SET2_CAEEL
ID SET2_CAEEL Reviewed; 1507 AA.
AC Q18221; Q95QU6; Q95QU7;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Histone-lysine N-methyltransferase set-2;
DE EC=2.1.1.- {ECO:0000269|PubMed:20555324, ECO:0000269|PubMed:21527717};
DE AltName: Full=SET domain-containing protein 2;
GN Name=set-2; ORFNames=C26E6.9;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2;
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]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND ALTERNATIVE
RP SPLICING.
RX PubMed=11729150; DOI=10.1093/genetics/159.3.1019;
RA Xu L., Strome S.;
RT "Depletion of a novel SET-domain protein enhances the sterility of mes-3
RT and mes-4 mutants of Caenorhabditis elegans.";
RL Genetics 159:1019-1029(2001).
RN [3]
RP FUNCTION.
RX PubMed=12242227; DOI=10.1093/genetics/162.1.113;
RA Colaiacovo M.P., Stanfield G.M., Reddy K.C., Reinke V., Kim S.K.,
RA Villeneuve A.M.;
RT "A targeted RNAi screen for genes involved in chromosome morphogenesis and
RT nuclear organization in the Caenorhabditis elegans germline.";
RL Genetics 162:113-128(2002).
RN [4]
RP FUNCTION.
RX PubMed=12724425; DOI=10.1128/mcb.23.10.3681-3691.2003;
RA Jedrusik M.A., Schulze E.;
RT "Telomeric position effect variegation in Saccharomyces cerevisiae by
RT Caenorhabditis elegans linker histones suggests a mechanistic connection
RT between germ line and telomeric silencing.";
RL Mol. Cell. Biol. 23:3681-3691(2003).
RN [5]
RP FUNCTION.
RX PubMed=17967446; DOI=10.1016/j.ydbio.2007.09.035;
RA Simonet T., Dulermo R., Schott S., Palladino F.;
RT "Antagonistic functions of SET-2/SET1 and HPL/HP1 proteins in C. elegans
RT development.";
RL Dev. Biol. 312:367-383(2007).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=20555324; DOI=10.1038/nature09195;
RA Greer E.L., Maures T.J., Hauswirth A.G., Green E.M., Leeman D.S.,
RA Maro G.S., Han S., Banko M.R., Gozani O., Brunet A.;
RT "Members of the H3K4 trimethylation complex regulate lifespan in a
RT germline-dependent manner in C. elegans.";
RL Nature 466:383-387(2010).
RN [7]
RP FUNCTION.
RX PubMed=22012258; DOI=10.1038/nature10572;
RA Greer E.L., Maures T.J., Ucar D., Hauswirth A.G., Mancini E., Lim J.P.,
RA Benayoun B.A., Shi Y., Brunet A.;
RT "Transgenerational epigenetic inheritance of longevity in Caenorhabditis
RT elegans.";
RL Nature 479:365-371(2011).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH WDR-5.1.
RX PubMed=21527717; DOI=10.1073/pnas.1019290108;
RA Xiao Y., Bedet C., Robert V.J., Simonet T., Dunkelbarger S.,
RA Rakotomalala C., Soete G., Korswagen H.C., Strome S., Palladino F.;
RT "Caenorhabditis elegans chromatin-associated proteins SET-2 and ASH-2 are
RT differentially required for histone H3 Lys 4 methylation in embryos and
RT adult germ cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:8305-8310(2011).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25124442; DOI=10.1126/science.1255885;
RA Zuryn S., Ahier A., Portoso M., White E.R., Morin M.C., Margueron R.,
RA Jarriault S.;
RT "Sequential histone-modifying activities determine the robustness of
RT transdifferentiation.";
RL Science 345:826-829(2014).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28379943; DOI=10.1038/nature21686;
RA Han S., Schroeder E.A., Silva-Garcia C.G., Hebestreit K., Mair W.B.,
RA Brunet A.;
RT "Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans
RT lifespan.";
RL Nature 544:185-190(2017).
RN [11] {ECO:0000305}
RP IDENTIFICATION IN THE SET2 COMPLEX.
