PRDX4_DICDI
ID PRDX4_DICDI Reviewed; 259 AA.
AC Q555L5; Q555L4; Q8MP16;
DT 20-APR-2010, integrated into UniProtKB/Swiss-Prot.
DT 13-OCT-2009, sequence version 2.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Peroxiredoxin-4;
DE EC=1.11.1.24 {ECO:0000250|UniProtKB:Q13162};
DE AltName: Full=Thioredoxin-dependent peroxiredoxin 4 {ECO:0000305};
GN Name=prdx4; ORFNames=DDB_G0274859;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 1).
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING
RP (ISOFORMS 1 AND 2).
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [3]
RP DEVELOPMENTAL STAGE [LARGE SCALE ANALYSIS].
RX PubMed=15470253; DOI=10.1128/ec.3.5.1241-1248.2004;
RA Maruo T., Sakamoto H., Iranfar N., Fuller D., Morio T., Urushihara H.,
RA Tanaka Y., Maeda M., Loomis W.F.;
RT "Control of cell type proportioning in Dictyostelium discoideum by
RT differentiation-inducing factor as determined by in situ hybridization.";
RL Eukaryot. Cell 3:1241-1248(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=AX2;
RX PubMed=16926386; DOI=10.1074/mcp.m600113-mcp200;
RA Gotthardt D., Blancheteau V., Bosserhoff A., Ruppert T., Delorenzi M.,
RA Soldati T.;
RT "Proteomics fingerprinting of phagosome maturation and evidence for the
RT role of a Galpha during uptake.";
RL Mol. Cell. Proteomics 5:2228-2243(2006).
RN [5]
RP INDUCTION [LARGE SCALE ANALYSIS].
RX PubMed=18990192; DOI=10.1111/j.1365-2958.2008.06497.x;
RA Choi C.H., Park S.J., Jeong S.Y., Yim H.S., Kang S.O.;
RT "Methylglyoxal accumulation by glutathione depletion leads to cell cycle
RT arrest in Dictyostelium.";
RL Mol. Microbiol. 70:1293-1304(2008).
RN [6]
RP IDENTIFICATION [LARGE SCALE ANALYSIS].
RX PubMed=19482547; DOI=10.1016/j.ijmm.2009.03.006;
RA Shevchuk O., Batzilla C., Haegele S., Kusch H., Engelmann S., Hecker M.,
RA Haas A., Heuner K., Gloeckner G., Steinert M.;
RT "Proteomic analysis of Legionella-containing phagosomes isolated from
RT Dictyostelium.";
RL Int. J. Med. Microbiol. 299:489-508(2009).
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. Regulates the activation of NF-kappa-B in the cytosol
CC by a modulation of I-kappa-B-alpha phosphorylation.
CC {ECO:0000250|UniProtKB:Q13162}.
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:0000250|UniProtKB:Q13162};
CC -!- SUBUNIT: Homodimer; disulfide-linked, upon oxidation. 5 homodimers
CC assemble to form a ring-like decamer. {ECO:0000250|UniProtKB:Q13162}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13162}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:Q13162}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q555L5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q555L5-2; Sequence=VSP_038918;
CC -!- DEVELOPMENTAL STAGE: Pre-spore specific. {ECO:0000269|PubMed:15470253}.
CC -!- INDUCTION: Up-regulated in gcsA null cells devoid of glutathione.
CC {ECO:0000269|PubMed:18990192}.
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:Q13162}.
CC -!- SIMILARITY: Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.
CC {ECO:0000305}.
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DR EMBL; AC123513; AAM44383.1; -; Genomic_DNA.
DR EMBL; AAFI02000012; EAL70321.2; -; Genomic_DNA.
DR EMBL; AAFI02000012; EAL70322.1; -; Genomic_DNA.
DR RefSeq; XP_644051.2; XM_638959.2.
DR RefSeq; XP_644052.1; XM_638960.1.
DR AlphaFoldDB; Q555L5; -.
DR SMR; Q555L5; -.
DR STRING; 44689.DDB0305016; -.
DR PeroxiBase; 4100; Dd2CysPrx.
DR PaxDb; Q555L5; -.
DR EnsemblProtists; EAL70321; EAL70321; DDB_G0274859.
DR EnsemblProtists; EAL70322; EAL70322; DDB_G0274859.
DR GeneID; 8619481; -.
DR KEGG; ddi:DDB_G0274859; -.
DR dictyBase; DDB_G0274859; prdx4.
DR eggNOG; KOG0852; Eukaryota.
DR HOGENOM; CLU_042529_21_0_1; -.
DR InParanoid; Q555L5; -.
DR OMA; EDSESCY; -.
DR PhylomeDB; Q555L5; -.
DR Reactome; R-DDI-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-DDI-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-DDI-6798695; Neutrophil degranulation.
DR Reactome; R-DDI-9755511; KEAP1-NFE2L2 pathway.
DR PRO; PR:Q555L5; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0045335; C:phagocytic vesicle; HDA:dictyBase.
DR GO; GO:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR GO; GO:0051920; F:peroxiredoxin activity; IEA:UniProtKB-EC.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0046689; P:response to mercury ion; IDA:dictyBase.
DR InterPro; IPR000866; AhpC/TSA.
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 SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Antioxidant; Cytoplasm; Disulfide bond;
KW Endoplasmic reticulum; Oxidoreductase; Peroxidase; Redox-active center;
KW Reference proteome.
FT CHAIN 1..259
FT /note="Peroxiredoxin-4"
FT /id="PRO_0000393334"
FT DOMAIN 66..224
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT ACT_SITE 111
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q13162"
FT DISULFID 111
FT /note="Interchain (with C-232); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q13162"
FT DISULFID 232
FT /note="Interchain (with C-111); in linked form"
FT /evidence="ECO:0000250|UniProtKB:Q13162"
FT VAR_SEQ 1..64
FT /note="MRSATKLFKNLSKSVVQLKTVKPVSSLNFGYIKTRQFSTSTTDSSNLFLNNN
FT NQFQNFTFPTKQ -> MTHPHCHKKE (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_038918"
SQ SEQUENCE 259 AA; 29040 MW; 336598CD44F11295 CRC64;
MRSATKLFKN LSKSVVQLKT VKPVSSLNFG YIKTRQFSTS TTDSSNLFLN NNNQFQNFTF
PTKQQIRIRK PAPAFKGQAV VNGEFKEISL DDYKGKYLYL FFYPLDFTFV CPTEIIAFSN
AAEEFKKAGC ELVGCSIDSP FTHLAWINTP RKEGGLGGIN IPLLSDLTHQ ISKDYGVYIE
EDGHTIRGSI LIDKEGLVRV ITMNDNPVGR SVDEAIRTLK ALKFTDQFGE VCPANWSEGD
KSMKADPKGS KEYFEAVNK
