PRDX_CAEEL
ID PRDX_CAEEL Reviewed; 201 AA.
AC A0A0K3AUJ9; H2KZL7; Q8IG31;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 11-NOV-2015, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Peroxiredoxin prdx-2 {ECO:0000305};
DE EC=1.11.1.24 {ECO:0000269|PubMed:15099742};
DE AltName: Full=2-Cys peroxiredoxin 2 {ECO:0000303|PubMed:19064914};
GN Name=prdx-2 {ECO:0000312|WormBase:F09E5.15c};
GN Synonyms=prx2 {ECO:0000303|PubMed:15099742},
GN tag-56 {ECO:0000312|WormBase:F09E5.15c};
GN ORFNames=F09E5.15 {ECO:0000312|WormBase:F09E5.15c};
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, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=15099742; DOI=10.1016/j.jmb.2004.03.021;
RA Isermann K., Liebau E., Roeder T., Bruchhaus I.;
RT "A peroxiredoxin specifically expressed in two types of pharyngeal neurons
RT is required for normal growth and egg production in Caenorhabditis
RT elegans.";
RL J. Mol. Biol. 338:745-755(2004).
RN [3] {ECO:0000305}
RP FUNCTION, ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=19064914; DOI=10.1073/pnas.0805507105;
RA Olahova M., Taylor S.R., Khazaipoul S., Wang J., Morgan B.A., Matsumoto K.,
RA Blackwell T.K., Veal E.A.;
RT "A redox-sensitive peroxiredoxin that is important for longevity has
RT tissue- and stress-specific roles in stress resistance.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:19839-19844(2008).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=20964547; DOI=10.1089/ars.2010.3717;
RA Thamsen M., Kumsta C., Li F., Jakob U.;
RT "Is overoxidation of peroxiredoxin physiologically significant?";
RL Antioxid. Redox Signal. 14:725-730(2011).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=20649472; DOI=10.1089/ars.2010.3203;
RA Kumsta C., Thamsen M., Jakob U.;
RT "Effects of oxidative stress on behavior, physiology, and the redox thiol
RT proteome of Caenorhabditis elegans.";
RL Antioxid. Redox Signal. 14:1023-1037(2011).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=25204677; DOI=10.1186/s12915-014-0064-6;
RA Crook-McMahon H.M., Olahova M., Button E.L., Winter J.J., Veal E.A.;
RT "Genome-wide screening identifies new genes required for stress-induced
RT phase 2 detoxification gene expression in animals.";
RL BMC Biol. 12:64-64(2014).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=24889636; DOI=10.1073/pnas.1321776111;
RA De Haes W., Frooninckx L., Van Assche R., Smolders A., Depuydt G.,
RA Billen J., Braeckman B.P., Schoofs L., Temmerman L.;
RT "Metformin promotes lifespan through mitohormesis via the peroxiredoxin
RT PRDX-2.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E2501-E2509(2014).
RN [8] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25808059; DOI=10.1111/acel.12321;
RA Olahova M., Veal E.A.;
RT "A peroxiredoxin, PRDX-2, is required for insulin secretion and
RT insulin/IIS-dependent regulation of stress resistance and longevity.";
RL Aging Cell 14:558-568(2015).
RN [9] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=25640076; DOI=10.1016/j.neuron.2014.12.061;
RA Bhatla N., Horvitz H.R.;
RT "Light and hydrogen peroxide inhibit C. elegans Feeding through gustatory
RT receptor orthologs and pharyngeal neurons.";
RL Neuron 85:804-818(2015).
RN [10] {ECO:0000305}
RP DEVELOPMENTAL STAGE.
RX PubMed=29055282; DOI=10.1016/j.redox.2017.10.003;
RA Henderson D., Huebner C., Markowitz M., Taube N., Harvanek Z.M., Jakob U.,
RA Knoefler D.;
RT "Do developmental temperatures affect redox level and lifespan in C.
RT elegans through upregulation of peroxiredoxin?";
RL Redox Biol. 14:386-390(2018).
