GenomeNet

Database: UniProt
Entry: Q18221
LinkDB: Q18221
Original site: Q18221 
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   10-APR-2019, entry version 141.
DE   RecName: Full=Histone-lysine N-methyltransferase set-2;
DE            EC=2.1.1.43 {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
RP   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
RT   investigating biology.";
RL   Science 282:2012-2018(1998).
RN   [2]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND ALTERNATIVE
RP   SPLICING.
RX   PubMed=11729150;
RA   Xu L., Strome S.;
RT   "Depletion of a novel SET-domain protein enhances the sterility of
RT   mes-3 and mes-4 mutants of Caenorhabditis elegans.";
RL   Genetics 159:1019-1029(2001).
RN   [3]
RP   FUNCTION.
RX   PubMed=12242227;
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
RT   and 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
RT   connection 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.
RT   elegans 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.,
RA   Lim J.P., Benayoun B.A., Shi Y., Brunet A.;
RT   "Transgenerational epigenetic inheritance of longevity in
RT   Caenorhabditis 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
RT   are differentially required for histone H3 Lys 4 methylation in
RT   embryos and 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).
CC   -!- FUNCTION: Histone methyltransferase that specifically di- and
CC       trimethylates 'Lys-4' of histone H3 at all developmental stages
CC       and in adult germ cells (PubMed:21527717, PubMed:20555324). H3
CC       'Lys-4' methylation represents a specific tag for epigenetic
CC       transcriptional activation (PubMed:21527717). Implicated in the
CC       epigenetic inheritance of lifespan over several generations
CC       (PubMed:22012258). Acts in the germline to limit the longevity of
CC       the soma, probably by regulating a lipid metabolism pathway that
CC       signals from the germline to the intestine, thereby preventing
CC       accumulation of mono-unsaturated fatty acids (PubMed:20555324,
CC       PubMed:28379943). Methylation in the germline is required for
CC       germline development and fertility, possibly by ensuring genome
CC       stability (PubMed:21527717, PubMed:12242227). May act redundantly
CC       with mes-3 and mes-4 proteins in the development of a fertile
CC       germline (PubMed:11729150). Required for RNAi (PubMed:17967446).
CC       Functions as an antagonist of hpl-1 and hpl-2 activity in growth
CC       and somatic gonad development (PubMed:17967446). Cooperates with
CC       jmjd-3.1 and egl-27 to ensure robust transdifferentiation of the Y
CC       rectal cell to the PDA motor neuron during larval development
CC       (PubMed:25124442). {ECO:0000269|PubMed:11729150,
CC       ECO:0000269|PubMed:12242227, ECO:0000269|PubMed:12724425,
CC       ECO:0000269|PubMed:17967446, ECO:0000269|PubMed:20555324,
CC       ECO:0000269|PubMed:21527717, ECO:0000269|PubMed:22012258,
CC       ECO:0000269|PubMed:25124442, ECO:0000269|PubMed:28379943}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43;
CC         Evidence={ECO:0000269|PubMed:20555324,
CC         ECO:0000269|PubMed:21527717};
CC   -!- SUBUNIT: Interacts with wdr-5.1. {ECO:0000269|PubMed:21527717}.
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         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Expressed in all cells of embryo. In L1 larva,
CC       it is predominantly expressed in Z2 and Z3 primordial germ cells.
CC       In 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
CC       disruption of invariant Y-to-PDA transdifferentiation
CC       (PubMed:25124442). Results in decreased trimethylation at 'Lys-4'
CC       of histone H3 (PubMed:20555324). Leads to an extension of lifespan
CC       (PubMed:20555324). Leads to a deregulation of fat metabolism and
CC       to an enrichment of mono-unsaturated fatty acids
CC       (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
CC       methyltransferase superfamily. {ECO:0000255|PROSITE-
CC       ProRule:PRU00190}.
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   UniGene; Cel.8145; -.
DR   ProteinModelPortal; Q18221; -.
DR   SMR; Q18221; -.
DR   BioGrid; 40896; 2.
DR   ELM; Q18221; -.
DR   STRING; 6239.C26E6.9c; -.
DR   EPD; Q18221; -.
DR   PaxDb; Q18221; -.
DR   PeptideAtlas; Q18221; -.
DR   PRIDE; Q18221; -.
DR   EnsemblMetazoa; C26E6.9a; C26E6.9a; WBGene00004782. [Q18221-1]
DR   EnsemblMetazoa; C26E6.9b; C26E6.9b; WBGene00004782. [Q18221-2]
DR   EnsemblMetazoa; C26E6.9c; C26E6.9c; 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   eggNOG; COG2940; LUCA.
DR   GeneTree; ENSGT00940000169211; -.
DR   HOGENOM; HOG000021414; -.
DR   InParanoid; Q18221; -.
DR   KO; K11422; -.
DR   OMA; TIAQDEM; -.
DR   OrthoDB; 1234689at2759; -.
DR   PRO; PR:Q18221; -.
DR   Proteomes; UP000001940; Chromosome III.
DR   Bgee; WBGene00004782; Expressed in 5 organ(s), highest expression level in multi-cellular organism.
DR   GO; GO:0005634; C:nucleus; IDA:WormBase.
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: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; 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; IPR001214; SET_dom.
DR   InterPro; IPR037861; SETD1-like.
DR   PANTHER; PTHR22884:SF464; PTHR22884:SF464; 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   PROSITE; PS50868; POST_SET; 1.
DR   PROSITE; PS50280; SET; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Chromatin regulator; Complete proteome;
KW   Developmental protein; Methyltransferase; Nucleus; Reference proteome;
KW   RNA-binding; S-adenosyl-L-methionine; Transcription;
KW   Transcription regulation; Transferase.
FT   CHAIN         1   1507       Histone-lysine N-methyltransferase set-2.
FT                                /FTId=PRO_0000097695.
FT   DOMAIN      128    199       RRM.
FT   DOMAIN     1368   1485       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   DOMAIN     1491   1507       Post-SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00155}.
FT   COMPBIAS    296    354       Pro-rich.
FT   COMPBIAS    554    664       Pro-rich.
FT   COMPBIAS    870   1011       Ser-rich.
FT   VAR_SEQ       1    768       Missing (in isoform b). {ECO:0000305}.
FT                                /FTId=VSP_007217.
FT   VAR_SEQ     769    831       MDELSRKVAEDIRQQIMRQCFAALDEKLHLKAIADEEKRKK
FT                                EREEKARQEAEKPSNHLIADMM -> MYNNSAPYLNHSSLN
FT                                TVRKKVVTVRRVLPSLPPPPPPPPSLYPPCSVFKVPYIPQR
FT                                VYRSINS (in isoform b). {ECO:0000305}.
FT                                /FTId=VSP_007218.
FT   VAR_SEQ     831    831       M -> MPSQ (in isoform c). {ECO:0000305}.
FT                                /FTId=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
//
DBGET integrated database retrieval system