SET25_CAEEL
ID SET25_CAEEL Reviewed; 714 AA.
AC G5EEU2;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Histone-lysine N-methyltransferase set-25 {ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:22939621};
DE EC=2.1.1.366 {ECO:0000269|PubMed:22939621};
DE AltName: Full=Histone H3-K9 methyltransferase set-25 {ECO:0000305};
GN Name=set-25 {ECO:0000312|WormBase:Y43F4B.3};
GN ORFNames=Y43F4B.3 {ECO:0000312|WormBase:Y43F4B.3};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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 [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS
RP OF CYS-645.
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 [3] {ECO:0000305}
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 [4] {ECO:0000305}
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 that specifically trimethylates
CC 'Lys-9' of histone H3 using mono- and dimethylated H3 'Lys-9' as
CC substrate (PubMed:22939621). Acts redundantly with the
CC methyltransferase met-2 to position chromosome arms at the nuclear
CC lamina (PubMed:22939621). Required for small-RNA-induced H3K9
CC methylation (PubMed:26365259). Together with met-2, protects and
CC stabilizes repeat-rich genomic regions by suppressing transcription-
CC induced replication stress through methylation of H3K9
CC (PubMed:27668659). {ECO:0000269|PubMed:22939621,
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:0000269|PubMed:22939621};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-
CC methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3]
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60288, Rhea:RHEA-
CC COMP:15538, Rhea:RHEA-COMP:15541, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961,
CC ChEBI:CHEBI:61976; EC=2.1.1.366;
CC Evidence={ECO:0000269|PubMed:22939621};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22939621}. Chromosome
CC {ECO:0000269|PubMed:22939621}. Nucleus lamina
CC {ECO:0000269|PubMed:22939621}. Note=Colocalizes with its own product
CC and hpl-1 in foci in the peripheral region of the nucleus, in a manner
CC dependent on H3K9me3. {ECO:0000269|PubMed:22939621}.
CC -!- DOMAIN: The SET domain is not required for localization to nuclear
CC foci. {ECO:0000269|PubMed:22939621}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU00190}.
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DR EMBL; BX284603; CAA16332.3; -; Genomic_DNA.
DR RefSeq; NP_499738.3; NM_067337.4.
DR AlphaFoldDB; G5EEU2; -.
DR STRING; 6239.Y43F4B.3; -.
DR EPD; G5EEU2; -.
DR PaxDb; G5EEU2; -.
DR PRIDE; G5EEU2; -.
DR EnsemblMetazoa; Y43F4B.3.1; Y43F4B.3.1; WBGene00012802.
DR GeneID; 3565129; -.
DR KEGG; cel:CELE_Y43F4B.3; -.
DR CTD; 3565129; -.
DR WormBase; Y43F4B.3; CE41469; WBGene00012802; set-25.
DR eggNOG; KOG1082; Eukaryota.
DR HOGENOM; CLU_018364_1_0_1; -.
DR InParanoid; G5EEU2; -.
DR OMA; ITIAYYE; -.
DR OrthoDB; 753093at2759; -.
DR PRO; PR:G5EEU2; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00012802; Expressed in embryo and 9 other tissues.
DR GO; GO:0000792; C:heterochromatin; IDA:WormBase.
DR GO; GO:0005652; C:nuclear lamina; IEA:UniProtKB-SubCell.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0042054; F:histone methyltransferase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016571; P:histone methylation; IBA:GO_Central.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW Chromosome; Metal-binding; Methyltransferase; Nucleus; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; Zinc.
FT CHAIN 1..714
FT /note="Histone-lysine N-methyltransferase set-25"
FT /id="PRO_0000438541"
FT DOMAIN 547..687
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 696..712
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT REGION 1..214
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 586..611
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..39
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 41..56
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..85
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 112..127
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 131..156
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 169..184
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 595..611
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 645
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190,
FT ECO:0000305"
FT BINDING 686
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 700
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT BINDING 702
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT BINDING 707
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT MUTAGEN 645
FT /note="C->A: No effect on localization to nuclear foci."
FT /evidence="ECO:0000269|PubMed:22939621"
SQ SEQUENCE 714 AA; 79618 MW; 9FE70D1209CA0D41 CRC64;
MLPAWGTSTE ATASHAGWDG DDEGDIRAAY TEDEKKENIP PISLTSVSTN GAYPGQKRRR
SESVRTLKPE CPPEETQRLR QRRRISATDA TQSSRTMNVI EDRKPRVNRA RKSQDAPSTS
TCGFETPVGT KRKSKAADSQ KPPKQSKLRK IDEASTSKAV DNSSKDGKKT TKPAVTQSNR
RRSGLSLRPV PIETIFSESS GRESSTEDEA DVSHQQRVEK IAKNPIMVVV LPLGPGNYPN
NERITVVSTY KSRVNKNCNE ARRAQRHGSW SRKGIAFPGI PTKKFTKSDL AKYGAHASNW
PAQAAFRSEE GKILIYYEGW TCLTLHRLSV EECARTAPTI LEEMSIRDKF IETVKSAAAE
EAKLVVEKNQ ENGIELTLDE ALKQIFIEPV PQSSPENVFW IYQDLSYFHT MDNRDLGLAP
VFYISSYTQS VRPPCYAYTA INIVDVDAYK RCLESRANMS FADLTGQKIW MPTRSKACEN
GTKCKCDARF MFLYDPHDVT NLECTPDGKV DFTDFKIDNA RIVMECSDAC GCSLDCPRRS
LQRGQQHPLA VYYEGPEKGF GVRAAANIKA GELVCEYTGD VTLLPTSDPV ASSSTKTDDG
EEQENPEAPE RVDSSYDAAF NAMDTKIIIS AKKTGNISRF INHSCDPSSV FVEVYSRRFE
EDPLIPRVAV YAIKDIALGE EITIAYYEPG IEWKRSSVKC RCKSTKCMGT LPAF
