SMY2A_DANRE
ID SMY2A_DANRE Reviewed; 435 AA.
AC Q5BJI7;
DT 08-MAR-2011, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=N-lysine methyltransferase SMYD2-A;
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q9NRG4};
DE AltName: Full=Histone methyltransferase SMYD2-A;
DE EC=2.1.1.354 {ECO:0000250|UniProtKB:Q9NRG4};
DE AltName: Full=SET and MYND domain-containing protein 2A;
GN Name=smyd2a; Synonyms=smyd2; ORFNames=zgc:110553;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
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 -!- 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; BC091465; AAH91465.1; -; mRNA.
DR RefSeq; NP_001013568.1; NM_001013550.1.
DR AlphaFoldDB; Q5BJI7; -.
DR SMR; Q5BJI7; -.
DR STRING; 7955.ENSDARP00000071926; -.
DR PaxDb; Q5BJI7; -.
DR GeneID; 541423; -.
DR KEGG; dre:541423; -.
DR CTD; 541423; -.
DR ZFIN; ZDB-GENE-050320-126; smyd2a.
DR eggNOG; KOG2084; Eukaryota.
DR InParanoid; Q5BJI7; -.
DR OrthoDB; 981799at2759; -.
DR PhylomeDB; Q5BJI7; -.
DR Reactome; R-DRE-3214841; PKMTs methylate histone lysines.
DR Reactome; R-DRE-6804760; Regulation of TP53 Activity through Methylation.
DR PRO; PR:Q5BJI7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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 methyltransferase activity (H3-K36 specific); ISS:UniProtKB.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0033336; P:caudal fin development; IMP:ZFIN.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0060047; P:heart contraction; IMP:ZFIN.
DR GO; GO:0007507; P:heart development; IMP:ZFIN.
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; 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 GO; GO:0060297; P:regulation of sarcomere organization; IMP:ZFIN.
DR GO; GO:0007519; P:skeletal muscle tissue development; IMP:ZFIN.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
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; SSF82199; SSF82199; 1.
DR PROSITE; PS50280; SET; 1.
DR PROSITE; PS01360; ZF_MYND_1; 1.
DR PROSITE; PS50865; ZF_MYND_2; 1.
PE 2: Evidence at transcript level;
KW Chromatin regulator; Cytoplasm; Metal-binding; Methyltransferase; Nucleus;
KW Reference proteome; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..435
FT /note="N-lysine methyltransferase SMYD2-A"
FT /id="PRO_0000405848"
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"
SQ SEQUENCE 435 AA; 50064 MW; 4A18A0D8C01FE29A CRC64;
MKKEGIEGTE RFLSPGKGRG LKAIKHFKVG DLVFACPAYA YVLTVNERGG RCECCFTRKE
GLSKCGKCKQ AYYCNVECQR GDWPMHKLEC SAMCAYGENW CPSETVRLVA RIILKQKHQT
ERTPSERVLT LRELEAHLDK LDNEKNEMND TDIAALHHFY SRHLDFPDNA ALTELIAQVN
CNGFTIEDEE LSHLGSALFP DVALMNHSCS PNVIVTYKGT VAEVRAVQEI NPEEEIFNSY
IDLLYPTEDR IERLKDSYFF NCDCKECTSK SKDEAKMEIR QKLSIPPEEE EIKQMVIYAR
NVIEEFRRAK HYKTPSELLE ICELSMEKMG AIFAETNVYM LHMMYQAMGV CLYMQDWDGA
MKYGEKIIHP YSVHYPPYSL NVASMYLKLG RLYLGLEKRT QGVKALKKAL AIMDIAHGKD
HPYIDEIKKE MEEQT
