ID   SMYD3_MOUSE             Reviewed;         428 AA.
AC   Q9CWR2; Q6P7V6; Q8BG90;
DT   16-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   27-MAR-2024, entry version 144.
DE   RecName: Full=Histone-lysine N-methyltransferase SMYD3;
DE            EC=2.1.1.354 {ECO:0000250|UniProtKB:Q9H7B4, ECO:0000255|PROSITE-ProRule:PRU00907};
DE   AltName: Full=SET and MYND domain-containing protein 3;
DE   AltName: Full=Zinc finger MYND domain-containing protein 1;
GN   Name=Smyd3; Synonyms=Zmynd1;
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;
RC   TISSUE=Brain cortex, Embryonic stem cell, and Medulla oblongata;
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].
RC   STRAIN=C57BL/6J, and FVB/N-3; TISSUE=Brain, and Mammary tumor;
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).
CC   -!- FUNCTION: Histone methyltransferase. Specifically methylates 'Lys-4' of
CC       histone H3, inducing di- and tri-methylation, but not monomethylation.
CC       Also methylates 'Lys-5' of histone H4. Plays an important role in
CC       transcriptional activation as a member of an RNA polymerase complex.
CC       Binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences.
CC       {ECO:0000250|UniProtKB:Q9H7B4}.
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:Q9H7B4, ECO:0000255|PROSITE-
CC         ProRule:PRU00907};
CC   -!- ACTIVITY REGULATION: Histone methyltransferase activity strongly
CC       stimulated by HSPCA. {ECO:0000250|UniProtKB:Q9H7B4}.
CC   -!- SUBUNIT: Interacts with HSPCA. Interacts with HELZ. Interacts with
CC       POLR2A; the interaction may be indirect and may be mediated by HELZ.
CC       Interacts with HSP90AA1; this interaction enhances SMYD3 histone-lysine
CC       N-methyltransferase. {ECO:0000250|UniProtKB:Q9H7B4}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9H7B4}. Nucleus
CC       {ECO:0000250|UniProtKB:Q9H7B4}. Note=Mainly cytoplasmic when cells are
CC       arrested at G0/G1. Accumulates in the nucleus at S phase and G2/M.
CC       {ECO:0000250|UniProtKB:Q9H7B4}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC       superfamily. Histone-lysine methyltransferase family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00907}.
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DR   EMBL; AK010447; BAB26947.1; -; mRNA.
DR   EMBL; AK044168; BAC31804.1; -; mRNA.
DR   EMBL; AK046829; BAC32887.1; -; mRNA.
DR   EMBL; BC052431; AAH52431.1; -; mRNA.
DR   EMBL; BC061485; AAH61485.1; -; mRNA.
DR   CCDS; CCDS15560.1; -.
DR   RefSeq; NP_081464.1; NM_027188.3.
DR   RefSeq; XP_006497045.1; XM_006496982.3.
DR   RefSeq; XP_017167700.1; XM_017312211.1.
DR   RefSeq; XP_017167702.1; XM_017312213.1.
DR   AlphaFoldDB; Q9CWR2; -.
DR   SMR; Q9CWR2; -.
DR   BioGRID; 213640; 2.
DR   IntAct; Q9CWR2; 4.
DR   MINT; Q9CWR2; -.
DR   STRING; 10090.ENSMUSP00000117410; -.
DR   iPTMnet; Q9CWR2; -.
DR   PhosphoSitePlus; Q9CWR2; -.
DR   EPD; Q9CWR2; -.
DR   MaxQB; Q9CWR2; -.
DR   PaxDb; 10090-ENSMUSP00000117410; -.
DR   ProteomicsDB; 261283; -.
DR   Pumba; Q9CWR2; -.
DR   Antibodypedia; 34720; 338 antibodies from 37 providers.
DR   DNASU; 69726; -.
DR   Ensembl; ENSMUST00000128302.8; ENSMUSP00000117410.2; ENSMUSG00000055067.16.
DR   GeneID; 69726; -.
DR   KEGG; mmu:69726; -.
DR   UCSC; uc007dvj.1; mouse.
DR   AGR; MGI:1916976; -.
DR   CTD; 64754; -.
DR   MGI; MGI:1916976; Smyd3.
DR   VEuPathDB; HostDB:ENSMUSG00000055067; -.
DR   eggNOG; KOG2084; Eukaryota.
DR   GeneTree; ENSGT00940000156766; -.
DR   HOGENOM; CLU_018406_2_0_1; -.
