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Database: UniProt
Entry: O17514
LinkDB: O17514
Original site: O17514 
ID   MES2_CAEEL              Reviewed;         773 AA.
AC   O17514; O62335;
DT   28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT   28-MAR-2003, sequence version 2.
DT   13-FEB-2019, entry version 140.
DE   RecName: Full=Histone-lysine N-methyltransferase mes-2;
DE            EC=2.1.1.43;
DE   AltName: Full=E(z) homolog;
DE   AltName: Full=Maternal-effect sterile protein 2;
GN   Name=mes-2; ORFNames=R06A4.7;
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 [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP   DEVELOPMENTAL STAGE, AND MUTAGENESIS OF 628-SER-LYS-629 AND TYR-674.
RC   STRAIN=Bristol N2;
RX   PubMed=9609829;
RA   Holdeman R., Nehrt S., Strome S.;
RT   "MES-2, a maternal protein essential for viability of the germline in
RT   Caenorhabditis elegans, is homologous to a Drosophila Polycomb group
RT   protein.";
RL   Development 125:2457-2467(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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   [3]
RP   IDENTIFICATION IN A COMPLEX WITH MES-3 AND MES-6.
RX   PubMed=11320248; DOI=10.1073/pnas.081016198;
RA   Xu L., Fong Y., Strome S.;
RT   "The Caenorhabditis elegans maternal-effect sterile proteins, MES-2,
RT   MES-3, and MES-6, are associated in a complex in embryos.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:5061-5066(2001).
RN   [4]
RP   FUNCTION.
RX   PubMed=12077420; DOI=10.1126/science.1070790;
RA   Fong Y., Bender L., Wang W., Strome S.;
RT   "Regulation of the different chromatin states of autosomes and X
RT   chromosomes in the germ line of C. elegans.";
RL   Science 296:2235-2238(2002).
RN   [5]
RP   FUNCTION, IDENTIFICATION IN A COMPLEX WITH MES-3 AND MES-6, AND
RP   MUTAGENESIS OF 628-SER-LYS-629 AND TYR-674.
RX   PubMed=15380065; DOI=10.1016/j.cub.2004.08.062;
RA   Bender L.B., Cao R., Zhang Y., Strome S.;
RT   "The MES-2/MES-3/MES-6 complex and regulation of histone H3
RT   methylation in C. elegans.";
RL   Curr. Biol. 14:1639-1643(2004).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=22212395; DOI=10.1111/j.1474-9726.2011.00785.x;
RA   Ni Z., Ebata A., Alipanahiramandi E., Lee S.S.;
RT   "Two SET domain containing genes link epigenetic changes and aging in
RT   Caenorhabditis elegans.";
RL   Aging Cell 11:315-325(2012).
RN   [7]
RP   FUNCTION.
RX   PubMed=26365259; DOI=10.1016/j.cub.2015.07.051;
RA   Mao H., Zhu C., Zong D., Weng C., Yang X., Huang H., Liu D., Feng X.,
RA   Guang S.;
RT   "The Nrde pathway mediates small-RNA-directed histone H3 lysine 27
RT   trimethylation in Caenorhabditis elegans.";
RL   Curr. Biol. 25:2398-2403(2015).
RN   [8]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=26904949; DOI=10.1016/j.celrep.2016.01.065;
RA   Lee B.C., Lin Z., Yuen K.W.;
RT   "RbAp46/48(LIN-53) is required for holocentromere assembly in
RT   Caenorhabditis elegans.";
RL   Cell Rep. 14:1819-1828(2016).
CC   -!- FUNCTION: Polycomb group (PcG) protein. Catalytic subunit of a the
CC       mes-2/mes-3/mes-6 complex, which methylates 'Lys-27' of histone
CC       H3, leading to transcriptional repression of the affected target
CC       genes. PcG proteins act by forming multiprotein complexes, which
CC       are required to maintain the transcriptionally repressive state of
CC       homeotic genes throughout development. PcG proteins are not
CC       required to initiate repression, but to maintain it during later
CC       stages of development. The mes-2/mes-3/mes-6 complex may
CC       participate in the global inactivation of the X chromosomes in
CC       germline cells. This complex is required to exclude mes-4 from the
CC       inactivated X-chromosomes in germline cells (PubMed:12077420,
CC       PubMed:15380065). Required for small-RNA-induced H3K27
CC       trimethylation (PubMed:26365259). Involved in the negative
CC       regulation of lifespan in a germline-independent fashion
CC       (PubMed:22212395). {ECO:0000269|PubMed:12077420,
CC       ECO:0000269|PubMed:15380065, ECO:0000269|PubMed:22212395,
CC       ECO:0000269|PubMed:26365259}.
