PRDX1_DROME
ID PRDX1_DROME Reviewed; 194 AA.
AC Q9V3P0; Q0KHT0;
DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Peroxiredoxin 1;
DE EC=1.11.1.24 {ECO:0000269|PubMed:11677042};
DE AltName: Full=Cytosolic thioredoxin peroxidase;
DE Short=DPx-4783;
DE Short=DmTPx-1;
DE AltName: Full=Thioredoxin peroxidase;
DE AltName: Full=Thioredoxin-dependent peroxiredoxin 1 {ECO:0000305};
GN Name=Jafrac1; Synonyms=TPX-1; ORFNames=CG1633;
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 [MRNA].
RX PubMed=10632718; DOI=10.1046/j.1432-1327.2000.01022.x;
RA Rodriguez J., Agudo M., Van Damme J., Vandekerckhove J., Santaren J.F.;
RT "Polypeptides differentially expressed in imaginal discs define the
RT peroxiredoxin family of genes in Drosophila.";
RL Eur. J. Biochem. 267:487-497(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=11677042; DOI=10.1016/s0891-5849(01)00692-x;
RA Radyuk S.N., Klichko V.I., Spinola B., Sohal R.S., Orr W.C.;
RT "The peroxiredoxin gene family in Drosophila melanogaster.";
RL Free Radic. Biol. Med. 31:1090-1100(2001).
RN [3]
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Ovary;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E.;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=11877442; DOI=10.1074/jbc.m200636200;
RA Bauer H., Kanzok S.M., Schirmer R.H.;
RT "Thioredoxin-2 but not thioredoxin-1 is a substrate of thioredoxin
RT peroxidase-1 from Drosophila melanogaster: isolation and characterization
RT of a second thioredoxin in D.melanogaster and evidence for distinct
RT biological functions of Trx-1 and Trx-2.";
RL J. Biol. Chem. 277:17457-17463(2002).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-193 AND SER-194, AND
RP IDENTIFICATION BY 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 [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=26715182; DOI=10.1007/s00018-015-2121-x;
RA Khoshnood B., Dacklin I., Grabbe C.;
RT "Urm1: an essential regulator of JNK signaling and oxidative stress in
RT Drosophila melanogaster.";
RL Cell. Mol. Life Sci. 73:1939-1954(2016).
RN [10]
RP URMYLATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=28953965; DOI=10.1371/journal.pone.0185611;
RA Khoshnood B., Dacklin I., Grabbe C.;
RT "A proteomics approach to identify targets of the ubiquitin-like molecule
RT Urm1 in Drosophila melanogaster.";
RL PLoS ONE 12:E0185611-E0185611(2017).
CC -!- FUNCTION: Thiol-specific peroxidase that catalyzes the reduction of
CC hydrogen peroxide and organic hydroperoxides to water and alcohols,
CC respectively. Plays a role in cell protection against oxidative stress
CC by detoxifying peroxides and as sensor of hydrogen peroxide-mediated
CC signaling events. Might participate in the signaling cascades of growth
CC factors and tumor necrosis factor-alpha by regulating the intracellular
CC concentrations of H(2)O(2) (By similarity). Reduces an intramolecular
CC disulfide bond in GDPD5 that gates the ability to GDPD5 to drive
CC postmitotic motor neuron differentiation (By similarity).
CC {ECO:0000250|UniProtKB:P0CB50, ECO:0000250|UniProtKB:Q06830}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-dithiol + a hydroperoxide = [thioredoxin]-
CC disulfide + an alcohol + H2O; Xref=Rhea:RHEA:62620, Rhea:RHEA-
CC COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:30879, ChEBI:CHEBI:35924,
CC ChEBI:CHEBI:50058; EC=1.11.1.24;
CC Evidence={ECO:0000269|PubMed:11677042};
CC -!- SUBUNIT: Homodimer; disulfide-linked, upon oxidation. 5 homodimers
CC assemble to form a ring-like decamer (By similarity). Interacts with
CC GDPD5; forms a mixed-disulfide with GDPD5 (By similarity). Interacts
CC with SESN1 and SESN2 (By similarity). {ECO:0000250|UniProtKB:P0CB50,
CC ECO:0000250|UniProtKB:Q06830}.
CC -!- INTERACTION:
CC Q9V3P0; P11956: MtnB; NbExp=2; IntAct=EBI-82319, EBI-88468;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11677042}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed during embryogenesis, weakly
CC expressed during larval stages. {ECO:0000269|PubMed:11677042,
CC ECO:0000269|PubMed:11877442}.
CC -!- PTM: The enzyme can be inactivated by further oxidation of the cysteine
CC sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) instead of its
CC condensation to a disulfide bond. It can be reactivated by forming a
CC transient disulfide bond with sulfiredoxin SRXN1, which reduces the
CC cysteine sulfinic acid in an ATP- and Mg-dependent manner.
CC {ECO:0000250|UniProtKB:Q06830}.
CC -!- PTM: Conjugated to URM1, a ubiquitin-like protein.
CC {ECO:0000269|PubMed:28953965}.
CC -!- DISRUPTION PHENOTYPE: Results in reduced resistance to oxidative stress
CC (PubMed:26715182). Simultaneous knockout of Urm1 restores normal
CC sensitivity to oxidative stress (PubMed:26715182).
CC {ECO:0000269|PubMed:26715182}.
