015; RA Xu S., Zhong C., Zhang T., Ding J.; RT "Structure of human lysine methyltransferase Smyd2 reveals insights into RT the substrate divergence in Smyd proteins."; RL J. Mol. Cell Biol. 3:293-300(2011). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEXES WITH TP53/P53 PEPTIDE; RP S-ADENOSYL-L-METHIONINE AND ZINC IONS, FUNCTION IN P53/TP53 METHYLATION, RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-187; GLU-189; GLU-190; TYR-245; RP ASP-252; ARG-253; ARG-306; TYR-374; GLU-429 AND GLU-431. RX PubMed=21880715; DOI=10.1074/jbc.m111.262410; RA Wang L., Li L., Zhang H., Luo X., Dai J., Zhou S., Gu J., Zhu J., RA Atadja P., Lu C., Li E., Zhao K.; RT "Structure of human SMYD2 protein reveals the basis of p53 tumor suppressor RT methylation."; RL J. Biol. Chem. 286:38725-38737(2011). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEXES WITH P53/TP53 PEPTIDE; RP S-ADENOSYL-L-METHIONINE; SYNTHETIC INHIBITOR AND ZINC IONS, FUNCTION, RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-240. RX PubMed=21782458; DOI=10.1016/j.str.2011.06.011; RA Ferguson A.D., Larsen N.A., Howard T., Pollard H., Green I., Grande C., RA Cheung T., Garcia-Arenas R., Cowen S., Wu J., Godin R., Chen H., Keen N.; RT "Structural basis of substrate methylation and inhibition of SMYD2."; RL Structure 19:1262-1273(2011). CC -!- FUNCTION: Protein-lysine N-methyltransferase that methylates both CC histones and non-histone proteins, including p53/TP53 and RB1. CC Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The CC activity requires interaction with HSP90alpha. Shows even higher CC methyltransferase activity on p53/TP53. Monomethylates 'Lys-370' of CC p53/TP53, leading to decreased DNA-binding activity and subsequent CC transcriptional regulation activity of p53/TP53. Monomethylates RB1 at CC 'Lys-860'. {ECO:0000269|PubMed:17108971, ECO:0000269|PubMed:17805299, CC ECO:0000269|PubMed:18065756, ECO:0000269|PubMed:20870719, CC ECO:0000269|PubMed:21782458, ECO:0000269|PubMed:21880715}. 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:0000269|PubMed:18065756, ECO:0000269|PubMed:21782458, CC ECO:0000269|PubMed:21880715}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)- CC methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; CC Evidence={ECO:0000269|PubMed:18065756, ECO:0000269|PubMed:21782458, CC ECO:0000269|PubMed:21880715}; CC -!- SUBUNIT: Interacts with RNA polymerase II and HELZ. Interacts with CC SIN3A and HDAC1 (By similarity). Interacts (via MYND-type zinc finger) CC with EPB41L3. Interacts (via SET domain) with p53/TP53. Interacts with CC RB1 and HSP90AA1. {ECO:0000250, ECO:0000269|PubMed:17108971, CC ECO:0000269|PubMed:18065756, ECO:0000269|PubMed:20870719, CC ECO:0000269|PubMed:21724641}. CC -!- INTERACTION: CC Q9NRG4; P20290-2: BTF3; NbExp=3; IntAct=EBI-1055671, EBI-1054703; CC Q9NRG4; Q96K17: BTF3L4; NbExp=3; IntAct=EBI-1055671, EBI-6137496; CC Q9NRG4; Q9UPZ9: CILK1; NbExp=2; IntAct=EBI-1055671, EBI-6381479; CC Q9NRG4; Q9Y5W9: SNX11; NbExp=3; IntAct=EBI-1055671, EBI-10329449; CC Q9NRG4; P04637: TP53; NbExp=6; IntAct=EBI-1055671, EBI-366083; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Nucleus CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NRG4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NRG4-2; Sequence=VSP_056005; CC -!