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Database: UniProt
Entry: P34544
LinkDB: P34544
Original site: P34544 
ID   MET2_CAEEL              Reviewed;        1304 AA.
AC   P34544; Q8WTP5;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   14-MAY-2014, sequence version 5.
DT   16-JAN-2019, entry version 138.
DE   RecName: Full=Histone-lysine N-methyltransferase met-2;
DE            EC=2.1.1.43;
GN   Name=met-2; ORFNames=R05D3.11;
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].
RC   STRAIN=Bristol N2;
RX   PubMed=7906398; DOI=10.1038/368032a0;
RA   Wilson R., Ainscough R., Anderson K., Baynes C., Berks M.,
RA   Bonfield J., Burton J., Connell M., Copsey T., Cooper J., Coulson A.,
RA   Craxton M., Dear S., Du Z., Durbin R., Favello A., Fraser A.,
RA   Fulton L., Gardner A., Green P., Hawkins T., Hillier L., Jier M.,
RA   Johnston L., Jones M., Kershaw J., Kirsten J., Laisster N.,
RA   Latreille P., Lightning J., Lloyd C., Mortimore B., O'Callaghan M.,
RA   Parsons J., Percy C., Rifken L., Roopra A., Saunders D., Shownkeen R.,
RA   Sims M., Smaldon N., Smith A., Smith M., Sonnhammer E., Staden R.,
RA   Sulston J., Thierry-Mieg J., Thomas K., Vaudin M., Vaughan K.,
RA   Waterston R., Watson A., Weinstock L., Wilkinson-Sproat J.,
RA   Wohldman P.;
RT   "2.2 Mb of contiguous nucleotide sequence from chromosome III of C.
RT   elegans.";
RL   Nature 368:32-38(1994).
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   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=15990876; DOI=10.1038/sj.emboj.7600726;
RA   Poulin G., Dong Y., Fraser A.G., Hopper N.A., Ahringer J.;
RT   "Chromatin regulation and sumoylation in the inhibition of Ras-induced
RT   vulval development in Caenorhabditis elegans.";
RL   EMBO J. 24:2613-2623(2005).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=17634190; DOI=10.1242/dev.009373;
RA   Andersen E.C., Horvitz H.R.;
RT   "Two C. elegans histone methyltransferases repress lin-3 EGF
RT   transcription to inhibit vulval development.";
RL   Development 134:2991-2999(2007).
RN   [5]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=20107519; DOI=10.1371/journal.pgen.1000830;
RA   Bessler J.B., Andersen E.C., Villeneuve A.M.;
RT   "Differential localization and independent acquisition of the H3K9me2
RT   and H3K9me3 chromatin modifications in the Caenorhabditis elegans
RT   adult germ line.";
RL   PLoS Genet. 6:E1000830-E1000830(2010).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=21437264; DOI=10.1371/journal.pgen.1002017;
RA   Koester-Eiserfunke N., Fischle W.;
RT   "H3K9me2/3 binding of the MBT domain protein LIN-61 is essential for
RT   Caenorhabditis elegans vulva development.";
RL   PLoS Genet. 7:E1002017-E1002017(2011).
RN   [7]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=21909284; DOI=10.1371/journal.pgen.1002267;
RA   Checchi P.M., Engebrecht J.;
RT   "Caenorhabditis elegans histone methyltransferase MET-2 shields the
RT   male X chromosome from checkpoint machinery and mediates meiotic sex
RT   chromosome inactivation.";
RL   PLoS Genet. 7:E1002267-E1002267(2011).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=22939621; DOI=10.1016/j.cell.2012.06.051;
RA   Towbin B.D., Gonzalez-Aguilera C., Sack R., Gaidatzis D., Kalck V.,
RA   Meister P., Askjaer P., Gasser S.M.;
RT   "Step-wise methylation of histone H3K9 positions heterochromatin at
RT   the nuclear periphery.";
RL   Cell 150:934-947(2012).
RN   [9]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=24685137; DOI=10.1016/j.celrep.2014.02.044;
RA   Greer E.L., Beese-Sims S.E., Brookes E., Spadafora R., Zhu Y.,
RA   Rothbart S.B., Aristizabal-Corrales D., Chen S., Badeaux A.I., Jin Q.,
RA   Wang W., Strahl B.D., Colaiacovo M.P., Shi Y.;
RT   "A histone methylation network regulates transgenerational epigenetic
RT   memory in C. elegans.";
RL   Cell Rep. 7:113-126(2014).