CC -!- MISCELLANEOUS: The active site is a conserved redox-active cysteine
CC residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic
CC attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to
CC cysteine sulfenic acid (C(P)-SOH), which then reacts with another
CC cysteine residue, the resolving cysteine (C(R)), to form a disulfide
CC bridge. The disulfide is subsequently reduced by an appropriate
CC electron donor to complete the catalytic cycle. In this typical 2-Cys
CC peroxiredoxin, C(R) is provided by the other dimeric subunit to form an
CC intersubunit disulfide. The disulfide is subsequently reduced by
CC thioredoxin (By similarity). As a reducing substrate, thioredoxin 2 is
CC preferred over thioredoxin 1 (PubMed:11877442).
CC {ECO:0000250|UniProtKB:Q06830, ECO:0000269|PubMed:11877442}.
CC -!- SIMILARITY: Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.
CC {ECO:0000305}.
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DR EMBL; AF167098; AAF42985.1; -; mRNA.
DR EMBL; AF321615; AAK06770.1; -; mRNA.
DR EMBL; AF321616; AAK06771.1; -; mRNA.
DR EMBL; AE014298; AAF48253.1; -; Genomic_DNA.
DR EMBL; AY070534; AAL48005.1; -; mRNA.
DR EMBL; BT014630; AAT27254.1; -; mRNA.
DR RefSeq; NP_001285202.1; NM_001298273.1.
DR RefSeq; NP_001285203.1; NM_001298274.1.
DR RefSeq; NP_001285204.1; NM_001298275.1.
DR RefSeq; NP_477510.1; NM_058162.3.
DR RefSeq; NP_727689.1; NM_167359.2.
DR AlphaFoldDB; Q9V3P0; -.
DR SMR; Q9V3P0; -.
DR BioGRID; 72802; 25.
DR DIP; DIP-17916N; -.
DR IntAct; Q9V3P0; 16.
DR MINT; Q9V3P0; -.
DR STRING; 7227.FBpp0073594; -.
DR iPTMnet; Q9V3P0; -.
DR PaxDb; Q9V3P0; -.
DR PRIDE; Q9V3P0; -.
DR DNASU; 53578; -.
DR EnsemblMetazoa; FBtr0073763; FBpp0073594; FBgn0040309.
DR EnsemblMetazoa; FBtr0073764; FBpp0073595; FBgn0040309.
DR EnsemblMetazoa; FBtr0339699; FBpp0308756; FBgn0040309.
DR EnsemblMetazoa; FBtr0339700; FBpp0308757; FBgn0040309.
DR EnsemblMetazoa; FBtr0345161; FBpp0311371; FBgn0040309.
DR GeneID; 53578; -.
DR KEGG; dme:Dmel_CG1633; -.
DR CTD; 53578; -.
DR FlyBase; FBgn0040309; Jafrac1.
DR VEuPathDB; VectorBase:FBgn0040309; -.
DR eggNOG; KOG0852; Eukaryota.
DR HOGENOM; CLU_042529_21_1_1; -.
DR InParanoid; Q9V3P0; -.
DR OMA; FWYPKDF; -.
DR OrthoDB; 1326484at2759; -.
DR PhylomeDB; Q9V3P0; -.
DR Reactome; R-DME-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-DME-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-DME-9755511; KEAP1-NFE2L2 pathway.
DR SignaLink; Q9V3P0; -.
DR BioGRID-ORCS; 53578; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 53578; -.
DR PRO; PR:Q9V3P0; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0040309; Expressed in secondary oocyte and 38 other tissues.
DR ExpressionAtlas; Q9V3P0; baseline and differential.
DR Genevisible; Q9V3P0; DM.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IDA:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IMP:FlyBase.
DR GO; GO:0045454; P:cell redox homeostasis; IDA:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:0007281; P:germ cell development; IMP:FlyBase.
DR GO; GO:0008354; P:germ cell migration; IMP:FlyBase.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:FlyBase.
DR GO; GO:0045321; P:leukocyte activation; IBA:GO_Central.
DR GO; GO:0019430; P:removal of superoxide radicals; IBA:GO_Central.
DR GO; GO:0006979; P:response to oxidative stress; IMP:FlyBase.
DR GO; GO:0042594; P:response to starvation; IMP:FlyBase.
DR InterPro; IPR000866; AhpC/TSA.
DR InterPro; IPR024706; Peroxiredoxin_AhpC-typ.
DR InterPro; IPR019479; Peroxiredoxin_C.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR013766; Thioredoxin_domain.
DR Pfam; PF10417; 1-cysPrx_C; 1.
DR Pfam; PF00578; AhpC-TSA; 1.
DR PIRSF; PIRSF000239; AHPC; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW Antioxidant; Cytoplasm; Disulfide bond; Oxidoreductase; Peroxidase;
KW Phosphoprotein; Redox-active center; Reference proteome; Ubl conjugation.
FT CHAIN 1..194
FT /note="Peroxiredoxin 1"
FT /id="PRO_0000135085"
FT DOMAIN 2..160
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT ACT_SITE 47
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q06830"
FT MOD_RES 193
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT DISULFID 47
FT /note="Interchain (with C-168); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q06830"
FT DISULFID 168
FT /note="Interchain (with C-47); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q06830"
SQ SEQUENCE 194 AA; 21738 MW; 93ED319BE144E8D1 CRC64;
MPQLQKPAPA FAGTAVVNGV FKDIKLSDYK GKYLVLFFYP LDFTFVCPTE IIAFSESAAE
FRKINCEVIG CSTDSQFTHL AWINTPRKQG GLGSMDIPLL ADKSMKVARD YGVLDEETGI
PFRGLFIIDD KQNLRQITVN DLPVGRSVEE TLRLVQAFQY TDKYGEVCPA NWKPGQKTMV
ADPTKSKEYF ETTS