RX PubMed=31602465; DOI=10.1093/nar/gkz880;
RA Beurton F., Stempor P., Caron M., Appert A., Dong Y., Chen R.A., Cluet D.,
RA Coute Y., Herbette M., Huang N., Polveche H., Spichty M., Bedet C.,
RA Ahringer J., Palladino F.;
RT "Physical and functional interaction between SET1/COMPASS complex component
RT CFP-1 and a Sin3S HDAC complex in C. elegans.";
RL Nucleic Acids Res. 47:11164-11180(2019).
CC -!- FUNCTION: Histone methyltransferase that specifically di- and
CC trimethylates 'Lys-4' of histone H3 at all developmental stages and in
CC adult germ cells (PubMed:21527717, PubMed:20555324). H3 'Lys-4'
CC methylation represents a specific tag for epigenetic transcriptional
CC activation (PubMed:21527717). Implicated in the epigenetic inheritance
CC of lifespan over several generations (PubMed:22012258). Acts in the
CC germline to limit the longevity of the soma, probably by regulating a
CC lipid metabolism pathway that signals from the germline to the
CC intestine, thereby preventing accumulation of mono-unsaturated fatty
CC acids (PubMed:20555324, PubMed:28379943). Methylation in the germline
CC is required for germline development and fertility, possibly by
CC ensuring genome stability (PubMed:21527717, PubMed:12242227). May act
CC redundantly with mes-3 and mes-4 proteins in the development of a
CC fertile germline (PubMed:11729150). Required for RNAi
CC (PubMed:17967446). Functions as an antagonist of hpl-1 and hpl-2
CC activity in growth and somatic gonad development (PubMed:17967446).
CC Cooperates with jmjd-3.1 and egl-27 to ensure robust
CC transdifferentiation of the Y rectal cell to the PDA motor neuron
CC during larval development (PubMed:25124442).
CC {ECO:0000269|PubMed:11729150, ECO:0000269|PubMed:12242227,
CC ECO:0000269|PubMed:12724425, ECO:0000269|PubMed:17967446,
CC ECO:0000269|PubMed:20555324, ECO:0000269|PubMed:21527717,
CC ECO:0000269|PubMed:22012258, ECO:0000269|PubMed:25124442,
CC ECO:0000269|PubMed:28379943}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60268, Rhea:RHEA-COMP:15540, Rhea:RHEA-
CC COMP:15543, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000269|PubMed:20555324, ECO:0000269|PubMed:21527717};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-
CC methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3]
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60272, Rhea:RHEA-
CC COMP:15537, Rhea:RHEA-COMP:15540, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961,
CC ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:20555324,
CC ECO:0000269|PubMed:21527717};
CC -!- SUBUNIT: Component of the SET2 complex (also known as the SET1/COMPASS
CC complex), which contains at least set-2, swd-2.1, cfp-1, rbbp-5, wdr-
CC 5.1, dpy-30 and ash-2. {ECO:0000269|PubMed:31602465}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11729150}.
CC Note=Localized in mitotic and mid-late-stage meiotic nuclei but is
CC undetectable in early pachytene nuclei.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a; Synonyms=L;
CC IsoId=Q18221-1; Sequence=Displayed;
CC Name=b; Synonyms=S;
CC IsoId=Q18221-2; Sequence=VSP_007217, VSP_007218;
CC Name=c;
CC IsoId=Q18221-3; Sequence=VSP_038347;
CC -!- TISSUE SPECIFICITY: Expressed in all cells of embryo. In L1 larva, it
CC is predominantly expressed in Z2 and Z3 primordial germ cells. In
CC adults, it is predominantly expressed in the germline.
CC {ECO:0000269|PubMed:11729150}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout embryogenesis.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in disruption of
CC invariant Y-to-PDA transdifferentiation (PubMed:25124442). Results in
CC decreased trimethylation at 'Lys-4' of histone H3 (PubMed:20555324).