- INDUCTION: Expression is repressed by CEBPA. CC {ECO:0000269|PubMed:17242690}. CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/47098/SMYD2"; 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; AF226053; AAF86953.1; -; mRNA. DR EMBL; AK313868; BAG36596.1; -; mRNA. DR EMBL; AL929236; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC017080; AAH17080.2; -; mRNA. DR EMBL; BC098276; AAH98276.1; -; mRNA. DR EMBL; BC098133; AAH98133.1; -; mRNA. DR EMBL; BC098305; AAH98305.1; -; mRNA. DR EMBL; BC098335; AAH98335.1; -; mRNA. DR CCDS; CCDS31022.1; -. [Q9NRG4-1] DR RefSeq; NP_064582.2; NM_020197.2. [Q9NRG4-1] DR PDB; 3RIB; X-ray; 2.79 A; A/B=1-433. DR PDB; 3S7B; X-ray; 2.42 A; A=1-433. DR PDB; 3S7D; X-ray; 2.30 A; A=1-433. DR PDB; 3S7F; X-ray; 2.85 A; A=1-433. DR PDB; 3S7J; X-ray; 3.04 A; A=1-433. DR PDB; 3TG4; X-ray; 2.00 A; A=1-433. DR PDB; 3TG5; X-ray; 2.30 A; A=1-433. DR PDB; 4O6F; X-ray; 2.82 A; A=1-433. DR PDB; 4WUY; X-ray; 1.63 A; A=1-433. DR PDB; 4YND; X-ray; 2.79 A; A=1-433. DR PDB; 5ARF; X-ray; 1.92 A; A=2-433. DR PDB; 5ARG; X-ray; 1.99 A; A=2-433. DR PDB; 5KJK; X-ray; 1.93 A; A=5-433. DR PDB; 5KJL; X-ray; 2.70 A; A=5-433. DR PDB; 5KJM; X-ray; 2.19 A; A=5-433. DR PDB; 5KJN; X-ray; 2.72 A; A=5-433. DR PDB; 5V3H; X-ray; 2.69 A; A=1-433. DR PDB; 5WCG; X-ray; 2.02 A; A=1-433. DR PDB; 6CBX; X-ray; 1.94 A; A/B=1-433. DR PDB; 6CBY; X-ray; 2.55 A; A/B=1-433. DR PDB; 6MON; X-ray; 2.71 A; A/B=5-433. DR PDB; 6N3G; X-ray; 2.43 A; A=1-433. DR PDBsum; 3RIB; -. DR PDBsum; 3S7B; -. DR PDBsum; 3S7D; -. DR PDBsum; 3S7F; -. DR PDBsum; 3S7J; -. DR PDBsum; 3TG4; -. DR PDBsum; 3TG5; -. DR PDBsum; 4O6F; -. DR PDBsum; 4WUY; -. DR PDBsum; 4YND; -. DR PDBsum; 5ARF; -. DR PDBsum; 5ARG; -. DR PDBsum; 5KJK; -. DR PDBsum; 5KJL; -. DR PDBsum; 5KJM; -. DR PDBsum; 5KJN; -. DR PDBsum; 5V3H; -. DR PDBsum; 5WCG; -. DR PDBsum; 6CBX; -. DR PDBsum; 6CBY; -. DR PDBsum; 6MON; -. DR PDBsum; 6N3G; -. DR AlphaFoldDB; Q9NRG4; -. DR SMR; Q9NRG4; -. DR BioGRID; 121274; 64. DR DIP; DIP-50202N; -. DR IntAct; Q9NRG4; 41. DR MINT; Q9NRG4; -. DR STRING; 9606.ENSP00000355924; -. DR BindingDB; Q9NRG4; -. DR ChEMBL; CHEMBL2169716; -. DR GuidetoPHARMACOLOGY; 2714; -. DR GlyGen; Q9NRG4; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NRG4; -. DR PhosphoSitePlus; Q9NRG4; -. DR BioMuta; SMYD2; -. DR DMDM; 90185234; -. DR EPD; Q9NRG4; -. DR jPOST; Q9NRG4; -. DR MassIVE; Q9NRG4; -. DR MaxQB; Q9NRG4; -. DR PaxDb; 9606-ENSP00000355924; -. DR PeptideAtlas; Q9NRG4; -. DR ProteomicsDB; 82355; -. [Q9NRG4-1] DR Pumba; Q9NRG4; -. DR ABCD; Q9NRG4; 3 sequenced antibodies. DR Antibodypedia; 34617; 379 antibodies from 37 providers. DR DNASU; 56950; -. DR Ensembl; ENST00000366957.10; ENSP00000355924.5; ENSG00000143499.14. [Q9NRG4-1] DR GeneID; 56950; -. DR KEGG; hsa:56950; -. DR MANE-Select; ENST00000366957.10; ENSP00000355924.5; NM_020197.3; NP_064582.2. DR UCSC; uc057pjy.1; human. [Q9NRG4-1] DR AGR; HGNC:20982; -. DR CTD; 56950; -. DR DisGeNET; 56950; -. DR GeneCards; SMYD2; -. DR HGNC; HGNC:20982; SMYD2. DR HPA; ENSG00000143499; Tissue enhanced (heart). DR MIM; 610663; gene. DR neXtProt; NX_Q9NRG4; -. DR OpenTargets; ENSG00000143499; -. DR PharmGKB; PA134930268; -. DR VEuPathDB; HostDB:ENSG00000143499; -. DR eggNOG; KOG2084; Eukaryota. DR GeneTree; ENSGT00940000157082; -. DR HOGENOM; CLU_018406_0_0_1; -. DR InParanoid; Q9NRG4; -. DR OMA; QNWHPSE; -. DR OrthoDB; 166337at2759; -. DR PhylomeDB; Q9NRG4; -. DR TreeFam; TF106487; -. DR BioCyc; MetaCyc:ENSG00000143499-MONOMER; -. DR PathwayCommons; Q9NRG4; -. DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines. DR Reactome; R-HSA-6804760; Regulation of TP53 Activity through Methylation. DR SignaLink; Q9NRG4; -. DR SIGNOR; Q9NRG4; -. DR BioGRID-ORCS; 56950; 8 hits in 1158 CRISPR screens. DR ChiTaRS; SMYD2; human. DR GenomeRNAi; 56950; -. DR Pharos; Q9NRG4; Tchem. DR PRO; PR:Q9NRG4; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9NRG4; Protein. DR Bgee; ENSG00000143499; Expressed in left ventricle myocardium and 213 other cell types or tissues. DR ExpressionAtlas; Q9NRG4; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0140938; F:histone H3 methyltransferase activity; TAS:Reactome. DR GO; GO:0046975; F:histone H3K36 methyltransferase activity; ISS:UniProtKB. DR GO; GO:0140999; F:histone H3K4 trimethyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0016278; F:lysine N-methyltransferase activity; TAS:Reactome. