ID SMYD2_RAT Reviewed; 433 AA.
AC Q7M6Z3;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 1.
DT 24-JAN-2024, entry version 123.
DE RecName: Full=N-lysine methyltransferase SMYD2;
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q9NRG4};
DE AltName: Full=Histone methyltransferase SMYD2;
DE EC=2.1.1.354 {ECO:0000250|UniProtKB:Q9NRG4};
DE AltName: Full=SET and MYND domain-containing protein 2;
GN Name=Smyd2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12783626; DOI=10.1186/1471-2164-4-22;
RA Oduru S., Campbell J.L., Karri S., Hendry W.J., Khan S.A., Williams S.C.;
RT "Gene discovery in the hamster: a comparative genomics approach for gene
RT annotation by sequencing of hamster testis cDNAs.";
RL BMC Genomics 4:22-22(2003).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:0000250|UniProtKB:Q9NRG4}.
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:0000250|UniProtKB:Q9NRG4};
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:0000250|UniProtKB:Q9NRG4};
CC -!- SUBUNIT: Interacts with RNA polymerase II and HELZ. Interacts with
CC SIN3A and HDAC1. Interacts (via MYND-type zinc finger) with EPB41L3.
CC Interacts (via SET domain) with p53/TP53. Interacts with RB1 and
CC HSP90AA1 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Nucleus
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; BK001057; DAA01315.1; -; mRNA.
DR RefSeq; NP_996733.1; NM_206851.1.
DR AlphaFoldDB; Q7M6Z3; -.
DR SMR; Q7M6Z3; -.
DR STRING; 10116.ENSRNOP00000004783; -.
DR iPTMnet; Q7M6Z3; -.
DR PhosphoSitePlus; Q7M6Z3; -.
DR jPOST; Q7M6Z3; -.
DR PaxDb; 10116-ENSRNOP00000004783; -.
DR Ensembl; ENSRNOT00000004783.7; ENSRNOP00000004783.4; ENSRNOG00000003583.7.
DR Ensembl; ENSRNOT00055018776; ENSRNOP00055015135; ENSRNOG00055011078.
DR GeneID; 289372; -.
DR KEGG; rno:289372; -.
DR AGR; RGD:727785; -.
DR CTD; 56950; -.
DR RGD; 727785; Smyd2.
DR eggNOG; KOG2084; Eukaryota.
DR GeneTree; ENSGT00940000157082; -.
DR HOGENOM; CLU_018406_0_0_1; -.
DR InParanoid; Q7M6Z3; -.
DR OMA; HRIMDYL; -.
DR OrthoDB; 166337at2759; -.
DR PhylomeDB; Q7M6Z3; -.
DR TreeFam; TF106487; -.
DR Reactome; R-RNO-3214841; PKMTs methylate histone lysines.
DR Reactome; R-RNO-6804760; Regulation of TP53 Activity through Methylation.
DR PRO; PR:Q7M6Z3; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000003583; Expressed in skeletal muscle tissue and 20 other cell types or tissues.
DR Genevisible; Q7M6Z3; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002039; F:p53 binding; ISO:RGD.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0000993; F:RNA polymerase II complex binding; ISS:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; ISO:RGD.
DR GO; GO:0007507; P:heart development; IEP:RGD.
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; ISS:UniProtKB.
DR GO; GO:0018027; P:peptidyl-lysine dimethylation; ISS:UniProtKB.
DR GO; GO:0018026; P:peptidyl-lysine monomethylation; ISS:UniProtKB.
DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB.
DR CDD; cd19202; SET_SMYD2; 1.
DR Gene3D; 1.10.220.160; -; 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 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 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.
PE 1: Evidence at protein level;
KW Chromatin regulator; Cytoplasm; Metal-binding; Methyltransferase; Nucleus;
KW Phosphoprotein; 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_0000218311"
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 /evidence="ECO:0000250"
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 BINDING 206..207
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 258..260
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 433 AA; 49648 MW; 7CE05492B8CA1578 CRC64;
MRAEARGGLE RFCSAGKGRG LRALRPFHVG DLLFSCPAYA CVLTVGERGH HCECCFARKE
GLSKCGRCKQ AFYCDVECQK EDWPLHKLEC SSMVVFGENW NPSETVRLTA RILAKQKMHP
ERTPSEKLLA VREFESHLDK LDNEKKDLIQ SDIAALHQFY SKHLEFPDHS SLVVLFAQVN
CNGFTIEDEE LSHLGSAIFP DVALMNHSCC PNVIVTYKGT LAEVRAVQEI HPGDEVFTSY
IDLLYPTEDR NDRLRDSYFF TCECRECTTK DKDKAKVEIR KLSNPPQAEA IRDMVRYARN
VIEEFRRAKH YKSPSELLEI CELSQEKMSS VFEDSNVYML HMMYQAMGVC LYMQDWEGAL
KYGQKIIKPY SKHYPVYSLN VASMWLKLGR LYMGLENKAA GEKALKKAIA IMEIAHGKDH
PYISEIKQEI ESH
//