RN   [10]
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   [11]
RP   FUNCTION.
RX   PubMed=27668659; DOI=10.1038/ng.3672;
RA   Zeller P., Padeken J., van Schendel R., Kalck V., Tijsterman M.,
RA   Gasser S.M.;
RT   "Histone H3K9 methylation is dispensable for Caenorhabditis elegans
RT   development but suppresses RNA:DNA hybrid-associated repeat
RT   instability.";
RL   Nat. Genet. 48:1385-1395(2016).
CC   -!- FUNCTION: Histone methyltransferase which is required for the
CC       mono- and dimethylation of 'Lys-9' of histone H3 (PubMed:20107519,
CC       PubMed:22939621). This increases the efficiency of set-25-mediated
CC       trimethylation of histone H3 'Lys-9' (PubMed:22939621). Involved
CC       in the transcriptional repression of lin-3 which is required for
CC       the negative regulation of vulval cell fate specification during
CC       postembryonic development (PubMed:17634190). Has a role in
CC       blocking checkpoint signaling and mediating the transcriptional
CC       silencing of meiotic sex chromosome inactivation; a mechanism
CC       which enables checkpoint proteins to distinguish between the
CC       partnerless male X chromosome and asynapsed chromosomes thereby
CC       shielding the lone X from inappropriate activation of an apoptotic
CC       program (PubMed:21909284). Operates redundantly with set-25 to
CC       position chromatin at the nuclear periphery (PubMed:22939621).
CC       Required for small-RNA-induced H3K9 methylation (PubMed:26365259).
CC       Together with set-25, protects and stabilizes repeat-rich genomic
CC       regions by suppressing transcription-induced replication stress
CC       through methylation of H3K9 (PubMed:27668659). Together with spr-
CC       5, required for transgenerational fertility (PubMed:24685137).
CC       {ECO:0000269|PubMed:15990876, ECO:0000269|PubMed:17634190,
CC       ECO:0000269|PubMed:20107519, ECO:0000269|PubMed:21437264,
CC       ECO:0000269|PubMed:21909284, ECO:0000269|PubMed:22939621,
CC       ECO:0000269|PubMed:24685137, ECO:0000269|PubMed:26365259,
CC       ECO:0000269|PubMed:27668659}.
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   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22939621}.
CC       Chromosome {ECO:0000305|PubMed:22939621}. Cytoplasm
CC       {ECO:0000269|PubMed:22939621}.
CC   -!- DOMAIN: In the pre-SET domain, Cys residues bind 3 zinc ions that
CC       are arranged in a triangular cluster; some of these Cys residues
CC       contribute to the binding of two zinc ions within the cluster.
CC       {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Induced vulval precursor cells in the
CC       absence of lin-15A (PubMed:15990876). Multi-vulval phenotype is
CC       apparent when grown at 24.5 degrees Celsius in the absence of lin-
CC       61 and when grown at 20 degrees Celsius in the absence of hpl-2 or
CC       met-1 (PubMed:17634190, PubMed:21437264). Reduced lamin
CC       interaction of chromosome arms in the absence of set-25
CC       (PubMed:22939621). Increased apoptosis and increased occurrence of
CC       the recombination checkpoint XO germ lines (PubMed:21909284). High
CC       incidence of endomitotic oocytes (PubMed:20107519). In spr-5 null
CC       mutants, accelerates the progressive sterility over generations,
CC       which is seen in spr-5 mutants with complete sterility achieved by
CC       generation 2 (PubMed:24685137). {ECO:0000269|PubMed:15990876,
CC       ECO:0000269|PubMed:17634190, ECO:0000269|PubMed:20107519,
CC       ECO:0000269|PubMed:21437264, ECO:0000269|PubMed:21909284,
CC       ECO:0000269|PubMed:22939621, ECO:0000269|PubMed:24685137}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. {ECO:0000255|PROSITE-
CC       ProRule:PRU00190}.
DR   EMBL; FO081667; CCD73198.2; -; Genomic_DNA.
