PSMF1_DROME
ID PSMF1_DROME Reviewed; 270 AA.
AC Q9V637; A4UZD9; Q0E9B8;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Proteasome inhibitor PI31 subunit;
GN Name=PI31; ORFNames=CG8979;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
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]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
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]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168 AND SER-189, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17372656; DOI=10.1039/b617545g;
RA Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A.,
RA Eng J.K., Aebersold R., Tao W.A.;
RT "An integrated chemical, mass spectrometric and computational strategy for
RT (quantitative) phosphoproteomics: application to Drosophila melanogaster
RT Kc167 cells.";
RL Mol. Biosyst. 3:275-286(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH NTC,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DOMAIN,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ILE-96; ILE-103 AND
RP 268-TYR--TYR-270.
RX PubMed=21529711; DOI=10.1016/j.cell.2011.03.021;
RA Bader M., Benjamin S., Wapinski O.L., Smith D.M., Goldberg A.L.,
RA Steller H.;
RT "A conserved F box regulatory complex controls proteasome activity in
RT Drosophila.";
RL Cell 145:371-382(2011).
RN [7]
RP FUNCTION, INTERACTION WITH TNKS, INTERACTION WITH 20S PROTEASOME SUBUNITS
RP PROSALPHA1; PROSALPHA3; PROSALPHA4 AND PROSALPHA6, INTERACTION WITH PMSD5
RP AND PSMD9, ADP-RIBOSYLATION BY TNKS, AND MUTAGENESIS OF ARG-49; GLY-54;
RP LEU-210; ASP-211; PHE-241; PRO-243 AND 268-TYR--TYR-270.
RX PubMed=23622245; DOI=10.1016/j.cell.2013.03.040;
RA Cho-Park P.F., Steller H.;
RT "Proteasome regulation by ADP-ribosylation.";
RL Cell 153:614-627(2013).
CC -!- FUNCTION: Plays an important role in the control of proteasome
CC function. Inhibits the hydrolysis of protein and peptide substrates by
CC the 20S proteasome. Enhances 26S proteasome function by promoting its
CC assembly through the interaction with the assembly chaperones PSMD9 and
CC PMSD5. Functions together with ntc to control non-apoptotic caspase
CC activation during sperm individualization. In testis, is required for
CC proper protein degradation and germline cell cycle progression.
CC {ECO:0000269|PubMed:21529711, ECO:0000269|PubMed:23622245}.
CC -!- SUBUNIT: Interacts with ntc. Interacts with Tnks (via ANK repeats).
CC Interacts with 20S proteasome subunits Prosalpha1, Prosalpha3,
CC Prosalpha4 and Prosalpha6, but not with Prosalpha2 and Prosalpha5. The
CC interaction with Prosalpha4 is reduced by PI31 ADP-ribosylation.
CC Interacts with the 19S assembly chaperones PSMD5 and PSMD9; these
CC interactions are increased by PI31 ADP-ribosylation.
CC {ECO:0000269|PubMed:21529711, ECO:0000269|PubMed:23622245}.
CC -!- INTERACTION:
CC Q9V637; Q9VYG1: CG12096; NbExp=2; IntAct=EBI-144377, EBI-129453;
CC Q9V637; Q9VFS8: CG9588; NbExp=3; IntAct=EBI-144377, EBI-166054;
CC Q9V637; Q8SX86: ntc; NbExp=6; IntAct=EBI-144377, EBI-137714;
CC Q9V637; P18053: Prosalpha3; NbExp=2; IntAct=EBI-144377, EBI-138951;
CC Q9V637; Q9VBP3: Tnks; NbExp=3; IntAct=EBI-144377, EBI-124451;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21529711}. Note=In
CC the spermatid, localizes to the actin-based individualization complex.
CC -!- TISSUE SPECIFICITY: In testis, expressed in germline stem cells and
CC primary spermatocytes (at protein level).
CC {ECO:0000269|PubMed:21529711}.
CC -!- DEVELOPMENTAL STAGE: Expressed in adults.
CC {ECO:0000269|PubMed:21529711}.
CC -!- DOMAIN: The Hydrophobic-Tyrosine-X (HbYX) motif is involved in
CC proteasome activation. {ECO:0000269|PubMed:21529711}.
CC -!- PTM: ADP-ribosylation by Tnks increases its affinity for assembly
CC chaperones PSMD9 and PMSD5, sequestering them away from the proteasome
CC Rpt base subunits and promoting in this way 26S proteasome assembly.
