MES4_CAEEL
ID MES4_CAEEL Reviewed; 898 AA.
AC Q9NH52; Q9XXS4;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Histone-lysine N-methyltransferase mes-4;
DE EC=2.1.1.357 {ECO:0000269|PubMed:16968818};
DE AltName: Full=Maternal-effect sterile protein 4;
GN Name=mes-4 {ECO:0000312|WormBase:Y2H9A.1};
GN ORFNames=Y2H9A.1 {ECO:0000312|WormBase:Y2H9A.1};
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], CHARACTERIZATION, DEVELOPMENTAL STAGE,
RP FUNCTION, MUTAGENESIS OF 877-VAL--ILE-898, AND DISRUPTION PHENOTYPE.
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 [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 FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP 877-VAL--ILE-898, AND DISRUPTION PHENOTYPE.
RX PubMed=16968818; DOI=10.1242/dev.02584;
RA Bender L.B., Suh J., Carroll C.R., Fong Y., Fingerman I.M., Briggs S.D.,
RA Cao R., Zhang Y., Reinke V., Strome S.;
RT "MES-4: an autosome-associated histone methyltransferase that participates
RT in silencing the X chromosomes in the C. elegans germ line.";
RL Development 133:3907-3917(2006).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16507136; DOI=10.1186/gb-2006-7-1-r4;
RA Lehner B., Calixto A., Crombie C., Tischler J., Fortunato A., Chalfie M.,
RA Fraser A.G.;
RT "Loss of LIN-35, the Caenorhabditis elegans ortholog of the tumor
RT suppressor p105Rb, results in enhanced RNA interference.";
RL Genome Biol. 7:R4.1-R4.10(2006).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF HIS-206.
RX PubMed=16710447; DOI=10.1371/journal.pgen.0020074;
RA Cui M., Kim E.B., Han M.;
RT "Diverse chromatin remodeling genes antagonize the Rb-involved SynMuv
RT pathways in C. elegans.";
RL PLoS Genet. 2:E74-E74(2006).
RN [6]
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).
CC -!- FUNCTION: Histone methyltransferase. Dimethylates 'Lys-36' of histone
CC H3, a specific tag for epigenetic transcriptional activation. Plays a
CC central role in early development and is responsible for all H3 'Lys-
CC 36' dimethylation until about the 40-cell stage. Indirectly involved in
CC the global inactivation of the X chromosomes in germline cells,
CC possibly by excluding the mes-2-mes-3-mes-6 repressive Polycomb complex
CC from the autosomes (PubMed:12077420, PubMed:16968818). Not related to
CC transcription elongation (PubMed:12077420, PubMed:16968818). Required
CC for small-RNA-induced H3K27 trimethylation (PubMed:26365259). May
CC suppress sensitivity to RNAi (PubMed:16507136). May regulate the
CC expression of genes required for vulval development (PubMed:16507136,
CC PubMed:16710447). {ECO:0000269|PubMed:12077420,
CC ECO:0000269|PubMed:16507136, ECO:0000269|PubMed:16710447,
CC ECO:0000269|PubMed:16968818, ECO:0000269|PubMed:26365259}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-methionine = 2 H(+)
CC + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60308, Rhea:RHEA-COMP:9785, Rhea:RHEA-
CC COMP:9787, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61976; EC=2.1.1.357;
CC Evidence={ECO:0000269|PubMed:16968818};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16968818}. Chromosome
CC {ECO:0000269|PubMed:16968818}. Note=Specifically associated with the
CC autosomes and with the distal tip of chromosome X. Colocalizes with
CC methylated 'Lys-4' of histone H3.
CC -!- TISSUE SPECIFICITY: In adults, it is predominantly expressed in the
CC germline, and weakly expressed in intestinal cells.
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 in somatic cells, while it is expressed at
CC intermediate levels in the primordial germ cells Z2 and Z3.
CC {ECO:0000269|PubMed:12077420}.
CC -!- DISRUPTION PHENOTYPE: Derepression of X-linked genes in the germline.
CC RNAi-mediated knockdown results in sterility (PubMed:16710447). RNAi-
CC mediated knockdown suppresses the multivulval phenotype of the lin-
CC 15A/B n765 mutant (PubMed:16507136, PubMed:16710447). RNAi-mediated
CC knockdown at 25 degrees Celsius rescues the larval lethality phenotype
CC of the mep-1 (q660) single mutants (PubMed:16710447).
CC {ECO:0000269|PubMed:12077420, ECO:0000269|PubMed:16507136,
CC ECO:0000269|PubMed:16710447, ECO:0000269|PubMed:16968818}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. SET2 subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; AF233290; AAF62516.1; -; mRNA.
DR EMBL; BX284605; CAA16276.2; -; Genomic_DNA.
DR PIR; T26577; T26577.
DR RefSeq; NP_506333.1; NM_073932.4.
DR AlphaFoldDB; Q9NH52; -.
DR BioGRID; 44841; 18.
DR IntAct; Q9NH52; 3.
DR STRING; 6239.Y2H9A.1; -.
DR EPD; Q9NH52; -.
DR PaxDb; Q9NH52; -.
DR PeptideAtlas; Q9NH52; -.
