WDR51_CAEEL
ID WDR51_CAEEL Reviewed; 376 AA.
AC Q17963;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=WD repeat-containing protein wdr-5.1;
GN Name=wdr-5.1; Synonyms=swd-3.1, tag-125; ORFNames=C14B1.4;
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=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]
RP FUNCTION.
RX PubMed=16710447; DOI=10.1371/journal.pgen.0020074;
RA Cui M., Kim E.B., Han M.;
RT "Diverse chromatin remodeling genes antagonize the Rb-involved SynMuv
RT pathways in C. elegans.";
RL PLoS Genet. 2:E74-E74(2006).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=17967446; DOI=10.1016/j.ydbio.2007.09.035;
RA Simonet T., Dulermo R., Schott S., Palladino F.;
RT "Antagonistic functions of SET-2/SET1 and HPL/HP1 proteins in C. elegans
RT development.";
RL Dev. Biol. 312:367-383(2007).
RN [4]
RP FUNCTION.
RX PubMed=20188723; DOI=10.1016/j.ydbio.2010.02.023;
RA Fisher K., Southall S.M., Wilson J.R., Poulin G.B.;
RT "Methylation and demethylation activities of a C. elegans MLL-like complex
RT attenuate RAS signalling.";
RL Dev. Biol. 341:142-153(2010).
RN [5]
RP FUNCTION.
RX PubMed=20555324; DOI=10.1038/nature09195;
RA Greer E.L., Maures T.J., Hauswirth A.G., Green E.M., Leeman D.S.,
RA Maro G.S., Han S., Banko M.R., Gozani O., Brunet A.;
RT "Members of the H3K4 trimethylation complex regulate lifespan in a
RT germline-dependent manner in C. elegans.";
RL Nature 466:383-387(2010).
RN [6]
RP FUNCTION, AND INTERACTION WITH HISTONE H3.
RX PubMed=21455483; DOI=10.1371/journal.pgen.1001349;
RA Li T., Kelly W.G.;
RT "A role for Set1/MLL-related components in epigenetic regulation of the
RT Caenorhabditis elegans germ line.";
RL PLoS Genet. 7:E1001349-E1001349(2011).
RN [7]
RP FUNCTION.
RX PubMed=22012258; DOI=10.1038/nature10572;
RA Greer E.L., Maures T.J., Ucar D., Hauswirth A.G., Mancini E., Lim J.P.,
RA Benayoun B.A., Shi Y., Brunet A.;
RT "Transgenerational epigenetic inheritance of longevity in Caenorhabditis
RT elegans.";
RL Nature 479:365-371(2011).
RN [8]
RP FUNCTION, AND INTERACTION WITH SET-2.
RX PubMed=21527717; DOI=10.1073/pnas.1019290108;
RA Xiao Y., Bedet C., Robert V.J., Simonet T., Dunkelbarger S.,
RA Rakotomalala C., Soete G., Korswagen H.C., Strome S., Palladino F.;
RT "Caenorhabditis elegans chromatin-associated proteins SET-2 and ASH-2 are
RT differentially required for histone H3 Lys 4 methylation in embryos and
RT adult germ cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:8305-8310(2011).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=24682813; DOI=10.1093/nar/gku221;
RA Li T., Kelly W.G.;
RT "A role for WDR5 in TRA-1/Gli mediated transcriptional control of the
RT sperm/oocyte switch in C. elegans.";
RL Nucleic Acids Res. 42:5567-5581(2014).
RN [10]
RP FUNCTION, AND INTERACTION WITH JMJD-3.1; CEH-6; SOX-2; SEM-4 AND EGL-17.
