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SET17_CAEEL
ID   SET17_CAEEL             Reviewed;         277 AA.
AC   A0A163UT06; A0A168H266;
DT   22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT   06-JUL-2016, sequence version 1.
DT   03-AUG-2022, entry version 36.
DE   RecName: Full=Histone-lysine N-methyltransferase set-17 {ECO:0000305};
DE            EC=2.1.1.- {ECO:0000269|PubMed:24685137};
DE            EC=2.1.1.364 {ECO:0000269|PubMed:24685137};
DE   AltName: Full=SET domain-containing protein 17 {ECO:0000312|WormBase:T21B10.5a};
GN   Name=set-17 {ECO:0000312|WormBase:T21B10.5a};
GN   ORFNames=T21B10.5 {ECO:0000312|WormBase:T21B10.5a};
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, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP   1-MET--PHE-135.
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   [3] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP   AND MUTAGENESIS OF 1-MET--PHE-135 AND 84-TYR--ARG-277.
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: Histone methyltransferase that specifically mono- and di-
CC       methylates 'Lys-4' of histone H3 in vitro (PubMed:24685137). Does not
CC       tri-methylate 'Lys-4' of histone H3 in vitro (PubMed:24685137).
CC       Promotes spermatid development and fertility by positively regulating
CC       the transcription of spermatocyte-specific genes in primary
CC       spermatocytes (PubMed:29702639). Together with spr-5, required for
CC       transgenerational fertility (PubMed:24685137).
CC       {ECO:0000269|PubMed:24685137, ECO:0000269|PubMed:29702639}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine
CC         = H(+) + N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-
CC         homocysteine; Xref=Rhea:RHEA:60268, Rhea:RHEA-COMP:15540, Rhea:RHEA-
CC         COMP:15543, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC         ChEBI:CHEBI:61929, ChEBI:CHEBI:61976;
CC         Evidence={ECO:0000269|PubMed:24685137};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:60264, Rhea:RHEA-COMP:15543, Rhea:RHEA-COMP:15547,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.364;
CC         Evidence={ECO:0000269|PubMed:24685137};
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29702639}. Note=In
CC       males and hermaphrodites, localizes to foci in the nucleus of
CC       spermatocytes, which express the mono- and di-methyl states of 'Lys-4'
CC       of histone H3 (PubMed:29702639). These foci are stable nuclear
CC       structures with slow diffusion and liquid-like properties
CC       (PubMed:29702639). In turn, these foci co-localize with the
CC       transcription start sites for major sperm proteins (PubMed:29702639).
CC       {ECO:0000269|PubMed:29702639}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=a {ECO:0000312|WormBase:T21B10.5a};
CC         IsoId=A0A163UT06-1; Sequence=Displayed;
CC       Name=b {ECO:0000312|WormBase:T21B10.5b};
CC         IsoId=A0A163UT06-2; Sequence=VSP_060571;
CC   -!- TISSUE SPECIFICITY: Expressed in the germline (PubMed:29702639).
CC       Predominantly expressed in primary spermatocytes (PubMed:29702639).
CC       Also expressed in the oocyte-producing germline of hermaphrodites
CC       (PubMed:29702639). {ECO:0000269|PubMed:29702639}.
CC   -!- DEVELOPMENTAL STAGE: Broadly expressed in tissues at the L1 larval
CC       stage (PubMed:29702639). In the male germline, first expressed in
CC       primary spermatocytes at the L4 larval stage and expression increases
CC       as spermatocyte differentiation progresses (PubMed:29702639).
CC       {ECO:0000269|PubMed:29702639}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown partially suppresses the
CC       sterility of spr-5 mutants (by101) and results in a slightly increased
CC       number of eggs laid as compared to the spr-5 single mutant.
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; BX284602; SAP35533.1; -; Genomic_DNA.
DR   EMBL; BX284602; SAP35534.1; -; Genomic_DNA.
DR   RefSeq; NP_001317778.1; NM_001330955.1. [A0A163UT06-1]
DR   RefSeq; NP_001317779.1; NM_001330956.1.
DR   AlphaFoldDB; A0A163UT06; -.
DR   SMR; A0A163UT06; -.
DR   STRING; 6239.T21B10.5; -.
DR   EnsemblMetazoa; T21B10.5a.1; T21B10.5a.1; WBGene00011887. [A0A163UT06-1]
DR   EnsemblMetazoa; T21B10.5b.1; T21B10.5b.1; WBGene00011887. [A0A163UT06-2]
DR   GeneID; 174425; -.
DR   KEGG; cel:CELE_T21B10.5; -.
DR   CTD; 174425; -.
DR   WormBase; T21B10.5a; CE51660; WBGene00011887; set-17. [A0A163UT06-1]
DR   WormBase; T21B10.5b; CE51577; WBGene00011887; set-17. [A0A163UT06-2]
DR   eggNOG; KOG2461; Eukaryota.
DR   GeneTree; ENSGT00940000158211; -.
DR   OrthoDB; 1318335at2759; -.
DR   PRO; PR:A0A163UT06; -.
DR   Proteomes; UP000001940; Chromosome II.
DR   Bgee; WBGene00011887; Expressed in adult organism and 8 other tissues.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IDA:WormBase.
DR   GO; GO:0051568; P:histone H3-K4 methylation; IDA:WormBase.
DR   GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR   CDD; cd19193; PR-SET_PRDM7_9; 1.
DR   Gene3D; 2.170.270.10; -; 1.
DR   InterPro; IPR044417; PRDM7_9_PR-SET.
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   Alternative splicing; Methyltransferase; Nucleus; Reference proteome;
KW   S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..277
FT                   /note="Histone-lysine N-methyltransferase set-17"
FT                   /id="PRO_0000449791"
FT   DOMAIN          135..246
FT                   /note="SET"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   BINDING         245
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT   VAR_SEQ         1..12
FT                   /note="Missing (in isoform b)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_060571"
FT   MUTAGEN         1..135
FT                   /note="Missing: In n5017; Reduces the number of eggs laid.
FT                   In males, there is a 50% reduction in the number of
FT                   spermatids per spermatheca which reduces male fertility.
FT                   Reduces the transcription of major sperm proteins and the
FT                   number of fibrous-body membranous organelles in the
FT                   cytoplasm of spermatocytes. Reduces the methylation of
FT                   'Lys-4' of histone H3."
FT                   /evidence="ECO:0000269|PubMed:24685137,
FT                   ECO:0000269|PubMed:29702639"
FT   MUTAGEN         84..277
FT                   /note="Missing: In gk417488; reduces fertility."
FT                   /evidence="ECO:0000269|PubMed:29702639"
SQ   SEQUENCE   277 AA;  32028 MW;  A7B0D232C1BB1342 CRC64;
     MNIKHNYISY FQMNGIQIPG ISNPEAIIPI TGEKKSYKLV LDFNDGAISI IEARYLDSKL
     HREIQDLSDN DVTILGTEIS DGAYDENLDI HCDKCNKFYR PYCRLHPLFK IPDRVLKRDE
     SSNLSFSQQT LPILFRIEES KLPNAGLGVI AEVFIPVGMV FGPYKGRRCQ KKTDFYKDGY
     AWLIKSGDKR FYIDGSDAER SNWLRYINSP RFEDEQNMLA FQTNGKIFYR VIKPIRINQE
     LLVWYGSSYG NEFVESENGN KYKKPAKNPF ICVGAQR
 
 
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