CC Leads to an extension of lifespan (PubMed:20555324). Leads to a
CC deregulation of fat metabolism and to an enrichment of mono-unsaturated
CC fatty acids (PubMed:28379943). {ECO:0000269|PubMed:20555324,
CC ECO:0000269|PubMed:25124442, ECO:0000269|PubMed:28379943}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; FO080680; CCD65735.1; -; Genomic_DNA.
DR EMBL; FO080680; CCD65734.1; -; Genomic_DNA.
DR EMBL; FO080680; CCD65736.1; -; Genomic_DNA.
DR PIR; A88445; A88445.
DR RefSeq; NP_498039.1; NM_065638.3. [Q18221-3]
DR RefSeq; NP_498040.1; NM_065639.4. [Q18221-1]
DR RefSeq; NP_498041.1; NM_065640.3. [Q18221-2]
DR AlphaFoldDB; Q18221; -.
DR SMR; Q18221; -.
DR BioGRID; 40896; 3.
DR ELM; Q18221; -.
DR STRING; 6239.C26E6.9c; -.
DR EPD; Q18221; -.
DR PaxDb; Q18221; -.
DR PeptideAtlas; Q18221; -.
DR PRIDE; Q18221; -.
DR EnsemblMetazoa; C26E6.9a.1; C26E6.9a.1; WBGene00004782. [Q18221-1]
DR EnsemblMetazoa; C26E6.9b.1; C26E6.9b.1; WBGene00004782. [Q18221-2]
DR EnsemblMetazoa; C26E6.9c.1; C26E6.9c.1; WBGene00004782. [Q18221-3]
DR GeneID; 175662; -.
DR KEGG; cel:CELE_C26E6.9; -.
DR UCSC; C26E6.9a; c. elegans. [Q18221-1]
DR CTD; 175662; -.
DR WormBase; C26E6.9a; CE27735; WBGene00004782; set-2. [Q18221-1]
DR WormBase; C26E6.9b; CE01158; WBGene00004782; set-2. [Q18221-2]
DR WormBase; C26E6.9c; CE27736; WBGene00004782; set-2. [Q18221-3]
DR eggNOG; KOG1080; Eukaryota.
DR GeneTree; ENSGT00940000169211; -.
DR InParanoid; Q18221; -.
DR OMA; TIAQDEM; -.
DR OrthoDB; 1234689at2759; -.
DR Reactome; R-CEL-3214841; PKMTs methylate histone lysines.
DR Reactome; R-CEL-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR PRO; PR:Q18221; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00004782; Expressed in germ line (C elegans) and 8 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0048188; C:Set1C/COMPASS complex; IBA:GO_Central.
DR GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IDA:WormBase.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0051568; P:histone H3-K4 methylation; IDA:WormBase.
DR GO; GO:0060290; P:transdifferentiation; IMP:WormBase.
DR Gene3D; 2.170.270.10; -; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR024657; COMPASS_Set1_N-SET.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR003616; Post-SET_dom.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR044570; Set1-like.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR PANTHER; PTHR45814; PTHR45814; 1.
DR Pfam; PF00076; RRM_1; 1.
DR Pfam; PF00856; SET; 1.
DR SMART; SM01291; N-SET; 1.
DR SMART; SM00508; PostSET; 1.
DR SMART; SM00360; RRM; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50868; POST_SET; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromatin regulator; Developmental protein;
KW Methyltransferase; Nucleus; Reference proteome; RNA-binding;
KW S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase.
