MET2_CAEEL
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 03-AUG-2022, entry version 152.
DE RecName: Full=Histone-lysine N-methyltransferase met-2;
DE EC=2.1.1.- {ECO:0000305|PubMed:22939621};
DE EC=2.1.1.367 {ECO:0000305|PubMed:22939621};
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., Bonfield J.,
RA Burton J., Connell M., Copsey T., Cooper J., Coulson A., Craxton M.,
RA Dear S., Du Z., Durbin R., Favello A., Fraser A., Fulton L., Gardner A.,
RA Green P., Hawkins T., Hillier L., Jier M., Johnston L., Jones M.,
RA Kershaw J., Kirsten J., Laisster N., Latreille P., Lightning J., Lloyd C.,
RA Mortimore B., O'Callaghan M., Parsons J., Percy C., Rifken L., Roopra A.,
RA Saunders D., Shownkeen R., Sims M., Smaldon N., Smith A., Smith M.,
RA Sonnhammer E., Staden R., Sulston J., Thierry-Mieg J., Thomas K.,
RA Vaudin M., Vaughan K., Waterston R., Watson A., Weinstock L.,
RA Wilkinson-Sproat J., 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 investigating
RT 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 transcription
RT 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 and
RT H3K9me3 chromatin modifications in the Caenorhabditis elegans adult germ
RT 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 male X
RT chromosome from checkpoint machinery and mediates meiotic sex chromosome
RT 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 the
RT 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 instability.";
RL Nat. Genet. 48:1385-1395(2016).
CC -!- FUNCTION: Histone methyltransferase which is required for the mono- and
CC 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 in the
CC transcriptional repression of lin-3 which is required for the negative
CC regulation of vulval cell fate specification during postembryonic
CC development (PubMed:17634190). Has a role in blocking checkpoint
CC signaling and mediating the transcriptional silencing of meiotic sex
CC chromosome inactivation; a mechanism which enables checkpoint proteins
CC to distinguish between the partnerless male X chromosome and asynapsed
CC chromosomes thereby shielding the lone X from inappropriate activation
CC of an apoptotic program (PubMed:21909284). Operates redundantly with
CC set-25 to position chromatin at the nuclear periphery
CC (PubMed:22939621). Required for small-RNA-induced H3K9 methylation
CC (PubMed:26365259). Together with set-25, protects and stabilizes
CC repeat-rich genomic regions by suppressing transcription-induced
CC replication stress through methylation of H3K9 (PubMed:27668659).
CC Together with spr-5, required for transgenerational fertility
CC (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 ECO:0000269|PubMed:26365259, ECO:0000269|PubMed:27668659}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60284, Rhea:RHEA-COMP:15541, Rhea:RHEA-
CC COMP:15542, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000305|PubMed:22939621};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60280, Rhea:RHEA-COMP:15542, Rhea:RHEA-COMP:15546,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.367;
CC Evidence={ECO:0000305|PubMed:22939621};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22939621}. Chromosome
CC {ECO:0000305|PubMed:22939621}. Cytoplasm {ECO:0000269|PubMed:22939621}.
CC -!- DOMAIN: In the pre-SET domain, Cys residues bind 3 zinc ions that are
CC arranged in a triangular cluster; some of these Cys residues contribute
CC to the binding of two zinc ions within the cluster. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Induced vulval precursor cells in the absence of
CC lin-15A (PubMed:15990876). Multi-vulval phenotype is apparent when
CC grown at 24.5 degrees Celsius in the absence of lin-61 and when grown
CC at 20 degrees Celsius in the absence of hpl-2 or met-1
CC (PubMed:17634190, PubMed:21437264). Reduced lamin interaction of
CC chromosome arms in the absence of set-25 (PubMed:22939621). Increased
CC apoptosis and increased occurrence of the recombination checkpoint XO
CC germ lines (PubMed:21909284). High incidence of endomitotic oocytes
CC (PubMed:20107519). In spr-5 null mutants, accelerates the progressive
CC sterility over generations, which is seen in spr-5 mutants with
CC complete sterility achieved by generation 2 (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}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; FO081667; CCD73198.2; -; Genomic_DNA.
DR RefSeq; NP_498848.4; NM_066447.5.
DR AlphaFoldDB; P34544; -.
DR BioGRID; 41387; 4.
DR STRING; 6239.R05D3.11; -.
DR EPD; P34544; -.
DR PaxDb; P34544; -.
DR PeptideAtlas; P34544; -.
DR EnsemblMetazoa; R05D3.11.1; R05D3.11.1; 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 GeneTree; ENSGT00940000169356; -.
DR HOGENOM; CLU_263084_0_0_1; -.
DR InParanoid; P34544; -.
DR OMA; CEELLDW; -.
DR OrthoDB; 405994at2759; -.
DR PhylomeDB; P34544; -.
DR Reactome; R-CEL-3214841; PKMTs methylate histone lysines.
DR PRO; PR:P34544; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00019883; Expressed in germ line (C elegans) and 9 other tissues.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0046974; F:histone methyltransferase activity (H3-K9 specific); IBA:GO_Central.
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:0070828; P:heterochromatin organization; IBA:GO_Central.
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:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; IBA:GO_Central.
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 Gene3D; 2.170.270.10; -; 1.
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 InterPro; IPR046341; SET_dom_sf.
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 SUPFAM; SSF82199; SSF82199; 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; Cytoplasm; Differentiation; Meiosis;
KW Metal-binding; Methyltransferase; Nucleus; Reference proteome; Repeat;
KW S-adenosyl-L-methionine; Sexual differentiation; Transcription;
KW Transcription regulation; Transferase; Zinc.
FT CHAIN 1..1304
FT /note="Histone-lysine N-methyltransferase met-2"
FT /id="PRO_0000186066"
FT DOMAIN 834..909
FT /note="MBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00338"
FT DOMAIN 971..1049
FT /note="Pre-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00157"
FT DOMAIN 1052..1277
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 1286..1302
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1113..1201
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 97..129
FT /evidence="ECO:0000255"
FT COMPBIAS 1127..1141
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1142..1168
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1177..1201
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 973
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 973
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 975
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 979
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 979
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 985
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 987
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1030
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1030
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 1034
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 1036
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 1041
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 1062..1064
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1098
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 1100
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 1231
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 1234..1235
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 1237
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1290
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1292
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 1297
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
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
