SMYD5_MOUSE
ID SMYD5_MOUSE Reviewed; 416 AA.
AC Q3TYX3; Q3TRB2; Q91YL6;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Histone-lysine N-trimethyltransferase SMYD5;
DE EC=2.1.1.372 {ECO:0000269|PubMed:22921934, ECO:0000269|PubMed:28250819};
DE AltName: Full=Protein NN8-4AG;
DE AltName: Full=Retinoic acid-induced protein 15;
DE AltName: Full=SET and MYND domain-containing protein 5;
DE AltName: Full=[histone H4]-lysine20 N-trimethyltransferase SMYD5;
GN Name=Smyd5; Synonyms=Rai15;
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=Inner ear, and Spinal cord;
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=FVB/N; TISSUE=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).
RN [3]
RP INDUCTION.
RX PubMed=8754834; DOI=10.1128/mcb.16.8.4337;
RA Shago M., Giguere V.;
RT "Isolation of a novel retinoic acid-responsive gene by selection of genomic
RT fragments derived from CpG-island-enriched DNA.";
RL Mol. Cell. Biol. 16:4337-4348(1996).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH N-COR COMPLEX.
RX PubMed=22921934; DOI=10.1016/j.molcel.2012.07.020;
RA Stender J.D., Pascual G., Liu W., Kaikkonen M.U., Do K., Spann N.J.,
RA Boutros M., Perrimon N., Rosenfeld M.G., Glass C.K.;
RT "Control of proinflammatory gene programs by regulated trimethylation and
RT demethylation of histone H4K20.";
RL Mol. Cell 48:28-38(2012).
RN [6]
RP FUNCTION.
RX PubMed=28951459; DOI=10.1158/0008-5472.can-17-0828;
RA Kidder B.L., He R., Wangsa D., Padilla-Nash H.M., Bernardo M.M., Sheng S.,
RA Ried T., Zhao K.;
RT "SMYD5 Controls Heterochromatin and Chromosome Integrity during Embryonic
RT Stem Cell Differentiation.";
RL Cancer Res. 77:6729-6745(2017).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH EHMT2 AND CBX5.
RX PubMed=28250819; DOI=10.1186/s13072-017-0115-7;
RA Kidder B.L., Hu G., Cui K., Zhao K.;
RT "SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-
RT renewal and prevent spurious differentiation.";
RL Epigenetics Chromatin 10:8-8(2017).
CC -!- FUNCTION: Histone methyltransferase that specifically trimethylates
CC 'Lys-20' of histone H4 to form trimethylated histone H4 lysine 20
CC (H4K20me3) which represents a specific tag for epigenetic
CC transcriptional repression (PubMed:22921934, PubMed:28250819). In
CC association with the NCoR corepressor complex, is involved in the
CC repression of toll-like receptor 4 (TLR4)-target inflammatory genes in
CC macrophages by catalyzing the formation of H4K20me3 at the gene
CC promoters (PubMed:22921934). Plays an important role in embryonic stem
CC (ES) cell self-renewal and differentiation (PubMed:28951459). Promotes
CC ES cell maintenance by silencing differentiation genes through
CC deposition of H4K20me3 marks (PubMed:28951459). Maintains genome
CC stability of ES cells during differentiation through regulation of
CC heterochromatin formation and repression of endogenous repetitive DNA
CC elements by depositing H4K20me3 marks (PubMed:28250819).
CC {ECO:0000269|PubMed:22921934, ECO:0000269|PubMed:28250819,
CC ECO:0000269|PubMed:28951459}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(20)-[histone H4] + 3 S-adenosyl-L-methionine = 3 H(+)
CC + N(6),N(6),N(6)-trimethyl-L-lysyl(20)-[histone H4] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:64456, Rhea:RHEA-COMP:15554, Rhea:RHEA-
CC COMP:15998, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.372;
CC Evidence={ECO:0000269|PubMed:22921934, ECO:0000269|PubMed:28250819};
CC -!- SUBUNIT: Interacts with the N-CoR complex (PubMed:22921934). Interacts
CC with EHMT2 and CBX5 (PubMed:28250819). {ECO:0000269|PubMed:22921934,
CC ECO:0000269|PubMed:28250819}.