RX PubMed=25124442; DOI=10.1126/science.1255885;
RA Zuryn S., Ahier A., Portoso M., White E.R., Morin M.C., Margueron R.,
RA Jarriault S.;
RT "Sequential histone-modifying activities determine the robustness of
RT transdifferentiation.";
RL Science 345:826-829(2014).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28379943; DOI=10.1038/nature21686;
RA Han S., Schroeder E.A., Silva-Garcia C.G., Hebestreit K., Mair W.B.,
RA Brunet A.;
RT "Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans
RT lifespan.";
RL Nature 544:185-190(2017).
RN [12] {ECO:0000305}
RP IDENTIFICATION IN THE SET2 COMPLEX, AND INTERACTION WITH CFP-1; ASH-2;
RP DPY-30 AND HDA-1.
RX PubMed=31602465; DOI=10.1093/nar/gkz880;
RA Beurton F., Stempor P., Caron M., Appert A., Dong Y., Chen R.A., Cluet D.,
RA Coute Y., Herbette M., Huang N., Polveche H., Spichty M., Bedet C.,
RA Ahringer J., Palladino F.;
RT "Physical and functional interaction between SET1/COMPASS complex component
RT CFP-1 and a Sin3S HDAC complex in C. elegans.";
RL Nucleic Acids Res. 47:11164-11180(2019).
CC -!- FUNCTION: Contributes to histone modification (PubMed:16710447,
CC PubMed:17967446, PubMed:20188723, PubMed:20555324, PubMed:21455483,
CC PubMed:22012258). May position the N-terminus of histone H3 for
CC efficient trimethylation at 'Lys-4' (PubMed:21455483). Required for
CC di- and trimethylation, particularly for the trimethylation at 'Lys-4'
CC of histone H3 (PubMed:20555324, PubMed:21455483, PubMed:24682813,
CC PubMed:21527717). Not required for demethylation of histone H3 'Lys-27'
CC (PubMed:21455483). H3 'Lys-4' methylation represents a specific tag for
CC epigenetic transcriptional activation, germline establishment,
CC maintenance and function (PubMed:21455483). Implicated in the
CC epigenetic inheritance of lifespan over several generations
CC (PubMed:22012258). Acts in the germline to limit the longevity of the
CC soma, probably by regulating a lipid metabolism pathway that signals
CC from the germline to the intestine, thereby preventing accumulation of
CC mono-unsaturated fatty acids (PubMed:17967446, PubMed:20555324,
CC PubMed:28379943). Required for RNA interference with probable
CC antagonistic role against hpl-2 function (PubMed:17967446). Plays a
CC role in vulval cell fate specification by acting in the synthetic
CC multivulva pathway independent of set-2 (PubMed:17967446). Sex
CC determining protein required in the germline to promote the
CC spermatogenesis to oogenesis switch during the late larval stages of
CC development (PubMed:24682813). Acts with the sex determining factor
CC tra-1, and redundantly with wdr-5.2, to regulate fog-3 expression,
CC which in turn determines germ cell fate (PubMed:24682813). Cooperates
CC with jmjd-3.1, egl-27 and unc-3 to ensure robust transdifferentiation
CC of the Y rectal cell to the PDA motor neuron during larval development
CC (PubMed:25124442). {ECO:0000269|PubMed:16710447,
CC ECO:0000269|PubMed:17967446, ECO:0000269|PubMed:20188723,
CC ECO:0000269|PubMed:20555324, ECO:0000269|PubMed:21455483,
CC ECO:0000269|PubMed:21527717, ECO:0000269|PubMed:22012258,
CC ECO:0000269|PubMed:24682813, ECO:0000269|PubMed:25124442,
CC ECO:0000269|PubMed:28379943}.
CC -!- SUBUNIT: Component of the SET2 complex (also known as the SET1/COMPASS
CC complex), which contains at least set-2, swd-2.1, cfp-1, rbbp-5, wdr-
CC 5.1, dpy-30 and ash-2 (PubMed:31602465). Within the complex, interacts
CC with cfp-1, ash-2, dpy-30 and hda-1 (PubMed:31602465). Interacts with
CC histone H3 both unmethylated and methylated at 'Lys-4'
CC (PubMed:21455483). Interacts with jmjd-3.1, ceh-6, sox-2, sem-4 and
CC egl-27 (PubMed:25124442). Interacts with set-2 (PubMed:21527717).