CC Also interferes with its inhibitory effect on 20S proteasome.
CC -!- DISRUPTION PHENOTYPE: Larval lethal. Mutant larvae develop melanotic
CC tumors. {ECO:0000269|PubMed:21529711}.
CC -!- SIMILARITY: Belongs to the proteasome inhibitor PI31 family.
CC {ECO:0000305}.
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DR EMBL; AE013599; AAF58602.1; -; Genomic_DNA.
DR EMBL; AE013599; AAM68702.1; -; Genomic_DNA.
DR EMBL; AY058250; AAL13479.1; -; mRNA.
DR RefSeq; NP_001260905.1; NM_001273976.2.
DR RefSeq; NP_001260907.1; NM_001273978.2.
DR RefSeq; NP_610715.1; NM_136871.4.
DR RefSeq; NP_725092.1; NM_165854.3.
DR RefSeq; NP_725093.1; NM_165855.3.
DR AlphaFoldDB; Q9V637; -.
DR SMR; Q9V637; -.
DR BioGRID; 62061; 11.
DR DIP; DIP-18931N; -.
DR IntAct; Q9V637; 19.
DR STRING; 7227.FBpp0301842; -.
DR iPTMnet; Q9V637; -.
DR PaxDb; Q9V637; -.
DR PRIDE; Q9V637; -.
DR DNASU; 36277; -.
DR EnsemblMetazoa; FBtr0088051; FBpp0087157; FBgn0033669.
DR EnsemblMetazoa; FBtr0088052; FBpp0087158; FBgn0033669.
DR EnsemblMetazoa; FBtr0088053; FBpp0087159; FBgn0033669.
DR EnsemblMetazoa; FBtr0310157; FBpp0301842; FBgn0033669.
DR EnsemblMetazoa; FBtr0310159; FBpp0301844; FBgn0033669.
DR GeneID; 36277; -.
DR KEGG; dme:Dmel_CG8979; -.
DR UCSC; CG8979-RA; d. melanogaster.
DR CTD; 36277; -.
DR FlyBase; FBgn0033669; PI31.
DR VEuPathDB; VectorBase:FBgn0033669; -.
DR eggNOG; KOG4761; Eukaryota.
DR GeneTree; ENSGT00390000012257; -.
DR HOGENOM; CLU_090116_0_0_1; -.
DR InParanoid; Q9V637; -.
DR OMA; NICVEPE; -.
DR OrthoDB; 1614691at2759; -.
DR PhylomeDB; Q9V637; -.
DR Reactome; R-DME-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-DME-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-DME-1236978; Cross-presentation of soluble exogenous antigens (endosomes).
DR Reactome; R-DME-174084; Autodegradation of Cdh1 by Cdh1:APC/C.
DR Reactome; R-DME-174154; APC/C:Cdc20 mediated degradation of Securin.
DR Reactome; R-DME-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
DR Reactome; R-DME-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR Reactome; R-DME-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-DME-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-DME-202424; Downstream TCR signaling.
DR Reactome; R-DME-2467813; Separation of Sister Chromatids.
DR Reactome; R-DME-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-DME-350562; Regulation of ornithine decarboxylase (ODC).
DR Reactome; R-DME-382556; ABC-family proteins mediated transport.
DR Reactome; R-DME-450408; AUF1 (hnRNP D0) binds and destabilizes mRNA.
DR Reactome; R-DME-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-DME-4641257; Degradation of AXIN.
DR Reactome; R-DME-4641258; Degradation of DVL.
DR Reactome; R-DME-5358346; Hedgehog ligand biogenesis.
DR Reactome; R-DME-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-DME-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-DME-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-DME-5610785; GLI3 is processed to GLI3R by the proteasome.
DR Reactome; R-DME-5632684; Hedgehog 'on' state.
DR Reactome; R-DME-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-DME-5689603; UCH proteinases.
DR Reactome; R-DME-5689880; Ub-specific processing proteases.
DR Reactome; R-DME-68867; Assembly of the pre-replicative complex.
DR Reactome; R-DME-68949; Orc1 removal from chromatin.
DR Reactome; R-DME-69017; CDK-mediated phosphorylation and removal of Cdc6.
DR Reactome; R-DME-69601; Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
DR Reactome; R-DME-75815; Ubiquitin-dependent degradation of Cyclin D.