DR   RefSeq; NP_498848.4; NM_066447.5.
DR   SMR; P34544; -.
DR   STRING; 6239.R05D3.11; -.
DR   EPD; P34544; -.
DR   PaxDb; P34544; -.
DR   PeptideAtlas; P34544; -.
DR   PRIDE; P34544; -.
DR   EnsemblMetazoa; R05D3.11; R05D3.11; WBGene00019883.
DR   GeneID; 176183; -.
DR   KEGG; cel:CELE_R05D3.11; -.
DR   UCSC; R05D3.11; c. elegans.
DR   CTD; 176183; -.
DR   WormBase; R05D3.11; CE47959; WBGene00019883; met-2.
DR   eggNOG; KOG1141; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   GeneTree; ENSGT00940000169356; -.
DR   HOGENOM; HOG000021401; -.
DR   InParanoid; P34544; -.
DR   KO; K11421; -.
DR   OMA; FICTYVG; -.
DR   OrthoDB; 405994at2759; -.
DR   PRO; PR:P34544; -.
DR   Proteomes; UP000001940; Chromosome III.
DR   Bgee; WBGene00019883; Expressed in 5 organ(s), highest expression level in multi-cellular organism.
DR   GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR   GO; GO:0005634; C:nucleus; IC:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR   GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IC:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0010452; P:histone H3-K36 methylation; IMP:WormBase.
DR   GO; GO:0051567; P:histone H3-K9 methylation; IMP:WormBase.
DR   GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR   GO; GO:0045835; P:negative regulation of meiotic nuclear division; IMP:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:WormBase.
DR   GO; GO:0040027; P:negative regulation of vulval development; IGI:WormBase.
DR   GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:WormBase.
DR   GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0072325; P:vulval cell fate commitment; IMP:UniProtKB.
DR   InterPro; IPR016177; DNA-bd_dom_sf.
DR   InterPro; IPR001739; Methyl_CpG_DNA-bd.
DR   InterPro; IPR003616; Post-SET_dom.
DR   InterPro; IPR007728; Pre-SET_dom.
DR   InterPro; IPR001214; SET_dom.
DR   Pfam; PF01429; MBD; 1.
DR   Pfam; PF05033; Pre-SET; 1.
DR   Pfam; PF00856; SET; 1.
DR   SMART; SM00391; MBD; 1.
DR   SMART; SM00508; PostSET; 1.
DR   SMART; SM00468; PreSET; 1.
DR   SMART; SM00317; SET; 1.
DR   SUPFAM; SSF54171; SSF54171; 1.
DR   PROSITE; PS50982; MBD; 1.
DR   PROSITE; PS50868; POST_SET; 1.
DR   PROSITE; PS50867; PRE_SET; 1.
DR   PROSITE; PS50280; SET; 1.
PE   3: Inferred from homology;
KW   Chromosome; Coiled coil; Complete proteome; Cytoplasm;
KW   Differentiation; Meiosis; Metal-binding; Methyltransferase; Nucleus;
KW   Reference proteome; Repeat; S-adenosyl-L-methionine;
KW   Sexual differentiation; Transcription; Transcription regulation;
KW   Transferase; Zinc.
FT   CHAIN         1   1304       Histone-lysine N-methyltransferase met-2.
FT                                /FTId=PRO_0000186066.
FT   DOMAIN      834    909       MBD. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00338}.
FT   DOMAIN      971   1049       Pre-SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00157}.
FT   DOMAIN     1052   1277       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   DOMAIN     1286   1302       Post-SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00155}.
FT   REGION     1062   1064       S-adenosyl-L-methionine binding.
FT                                {ECO:0000250}.
FT   REGION     1234   1235       S-adenosyl-L-methionine binding.
FT                                {ECO:0000250}.
FT   COILED       97    129       {ECO:0000255}.
FT   METAL       973    973       Zinc 1. {ECO:0000250}.
FT   METAL       973    973       Zinc 2. {ECO:0000250}.
FT   METAL       975    975       Zinc 1. {ECO:0000250}.
FT   METAL       979    979       Zinc 1. {ECO:0000250}.
FT   METAL       979    979       Zinc 3. {ECO:0000250}.
FT   METAL       985    985       Zinc 1. {ECO:0000250}.