CC {ECO:0000269|PubMed:21455483, ECO:0000269|PubMed:21527717,
CC ECO:0000269|PubMed:25124442, ECO:0000269|PubMed:31602465}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17967446,
CC ECO:0000269|PubMed:24682813}. Note=Localized on chromatin in the
CC nucleus. {ECO:0000269|PubMed:24682813}.
CC -!- TISSUE SPECIFICITY: Enriched in the germline (PubMed:17967446,
CC PubMed:24682813). Detected in all nuclei of the embryo
CC (PubMed:17967446). In larvae, expression is detected in the nuclei of
CC seam cells, somatic gonad precursor cells Z1 and Z4, vulval precursor
CC cells, distal tip cells, hypodermal cells, intestinal and muscle cells
CC (PubMed:17967446). Also detected in the neurons from the ventral nerve
CC cord, head and tail region (PubMed:17967446). Expressed in the head and
CC tail region, intestinal cells, muscle cells, cells of the vulva,
CC spermatheca and sheath cells in adults (PubMed:17967446).
CC {ECO:0000269|PubMed:17967446, ECO:0000269|PubMed:24682813}.
CC -!- DEVELOPMENTAL STAGE: Detected from the 20 cell embryo stage and
CC continues through to adult, although in a restricted manner.
CC {ECO:0000269|PubMed:17967446}.
CC -!- DISRUPTION PHENOTYPE: Increase in life span (PubMed:17967446). Longer
CC time span to reach adulthood and reduced brood size resulting in
CC sterility between generations F3 and F4 (PubMed:17967446). Associated
CC embryonic lethality and additional somatic defects at elevated
CC temperatures (PubMed:17967446). Defects in germ cells including
CC defective sperm development and endomitotic oocytes (PubMed:17967446,
CC PubMed:24682813). Significantly reduced H3 'Lys-4' trimethylation in
CC both embryonic and adult germ cells in a sex-independent manner
CC (PubMed:17967446). Increased fog-3 expression at 20 degrees Celsius
CC (PubMed:24682813). At 20 and 25 degrees Celsius, double knockdown
CC mutants with wdr-5.2 have increased fog-3 expression (PubMed:24682813).
CC At 25 degrees Celsius, these mutants have increased wdr-5.2 and fog-1
CC expression, reduced brood size accompanied by 42% embryonic lethality
CC with 100% of the surviving progeny being sterile (PubMed:24682813).
CC Surviving progeny display enhanced defects in the spermatogenesis to
CC oogenesis transition compared to the single wdr-5.1 knockout with 88%
CC of the gonads only containing sperm (PubMed:24682813). The remaining
CC germ cells in the gonads switch to oogenesis, but the oocytes display
CC either an endoreplication or endomitotic phenotype (PubMed:24682813).
CC Germ cells also have increased expression of the sex determining factor
CC tra-1 in the cytoplasm and as a result there is reduced binding of tra-
CC 1 to the fog-3 promoter (PubMed:24682813). RNAi-mediated knockdown
CC leads to an enrichment of mono-unsaturated fatty acids
CC (PubMed:28379943). {ECO:0000269|PubMed:17967446,
CC ECO:0000269|PubMed:24682813, ECO:0000269|PubMed:28379943}.
CC -!- SIMILARITY: Belongs to the WD repeat WDR5/wds family. {ECO:0000305}.
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DR EMBL; Z37139; CAA85487.1; -; Genomic_DNA.
DR PIR; T19266; T19266.
DR RefSeq; NP_497749.1; NM_065348.7.
DR AlphaFoldDB; Q17963; -.
DR SMR; Q17963; -.
DR BioGRID; 40714; 20.
DR DIP; DIP-55118N; -.
