PWP1_DROME
ID PWP1_DROME Reviewed; 459 AA.
AC A1Z8D0; B5X0K1; Q8SY06;
DT 12-SEP-2018, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Periodic tryptophan protein 1 homolog {ECO:0000303|PubMed:29065309};
DE Short=PWP1 {ECO:0000303|PubMed:29065309};
DE AltName: Full=Protein no child left behind {ECO:0000303|PubMed:21752937, ECO:0000312|FlyBase:FBgn0263510};
GN Name=nclb {ECO:0000303|PubMed:21752937, ECO:0000312|FlyBase:FBgn0263510};
GN Synonyms=dpwp1 {ECO:0000303|PubMed:29065309};
GN ORFNames=CG6751 {ECO:0000312|FlyBase:FBgn0263510};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAL68278.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL68278.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAL68278.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000312|EMBL:ACI16532.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:ACI16532.1};
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=21752937; DOI=10.1242/dev.067942;
RA Casper A.L., Baxter K., Van Doren M.;
RT "no child left behind encodes a novel chromatin factor required for
RT germline stem cell maintenance in males but not females.";
RL Development 138:3357-3366(2011).
RN [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH MYBBP1A, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, PHOSPHORYLATION AT SER-385, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP SER-252 AND SER-385.
RX PubMed=29065309; DOI=10.1016/j.devcel.2017.09.022;
RA Liu Y., Mattila J., Ventelae S., Yadav L., Zhang W., Lamichane N.,
RA Sundstroem J., Kauko O., Grenman R., Varjosalo M., Westermarck J.,
RA Hietakangas V.;
RT "PWP1 Mediates Nutrient-Dependent Growth Control through Nucleolar
RT Regulation of Ribosomal Gene Expression.";
RL Dev. Cell 43:240-252(2017).
CC -!- FUNCTION: Chromatin-associated factor that regulates transcription
CC (PubMed:21752937). Regulates Pol I-mediated rRNA biogenesis and,
CC probably, Pol III-mediated transcription (PubMed:29065309). Regulates
CC the localization to the nucleolus of Cdk7, a regulator of the Pol I-
CC elongation factor TFIIH (PubMed:29065309). Acts as regulator of cell
CC proliferation and tissue growth as part of the TORC1 and Myc signaling
CC pathway in response to nutrients (PubMed:29065309). Required in males
CC for both germline stem cell (GSC) maintenance and early stages of germ
CC cell differentiation of germ cell cysts (PubMed:21752937). Not required
CC for female germline stem cell (GSC) maintenance, but necessary to
CC regulate germ cell differentiation and egg chamber development
CC (PubMed:21752937). In female somatic cells, required for follicle stem
CC cell survival and maintenance (PubMed:21752937).
CC {ECO:0000269|PubMed:21752937, ECO:0000269|PubMed:29065309}.
CC -!- SUBUNIT: Interacts with Mybbp1A. {ECO:0000269|PubMed:29065309}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21752937}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:29065309}. Chromosome
CC {ECO:0000269|PubMed:21752937}. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:29065309}. Note=Co-localizes with active forms of
CC RNA polymerase II (PubMed:21752937). Associates with open chromatin and
CC chromosomal puffs of polytene chromosomes in larval salivary glands
CC (PubMed:21752937). Nucleolar localization is controlled by mTORC1
CC signaling (PubMed:29065309). {ECO:0000269|PubMed:21752937,
CC ECO:0000269|PubMed:29065309}.
CC -!- TISSUE SPECIFICITY: Detected in the germline of adult testis and ovary
CC (at protein level) (PubMed:21752937). Detected in ovary somatic cells,
CC in zfh1-positive cyst cells in the testis and absent in differentiated
CC cyst cells (at protein level) (PubMed:21752937).
CC {ECO:0000269|PubMed:21752937}.
CC -!- DEVELOPMENTAL STAGE: Detected in embryonic cell types, including germ
CC cells (at protein level) (PubMed:21752937). In early third instar
CC larvae, detected in the fat body (at protein level) (PubMed:29065309).
CC Detected in the larval salivary glands and fat body (at protein level)
CC (PubMed:21752937). Expressed in stage 17 embryos in male but not female
CC gonads (PubMed:21752937). {ECO:0000269|PubMed:21752937,
CC ECO:0000269|PubMed:29065309}.
CC -!- INDUCTION: Increased expression upon activation of the Insulin/TOR/Myc
CC pathway in response to protein diet. {ECO:0000269|PubMed:29065309}.
CC -!- PTM: Phosphorylated in response to nutrient-activated TORC1 signaling.
CC {ECO:0000269|PubMed:29065309}.
CC -!- DISRUPTION PHENOTYPE: Larval mutants exhibit altered cell transcription
CC with reduced levels of Pol I-dependent rRNA biogenesis and, to a
CC certain extent, of III-dependent transcription leading to reduced
CC growth (PubMed:21752937, PubMed:29065309). Displays delayed pupation
CC kinetics and reduced pupal volume (PubMed:29065309). Exhibits reduced
CC number of germline cells leading to fertility defects; female flies
CC have limited fertility, whereas male flies are sterile
CC (PubMed:21752937). In male larvae, germ cells can enter differentiation
CC but spermatogenic cysts cannot develop normally (PubMed:21752937).
