PRDX4_HUMAN
ID PRDX4_HUMAN Reviewed; 271 AA.
AC Q13162; Q6FHT3;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Peroxiredoxin-4;
DE EC=1.11.1.24 {ECO:0000269|PubMed:21916849, ECO:0000269|PubMed:9388242};
DE AltName: Full=Antioxidant enzyme AOE372;
DE Short=AOE37-2;
DE AltName: Full=Peroxiredoxin IV;
DE Short=Prx-IV;
DE AltName: Full=Thioredoxin peroxidase AO372;
DE AltName: Full=Thioredoxin-dependent peroxide reductase A0372;
DE AltName: Full=Thioredoxin-dependent peroxiredoxin 4 {ECO:0000305};
DE Flags: Precursor;
GN Name=PRDX4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, AND SUBUNIT.
RX PubMed=9388242; DOI=10.1074/jbc.272.49.30952;
RA Jin D.-Y., Chae H.Z., Rhee S.G., Jeang K.-T.;
RT "Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB
RT activation.";
RL J. Biol. Chem. 272:30952-30961(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 38-46.
RC TISSUE=Leukemic T-cell;
RX PubMed=19892738; DOI=10.1073/pnas.0908958106;
RA Xu G., Shin S.B., Jaffrey S.R.;
RT "Global profiling of protease cleavage sites by chemoselective labeling of
RT protein N-termini.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009).
RN [5]
RP PROTEIN SEQUENCE OF 46-66; 81-99; 140-164; 174-208; 213-223 AND 231-263,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [6]
RP OVEROXIDATION AT CYS-124.
RX PubMed=12059788; DOI=10.1042/bj20020525;
RA Wagner E., Luche S., Penna L., Chevallet M., van Dorsselaer A.,
RA Leize-Wagner E., Rabilloud T.;
RT "A method for detection of overoxidation of cysteines: peroxiredoxins are
RT oxidized in vivo at the active-site cysteine during oxidative stress.";
RL Biochem. J. 366:777-785(2002).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=18052930; DOI=10.1042/bj20071428;
RA Tavender T.J., Sheppard A.M., Bulleid N.J.;
RT "Peroxiredoxin IV is an endoplasmic reticulum-localized enzyme forming
RT oligomeric complexes in human cells.";
RL Biochem. J. 411:191-199(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER GLY-37, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS), AND DISULFIDE BONDS.
RX PubMed=21994946; DOI=10.1074/jbc.m111.298810;
RA Cao Z., Tavender T.J., Roszak A.W., Cogdell R.J., Bulleid N.J.;
RT "Crystal structure of reduced and of oxidized peroxiredoxin IV enzyme
RT reveals a stable oxidized decamer and a non-disulfide-bonded intermediate
RT in the catalytic cycle.";
RL J. Biol. Chem. 286:42257-42266(2011).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS), AND CATALYTIC ACTIVITY.
RX PubMed=21916849; DOI=10.1042/bj20110380;
RA Wang X., Wang L., Wang X., Sun F., Wang C.C.;
RT "Structural insights into the peroxidase activity and inactivation of human
RT peroxiredoxin 4.";
RL Biochem. J. 441:113-118(2012).
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:0000269|PubMed:9388242}.
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:21916849, ECO:0000269|PubMed:9388242};
CC -!- SUBUNIT: Homodimer; disulfide-linked, upon oxidation (PubMed:9388242).
CC 5 homodimers assemble to form a ring-like decamer (PubMed:21994946).
CC Can form heterodimers with PRDX1 (PubMed:9388242).
CC {ECO:0000269|PubMed:21994946, ECO:0000269|PubMed:9388242}.
CC -!- INTERACTION:
CC Q13162; P54253: ATXN1; NbExp=4; IntAct=EBI-2211957, EBI-930964;
CC Q13162; P18428: LBP; NbExp=4; IntAct=EBI-2211957, EBI-3927059;
CC Q13162; P07237: P4HB; NbExp=2; IntAct=EBI-2211957, EBI-395883;
CC Q13162; P30101: PDIA3; NbExp=2; IntAct=EBI-2211957, EBI-979862;
CC Q13162; Q15084: PDIA6; NbExp=2; IntAct=EBI-2211957, EBI-1043087;
CC Q13162; P21731: TBXA2R; NbExp=3; IntAct=EBI-2211957, EBI-2625082;
CC Q13162; Q8NBS9: TXNDC5; NbExp=2; IntAct=EBI-2211957, EBI-2510815;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18052930,
CC ECO:0000269|PubMed:9388242}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:18052930}. Note=Cotranslationally translocated to
CC and retained within the endoplasmic reticulum. A small fraction of the
CC protein is cytoplasmic. {ECO:0000269|PubMed:18052930}.
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) and sulphonic
CC acid (C(P)-SO3H) instead of its condensation to a disulfide bond.
CC {ECO:0000269|PubMed:12059788, ECO:0000269|PubMed:21916849}.
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:0000305|PubMed:21994946}.
CC -!- SIMILARITY: Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U25182; AAB95175.1; -; mRNA.
DR EMBL; CR541668; CAG46469.1; -; mRNA.
DR EMBL; CR541705; CAG46506.1; -; mRNA.
DR EMBL; BC003609; AAH03609.1; -; mRNA.
