SMYDL_CAEEL
ID SMYDL_CAEEL Reviewed; 507 AA.
AC Q8I4F7; P91821;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Histone-lysine N-methyltransferase set-18 {ECO:0000303|PubMed:29514099};
DE EC=2.1.1.357 {ECO:0000269|PubMed:29514099};
GN Name=set-18 {ECO:0000312|WormBase:T22A3.4b};
GN ORFNames=T22A3.4 {ECO:0000312|WormBase:T22A3.4b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF TYR-245 AND ASP-247.
RX PubMed=29514099; DOI=10.1016/j.celrep.2018.02.029;
RA Su L., Li H., Huang C., Zhao T., Zhang Y., Ba X., Li Z., Zhang Y.,
RA Huang B., Lu J., Zhao Y., Li X.;
RT "Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan
RT of Caenorhabditis elegans by Repressing daf-16a Expression.";
RL Cell Rep. 22:2716-2729(2018).
CC -!- FUNCTION: Histone methyltransferase (PubMed:29514099). Specifically
CC methylates 'Lys-36' of histone H3, inducing di-methylation
CC (PubMed:29514099). Plays a role in modulating lifespan and oxidative
CC stress resistance, in a manner dependent upon daf-16/Forkhead box
CC protein O and the Insulin/IGF-1-like signaling (IIS) mediated pathway
CC (PubMed:29514099). Represses transcription of daf-16 isoform a, perhaps
CC by methylating histone H3 at the daf-16 promoter, which in turn leads
CC to recruitment of histone deacetylases and thus modulation of
CC expression (PubMed:29514099). {ECO:0000269|PubMed:29514099}.
CC -!- CATALYTIC ACTIVITY: [Histone-lysine N-methyltransferase set-18]:
CC Reaction=L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-methionine = 2 H(+)
CC + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60308, Rhea:RHEA-COMP:9785, Rhea:RHEA-
CC COMP:9787, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61976; EC=2.1.1.357;
CC Evidence={ECO:0000269|PubMed:29514099};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:T22A3.4b};
CC IsoId=Q8I4F7-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:T22A3.4a};
CC IsoId=Q8I4F7-2; Sequence=VSP_061521;
CC -!- TISSUE SPECIFICITY: Expressed in pharyngeal and body wall muscles.
CC {ECO:0000269|PubMed:29514099}.
CC -!- DEVELOPMENTAL STAGE: Muscle-specific expression increases in adults
CC between day 3 and day 11. {ECO:0000269|PubMed:29514099}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes lifespan
CC extension. {ECO:0000269|PubMed:29514099}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. {ECO:0000305}.
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DR EMBL; BX284601; CAB03382.1; -; Genomic_DNA.
DR EMBL; BX284601; CAD56600.1; -; Genomic_DNA.
DR PIR; T25093; T25093.
DR RefSeq; NP_492772.1; NM_060371.3.
DR RefSeq; NP_871849.1; NM_182049.4.
DR SMR; Q8I4F7; -.
DR DIP; DIP-24441N; -.
DR IntAct; Q8I4F7; 4.
DR STRING; 6239.T22A3.4b; -.
DR EPD; Q8I4F7; -.
DR PaxDb; Q8I4F7; -.
DR PeptideAtlas; Q8I4F7; -.
DR EnsemblMetazoa; T22A3.4b.1; T22A3.4b.1; WBGene00044070.
DR GeneID; 172949; -.
DR KEGG; cel:CELE_T22A3.4; -.
DR UCSC; T22A3.4b; c. elegans.
DR CTD; 172949; -.
DR WormBase; T22A3.4a; CE13918; WBGene00044070; set-18.
DR WormBase; T22A3.4b; CE32497; WBGene00044070; set-18.
DR eggNOG; KOG2084; Eukaryota.
DR GeneTree; ENSGT00940000167335; -.
DR HOGENOM; CLU_018406_6_0_1; -.
DR InParanoid; Q8I4F7; -.
DR OMA; YRVCLRP; -.
DR OrthoDB; 981799at2759; -.
DR PhylomeDB; Q8I4F7; -.
DR Reactome; R-CEL-3214841; PKMTs methylate histone lysines.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00044070; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR ExpressionAtlas; Q8I4F7; baseline.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:WormBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0030017; C:sarcomere; HDA:WormBase.
DR GO; GO:0055120; C:striated muscle dense body; HDA:WormBase.
DR GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); IDA:WormBase.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0010452; P:histone H3-K36 methylation; IDA:WormBase.
DR GO; GO:0034968; P:histone lysine methylation; IBA:GO_Central.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR002893; Znf_MYND.
DR Pfam; PF01753; zf-MYND; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS01360; ZF_MYND_1; 1.
DR PROSITE; PS50865; ZF_MYND_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Metal-binding; Reference proteome; Transferase; Zinc;
KW Zinc-finger.
FT CHAIN 1..507
FT /note="Histone-lysine N-methyltransferase set-18"
FT /id="PRO_0000455718"
FT ZN_FING 49..90
FT /note="MYND-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
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 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 VAR_SEQ 342..347
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_061521"
FT MUTAGEN 245
FT /note="Y->F: Decreased dimethylation of 'Lys-36' of histone
FT H3."
FT /evidence="ECO:0000269|PubMed:29514099"
FT MUTAGEN 247
FT /note="D->A: Decreased dimethylation of 'Lys-36' of histone
FT H3."
FT /evidence="ECO:0000269|PubMed:29514099"
SQ SEQUENCE 507 AA; 57399 MW; EAB3F5E08D3DEC00 CRC64;
MAVKKNKNVP KQEDPLVQKD EISSIHARIK IFETPFATQV LNPKVSEFCA NCLRGPAPGE
KLLRCGGCNF SMYCSKECQA TAWLVHKPEC KRLKASFPNL PLTEVLFLSK VIDRIQFLEK
NGDKLGIEAE RKFSSLVDHK VDIRDDEEKM AHFEKIFEKM GAFRGEEMIE KGEFFDVFCK
ATINSHSIHT NAGNEVGMAL DLGVSKYNHS CRPTCSMVFD GYRVCLRPLV PGVDAENTEE
AFISYIDVGR SKYIRRRDLN SRWYFNCECT RCMDPEDDAL TAIRCANPAC DAPILTSETE
EPMNIACEKC KTIVEEDTVK AAQEYMKTLP ASFDPKCPAE IEALPGKLKE LLAKAEQILH
PSNVYVARLR TALFHVTGTL TMDNLSSMHT QIYNNYKMCF PKADRHVGFQ LLHIVKALIE
KDERDEAMPY AFDAMNIFEV CFGLDHPYYL QTLALWTYLE KKIPKSTEEL VQLTNFSDNR
PIDIVSLLKR ANMLPPPPYA AGTPGVA