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   -!- SUBUNIT: Interacts directly with mes-6 via its N-terminal domain
CC       (PubMed:11320248). Forms a heterotrimeric complex with mes-3 and
CC       mes-6 (PubMed:11320248, PubMed:15380065). Does not interact with
CC       mes-4 (PubMed:11320248). {ECO:0000269|PubMed:11320248,
CC       ECO:0000269|PubMed:15380065}.
CC   -!- INTERACTION:
CC       Q9GYS1:mes-6; NbExp=5; IntAct=EBI-11615731, EBI-314965;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9609829}.
CC   -!- TISSUE SPECIFICITY: In adults, it is predominantly expressed in
CC       the germline, and weakly expressed in intestinal cells.
CC       {ECO:0000269|PubMed:9609829}.
CC   -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC       Expressed in all cells of early embryos. In late embryos and L1
CC       larva, it is weakly expressed, while it is expressed at
CC       intermediate levels in the germline of L4 larvae.
CC       {ECO:0000269|PubMed:9609829}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in extended
CC       lifespan in wild type worms and in a glp-1(e2141) mutant
CC       background which lacks a germline (PubMed:22212395). Also leads to
CC       reduced H3K27me3 levels on metaphase chromosomes
CC       (PubMed:26904949). {ECO:0000269|PubMed:22212395,
CC       ECO:0000269|PubMed:26904949}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. Histone-lysine methyltransferase
CC       family. EZ subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
DR   EMBL; AF011893; AAC27124.1; -; mRNA.
DR   EMBL; Z83120; CAB05589.2; -; Genomic_DNA.
DR   EMBL; Z81515; CAB05589.2; JOINED; Genomic_DNA.
DR   PIR; T21436; T21436.
DR   RefSeq; NP_496992.3; NM_064591.5.
DR   UniGene; Cel.19654; -.
DR   ProteinModelPortal; O17514; -.
DR   BioGrid; 40377; 2.
DR   ComplexPortal; CPX-368; Polycomb Repressive Complex 2.
DR   IntAct; O17514; 2.
DR   STRING; 6239.R06A4.7; -.
DR   EPD; O17514; -.
DR   PaxDb; O17514; -.
DR   PeptideAtlas; O17514; -.
DR   PRIDE; O17514; -.
DR   EnsemblMetazoa; R06A4.7; R06A4.7; WBGene00003220.
DR   GeneID; 175096; -.
DR   KEGG; cel:CELE_R06A4.7; -.
DR   UCSC; R06A4.7; c. elegans.
DR   CTD; 175096; -.
DR   WormBase; R06A4.7; CE28067; WBGene00003220; mes-2.
DR   eggNOG; KOG1079; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   InParanoid; O17514; -.
DR   KO; K11430; -.
DR   OMA; VHWIPIE; -.
DR   OrthoDB; 875190at2759; -.
DR   PhylomeDB; O17514; -.
DR   Reactome; R-CEL-2559580; Oxidative Stress Induced Senescence.
DR   Reactome; R-CEL-8943724; Regulation of PTEN gene transcription.
DR   Reactome; R-CEL-8953750; Transcriptional Regulation by E2F6.
DR   PRO; PR:O17514; -.
DR   Proteomes; UP000001940; Chromosome II.
DR   Bgee; WBGene00003220; Expressed in 5 organ(s), highest expression level in material anatomical entity.
DR   GO; GO:0000786; C:nucleosome; IDA:WormBase.
DR   GO; GO:0031519; C:PcG protein complex; IPI:WormBase.
DR   GO; GO:0042054; F:histone methyltransferase activity; IDA:WormBase.
DR   GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0007276; P:gamete generation; IMP:WormBase.
DR   GO; GO:0007281; P:germ cell development; IMP:WormBase.