CC -!- INDUCTION: Up-regulated by retinoic acid treatment in embryonic
CC carcinoma cells. Present at low levels in untreated cells.
CC {ECO:0000269|PubMed:8754834}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH16525.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK158267; BAE34438.1; -; mRNA.
DR EMBL; AK162926; BAE37118.1; -; mRNA.
DR EMBL; BC016525; AAH16525.1; ALT_INIT; mRNA.
DR CCDS; CCDS51827.1; -.
DR RefSeq; NP_659167.2; NM_144918.2.
DR AlphaFoldDB; Q3TYX3; -.
DR STRING; 10090.ENSMUSP00000048537; -.
DR iPTMnet; Q3TYX3; -.
DR PhosphoSitePlus; Q3TYX3; -.
DR EPD; Q3TYX3; -.
DR MaxQB; Q3TYX3; -.
DR PaxDb; Q3TYX3; -.
DR PeptideAtlas; Q3TYX3; -.
DR PRIDE; Q3TYX3; -.
DR ProteomicsDB; 261463; -.
DR Antibodypedia; 31318; 232 antibodies from 26 providers.
DR Ensembl; ENSMUST00000045693; ENSMUSP00000048537; ENSMUSG00000033706.
DR GeneID; 232187; -.
DR KEGG; mmu:232187; -.
DR UCSC; uc009cpq.1; mouse.
DR CTD; 10322; -.
DR MGI; MGI:108048; Smyd5.
DR VEuPathDB; HostDB:ENSMUSG00000033706; -.
DR eggNOG; KOG2084; Eukaryota.
DR GeneTree; ENSGT00510000047420; -.
DR HOGENOM; CLU_054216_0_0_1; -.
DR InParanoid; Q3TYX3; -.
DR OMA; LMAMYQQ; -.
DR OrthoDB; 1001347at2759; -.
DR PhylomeDB; Q3TYX3; -.
DR TreeFam; TF106419; -.
DR BioGRID-ORCS; 232187; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q3TYX3; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q3TYX3; protein.
DR Bgee; ENSMUSG00000033706; Expressed in otic placode and 226 other tissues.
DR Genevisible; Q3TYX3; MM.
DR GO; GO:0042799; F:histone methyltransferase activity (H4-K20 specific); IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0034773; P:histone H4-K20 trimethylation; IMP:UniProtKB.
DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; IMP:UniProtKB.
DR GO; GO:0010529; P:negative regulation of transposition; IMP:UniProtKB.
DR GO; GO:2000736; P:regulation of stem cell differentiation; IMP:UniProtKB.
DR GO; GO:2000035; P:regulation of stem cell division; IMP:UniProtKB.
DR CDD; cd10521; SET_SMYD5; 1.
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; IPR044422; SMYD5_SET.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW Metal-binding; Methyltransferase; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..416
FT /note="Histone-lysine N-trimethyltransferase SMYD5"
FT /id="PRO_0000227789"
FT DOMAIN 21..351
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT ZN_FING 98..136
FT /note="MYND-type"
FT REGION 383..416
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 387..416
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 350
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT CONFLICT 354
FT /note="C -> R (in Ref. 1; BAE34438)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 416 AA; 47095 MW; 2B9C3DFBF3362AD6 CRC64;
MAASMCDVFS FCVGVADRAR GSVEVRYVDS IKGKGLFATQ LIRKGETIFI ERPLVAAQFL
WNALYQYRAC DHCLRALEKA EENAQRLTGK PSQILPHPEL CSVRKDLHQN CPHCQVMYCS
AECRLAAAEQ YHQILCPGPS HDPRHPLNKL QEAWRSVHYP PETASIMLMA RMVATVKQAK
DKDHWVRLFN HFCSRTANQE QAIVHKLLKG KFKDQLELLL GLFKEALYEE ALSLWFTPEG
FRSLFALVGT NGQGIGTSSL SQWVHACDAL ELTPQDREQL DTFIDQLYKD IEAATGEFLN
CEGSGLFVLQ SCCNHSCVPN AETSFPENNF VLHVTALEDI KPGEEICISY LDCCQRERSR
HSRHKILREN YLFNCSCPKC LAEADDPNVT SEEEEEEDEE EGEPEDAELG DEMTDV