DR PRIDE; Q9NH52; -.
DR EnsemblMetazoa; Y2H9A.1.1; Y2H9A.1.1; WBGene00003222.
DR GeneID; 179824; -.
DR KEGG; cel:CELE_Y2H9A.1; -.
DR UCSC; Y2H9A.1; c. elegans.
DR CTD; 179824; -.
DR WormBase; Y2H9A.1; CE27781; WBGene00003222; mes-4.
DR eggNOG; KOG1081; Eukaryota.
DR HOGENOM; CLU_015168_0_0_1; -.
DR InParanoid; Q9NH52; -.
DR OMA; CYPAGAR; -.
DR OrthoDB; 1008807at2759; -.
DR PhylomeDB; Q9NH52; -.
DR PRO; PR:Q9NH52; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00003222; Expressed in germ line (C elegans) and 5 other tissues.
DR GO; GO:0030849; C:autosome; IDA:WormBase.
DR GO; GO:0000785; C:chromatin; IMP:UniProtKB.
DR GO; GO:0005694; C:chromosome; IDA:WormBase.
DR GO; GO:0000228; C:nuclear chromosome; IDA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000805; C:X chromosome; IDA:WormBase.
DR GO; GO:0042054; F:histone methyltransferase activity; IDA:WormBase.
DR GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); IMP:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0018992; P:germ-line sex determination; IMP:UniProtKB.
DR GO; GO:0031507; P:heterochromatin assembly; IMP:UniProtKB.
DR GO; GO:0010452; P:histone H3-K36 methylation; IMP:UniProtKB.
DR GO; GO:0016571; P:histone methylation; IDA:WormBase.
DR GO; GO:0060820; P:inactivation of X chromosome by heterochromatin assembly; IMP:GO_Central.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:WormBase.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR003616; Post-SET_dom.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00508; PostSET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50868; POST_SET; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; Chromosome; Developmental protein; Metal-binding;
KW Methyltransferase; Nucleus; Reference proteome; Repeat;
KW S-adenosyl-L-methionine; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..898
FT /note="Histone-lysine N-methyltransferase mes-4"
FT /id="PRO_0000186083"
FT DOMAIN 537..665
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 671..687
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT ZN_FING 126..214
FT /note="PHD-type 1"
FT ZN_FING 303..355
FT /note="PHD-type 2"
FT REGION 1..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 689..847
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..50
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 689..705
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 721..815
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 816..830
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 206
FT /note="H->Y: In bn67; suppresses the multivulval phenotype
FT of the lin-15A/B n765 mutant."
FT /evidence="ECO:0000269|PubMed:16710447"
FT MUTAGEN 877..898
FT /note="Missing: In BN87; maternal-effect mutation. Progeny
FT defects in gonad proliferation. Germ cell degeneration.
FT Abolishes histone methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:12077420,
FT ECO:0000269|PubMed:16968818"
SQ SEQUENCE 898 AA; 100065 MW; 0FA6BC754FC9E295 CRC64;
MLPSSGDSSK ENCAPQDGIV EKEGPNKPFK KKNVKQRNAT PQGAGSETSS NAEDKQEEAP
ILTNAPKDII SMQIQETKAF LSEYEEFVDT DYPKTTFTHV PRKFLSVSPF TPIEADAEGE
FLPDADSKCV ICHEEKDKTG KSDLITCHGY INGEMDDGKR LLGNIPMFPC RSKFHASCMI
NYNSGGFHFQ YAARLECQAR LLCPLHCCNS CNLDHHKQSA YVGDIAECAL CLRAFHLTSC
YPSGGRDLNV SITIGGKVEK FEMIICPAHY LPGADVQFYN KHKKRKNAVT VVPKADVTMK
SHIKACCVIG CEKSSNSKTI MCKTCCRSFH SGCREVETLN GKPIPDDQCE SCVCGDPIPQ
NTLILAKWTD NSFWLALTLD WYKYPTGNRG NINFERLGYT VVQWLIPQEN DKEKQPLMSI
VPVSDIARLT KNYFSLAKNS TLRNLWEEKY EEQADTALKR CPYVCKTVFG RLRTSVYYKC
EPKLEEYHNN EVCNCEGADR CTKLSCQYLA DDYECPPSCS KKGVCHNRQV SMGIVSEKIK
LAATLCKGYG VFAKGQIEKD EYICEYVGEI IDKAEKKRRL DSVSISRDFQ ANHYMMELHK
GLTVDAARYG NISRYINHSC DPNAASFVTK VFVKKTKEGS LYDTRSYIRA IRTIDDGDEI
TFSYNMNNEE NLPDCECGAE NCMGTMGKAK REKPEVADSS EKAAKKNKSS KKKSVKNQNR
KSQEAGKNGT ASKKSEISPS KPSTSSASST SFVQQASWPI SQNKKNLKKN SNQPVADTGS
TLSTSTELNF HEKPQELLSP VSSRSRAASS STPRAQKSKS RRDDVESEAP PVKRATPSLQ
TIQETGKAIE FPATKSAITK ARALSTQSVP SPHTVEVKVR AISTRGRVQK ETKRFEPI