DR EMBL; BC007107; AAH07107.1; -; mRNA.
DR EMBL; BC016770; AAH16770.1; -; mRNA.
DR CCDS; CCDS14206.1; -.
DR PIR; G01790; G01790.
DR RefSeq; NP_006397.1; NM_006406.1.
DR PDB; 2PN8; X-ray; 1.80 A; A/B/C/D/E/F/G/H/I/J=84-271.
DR PDB; 3TJB; X-ray; 2.38 A; A/B/C/D/E=38-271.
DR PDB; 3TJF; X-ray; 2.04 A; A/B/C/D/E=38-271.
DR PDB; 3TJG; X-ray; 2.24 A; A/B/C/D/E=38-271.
DR PDB; 3TJJ; X-ray; 1.91 A; A/B/C/D/E=38-271.
DR PDB; 3TJK; X-ray; 2.09 A; A/B/C/D/E=38-271.
DR PDB; 3TKP; X-ray; 2.49 A; A/B/C/D/E=38-271.
DR PDB; 3TKQ; X-ray; 2.22 A; A/B/C/D/E=38-271.
DR PDB; 3TKR; X-ray; 2.10 A; A/B/C/D/E/F/G/H/I/J=38-271.
DR PDB; 3TKS; X-ray; 2.40 A; A/B/C/D/E=38-271.
DR PDB; 4RQX; X-ray; 2.26 A; A/B/C/D/E=79-271.
DR PDB; 5HQP; X-ray; 2.60 A; A/B=38-271.
DR PDBsum; 2PN8; -.
DR PDBsum; 3TJB; -.
DR PDBsum; 3TJF; -.
DR PDBsum; 3TJG; -.
DR PDBsum; 3TJJ; -.
DR PDBsum; 3TJK; -.
DR PDBsum; 3TKP; -.
DR PDBsum; 3TKQ; -.
DR PDBsum; 3TKR; -.
DR PDBsum; 3TKS; -.
DR PDBsum; 4RQX; -.
DR PDBsum; 5HQP; -.
DR AlphaFoldDB; Q13162; -.
DR SMR; Q13162; -.
DR BioGRID; 115800; 174.
DR IntAct; Q13162; 73.
DR MINT; Q13162; -.
DR STRING; 9606.ENSP00000368646; -.
DR ChEMBL; CHEMBL4295812; -.
DR PeroxiBase; 4530; Hs2CysPrx04.
DR GlyGen; Q13162; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13162; -.
DR PhosphoSitePlus; Q13162; -.
DR SwissPalm; Q13162; -.
DR BioMuta; PRDX4; -.
DR DMDM; 3024727; -.
DR OGP; Q13162; -.
DR REPRODUCTION-2DPAGE; IPI00011937; -.
DR UCD-2DPAGE; Q13162; -.
DR CPTAC; CPTAC-1448; -.
DR CPTAC; CPTAC-1449; -.
DR CPTAC; CPTAC-1450; -.
DR CPTAC; CPTAC-1451; -.
DR CPTAC; CPTAC-713; -.
DR CPTAC; CPTAC-714; -.
DR EPD; Q13162; -.
DR jPOST; Q13162; -.
DR MassIVE; Q13162; -.
DR PaxDb; Q13162; -.
DR PeptideAtlas; Q13162; -.
DR PRIDE; Q13162; -.
DR ProteomicsDB; 59198; -.
DR TopDownProteomics; Q13162; -.
DR ABCD; Q13162; 2 sequenced antibodies.
DR Antibodypedia; 3275; 463 antibodies from 38 providers.
DR CPTC; Q13162; 5 antibodies.
DR DNASU; 10549; -.
DR Ensembl; ENST00000379341.9; ENSP00000368646.4; ENSG00000123131.13.
DR GeneID; 10549; -.
DR KEGG; hsa:10549; -.
DR MANE-Select; ENST00000379341.9; ENSP00000368646.4; NM_006406.2; NP_006397.1.
DR CTD; 10549; -.
DR DisGeNET; 10549; -.
DR GeneCards; PRDX4; -.
DR HGNC; HGNC:17169; PRDX4.
DR HPA; ENSG00000123131; Tissue enriched (pancreas).
DR MIM; 300927; gene.
DR neXtProt; NX_Q13162; -.
DR OpenTargets; ENSG00000123131; -.
DR PharmGKB; PA33725; -.
DR VEuPathDB; HostDB:ENSG00000123131; -.
DR eggNOG; KOG0852; Eukaryota.
DR GeneTree; ENSGT00940000153430; -.
DR HOGENOM; CLU_042529_21_1_1; -.
DR InParanoid; Q13162; -.
DR OMA; EDSESCY; -.
DR OrthoDB; 1326484at2759; -.
DR PhylomeDB; Q13162; -.
DR TreeFam; TF105181; -.
DR BRENDA; 1.11.1.24; 2681.
DR PathwayCommons; Q13162; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q13162; -.
DR BioGRID-ORCS; 10549; 15 hits in 705 CRISPR screens.
DR ChiTaRS; PRDX4; human.
DR EvolutionaryTrace; Q13162; -.
DR GeneWiki; PRDX4; -.
DR GenomeRNAi; 10549; -.
DR Pharos; Q13162; Tbio.
DR PRO; PR:