FT CHAIN 1..1507
FT /note="Histone-lysine N-methyltransferase set-2"
FT /id="PRO_0000097695"
FT DOMAIN 128..199
FT /note="RRM"
FT DOMAIN 1368..1485
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 1491..1507
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 280..578
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 650..697
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 803..826
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 842..1058
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1163..1199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..319
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 321..345
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 375..390
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 415..447
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 449..469
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 489..519
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 520..549
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 550..564
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 803..823
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 850..866
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 871..909
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 910..941
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 942..973
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 974..990
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 991..1017
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1018..1048
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1164..1179
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..768
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_007217"
FT VAR_SEQ 769..831
FT /note="MDELSRKVAEDIRQQIMRQCFAALDEKLHLKAIADEEKRKKEREEKARQEAE
FT KPSNHLIADMM -> MYNNSAPYLNHSSLNTVRKKVVTVRRVLPSLPPPPPPPPSLYPP
FT CSVFKVPYIPQRVYRSINS (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_007218"
FT VAR_SEQ 831
FT /note="M -> MPSQ (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_038347"
SQ SEQUENCE 1507 AA; 171683 MW; E7D9689DA720C34A CRC64;
MSTHDMNHHP PRKSHSKRDK PSSSNSGPKI ENHKCKWAWQ KVFETGKSFL RRDGFPQDCK
SKEDFERIKR TGVRKTSENM LEDPRKNFES LQQSSVYQTN SFRNPRYLCR AHLRVDSYYC
TIPPKREVSL FNMDDNCTEV LLRDFAKDCG KVEKAYVCIH PETKRHMKMA YVKFATVKEA
HNFYSMYHAQ NLLATKCTPR IDPFLSILNE EYEVATNGQV LPILPDDLAS IDPSVLRDLR
ANFLRDQNEK YELAMRNTYE DEGGMLSGVI MDTSDHYERD YTMDHDVGPS SMKMSPIPPP
PIKEESPPPP PPPPVASVSN LAPVPSVQLP YYNNIQPSSS TMHMPEFRPT EPPPSYSRED
PYRSTSRSSL SRHRNRSRSP SDGMDRSGRS SSRRTHRRPE SRNGSKNANG DVVKYETYKM
EKRKIKYEGG NKKYEQVHIK ERTAVIRGKN QLENVSSESA SGSSSVDTYP DFSDEERKKK
KRPKSPNRSK KDSRAFGWDS TDESDEDTRR RRSGRSQNRS SERKFQTTSS SSTRRELSST
HTNSVPNLKS HETPPPPPPK GHPSVHLQTP YQHVQPQMIP ATYYNLPPQH MAPPPITTSL
PPFCDFSQPP PGFTPTFKPI TNAPLPTPYQ ASNIPQPGLV QIAALSAAPE PFSSIPGPPP
GPAPIQEDVG RAESPEKPSL SERFSGIFGP TQREEPAQVE VEYDYPLKHS ESHDDRHSLE
DMDVEVSSDG ETVSNVEKIE CMEEKKRQDL ERIAIARTPI VKKCKKRMMD ELSRKVAEDI
RQQIMRQCFA ALDEKLHLKA IADEEKRKKE REEKARQEAE KPSNHLIADM MTLYNNQSFA
SSSRGFYRKQ KPIPKSHPKH QEHHHHAKAS VSTPVHSSST SRNSSVAPTP QRTVSTSSSS
SSAATSARVS EDESDSDSTP GEVQRRKTSV LSNDKRRRRA SFSSTSIQSS PERQRDVSSS
SRTSSSSSTS SMKQEETADE KSRKRKLIMS SDESSTTGST ATSVVSSRQS SLEPQQEKTD
GEPPKKKSQT DFISERVSKI EGEERPLPEP VETSGPIIGD SSYLPYKIVH WEKAGIIEMN
LPANSIRAHE YHPFTTEHCY FGIDDPRQPK IQIFDHSPCK SEPGSEPLKI TPAPWGPIDN
VAETGPLIYM DVVTAPKTVQ KKQKPRKQVF EKDPYEYYEP PPTKRPAPPP RFKKTFKPRS
EEEKKKIIGD CEDLPDLEDQ WYLRAALNEM QSEVKSADEL PWKKMLTFKE MLRSEDPLLR
LNPIRSKKGL PDAFYEDEEL DGVIPVAAGC SRARPYEKMT MKQKRSLVRR PDNESHPTAI
FSERDETAIR HQHLASKDMR LLQRRLLTSL GDANNDFFKI NQLKFRKKMI KFARSRIHGW
GLYAMESIAP DEMIVEYIGQ TIRSLVAEER EKAYERRGIG SSYLFRIDLH HVIDATKRGN
FARFINHSCQ PNCYAKVLTI EGEKRIVIYS RTIIKKGEEI TYDYKFPIED DKIDCLCGAK
TCRGYLN
