ID SMYD2_MOUSE Reviewed; 433 AA.
AC Q8R5A0; Q3UBQ2;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 24-JAN-2024, entry version 135.
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 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 MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-240, AND INTERACTION
RP WITH SIN3A AND HDAC1.
RX PubMed=16805913; DOI=10.1186/1476-4598-5-26;
RA Brown M.A., Sims R.J. III, Gottlieb P.D., Tucker P.W.;
RT "Identification and characterization of Smyd2: a split SET/MYND domain-
RT containing histone H3 lysine 36-specific methyltransferase that interacts
RT with the Sin3 histone deacetylase complex.";
RL Mol. Cancer 5:26-26(2006).
RN [4]
RP CAUTION.
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 [5]
RP TISSUE SPECIFICITY, INTERACTION WITH RNA POLYMERASE II AND HELZ, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20305823; DOI=10.1371/journal.pone.0009748;
RA Diehl F., Brown M.A., van Amerongen M.J., Novoyatleva T., Wietelmann A.,
RA Harriss J., Ferrazzi F., Bottger T., Harvey R.P., Tucker P.W., Engel F.B.;
RT "Cardiac deletion of Smyd2 is dispensable for mouse heart development.";
RL PLoS ONE 5:E9748-E9748(2010).
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, ECO:0000269|PubMed:16805913}.
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 (via MYND-type zinc finger) with EPB41L3. Interacts
CC (via SET domain) with p53/TP53. Interacts with RB1 and HSP90AA1 (By
CC similarity). Interacts with RNA polymerase II and HELZ. Interacts with
CC SIN3A and HDAC1. {ECO:0000250, ECO:0000269|PubMed:16805913,
CC ECO:0000269|PubMed:20305823}.
CC -!- INTERACTION:
CC Q8R5A0; P04637: TP53; Xeno; NbExp=3; IntAct=EBI-15612527, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Nucleus.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle and
CC brain tissue. During cardiac development, it is differentially
CC expressed with highest expression in the neonatal heart while very low
CC expression is detected at 12.5 dpc and adult. Specifically expressed in
CC cardiomyocytes (at protein level). {ECO:0000269|PubMed:20305823}.
CC -!- MISCELLANEOUS: Although specifically expressed in cardiomyocytes, a
CC conditional deletion in heart does not lead to any visible phenotype.
CC {ECO:0000305|PubMed:20305823}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC -!- CAUTION: The protein was previously thought to dimethylate histone 3
CC 'Lys-36', but this is now known not to take place in vivo.
CC {ECO:0000269|PubMed:18065756}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE29912.1; Type=Miscellaneous discrepancy; Note=Deletion within an exon that does not correspond to an intron.; Evidence={ECO:0000305};
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DR EMBL; AK150857; BAE29912.1; ALT_SEQ; mRNA.
DR EMBL; BC023119; AAH23119.1; -; mRNA.
DR CCDS; CCDS35821.1; -.
DR RefSeq; NP_081072.1; NM_026796.1.
DR PDB; 3QWV; X-ray; 2.03 A; A=1-433.
DR PDB; 3QWW; X-ray; 1.80 A; A=1-433.
DR PDBsum; 3QWV; -.
DR PDBsum; 3QWW; -.
DR AlphaFoldDB; Q8R5A0; -.
DR SMR; Q8R5A0; -.
DR BioGRID; 230559; 4.
DR DIP; DIP-60503N; -.
DR IntAct; Q8R5A0; 1.
DR STRING; 10090.ENSMUSP00000027897; -.
DR iPTMnet; Q8R5A0; -.
DR PhosphoSitePlus; Q8R5A0; -.
DR EPD; Q8R5A0; -.
DR MaxQB; Q8R5A0; -.
DR PaxDb; 10090-ENSMUSP00000027897; -.
DR PeptideAtlas; Q8R5A0; -.
DR ProteomicsDB; 261589; -.
DR Pumba; Q8R5A0; -.
DR Antibodypedia; 34617; 379 antibodies from 37 providers.
DR DNASU; 226830; -.
DR Ensembl; ENSMUST00000027897.8; ENSMUSP00000027897.8; ENSMUSG00000026603.14.
DR GeneID; 226830; -.
DR KEGG; mmu:226830; -.
DR UCSC; uc007eax.1; mouse.
DR AGR; MGI:1915889; -.