CC Adult testes shows fewer hub-proximal germ cells, lack of Stat92e
CC activation and general failure of germline stem cells (GSC) maintenance
CC (PubMed:21752937). RNAi-mediated knockdown in the posterior compartment
CC of the developing wing leads to reduced compartment size
CC (PubMed:29065309). RNAi-mediated knockdown in the fat body results in
CC delayed larval development and reduced pupal volume (PubMed:29065309).
CC {ECO:0000269|PubMed:21752937, ECO:0000269|PubMed:29065309}.
CC -!- SIMILARITY: Belongs to the WD repeat PWP1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ACI16532.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE013599; AAF58738.1; -; Genomic_DNA.
DR EMBL; AY075465; AAL68278.1; -; mRNA.
DR EMBL; BT044570; ACI16532.1; ALT_INIT; mRNA.
DR RefSeq; NP_610623.1; NM_136779.4.
DR AlphaFoldDB; A1Z8D0; -.
DR SMR; A1Z8D0; -.
DR IntAct; A1Z8D0; 1.
DR STRING; 7227.FBpp0087323; -.
DR iPTMnet; A1Z8D0; -.
DR PaxDb; A1Z8D0; -.
DR PRIDE; A1Z8D0; -.
DR DNASU; 36150; -.
DR EnsemblMetazoa; FBtr0088228; FBpp0087323; FBgn0263510.
DR GeneID; 36150; -.
DR KEGG; dme:Dmel_CG6751; -.
DR UCSC; CG6751-RA; d. melanogaster.
DR CTD; 36150; -.
DR FlyBase; FBgn0263510; nclb.
DR VEuPathDB; VectorBase:FBgn0263510; -.
DR eggNOG; KOG0270; Eukaryota.
DR GeneTree; ENSGT00390000017324; -.
DR HOGENOM; CLU_023867_1_1_1; -.
DR InParanoid; A1Z8D0; -.
DR OMA; CFVPRGV; -.
DR OrthoDB; 737539at2759; -.
DR PhylomeDB; A1Z8D0; -.
DR BioGRID-ORCS; 36150; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 36150; -.
DR PRO; PR:A1Z8D0; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0263510; Expressed in mouthpart and 73 other tissues.
DR Genevisible; A1Z8D0; DM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:FlyBase.
DR GO; GO:0005654; C:nucleoplasm; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0031490; F:chromatin DNA binding; IMP:FlyBase.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:FlyBase.
DR GO; GO:0007281; P:germ cell development; IMP:FlyBase.
DR GO; GO:0036098; P:male germ-line stem cell population maintenance; IMP:FlyBase.
DR GO; GO:0008584; P:male gonad development; IMP:FlyBase.
DR GO; GO:0030707; P:ovarian follicle cell development; IMP:FlyBase.
DR GO; GO:0030723; P:ovarian fusome organization; IMP:FlyBase.
DR GO; GO:0090070; P:positive regulation of ribosome biogenesis; IDA:FlyBase.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; IDA:FlyBase.
DR GO; GO:1901838; P:positive regulation of transcription of nucleolar large rRNA by RNA polymerase I; IDA:FlyBase.
DR GO; GO:0010468; P:regulation of gene expression; IMP:FlyBase.
DR GO; GO:0006364; P:rRNA processing; IEA:InterPro.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR044285; PWP1.
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 PANTHER; PTHR14091; PTHR14091; 1.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Chromosome; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ribosome biogenesis; Transcription; Transcription regulation; WD repeat.
FT CHAIN 1..459
FT /note="Periodic tryptophan protein 1 homolog"
FT /evidence="ECO:0000305"
FT /id="PRO_0000445033"
FT REPEAT 168..214
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 232..272
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 275..315
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 321..361
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 365..405
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REGION 44..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..73
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 385
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29065309"
FT MUTAGEN 252
FT /note="S->A: Reduces expression levels; does not affect
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:29065309"
FT MUTAGEN 385
FT /note="S->A: Abolishes phosphorylation by TORC1 signaling.
FT Results in loss of nucleolar localization."
FT /evidence="ECO:0000269|PubMed:29065309"
FT MUTAGEN 385
FT /note="S->E: Impairs nucleolar localization."
FT /evidence="ECO:0000269|PubMed:29065309"
FT CONFLICT 152
FT /note="W -> S (in Ref. 3; AAL68278)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 459 AA; 51391 MW; 2FBA9D1149599D75 CRC64;
MAEEGPPEPS IDFVPALCFV PRGVAKDRPD KIVLTQAELA RIIGDTQQEL DEESDDDAEE
GENAEEDQND MDVDDHADAN SENRDPQDEF QFQEYDNEAN ANVTSLANIV DAGEQIPDED
EDSEAEDEVI KPSDNLILVG HVQDDAASME VWVFNQEEEA LYTHHDFLLP SFPLCIEWMN
HDAGSEKAGN MCAIGCMDPI ITVWDLDIQD AIEPTFKLGS KGSRKQNKEQ YGHKDAVLDL
SWNTNFEHIL ASGSVDQTVI LWDMDEGQPH TTITAFGKQI QSLEFHPQEA QSILTGCADG
YVRLFDCRDA EGVNSSSIEW KVDGEVEKVL WHPTQTDYFI VGTNDGTLHY ADKRSPGQLL
WSVKAHNEEI SGVCFNNQKP NLLTSTSTEG TLKVWNFDGT EAKHVYEHEF NMGRLQCMRQ
CPEDPYTLAF GGEKPPRCAI FNIKNSIAVR RTFGIPDAE