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0002039; F:p53 binding; IPI:UniProtKB. DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0000993; F:RNA polymerase II complex binding; ISS:UniProtKB. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0018027; P:peptidyl-lysine dimethylation; ISS:UniProtKB. DR GO; GO:0018026; P:peptidyl-lysine monomethylation; IDA:UniProtKB. DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB. DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome. DR CDD; cd19202; SET_SMYD2; 1. DR Gene3D; 1.10.220.160; -; 1. DR Gene3D; 1.25.40.970; -; 1. DR Gene3D; 6.10.140.2220; -; 1. DR Gene3D; 2.170.270.10; SET domain; 1. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1. DR IDEAL; IID00329; -. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR046341; SET_dom_sf. DR InterPro; IPR044419; SMYD2_SET. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR002893; Znf_MYND. DR PANTHER; PTHR12197; HISTONE-LYSINE N-METHYLTRANSFERASE SMYD; 1. DR PANTHER; PTHR12197:SF193; N-LYSINE METHYLTRANSFERASE SMYD2; 1. DR Pfam; PF00856; SET; 1. DR Pfam; PF01753; zf-MYND; 1. DR SMART; SM00317; SET; 1. DR SUPFAM; SSF82199; SET domain; 1. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS50280; SET; 1. DR PROSITE; PS01360; ZF_MYND_1; 1. DR PROSITE; PS50865; ZF_MYND_2; 1. DR Genevisible; Q9NRG4; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromatin regulator; Cytoplasm; KW Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; KW Reference proteome; S-adenosyl-L-methionine; Transcription; KW Transcription regulation; Transferase; Zinc; Zinc-finger. FT CHAIN 1..433 FT /note="N-lysine methyltransferase SMYD2" FT /id="PRO_0000218309" FT DOMAIN 7..241 FT /note="SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT ZN_FING 52..90 FT /note="MYND-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 17..19 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 52 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 55 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 65 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 68 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 74 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 78 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 86 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 90 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 137 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190, FT ECO:0000269|PubMed:21724641" FT BINDING 206..207 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 258..260 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT MOD_RES 283 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 273..433 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056005" FT VARIANT 165 FT /note="G -> E (in dbSNP:rs1134647)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1" FT /id="VAR_023442" FT VARIANT 430 FT /note="I -> M (in dbSNP:rs11120301)" FT /id="VAR_052991" FT MUTAGEN 187 FT /note="E->K: Abolishes methyltransferase activity on FT p53/TP53." FT /evidence="ECO:0000269|PubMed:21880715" FT MUTAGEN 189 FT /note="E->K: Strongly reduces methyltransferase activity on FT p53/TP53." FT /evidence="ECO:0000269|PubMed:21880715" FT MUTAGEN 190 FT /note="E->K: Strongly reduces methyltransferase activity on FT p53/TP53." FT /evidence="ECO:0000269|PubMed:21880715" FT MUTAGEN 207 FT /note="H->A: Abolishes methyltransferase activity." FT /evidence="ECO:0000269|PubMed:17108971" FT MUTAGEN 240 FT /note="Y->F: Abolishes methyltransferase activity." FT /evidence="ECO:0000269|PubMed:20870719, FT ECO:0000269|PubMed:21782458" FT MUTAGEN 245 FT /note="Y->F: Strongly reduces methyltransferase activity on FT p53/TP53." FT /evidence="ECO:0000269|PubMed:21880715" FT MUTAGEN 252 FT /note="D->R: Slightly reduces methyltransferase activity on FT p53/TP53." FT /evidence="ECO:0000269|PubMed:21880715" FT MUTAGEN 253 FT /note="R->Q: No effect on methyltransferase activity on FT p53/TP53." FT /evidence="ECO:0000269|PubMed:21880715" FT MUTAGEN 306 FT /note="R->E: No effect on methyltransferase activity on FT p53/TP53." FT /evidence="ECO:0000269|PubMed:21880715" FT MUTAGEN 374 FT /note="Y->A: Abolishes methyltransferase activity on FT p53/TP53." FT /evidence="ECO:0000269|PubMed:21880715" FT MUTAGEN 429 FT /note="E->K: Reduces methyltransferase activity on FT p53/TP53." FT /evidence="ECO:0000269|PubMed:21880715" FT MUTAGEN 431 FT /note="E->K: Strongly reduces methyltransferase activity on FT p53/TP53." FT /evidence="ECO:0000269|PubMed:21880715" FT HELIX 1..4 FT /evidence="ECO:0007829|PDB:5V3H" FT TURN 5..8 FT /evidence="ECO:0007829|PDB:5V3H" FT STRAND 9..14 FT /evidence="ECO:0007829|PDB:4WUY" FT TURN 15..17 FT /evidence="ECO:0007829|PDB:4WUY" FT STRAND 18..25 FT /evidence="ECO:0007829|PDB:4WUY" FT STRAND 32..37 FT /evidence="ECO:0007829|PDB:4WUY" FT STRAND 39..43 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 45..47 FT /evidence="ECO:0007829|PDB:4WUY" FT TURN 48..50 FT /evidence="ECO:0007829|PDB:6CBX" FT TURN 53..55 FT /evidence="ECO:0007829|PDB:4WUY" FT TURN 66..68 FT /evidence="ECO:0007829|PDB:4WUY" FT STRAND 72..75 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 76..86 FT /evidence="ECO:0007829|PDB:4WUY" FT TURN 87..89 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 90..96 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 97..99 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 104..118 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 124..126 FT /evidence="ECO:0007829|PDB:6CBX" FT STRAND 127..129 FT /evidence="ECO:0007829|PDB:6N3G" FT HELIX 131..133 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 138..140 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 143..164 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 169..182 FT /evidence="ECO:0007829|PDB:4WUY" FT STRAND 184..187 FT /evidence="ECO:0007829|PDB:4WUY" FT STRAND 193..198 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 200..203 FT /evidence="ECO:0007829|PDB:4WUY" FT STRAND 205..207 FT /evidence="ECO:0007829|PDB:5ARF" FT STRAND 212..218 FT /evidence="ECO:0007829|PDB:4WUY" FT STRAND 221..228 FT /evidence="ECO:0007829|PDB:4WUY" FT STRAND 235..238 FT /evidence="ECO:0007829|PDB:6CBY" FT STRAND 243..245 FT /evidence="ECO:0007829|PDB:5KJL" FT HELIX 247..258 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 265..269 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 273..276 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 288..305 FT /evidence="ECO:0007829|PDB:4WUY" FT TURN 309..311 FT /evidence="ECO:0007829|PDB:5ARF" FT HELIX 318..329 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 337..353 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 356..373 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 379..394 FT /evidence="ECO:0007829|PDB:4WUY" FT HELIX 398..415 FT /evidence="ECO:0007829|PDB:4WUY" FT TURN 416..419 FT /evidence="ECO:0007829|PDB:5KJL" FT HELIX 421..432 FT /evidence="ECO:0007829|PDB:4WUY" SQ SEQUENCE 433 AA; 49688 MW; 3EEA5B8417870F5D CRC64; MRAEGLGGLE RFCSPGKGRG LRALQPFQVG DLLFSCPAYA YVLTVNERGN HCEYCFTRKE GLSKCGRCKQ AFYCNVECQK EDWPMHKLEC SPMVVFGENW NPSETVRLTA RILAKQKIHP ERTPSEKLLA VKEFESHLDK LDNEKKDLIQ SDIAALHHFY SKHLGFPDND SLVVLFAQVN CNGFTIEDEE LSHLGSAIFP DVALMNHSCC PNVIVTYKGT LAEVRAVQEI KPGEEVFTSY IDLLYPTEDR NDRLRDSYFF TCECQECTTK DKDKAKVEIR KLSDPPKAEA IRDMVRYARN VIEEFRRAKH YKSPSELLEI CELSQEKMSS VFEDSNVYML HMMYQAMGVC LYMQDWEGAL QYGQKIIKPY SKHYPLYSLN VASMWLKLGR LYMGLEHKAA GEKALKKAIA IMEVAHGKDH PYISEIKQEI ESH //