DR IntAct; Q17963; 7.
DR STRING; 6239.C14B1.4; -.
DR EPD; Q17963; -.
DR PaxDb; Q17963; -.
DR PeptideAtlas; Q17963; -.
DR EnsemblMetazoa; C14B1.4.1; C14B1.4.1; WBGene00006474.
DR GeneID; 175474; -.
DR KEGG; cel:CELE_C14B1.4; -.
DR CTD; 175474; -.
DR WormBase; C14B1.4; CE00901; WBGene00006474; wdr-5.1.
DR eggNOG; KOG0266; Eukaryota.
DR GeneTree; ENSGT00970000196638; -.
DR HOGENOM; CLU_000288_57_1_1; -.
DR InParanoid; Q17963; -.
DR OMA; RLWNYHT; -.
DR OrthoDB; 957291at2759; -.
DR PhylomeDB; Q17963; -.
DR Reactome; R-CEL-3214841; PKMTs methylate histone lysines.
DR Reactome; R-CEL-3214858; RMTs methylate histone arginines.
DR Reactome; R-CEL-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR Reactome; R-CEL-8951664; Neddylation.
DR PRO; PR:Q17963; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00006474; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0044666; C:MLL3/4 complex; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0048188; C:Set1C/COMPASS complex; IBA:GO_Central.
DR GO; GO:0042393; F:histone binding; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:WormBase.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
DR GO; GO:0051568; P:histone H3-K4 methylation; IMP:WormBase.
DR GO; GO:0012501; P:programmed cell death; IMP:UniProtKB.
DR GO; GO:0060290; P:transdifferentiation; IMP:WormBase.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF00400; WD40; 6.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 5.
DR PROSITE; PS50082; WD_REPEATS_2; 6.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; Developmental protein; Nucleus; Reference proteome;
KW Repeat; RNA-mediated gene silencing; Transcription;
KW Transcription regulation; WD repeat.
FT CHAIN 1..376
FT /note="WD repeat-containing protein wdr-5.1"
FT /id="PRO_0000051503"
FT REPEAT 85..115
FT /note="WD 1"
FT REPEAT 127..157
FT /note="WD 2"
FT REPEAT 169..199
FT /note="WD 3"
FT REPEAT 211..241
FT /note="WD 4"
FT REPEAT 254..284
FT /note="WD 5"
FT REPEAT 296..329
FT /note="WD 6"
FT REPEAT 341..373
FT /note="WD 7"
FT REGION 1..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 149
FT /note="Important for interaction with histone H3"
FT /evidence="ECO:0000250"
FT SITE 175
FT /note="Important for interaction with histone H3"
FT /evidence="ECO:0000250"
FT SITE 305
FT /note="Important for interaction with histone H3"
FT /evidence="ECO:0000250"
FT SITE 364
FT /note="Important for interaction with histone H3"
FT /evidence="ECO:0000250"
SQ SEQUENCE 376 AA; 40393 MW; 3204DC36FE58FC19 CRC64;
MDTSENAASA AEQQPTQQID QLTVPNAPDG GSSAPAPSTS PNSISPSNPT GTPAPGASAQ
TPNPNAAGAS ASGSANYKLM CTLEGHTKSI SSAKFSPCGK YLGTSSADKT VKIWNMDHMI
CERTLTGHKL GVNDIAWSSD SRCVVSASDD KTLKIFEIVT SRMTKTLKGH NNYVFCCNFN
PQSSLVVSGS FDESVRIWDV KTGMCIKTLP AHSDPVSAVS FNRDGSLIAS GSYDGLVRIW
DTANGQCIKT LVDDENPPVA FVKFSPNGKY ILASNLDSTL KLWDFSKGKT LKQYTGHENS
KYCIFANFSV TGGKWIISGS EDCKIYIWNL QTREIVQCLE GHTQPVLASD CHPVQNIIAS
GALEPDNKIH IWRSDV