DR CTD; 56950; -.
DR MGI; MGI:1915889; Smyd2.
DR VEuPathDB; HostDB:ENSMUSG00000026603; -.
DR eggNOG; KOG2084; Eukaryota.
DR GeneTree; ENSGT00940000157082; -.
DR HOGENOM; CLU_018406_0_0_1; -.
DR InParanoid; Q8R5A0; -.
DR OMA; QNWHPSE; -.
DR OrthoDB; 166337at2759; -.
DR PhylomeDB; Q8R5A0; -.
DR TreeFam; TF106487; -.
DR Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR Reactome; R-MMU-6804760; Regulation of TP53 Activity through Methylation.
DR BioGRID-ORCS; 226830; 3 hits in 83 CRISPR screens.
DR ChiTaRS; Smyd2; mouse.
DR EvolutionaryTrace; Q8R5A0; -.
DR PRO; PR:Q8R5A0; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8R5A0; Protein.
DR Bgee; ENSMUSG00000026603; Expressed in gastrocnemius and 266 other cell types or tissues.
DR Genevisible; Q8R5A0; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0046975; F:histone H3K36 methyltransferase activity; IDA: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:MGI.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0000993; F:RNA polymerase II complex binding; IDA:UniProtKB.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0018027; P:peptidyl-lysine dimethylation; IDA: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; 6.10.140.2220; -; 1.
DR Gene3D; 2.170.270.10; SET domain; 2.
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 3D-structure; Chromatin regulator; Cytoplasm; Metal-binding;
KW Methyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase; Zinc; Zinc-finger.
FT CHAIN 1..433
FT /note="N-lysine methyltransferase SMYD2"
FT /id="PRO_0000218310"
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:0000250|UniProtKB:Q9NRG4"
FT MUTAGEN 240
FT /note="Y->F: Abolishes methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:16805913"
FT STRAND 9..13
FT /evidence="ECO:0007829|PDB:3QWW"
FT STRAND 19..25
FT /evidence="ECO:0007829|PDB:3QWW"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:3QWW"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:3QWW"
FT TURN 48..50
FT /evidence="ECO:0007829|PDB:3QWW"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:3QWW"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:3QWW"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 76..86
FT /evidence="ECO:0007829|PDB:3QWW"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 90..95
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 104..118
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 143..160
FT /evidence="ECO:0007829|PDB:3QWW"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 169..182
FT /evidence="ECO:0007829|PDB:3QWW"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:3QWW"
FT STRAND 193..198
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:3QWW"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:3QWW"
FT STRAND 212..218
FT /evidence="ECO:0007829|PDB:3QWW"
FT STRAND 221..228
FT /evidence="ECO:0007829|PDB:3QWW"
FT STRAND 235..238
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 247..258
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 265..269
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 273..276
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 288..308
FT /evidence="ECO:0007829|PDB:3QWW"
FT TURN 309..311
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 314..328
FT /evidence="ECO:0007829|PDB:3QWW"
FT TURN 329..331
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 337..352
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 356..373
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 379..394
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 398..415
FT /evidence="ECO:0007829|PDB:3QWW"
FT HELIX 421..431
FT /evidence="ECO:0007829|PDB:3QWW"
SQ SEQUENCE 433 AA; 49567 MW; 5978E9A3FC2CDCE4 CRC64;
MRAEARGGLE RFCSAGKGRG LRALRPFHVG DLLFSCPAYA CVLTVGERGH HCECCFARKE
GLSKCGRCKQ AFYCDVECQK EDWPLHKLEC SSMVVLGENW NPSETVRLTA RILAKQKIHP
ERTPSEKLLA VREFESHLDK LDNEKKDLIQ SDIAALHQFY SKYLEFPDHS SLVVLFAQVN
CNGFTIEDEE LSHLGSAIFP DVALMNHSCC PNVIVTYKGT LAEVRAVQEI HPGDEVFTSY
IDLLYPTEDR NDRLRDSYFF TCECRECTTK DKDKAKVEVR KLSSPPQAEA IRDMVRYARN
VIEEFRRAKH YKSPSELLEI CELSQEKMSS VFEDSNVYML HMMYQAMGVC LYMQDWEGAL
KYGQKIIKPY SKHYPVYSLN VASMWLKLGR LYMGLENKAA GEKALKKAIA IMEVAHGKDH
PYISEIKQEI ESH
//
