MES2_CAEEL
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 03-AUG-2022, entry version 156.
DE RecName: Full=Histone-lysine N-methyltransferase mes-2;
DE EC=2.1.1.356;
DE AltName: Full=E(z) homolog;
DE AltName: Full=Maternal-effect sterile protein 2;
GN Name=mes-2 {ECO:0000312|WormBase:R06A4.7};
GN ORFNames=R06A4.7 {ECO:0000312|WormBase: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; DOI=10.1242/dev.125.13.2457;
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 investigating
RT 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, MES-3,
RT 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 MUTAGENESIS
RP 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 methylation in
RT C. elegans.";
RL Curr. Biol. 14:1639-1643(2004).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17574230; DOI=10.1016/j.ydbio.2007.05.021;
RA Deng H., Sun Y., Zhang Y., Luo X., Hou W., Yan L., Chen Y., Tian E.,
RA Han J., Zhang H.;
RT "Transcription factor NFY globally represses the expression of the C.
RT elegans Hox gene Abdominal-B homolog egl-5.";
RL Dev. Biol. 308:583-592(2007).
RN [7]
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 [8]
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 [9]
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).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=29702639; DOI=10.1371/journal.pgen.1007295;
RA Engert C.G., Droste R., van Oudenaarden A., Horvitz H.R.;
RT "A Caenorhabditis elegans protein with a PRDM9-like SET domain localizes to
RT chromatin-associated foci and promotes spermatocyte gene expression, sperm
RT production and fertility.";
RL PLoS Genet. 14:E1007295-E1007295(2018).
CC -!- FUNCTION: Polycomb group (PcG) protein. Catalytic subunit of a the mes-
CC 2/mes-3/mes-6 complex, which methylates 'Lys-27' of histone H3, leading
CC to transcriptional repression of the affected target genes. PcG
CC proteins act by forming multiprotein complexes, which are required to
CC maintain the transcriptionally repressive state of homeotic genes
CC throughout development. In association with the nfya-1-NF-Y complex,
CC may play a role in repressing the expression of the homeobox protein
CC egl-5 in tissues such as the head (PubMed:17574230). PcG proteins are
CC not required to initiate repression, but to maintain it during later
CC stages of development. The mes-2/mes-3/mes-6 complex may participate in
CC the global inactivation of the X chromosomes in germline cells. This
CC complex is required to exclude mes-4 from the inactivated X-chromosomes
CC in germline cells (PubMed:12077420, PubMed:15380065). Required for
CC small-RNA-induced H3K27 trimethylation (PubMed:26365259). Involved in
CC the negative regulation of lifespan in a germline-independent fashion
CC (PubMed:22212395). {ECO:0000269|PubMed:12077420,
CC ECO:0000269|PubMed:15380065, ECO:0000269|PubMed:17574230,
CC ECO:0000269|PubMed:22212395, ECO:0000269|PubMed:26365259}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(27)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+)
CC + N(6),N(6),N(6)-trimethyl-L-lysyl(27)-[histone H3] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60292, Rhea:RHEA-COMP:15535, Rhea:RHEA-
CC COMP:15548, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.356;
CC -!- SUBUNIT: Interacts directly with mes-6 via its N-terminal domain
CC (PubMed:11320248). Forms a heterotrimeric complex with mes-3 and mes-6
CC (PubMed:11320248, PubMed:15380065). Does not interact with mes-4
CC (PubMed:11320248). {ECO:0000269|PubMed:11320248,
CC ECO:0000269|PubMed:15380065}.
CC -!- INTERACTION:
CC O17514; 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 the
CC germline, and weakly expressed in intestinal cells (PubMed:9609829,
CC PubMed:29702639). Expressed in the hypoderm (PubMed:29702639).