CC -!- FUNCTION: Thiol-specific peroxidase that catalyzes the reduction of
CC hydrogen peroxide and organic hydroperoxides to water and alcohols,
CC respectively (PubMed:15099742). In I2 pharyngeal neurons, required for
CC the inhibition of feeding in response to light and hydrogen peroxide
CC (PubMed:25640076). In the intestine, plays a role in protecting cells
CC against oxidative stress by detoxifying peroxides such as hydrogen
CC peroxide (PubMed:15099742, PubMed:19064914, PubMed:20649472). In
CC addition, plays a role in the recovery from oxidative stress induced by
CC hydrogen peroxide (PubMed:20649472). In its hyperoxidized form (induced
CC by hydrogen peroxide), confers protection against heat stress
CC (PubMed:19064914). However, has a low tendency for overoxidation during
CC the normal lifespan (PubMed:20964547). Increases sensitivity to
CC cytotoxity caused by metalloids and heavy metals such as arsenic and
CC cadmium by playing a role in inhibiting the expression of phase II
CC detoxification genes such as gcs-1 in intestinal cells
CC (PubMed:19064914, PubMed:25204677). In addition, in response to
CC arsenite, promotes the secretion of the insulin ligand daf-28 into the
CC pseudocoelom, which negatively regulates the activities of daf-16 and
CC skn-1 (PubMed:25808059). Plays a role in promoting longevity
CC (PubMed:19064914, PubMed:24889636). Plays a role in the mitohormetic
CC pathway by promoting the activation of pmk-1 in response to the drug
CC metformin (PubMed:24889636). {ECO:0000269|PubMed:15099742,
CC ECO:0000269|PubMed:19064914, ECO:0000269|PubMed:20649472,
CC ECO:0000269|PubMed:20964547, ECO:0000269|PubMed:24889636,
CC ECO:0000269|PubMed:25204677, ECO:0000269|PubMed:25640076,
CC ECO:0000269|PubMed:25808059}.
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:15099742};
CC -!- ACTIVITY REGULATION: Activated following oxidation of the conserved
CC redox-active cysteine residue, which subsequently allows for the
CC oxidation and activation of substrates. {ECO:0000269|PubMed:15099742,
CC ECO:0000269|PubMed:19064914}.
CC -!- SUBUNIT: Monomer and homodimer; disulfide-linked (PubMed:19064914).
CC Under nonstress conditions, present in the reduced monomeric form
CC (PubMed:19064914). Forms active hyperoxidized monomers and disulfide-
CC linked homodimers upon oxidation by hydrogen peroxide
CC (PubMed:19064914). Forms active oxidized homodimers in response to the
CC drug metformin (PubMed:24889636). {ECO:0000269|PubMed:19064914,
CC ECO:0000269|PubMed:24889636}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19064914}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=c {ECO:0000312|WormBase:F09E5.15c};
CC IsoId=A0A0K3AUJ9-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:F09E5.15a};
CC IsoId=A0A0K3AUJ9-2; Sequence=VSP_060734;
CC Name=b {ECO:0000312|WormBase:F09E5.15b};
CC IsoId=A0A0K3AUJ9-3; Sequence=VSP_060735;
CC -!- TISSUE SPECIFICITY: Expressed in the gonad, neurons and intestine (at
CC protein level) (PubMed:19064914). Expressed in the pharyngeal inter-
CC neuron I4 and the sensory interneuron I2 (PubMed:15099742,
CC PubMed:25640076). Expressed in the intestine, pharyngeal muscle 1,
CC vulval muscle, body wall muscle, epithelial cells e1 and e3, and
CC neurons in the head and tail (PubMed:25640076).
CC {ECO:0000269|PubMed:15099742, ECO:0000269|PubMed:19064914,
CC ECO:0000269|PubMed:25640076}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout embryonic, larval and adult
CC stages (PubMed:15099742, PubMed:19064914). Highly expressed at the L3
CC larval stage at 25 degrees Celsius (PubMed:29055282).
CC {ECO:0000269|PubMed:15099742, ECO:0000269|PubMed:19064914,
CC ECO:0000269|PubMed:29055282}.
CC -!- INDUCTION: Up-regulated in response to the drug metformin.
CC {ECO:0000269|PubMed:24889636}.
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. {ECO:0000250|UniProtKB:Q06830}.
CC -!- DISRUPTION PHENOTYPE: Reduced size, egg production and brood size
CC (PubMed:15099742). Survival in response to heat and oxidative stress
CC induced by peroxides is comparable to wild-type (PubMed:15099742).