DR Reactome; R-DME-8854050; FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
DR Reactome; R-DME-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR Reactome; R-DME-8939902; Regulation of RUNX2 expression and activity.
DR Reactome; R-DME-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-DME-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-DME-8951664; Neddylation.
DR Reactome; R-DME-9020702; Interleukin-1 signaling.
DR Reactome; R-DME-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-DME-9762114; GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2.
DR Reactome; R-DME-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR BioGRID-ORCS; 36277; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 36277; -.
DR PRO; PR:Q9V637; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0033669; Expressed in testis and 30 other tissues.
DR ExpressionAtlas; Q9V637; baseline and differential.
DR Genevisible; Q9V637; DM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0070864; C:sperm individualization complex; IDA:FlyBase.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IEA:InterPro.
DR GO; GO:0070628; F:proteasome binding; IEA:InterPro.
DR GO; GO:0008584; P:male gonad development; IMP:FlyBase.
DR GO; GO:0007140; P:male meiotic nuclear division; IMP:FlyBase.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:FlyBase.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR GO; GO:0090364; P:regulation of proteasome assembly; IDA:FlyBase.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR InterPro; IPR045128; PI31-like.
DR InterPro; IPR021625; PI31_Prot_N.
DR PANTHER; PTHR13266; PTHR13266; 1.
DR Pfam; PF11566; PI31_Prot_N; 1.
PE 1: Evidence at protein level;
KW ADP-ribosylation; Cytoplasm; Developmental protein; Phosphoprotein;
KW Proteasome; Reference proteome.
FT CHAIN 1..270
FT /note="Proteasome inhibitor PI31 subunit"
FT /id="PRO_0000220924"
FT REGION 158..270
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 268..270
FT /note="HbYX motif"
FT COMPBIAS 158..172
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 229..243
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17372656,
FT ECO:0000269|PubMed:18327897"
FT MOD_RES 189
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17372656"
FT MUTAGEN 49
FT /note="R->A: Abolishes interaction with Tnks but does not
FT affect interaction with PSMD5 and PSMD9; when associated
FT with A-54."
FT /evidence="ECO:0000269|PubMed:23622245"
FT MUTAGEN 54
FT /note="G->A: Abolishes interaction with Tnks but does not
FT affect interaction with PSMD5 and PSMD9; when associated
FT with A-49."
FT /evidence="ECO:0000269|PubMed:23622245"
FT MUTAGEN 96
FT /note="I->E: Fails to rescue null mutant phenotype; when
FT associated with E-103."
FT /evidence="ECO:0000269|PubMed:21529711"
FT MUTAGEN 103
FT /note="I->E: Fails to rescue null mutant phenotype; when
FT associated with E-96."
FT /evidence="ECO:0000269|PubMed:21529711"
FT MUTAGEN 210
FT /note="L->A: Abolishes interaction with Tnks, PSMD5 and
FT PSMD9."
FT /evidence="ECO:0000269|PubMed:23622245"
FT MUTAGEN 211
FT /note="D->K: Does not affect interaction with Tnks."
FT /evidence="ECO:0000269|PubMed:23622245"
FT MUTAGEN 241
FT /note="F->A: Abolishes interaction with Tnks, PSMD5 and
FT PSMD9."
FT /evidence="ECO:0000269|PubMed:23622245"
FT MUTAGEN 243
FT /note="P->A: Does not affect interaction with Tnks."
FT /evidence="ECO:0000269|PubMed:23622245"
FT MUTAGEN 268..270
FT /note="Missing: Abolishes interaction with Tnks, PSMD5 and
FT PSMD9. Reduces 26S proteasome activation."
FT /evidence="ECO:0000269|PubMed:21529711,
FT ECO:0000269|PubMed:23622245"
SQ SEQUENCE 270 AA; 30088 MW; F7972E7634E80555 CRC64;
MESGSTAKTG DFFYGWDLLY KTVKADVSKK SDLLIALVHF LLTKHYNFRC VGVGDDKTLP
EEEGSELLPD SWNDDDTKYS LRYVHDKMLY LLLGHITEGS LLINLLDINT KKVSNICVEP
ETLVPEVKGG ITTIMPSASE IVERYRRELL DPVFTGNSRE VTTQTTNSPR PIGSDPDPLR
IGEPRRGGSF IPSAFEPRPF GFPDVGRGDL DPLGRGGHGN LFSFPSRPNM GPGPVPRFDP
FNPLNPNRPG QGGINPDHMR PPDWNPDYYM
