SET26_CAEEL
ID SET26_CAEEL Reviewed; 1645 AA.
AC Q9U263;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 3.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Histone-lysine N-methyltransferase set-26 {ECO:0000305};
DE EC=2.1.1.355 {ECO:0000269|PubMed:24685137};
GN Name=set-26 {ECO:0000312|WormBase:Y51H4A.12};
GN ORFNames=Y51H4A.12 {ECO:0000312|WormBase:Y51H4A.12};
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, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=22212395; DOI=10.1111/j.1474-9726.2011.00785.x;
RA Ni Z., Ebata A., Alipanahiramandi E., Lee S.S.;
RT "Two SET domain containing genes link epigenetic changes and aging in
RT Caenorhabditis elegans.";
RL Aging Cell 11:315-325(2012).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, 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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=29714684; DOI=10.7554/elife.34970;
RA Wang W., Chaturbedi A., Wang M., An S., Santhi S., Lee S.S.;
RT "SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline
RT development and longevity.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Histone methyltransferase that mediates trimethylation of
CC 'Lys-9' of histone H3 in vitro (PubMed:24685137). Involved in
CC transcriptional regulation (PubMed:29714684). Plays a role in the
CC negative regulation of lifespan and in heat resistance
CC (PubMed:29714684). Together with set-9, negatively regulates lifespan
CC in a germline-independent, partially daf-16-dependent fashion
CC (PubMed:22212395, PubMed:29714684). Together with set-9, plays a role
CC in germline development and maintenance and might play a role in the
CC restriction of the trimethylation mark on histone H3 'Lys-4'(H3K4me3)
CC to target genes specifically in the germline (PubMed:29714684).
CC Together with spr-5, required for transgenerational fertility
CC (PubMed:24685137). {ECO:0000269|PubMed:22212395,
CC ECO:0000269|PubMed:24685137, ECO:0000269|PubMed:29714684}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) +
CC N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60276, Rhea:RHEA-COMP:15538, Rhea:RHEA-
CC COMP:15546, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.355;
CC Evidence={ECO:0000269|PubMed:24685137};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22212395,
CC ECO:0000269|PubMed:29714684}.
CC -!- TISSUE SPECIFICITY: Expressed both in the germline and in somatic
CC tissues. {ECO:0000269|PubMed:22212395, ECO:0000269|PubMed:29714684}.
CC -!- DOMAIN: The PHD-type domain binds histone H3 when trimethylated at
CC 'Lys-4' (H3K4me3) in combination with a nearby acetylation (K9ac, K14ac
CC and/or K18ac), but not H3K4me3 alone. {ECO:0000269|PubMed:29714684}.
CC -!- DISRUPTION PHENOTYPE: Exhibits prolonged lifespan, increased resistance
CC to heat stress, reduced brood size and changes in gene expression
CC (PubMed:29714684). In a glp-1(e2141) mutant background which lacks a
CC germline, extended lifespan, increased H3 protein levels, decreased
CC levels of trimethylated histone H3 'Lys-9' (H3K9me3) and 'Lys-27'
CC (H3K27me3) and changes in gene expression (PubMed:22212395,
CC PubMed:29714684). In spr-5 null mutants, accelerates the progressive
CC sterility and accumulation of histone H3 'Lys-4' dimethylation
CC (H3K4me2) over generations which is seen in spr-5 mutants
CC (PubMed:24685137). Simultaneous RNAi-mediated knockdown of set-26 and
CC set-9 results in extended lifespan (PubMed:22212395).
CC {ECO:0000269|PubMed:22212395, ECO:0000269|PubMed:24685137,
CC ECO:0000269|PubMed:29714684}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000305}.
CC -!- CAUTION: Contrary to other SET-domain containing methyltransferases,
CC set-26 does not have the residues usually involved in cofactor binding:
CC instead of the highly conserved XGXG, Y and NH motifs, set-26 displays
CC AVEA (Ala-948-Ala-951), V (Val-967) and F (Phe-1063) and RR (Arg-1024-
CC Arg-1025) motifs (PubMed:29714684). However, histone methyltransferase
CC activity has been detected in vitro (PubMed:24685137).
CC {ECO:0000269|PubMed:24685137, ECO:0000303|PubMed:29714684}.
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DR EMBL; BX284604; CAB63382.3; -; Genomic_DNA.
DR RefSeq; NP_502971.3; NM_070570.3.
DR AlphaFoldDB; Q9U263; -.
DR STRING; 6239.Y51H4A.12; -.
DR EPD; Q9U263; -.
DR PaxDb; Q9U263; -.
DR PeptideAtlas; Q9U263; -.
DR EnsemblMetazoa; Y51H4A.12.1; Y51H4A.12.1; WBGene00013106.
DR UCSC; Y51H4A.12; c. elegans.
DR WormBase; Y51H4A.12; CE25361; WBGene00013106; set-26.
DR eggNOG; KOG1844; Eukaryota.
DR GeneTree; ENSGT00940000168747; -.
DR HOGENOM; CLU_243457_0_0_1; -.
DR InParanoid; Q9U263; -.
DR OMA; IHPQEGP; -.
DR OrthoDB; 790990at2759; -.