CC RNAi-mediated knockdown increases lifespan in response to the heavy
CC metal arsenite (PubMed:25808059). RNAi-mediated knockdown increases
CC expression of gcs-1 and further increases gcs-1 expression in response
CC to the heavy metal arsenite (PubMed:19064914). RNAi-mediated knockdown
CC increases the expression of isoform a of skn-1 in intestinal nuclei
CC (PubMed:25808059). {ECO:0000269|PubMed:15099742,
CC ECO:0000269|PubMed:19064914, ECO:0000269|PubMed:25808059}.
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. {ECO:0000250|UniProtKB:Q06830}.
CC -!- SIMILARITY: Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.
CC {ECO:0000305}.
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DR EMBL; BX284602; CCD68767.1; -; Genomic_DNA.
DR EMBL; BX284602; CCD68770.1; -; Genomic_DNA.
DR EMBL; BX284602; CTQ86475.1; -; Genomic_DNA.
DR RefSeq; NP_001122604.1; NM_001129132.2.
DR RefSeq; NP_001300536.1; NM_001313607.1. [A0A0K3AUJ9-1]
DR RefSeq; NP_872052.1; NM_182252.5.
DR AlphaFoldDB; A0A0K3AUJ9; -.
DR SMR; A0A0K3AUJ9; -.
DR STRING; 6239.F09E5.15b; -.
DR PeroxiBase; 4485; Cel2CysPrx02.
DR World-2DPAGE; 0020:Q8IG31; -.
DR EnsemblMetazoa; F09E5.15a.1; F09E5.15a.1; WBGene00006434. [A0A0K3AUJ9-2]
DR EnsemblMetazoa; F09E5.15b.1; F09E5.15b.1; WBGene00006434. [A0A0K3AUJ9-3]
DR EnsemblMetazoa; F09E5.15c.1; F09E5.15c.1; WBGene00006434. [A0A0K3AUJ9-1]
DR GeneID; 266858; -.
DR UCSC; F09E5.15b.1; c. elegans.
DR CTD; 266858; -.
DR WormBase; F09E5.15a; CE32361; WBGene00006434; prdx-2. [A0A0K3AUJ9-2]
DR WormBase; F09E5.15b; CE41559; WBGene00006434; prdx-2. [A0A0K3AUJ9-3]
DR WormBase; F09E5.15c; CE50863; WBGene00006434; prdx-2. [A0A0K3AUJ9-1]
DR eggNOG; KOG0852; Eukaryota.
DR HOGENOM; CLU_042529_21_1_1; -.
DR OMA; CPLGWKP; -.
DR OrthoDB; 1326484at2759; -.
DR BRENDA; 1.11.1.24; 1045.
DR Reactome; R-CEL-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-CEL-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-CEL-9755511; KEAP1-NFE2L2 pathway.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00006434; Expressed in embryo and 4 other tissues.
DR ExpressionAtlas; A0A0K3AUJ9; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IDA:WormBase.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IMP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0010286; P:heat acclimation; IMP:WormBase.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:WormBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:0090727; P:positive regulation of brood size; IMP:UniProtKB.
DR GO; GO:1902882; P:regulation of response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0042542; P:response to hydrogen peroxide; IMP:WormBase.
DR GO; GO:0010038; P:response to metal ion; IMP:WormBase.
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 Alternative splicing; Antioxidant; Cytoplasm; Disulfide bond;
KW Oxidoreductase; Peroxidase; Redox-active center; Reference proteome.
FT CHAIN 1..201
FT /note="Peroxiredoxin prdx-2"
FT /id="PRO_0000450862"
FT DOMAIN 10..168
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT ACT_SITE 55
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q06830"
FT DISULFID 55
FT /note="Interchain (with C-176); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q06830"
FT DISULFID 176
FT /note="Interchain (with C-55); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q06830"
FT VAR_SEQ 1..6
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_060734"
FT VAR_SEQ 1..6
FT /note="MSLAPK -> MYRQ (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060735"
SQ SEQUENCE 201 AA; 22413 MW; 3E0DD7ECF8C32FC4 CRC64;
MSLAPKMSKA FIGKPAPQFK TQAVVDGEFV DVSLSDYKGK YVVLFFYPLD FTFVCPTEII
AFSDRAEEFK AINTVVLAAS TDSVFSHLAW INQPRKHGGL GEMNIPVLAD TNHQISRDYG
VLKEDEGIAF RGLFIIDPSQ NLRQITINDL PVGRSVDETL RLVQAFQFVE KHGEVCPAGW
TPGSDTIKPG VKESQEYFKK H