FT   METAL       987    987       Zinc 2. {ECO:0000250}.
FT   METAL      1030   1030       Zinc 2. {ECO:0000250}.
FT   METAL      1030   1030       Zinc 3. {ECO:0000250}.
FT   METAL      1034   1034       Zinc 2. {ECO:0000250}.
FT   METAL      1036   1036       Zinc 3. {ECO:0000250}.
FT   METAL      1041   1041       Zinc 3. {ECO:0000250}.
FT   METAL      1237   1237       Zinc 4. {ECO:0000250}.
FT   METAL      1290   1290       Zinc 4. {ECO:0000250}.
FT   METAL      1292   1292       Zinc 4. {ECO:0000250}.
FT   METAL      1297   1297       Zinc 4. {ECO:0000250}.
FT   BINDING    1098   1098       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
FT   BINDING    1100   1100       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
FT   BINDING    1231   1231       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
SQ   SEQUENCE   1304 AA;  148155 MW;  E7D229260AF88A20 CRC64;
     MDQQEPSNNV DTSSILSDDG METQEQSSFV TATIDLTVDD YDETEIQEIL DNGKAEEGTD
     EDSDLVEGIL NANSDVQALL DAPSEQVAQA LNSFFGNESE QEAVAAQRRV DAEKTAKDEA
     ELKQQEEAED LIIEDSIVKT DEEKQAVRRL KINEFLSWFT RLLPEQFKNF EFTNPNYLTE
     SISDSPVVNV DKCKEIVKSF KESESLEGLS QKYELIDEDV LVAAICIGVL DTNNEEDVDF
     NVLCDDRIDD WSIEKCVTFL DYPNTGLNSK NGPLRFMQFT VTSPASAILM LTLIRLREEG
     HPCRLDFDSN PTDDLLLNFD QVEFSNNIID TAVKYWDDQK ENGAQDKIGR ELNDFFHEIE
     STSAEFKQHF ENAVGSRNEI IQLVNEKIPD FDGTEAAVNE SFTSDQRTEI INSRAIMETL
     KAEMKLAIAE AQKVYDTKTD FEKFFVLTVG DFCLARANPS DDAELTYAIV QDRVDAMTYK
     VKFIDTSQIR ECNIRDLAMT TQGMYDPSLN TFGDVGLRVA CRQVISSSQF GKKTIWLTGT
     AAGRRRAHRS DFLIFFDNGT DAYVSAPTMP GEPGYEVASE KKSVFSLKEM IAKMNAAQIA
     IMVGQPVGKE GNLDYFLTFH WIRQSHRSAY IRDFMKEFPE WPLLKMPVGM RICLYNSLVD
     RRKKMVTVIG TDRAFAIVRH EAPNPLAPGN RCTDFPCNDR NHQHIDEKIY RGSHRLEGAA
     HKKHMISTNN NLSQRRKDQL QSQFEPTDMI RSMPERNHQQ VVKKKTTGTN QNVASTNDAK
     SKREIEIRKK NQFLFNKIIV PIPVLTPLEN LKAHAQCGPD CLQKMDADPY EARFHRNSPI
     HTPLLCGWRR IMYTMSTGKK RGAVKKNIIY FSPCGAALHQ ISDVSEYIHV TRSLLTIDCF
     SFDARIDTAT YITVDDKYLK VADFSLGTEG IPIPLVNSVD NDEPPSLEYS KRRFQYNDQV
     DISSVSRDFC SGCSCDGDCS DASKCECQQL SIEAMKRLPH NLQFDGHDEL VPHYQNRLLS
     SKVISGLYEC NDQCSCHRKS CYNRVVQNNI KYPMHIFKTA QSGWGVRALT DIPQSTFICT
     YVGAILTDDL ADELRNADQY FADLDLKDTV ELEKGREDHE TDFGYGGDES DYDDEEGSDG
     DSGDDVMNKM VKRQDSSESG EETKRLTRQK RKQSKKSGKG GSVEKDDTTP RDSMEKDNIE
     SKDEPVFNWD KYFEPFPLYV IDAKQRGNLG RFLNHSCDPN VHVQHVMYDT HDLRLPWVAF
     FTRKYVKAGD ELTWDYQYTQ DQTATTQLTC HCGAENCTGR LLKS
//
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