DR   GO; GO:0042078; P:germ-line stem cell division; IMP:WormBase.
DR   GO; GO:0070734; P:histone H3-K27 methylation; IMP:WormBase.
DR   GO; GO:0098532; P:histone H3-K27 trimethylation; IMP:WormBase.
DR   GO; GO:0016571; P:histone methylation; IDA:WormBase.
DR   GO; GO:0007275; P:multicellular organism development; IEA:UniProtKB-KW.
DR   GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:WormBase.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:WormBase.
DR   InterPro; IPR026489; CXC_dom.
DR   InterPro; IPR001214; SET_dom.
DR   Pfam; PF00856; SET; 1.
DR   SMART; SM00317; SET; 1.
DR   PROSITE; PS51633; CXC; 1.
DR   PROSITE; PS50280; SET; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Developmental protein; Methyltransferase; Nucleus;
KW   Reference proteome; Repressor; S-adenosyl-L-methionine; Transcription;
KW   Transcription regulation; Transferase.
FT   CHAIN         1    773       Histone-lysine N-methyltransferase mes-2.
FT                                /FTId=PRO_0000213994.
FT   DOMAIN      505    614       CXC. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00970}.
FT   DOMAIN      616    737       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   REGION        1    194       Interaction with mes-6.
FT   COMPBIAS    531    600       Cys-rich.
FT   MUTAGEN     628    629       SK->PE: In bn48; maternal-effect
FT                                mutation. Progeny defects in gonad
FT                                proliferation. Germ cell degeneration.
FT                                Reduced levels of 'H3-K27Me2' and 'H3-
FT                                K27Me3'. {ECO:0000269|PubMed:15380065,
FT                                ECO:0000269|PubMed:9609829}.
FT   MUTAGEN     674    674       Y->H: In bn72; maternal-effect mutation.
FT                                Progeny defects in gonad proliferation.
FT                                Germ cell degeneration. Reduced levels of
FT                                'H3-K27Me2' and 'H3-K27Me3'.
FT                                {ECO:0000269|PubMed:15380065,
FT                                ECO:0000269|PubMed:9609829}.
FT   CONFLICT    483    484       RK -> VQ (in Ref. 1; AAC27124).
FT                                {ECO:0000305}.
SQ   SEQUENCE   773 AA;  88821 MW;  91ABEBAD94A1D51E CRC64;
     MSNSEPSTST PSGKTKKRGK KCETSMGKSK KSKNLPRFVK IQPIFSSEKI KETVCEQGIE
     ECKRMLKGHF NAIKDDYDIR VKDELDTDIK DWLKDASSSV NEYRRRLQEN LGEGRTIAKF
     SFKNCEKYEE NDYKVSDSTV TWIKPDRTEE GDLMKKFRAP CSRIEVGDIS PPMIYWVPIE
     QSVATPDQLR LTHMPYFGDG IDDGNIYEHL IDMFPDGIHG FSDNWSYVND WILYKLCRAA
     LKDYQGSPDV FYYTLYRLWP NKSSQREFSS AFPVLCENFA EKGFDPSSLE PWKKTKIAEG
     AQNLRNPTCY ACLAYTCAIH GFKAEIPIEF PNGEFYNAML PLPNNPENDG KMCSGNCWKS
     VTMKEVSEVL VPDSEEILQK EVKIYFMKSR IAKMPIEDGA LIVNIYVFNT YIPFCEFVKK
     YVDEDDEESK IRSCRDAYHL MMSMAENVSA RRLKMGQPSN RLSIKDRVNN FRRNQLSQEK
     AKRKLRHDSL RIQALRDGLD AEKLIREDDM RDSQRNSEKV RMTAVTPITA CRHAGPCNAT
     AENCACRENG VCSYMCKCDI NCSQRFPGCN CAAGQCYTKA CQCYRANWEC NPMTCNMCKC
     DAIDSNIIKC RNFGMTRMIQ KRTYCGPSKI AGNGLFLLEP AEKDEFITEY TGERISDDEA
     ERRGAIYDRY QCSYIFNIET GGAIDSYKIG NLARFANHDS KNPTCYARTM VVAGEHRIGF
     YAKRRLEISE ELTFDYSYSG EHQIAFRMVQ TKERSEKPSR PKSQKLSKPM TSE
//
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