SMYD2_HUMAN
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 03-AUG-2022, entry version 171.
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="http://atlasgeneticsoncology.org/Genes/SMYD2ID47098ch1q32.html";
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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; 61.
DR DIP; DIP-50202N; -.
DR IntAct; Q9NRG4; 40.
DR MINT; Q9NRG4; -.
DR STRING; 9606.ENSP00000355924; -.
DR BindingDB; Q9NRG4; -.
DR ChEMBL; CHEMBL2169716; -.
DR GuidetoPHARMACOLOGY; 2714; -.
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; Q9NRG4; -.
DR PeptideAtlas; Q9NRG4; -.
DR PRIDE; Q9NRG4; -.
DR ProteomicsDB; 82355; -. [Q9NRG4-1]
DR ABCD; Q9NRG4; 3 sequenced antibodies.
DR Antibodypedia; 34617; 348 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 CTD; 56950; -.
DR DisGeNET; 56950; -.
DR GeneCards; SMYD2; -.
DR HGNC; HGNC:20982; SMYD2.
DR HPA; ENSG00000143499; Group enriched (heart muscle, skeletal muscle).
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; YSRHLEF; -.
DR OrthoDB; 981799at2759; -.
DR PhylomeDB; Q9NRG4; -.
DR TreeFam; TF106487; -.
DR BioCyc; MetaCyc:ENSG00000143499-MON; -.
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; 7 hits in 1078 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 211 other tissues.
DR ExpressionAtlas; Q9NRG4; baseline and differential.
DR Genevisible; Q9NRG4; HS.
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:0046975; F:histone methyltransferase activity (H3-K36 specific); ISS:UniProtKB.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IBA:GO_Central.
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:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0034968; P:histone lysine methylation; IBA:GO_Central.
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; 1.25.40.10; -; 1.
DR Gene3D; 2.170.270.10; -; 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 Pfam; PF00856; SET; 1.
DR Pfam; PF01753; zf-MYND; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50280; SET; 1.
DR PROSITE; PS01360; ZF_MYND_1; 1.
DR PROSITE; PS50865; ZF_MYND_2; 1.
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