CC {ECO:0000269|PubMed:29702639, 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 larva,
CC it is weakly expressed, while it is expressed at intermediate levels in
CC the germline of L4 larvae. {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 background
CC which lacks a germline (PubMed:22212395). Also leads to reduced
CC H3K27me3 levels on metaphase chromosomes (PubMed:26904949). Double
CC RNAi-mediated knockdown together with mes-6 RNAi results in ectopic
CC expression of the homeobox protein egl-5 in the head region
CC (PubMed:17574230). This ectopic expression of egl-5 in the head region
CC is enhanced in a nfya-1 bp4 mutant background (PubMed:17574230). In
CC addition in this background in males, there is ectopic expression of
CC egl-5 in the mid-body region including in seam cells and hypodermal
CC nuclei, and there is ectopic ray formation (PubMed:17574230).
CC {ECO:0000269|PubMed:17574230, ECO:0000269|PubMed:22212395,
CC ECO:0000269|PubMed:26904949}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. EZ subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; AF011893; AAC27124.1; -; mRNA.
DR EMBL; BX284602; 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 AlphaFoldDB; O17514; -.
DR BioGRID; 40377; 6.
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 EnsemblMetazoa; R06A4.7.1; R06A4.7.1; 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 HOGENOM; CLU_014126_0_0_1; -.
DR InParanoid; O17514; -.
DR OMA; VHWIPIE; -.
DR OrthoDB; 875190at2759; -.
DR PhylomeDB; O17514; -.
DR Reactome; R-CEL-212300; PRC2 methylates histones and DNA.
DR Reactome; R-CEL-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-CEL-8943724; Regulation of PTEN gene transcription.
DR PRO; PR:O17514; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00003220; Expressed in adult organism and 5 other tissues.
DR GO; GO:0035098; C:ESC/E(Z) complex; IBA:GO_Central.
DR GO; GO:0000786; C:nucleosome; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0031519; C:PcG protein complex; IPI:WormBase.
DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR GO; GO:0042054; F:histone methyltransferase activity; IDA:WormBase.
DR GO; GO:0046976; F:histone methyltransferase activity (H3-K27 specific); IMP:WormBase.
DR GO; GO:0006338; P:chromatin remodeling; IEA:InterPro.
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:0031507; P:heterochromatin assembly; IBA:GO_Central.
DR GO; GO:0098532; P:histone H3-K27 trimethylation; IBA:GO_Central.
DR GO; GO:0016571; P:histone methylation; IDA:WormBase.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:ComplexPortal.
DR GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB.
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 GO; GO:0009888; P:tissue development; IMP:UniProtKB.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR026489; CXC_dom.
DR InterPro; IPR045318; EZH1/2-like.
DR InterPro; IPR041355; Pre-SET_CXC.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR PANTHER; PTHR45747; PTHR45747; 2.
DR Pfam; PF18264; preSET_CXC; 1.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS51633; CXC; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Methyltransferase; Nucleus; Reference proteome;
KW Repressor; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1..773
FT /note="Histone-lysine N-methyltransferase mes-2"
FT /id="PRO_0000213994"
FT DOMAIN 505..614
FT /note="CXC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00970"
FT DOMAIN 616..737
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 1..194
FT /note="Interaction with mes-6"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 749..773
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..30
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 749..763
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 628..629
FT /note="SK->PE: In bn48; maternal-effect mutation. Progeny
FT defects in gonad proliferation. Germ cell degeneration.
FT Reduced levels of 'H3-K27Me2' and 'H3-K27Me3'."
FT /evidence="ECO:0000269|PubMed:15380065,
FT ECO:0000269|PubMed:9609829"
FT MUTAGEN 674
FT /note="Y->H: In bn72; maternal-effect mutation. Progeny
FT defects in gonad proliferation. Germ cell degeneration.
FT Reduced levels of 'H3-K27Me2' and 'H3-K27Me3'."
FT /evidence="ECO:0000269|PubMed:15380065,
FT ECO:0000269|PubMed:9609829"
FT CONFLICT 483..484
FT /note="RK -> VQ (in Ref. 1; AAC27124)"
FT /evidence="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
