SMYD3_MOUSE
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 03-AUG-2022, entry version 135.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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; 1.
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; Q9CWR2; -.
DR PRIDE; Q9CWR2; -.
DR ProteomicsDB; 261283; -.
DR Antibodypedia; 34720; 292 antibodies from 37 providers.
DR DNASU; 69726; -.
DR Ensembl; ENSMUST00000128302; ENSMUSP00000117410; ENSMUSG00000055067.
DR GeneID; 69726; -.
DR KEGG; mmu:69726; -.
DR UCSC; uc007dvj.1; mouse.
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; WSKIFIS; -.
DR OrthoDB; 981799at2759; -.
DR PhylomeDB; Q9CWR2; -.
DR TreeFam; TF106487; -.
DR Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR BioGRID-ORCS; 69726; 1 hit in 75 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 163 other tissues.
DR ExpressionAtlas; Q9CWR2; baseline and differential.
DR Genevisible; Q9CWR2; MM.
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:0018024; F:histone-lysine N-methyltransferase activity; IDA:UniProtKB.
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:0034968; P:histone lysine methylation; IBA:GO_Central.
DR GO; GO:0014904; P:myotube cell development; IMP:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; 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; 1.25.40.10; -; 1.
DR Gene3D; 2.170.270.10; -; 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 Pfam; PF00856; SET; 1.
DR Pfam; PF01753; zf-MYND; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 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.
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