DR   InParanoid; Q9CWR2; -.
DR   OMA; LHMKLGK; -.
DR   OrthoDB; 166337at2759; -.
DR   PhylomeDB; Q9CWR2; -.
DR   TreeFam; TF106487; -.
DR   Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR   BioGRID-ORCS; 69726; 1 hit in 81 CRISPR screens.
DR   ChiTaRS; Smyd3; mouse.
DR   PRO; PR:Q9CWR2; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q9CWR2; Protein.
DR   Bgee; ENSMUSG00000055067; Expressed in secondary oocyte and 165 other cell types or tissues.
DR   ExpressionAtlas; Q9CWR2; baseline and differential.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0140954; F:histone H3K36 dimethyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0140999; F:histone H3K4 trimethyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0140939; F:histone H4 methyltransferase activity; ISO:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:0000993; F:RNA polymerase II complex binding; IDA:MGI.
DR   GO; GO:0001162; F:RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:0071549; P:cellular response to dexamethasone stimulus; IDA:MGI.
DR   GO; GO:0045184; P:establishment of protein localization; IMP:MGI.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0014904; P:myotube cell development; IMP:MGI.
DR   GO; GO:0006334; P:nucleosome assembly; IMP:MGI.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR   CDD; cd19203; SET_SMYD3; 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   InterPro; IPR025805; Hist-Lys_N-MeTrfase_SMYD3.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR046341; SET_dom_sf.
DR   InterPro; IPR044420; SMYD3_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:SF288; HISTONE-LYSINE N-METHYLTRANSFERASE SMYD3; 1.
DR   Pfam; PF00856; SET; 1.
DR   Pfam; PF01753; zf-MYND; 1.
DR   SMART; SM00317; SET; 1.
DR   SUPFAM; SSF82199; SET domain; 1.
DR   PROSITE; PS51574; SAM_MT43_2; 1.
DR   PROSITE; PS50280; SET; 1.
DR   PROSITE; PS01360; ZF_MYND_1; 1.
DR   PROSITE; PS50865; ZF_MYND_2; 1.
DR   Genevisible; Q9CWR2; MM.
PE   2: Evidence at transcript level;
KW   Acetylation; Chromatin regulator; Cytoplasm; Metal-binding;
KW   Methyltransferase; Nucleus; Reference proteome; S-adenosyl-L-methionine;
KW   Transferase; Zinc; Zinc-finger.
FT   CHAIN           1..428
FT                   /note="Histone-lysine N-methyltransferase SMYD3"
FT                   /id="PRO_0000218313"
FT   DOMAIN          4..240
FT                   /note="SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   ZN_FING         49..87
FT                   /note="MYND-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT   REGION          272..428
FT                   /note="C-terminal domain; essential for histone
FT                   methyltransferase activity, nuclear localization and
FT                   mediates interaction with HSP90AA1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H7B4"
FT   BINDING         14..16
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H7B4"
FT   BINDING         49
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
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         62
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
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         71
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT   BINDING         75
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT   BINDING         83
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT   BINDING         87
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT   BINDING         124
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   BINDING         132
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   BINDING         205..206
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H7B4"
FT   BINDING         239
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   BINDING         259
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H7B4"
FT   CONFLICT        318
FT                   /note="N -> D (in Ref. 2; AAH61485)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   428 AA;  49126 MW;  1EC765044E1FB0DA CRC64;
     MEALKVEKFT TANRGNGLRA VAPLRPGELL FRSDPLAYTV CKGSRGVVCD RCLLGKEKLM
     RCSQCRIAKY CSAKCQKKAW PDHRRECSCL KSCKPRYPPD SVRLLGRVIV KLMDEKPSES
     EKLYSFYDLE SNISKLTEDK KEGLRQLAMT FQHFMREEIQ DASQLPPSFD LFEAFAKVIC
     NSFTICNAEM QEVGVGLYPS MSLLNHSCDP NCSIVFNGPH LLLRAVREIE AGEELTICYL
     DMLMTSEERR KQLRDQYCFE CDCIRCQTQD KDADMLTGDE QIWKEVQESL KKIEELKAHW
     KWEQVLALCQ AIINSNSNRL PDINIYQLKV LDCAMDACIN LGMLEEALFY AMRTMEPYRI
     FFPGSHPVRG VQVMKVGKLQ LHQGMFPQAM KNLRLAFDIM KVTHGREHSL IEDLILLLEE
     CDANIRAS
//