SET6_CAEEL
ID SET6_CAEEL Reviewed; 708 AA.
AC O17679;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Histone-lysine N-methyltransferase set-6 {ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:32103178};
DE EC=2.1.1.366 {ECO:0000269|PubMed:32103178};
GN Name=set-6 {ECO:0000312|WormBase:C49F5.2};
GN ORFNames=C49F5.2 {ECO:0000312|WormBase:C49F5.2};
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, INTERACTION WITH BAZ-2, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=32103178; DOI=10.1038/s41586-020-2037-y;
RA Yuan J., Chang S.Y., Yin S.G., Liu Z.Y., Cheng X., Liu X.J., Jiang Q.,
RA Gao G., Lin D.Y., Kang X.L., Ye S.W., Chen Z., Yin J.A., Hao P., Jiang L.,
RA Cai S.Q.;
RT "Two conserved epigenetic regulators prevent healthy ageing.";
RL Nature 579:118-122(2020).
CC -!- FUNCTION: Histone methyltransferase that specifically di- and
CC trimethylates 'Lys-9' of histone H3 (H3K9me2 and H3K9me3,
CC respectively); involved in positively modulating the rate of age-
CC related behavioral deterioration (PubMed:32103178). May repress the
CC expression of mitochondrial function-related genes by occupying their
CC promoter regions, working in concert with probable chromatin reader
CC protein, baz-2 (PubMed:32103178). Involved in modulation of the
CC mitochondrial unfolded protein response (UPR) (PubMed:32103178).
CC Regulates level of expression of bas-1, a serotonin (5-HT) and dopamine
CC synthesizing enzyme (DOPA decarboxylase) (PubMed:32103178). Negatively
CC modulates levels of endogenous 5-HT and dopamine with aging
CC (PubMed:32103178). Involved in modulating longevity, probably as a
CC result of enhanced stress resistance via mechanisms related to dietary
CC restriction and mitochondrial function (PubMed:32103178).
CC {ECO:0000269|PubMed:32103178}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60284, Rhea:RHEA-COMP:15541, Rhea:RHEA-
CC COMP:15542, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000269|PubMed:32103178};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-
CC methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3]
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60288, Rhea:RHEA-
CC COMP:15538, Rhea:RHEA-COMP:15541, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961,
CC ChEBI:CHEBI:61976; EC=2.1.1.366;
CC Evidence={ECO:0000269|PubMed:32103178};
CC -!- SUBUNIT: Interacts with baz-2. {ECO:0000269|PubMed:32103178}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:32103178}. Chromosome
CC {ECO:0000269|PubMed:32103178}.
CC -!- TISSUE SPECIFICITY: Broadly expressed in the nervous system, including
CC head, body and tail neurons. {ECO:0000269|PubMed:32103178}.
CC -!- DEVELOPMENTAL STAGE: Expression increases with age.
CC {ECO:0000269|PubMed:32103178}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown prevents age-related
CC decline in the expression of bas-1, a serotonin (5-HT) and dopamine
CC synthesizing enzyme (DOPA decarboxylase) (PubMed:32103178). RNAi-
CC mediated knockdown improves behavioral performance in pharyngeal
CC pumping in aged worms (PubMed:32103178). {ECO:0000269|PubMed:32103178}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; BX284606; CAB03974.2; -; Genomic_DNA.
DR PIR; T20069; T20069.
DR RefSeq; NP_510003.2; NM_077602.4.
DR AlphaFoldDB; O17679; -.
DR IntAct; O17679; 2.
DR STRING; 6239.C49F5.2; -.
DR EPD; O17679; -.
DR PaxDb; O17679; -.
DR EnsemblMetazoa; C49F5.2.1; C49F5.2.1; WBGene00008206.
DR GeneID; 181371; -.
DR KEGG; cel:CELE_C49F5.2; -.
DR UCSC; C49F5.2; c. elegans.
DR CTD; 181371; -.
DR WormBase; C49F5.2; CE31454; WBGene00008206; set-6.
DR eggNOG; KOG1082; Eukaryota.
DR GeneTree; ENSGT00970000195973; -.
DR HOGENOM; CLU_389923_0_0_1; -.
DR InParanoid; O17679; -.
DR OMA; CENADAP; -.
DR OrthoDB; 1352508at2759; -.
DR PhylomeDB; O17679; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00008206; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0000785; C:chromatin; IMP:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0042054; F:histone methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0051567; P:histone H3-K9 methylation; IMP:UniProtKB.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_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 Chromosome; Methyltransferase; Nucleus; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..708
FT /note="Histone-lysine N-methyltransferase set-6"
FT /id="PRO_0000452178"
FT DOMAIN 455..599
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 36..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 127..142
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 598
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
SQ SEQUENCE 708 AA; 82093 MW; CF4B968F8BB88312 CRC64;
MERSRTGGSS TYSMSTANVP IITISDDDDE LTIWEEPRKS PISSNSYSDE RNHSLSSTSN
SSVERSIIIT ISDDESEATE RNQQEVVDRA ISNNLTEKRR RSVESFHRLH SKERKLEVKS
RKKSRTSSSS MEASTSCTFP ARQTKTKRHK RKTYSTISSF APHHSTICAE LRNVNPARIA
DFRHPSIFEY SDMSLNERRE HWKKEMKVIK KHNDIRLMHE EAVRFDDIIE LDPTLNGYYR
RFMGAEQSTR ALFMAVRCLA TFGRNFYEEP ERDHGEEEIP EELDRYFEKL IYVAPRTRIR
ITDDIHLSND THRIPVYTDA KGETLKTVKI PNPLLYDHII NNMVDKVKEP LLYEAIKIAG
SSENVIRCKC CSQDPVVNCF DNKDCPCFIA NQFLQSRNKT TDTNEKLKFH TFQPLMYNDG
NPTYYNTVGF ACSPKCACKG ACTNNATYLI QKKLYSIEIY RADPQIGFGI RSTLFIPAGT
PIIEYCGELV DGERLHSSLE NYSYQLTDCE GDKHLYNLLR EKYKNNPEYY DVLDELSKHH
FHLDAKMQGS VGRFANHSCT PNMEPLRLFK EGFTPANMRM IFFTLKDIFP GEPLTLDYGS
EYKVFRRQRC LCRTFACRSG PHYEKFSNLD GKLIASCFVR LHHASRIRYS VDLQLIERFY
SVGKVEEVRV DPCVSFSKYN LKWRRQLSTA TCERLENVIE IELSDEDS
