SMYD5_HUMAN
ID SMYD5_HUMAN Reviewed; 418 AA.
AC Q6GMV2; D6W5H3; Q13558;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Histone-lysine N-trimethyltransferase SMYD5;
DE EC=2.1.1.372 {ECO:0000250|UniProtKB:Q3TYX3};
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 7-418.
RC TISSUE=Brain;
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].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [5]
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).
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 (By similarity). In association with the
CC NCoR corepressor complex, is involved in the repression of toll-like
CC receptor 4 (TLR4)-target inflammatory genes in macrophages by
CC catalyzing the formation of H4K20me3 at the gene promoters (By
CC similarity). Plays an important role in embryonic stem (ES) cell self-
CC renewal and differentiation (By similarity). Promotes ES cell
CC maintenance by silencing differentiation genes through deposition of
CC H4K20me3 marks (By similarity). Maintains genome stability of ES cells
CC during differentiation through regulation of heterochromatin formation
CC and repression of endogenous repetitive DNA elements by depositing
CC H4K20me3 marks (PubMed:28951459). {ECO:0000250|UniProtKB:Q3TYX3,
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:0000250|UniProtKB:Q3TYX3};
CC -!- SUBUNIT: Interacts with the N-CoR complex (By similarity). Interacts
CC with EHMT2 and CBX5 (By similarity). {ECO:0000250|UniProtKB:Q3TYX3}.
CC -!- INTERACTION:
CC Q6GMV2; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-11057552, EBI-740727;
CC Q6GMV2; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-11057552, EBI-6427977;
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH73806.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; CH471053; EAW99744.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99745.1; -; Genomic_DNA.
DR EMBL; BC073806; AAH73806.1; ALT_INIT; mRNA.
DR EMBL; U50383; AAB38131.1; -; mRNA.
DR CCDS; CCDS33221.2; -.
DR PIR; G02453; G02453.
DR RefSeq; NP_006053.2; NM_006062.2.
DR AlphaFoldDB; Q6GMV2; -.
DR SMR; Q6GMV2; -.
DR BioGRID; 115606; 22.
DR IntAct; Q6GMV2; 8.
DR MINT; Q6GMV2; -.
DR STRING; 9606.ENSP00000374152; -.
DR GlyGen; Q6GMV2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6GMV2; -.
DR PhosphoSitePlus; Q6GMV2; -.
DR BioMuta; SMYD5; -.
DR DMDM; 90101758; -.
DR EPD; Q6GMV2; -.
DR jPOST; Q6GMV2; -.
DR MassIVE; Q6GMV2; -.
DR MaxQB; Q6GMV2; -.
DR PaxDb; Q6GMV2; -.
DR PeptideAtlas; Q6GMV2; -.
DR PRIDE; Q6GMV2; -.
DR ProteomicsDB; 66304; -.
DR Antibodypedia; 31318; 232 antibodies from 26 providers.
DR DNASU; 10322; -.
DR Ensembl; ENST00000389501.9; ENSP00000374152.4; ENSG00000135632.12.
DR GeneID; 10322; -.
DR KEGG; hsa:10322; -.
DR MANE-Select; ENST00000389501.9; ENSP00000374152.4; NM_006062.3; NP_006053.2.
DR UCSC; uc002siw.3; human.
DR CTD; 10322; -.
DR DisGeNET; 10322; -.
DR GeneCards; SMYD5; -.
DR HGNC; HGNC:16258; SMYD5.
DR HPA; ENSG00000135632; Low tissue specificity.
DR MIM; 619114; gene.
DR neXtProt; NX_Q6GMV2; -.
DR OpenTargets; ENSG00000135632; -.
DR PharmGKB; PA34190; -.
DR VEuPathDB; HostDB:ENSG00000135632; -.
DR eggNOG; KOG2084; Eukaryota.
DR GeneTree; ENSGT00510000047420; -.
DR HOGENOM; CLU_054216_0_0_1; -.
DR InParanoid; Q6GMV2; -.
DR OMA; LMAMYQQ; -.
DR OrthoDB; 1001347at2759; -.
DR PhylomeDB; Q6GMV2; -.
DR TreeFam; TF106419; -.
DR PathwayCommons; Q6GMV2; -.
DR SignaLink; Q6GMV2; -.
DR BioGRID-ORCS; 10322; 10 hits in 1087 CRISPR screens.
DR ChiTaRS; SMYD5; human.
DR GenomeRNAi; 10322; -.
DR Pharos; Q6GMV2; Tbio.
DR PRO; PR:Q6GMV2; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q6GMV2; protein.
DR Bgee; ENSG00000135632; Expressed in cortical plate and 125 other tissues.
DR ExpressionAtlas; Q6GMV2; baseline and differential.
DR Genevisible; Q6GMV2; HS.
DR GO; GO:0042799; F:histone methyltransferase activity (H4-K20 specific); ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0034773; P:histone H4-K20 trimethylation; ISS:UniProtKB.
DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; ISS: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; ISS:UniProtKB.
DR CDD; cd10521; SET_SMYD5; 1.
DR Gene3D; 2.170.270.10; -; 2.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR044422; SMYD5_SET.
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..418
FT /note="Histone-lysine N-trimethyltransferase SMYD5"
FT /id="PRO_0000227788"
FT DOMAIN 21..352
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT ZN_FING 98..136
FT /note="MYND-type"
FT REGION 385..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 388..418
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 351
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT CONFLICT 7
FT /note="D -> A (in Ref. 3; AAB38131)"
FT /evidence="ECO:0000305"
FT CONFLICT 280..281
FT /note="QL -> HV (in Ref. 3; AAB38131)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 418 AA; 47341 MW; 11073818FF5EEB83 CRC64;
MAASMCDVFS FCVGVAGRAR VSVEVRFVSS AKGKGLFATQ LIRKGETIFV ERPLVAAQFL
WNALYRYRAC DHCLRALEKA EENAQRLTGK PGQVLPHPEL CTVRKDLHQN CPHCQVMYCS
AECRLAATEQ YHQVLCPGPS QDDPLHPLNK LQEAWRSIHY PPETASIMLM ARMVATVKQA
KDKDRWIRLF SQFCNKTANE EEEIVHKLLG DKFKGQLELL RRLFTEALYE EAVSQWFTPD
GFRSLFALVG TNGQGIGTSS LSQWVHACDT LELKPQDREQ LDAFIDQLYK DIEAATGEFL
NCEGSGLFVL QSCCNHSCVP NAETSFPENN FLLHVTALED IKPGEEICIS YLDCCQRERS
RHSRHKILRE NYLFVCSCPK CLAEADEPNV TSEEEEEEEE EEEGEPEDAE LGDEMTDV