DR PRO; PR:Q9U263; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00013106; Expressed in pharyngeal muscle cell (C elegans) and 10 other tissues.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0046974; F:histone methyltransferase activity (H3-K9 specific); IDA:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0036124; P:histone H3-K9 trimethylation; IDA:WormBase.
DR Gene3D; 2.170.270.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF00628; PHD; 1.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00249; PHD; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Metal-binding; Methyltransferase; Nucleus; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1645
FT /note="Histone-lysine N-methyltransferase set-26"
FT /id="PRO_0000438927"
FT DOMAIN 973..1064
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT ZN_FING 794..842
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 1..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 109..132
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 200..228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 417..606
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 651..789
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 865..904
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1099..1333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1371..1536
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1548..1645
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1103..1217
FT /evidence="ECO:0000255"
FT COMPBIAS 208..228
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 500..514
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 557..574
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 589..605
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 651..687
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 879..894
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1099..1174
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1186..1219
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1251..1271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1293..1308
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1384..1454
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1465..1516
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1550..1569
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1645 AA; 181666 MW; 74BF8830788BED57 CRC64;
MADGEHTLPA DEELFEQPPL QQQQPEIAEP IVMAQEPIQG VSEDPQASEA THEAPDNYPV
DHQMENQEFY QEPQIPEPQQ IPQIPVFQPA AYNPPNYVAP QQRANNFGEP AAAADSRPLT
EEEQLAAERP TEDTVWIDSD DDTDVEEAIL RANFWLPYSD HNYDPPDPAD RIILPTEGPF
PCIAGLDEDC NIVKQWMPED AVGPGSPGTQ YRRNQQTGGG LPSTSVAPQQ QQLPVRHNIQ
NRPMVAAQPF SIGGNQVEYG GIGGMDSRMQ QRGVVRDGPQ YRVMNDFGNG LPMRGQLPPR
NSPAANAINR VREQQQQMYH QAGARGSLQQ RVPAPAAPTP GSYQHIVNAV PVGGANPMRR
VPPQARPGMI GGAANNNRAR PIHVTRPMDT QEFEHPVAPA AAAPPRRVVD VAPHRMTPEQ
RQELQQMNRQ RAAPQFPAAA AQRSAEKIVI QQRPGASSSR APRPSMAQED LLRSPTRRLS
ERVPQEHQTP VLEPRRFQVK VTDTYSTPIP KASDQLPAQL TEEDPPEESA AAAAPEDVPD
AAPEDPPKGI LKPTPPHRMT QEEKNAHFAR LTTDKEKPTS SASILPQDAA PPHVPPPPPP
PLVLRPHHQD ETLAMVQSVF ESKPRQPDTP KDKEAISKIA DLLRFSADEF TGQSGSSAAA
RQRTVSGSAA RAQTYQMHHQ QQQQHHHQMP MDQRKRHSSG RYDALMGAMP LQQQPPPPPP
SQFQHTDSIA HRPRGRPKGT RHPSVAVQPQ RSGGARTLPP RAQTVAMSAR NGANAKNSDS
ESEGIDEAAE ESWTMRCHCG MDHGDGDTIE CEGCKTWQHM ACMGLTLKSN TSKYKCEMCL
PRRLPVSKAE AAREQERILN RLRAAAKKQK RKSEPVEQKQ KSQPSTSRKS APMALQQQPA
EPRVAQLNDY SKQASALLFG MEQTAGADTL LAESRLHKKA RRMFVEEAVE ALVTTDLVQI
RQVILEVNGH VSMSNEVKRQ PGGGNCIFMY DGLMKGTAGE DMGDGQELVC IDTKRKGNDT
KFTRRSCVPN CVLKHVLGSN ATLGIMIVAT KDITRNTEVT LPFDADWRES EVELECAEHM
KELQACPFES ERRRFAAERH RAMDHKKREA EEARRADEER RRLEEEVRRE RAAKTKQMDE
AEKARLEAEK AAEKEKKAKE REEAKERKKM EVEASAAAAP ESSNSITARE ERRIQQAEEM
FRRQEEEGKR KEARRRSKSV TPGVLEAAGT AAREDAPEAS IPAPAPSPPA SRRSVSRTTQ
PSTSSFATPT EPPAKNKRMR SVVPPKSEPA SSAKRVRATT VATPKDTTAS NDSRKRKSSA
TGKTPVAKRS KNVVPTSFGL ALIEKELREQ ARDSTVLEMI LPDYIMKEKR SGLLAGQSPD
FSEVRAQIEE ENRMKERFTK REAKKKAVEK AKEKEKKEHR KEPKKANEPG PAPKSEKAVE
KAVEKVEKKP KSPQKPPAKP TAQKPPLKKT EEVDGIEREA SESSSKESSV APEEKKNPKK
ITFAEYNSRR SQKREAGECS TPPAVTRRGF IPSTEGEDLV NVELSAIPLD DHPSSSNTAP
TTTIAPSVGG APKPTSVVVK SPSTRSRTRG AASESVDDAP AEHSMSLQDR VFSMFGSTVD
APAPPPPPPA SAETNSRRSR STRWN
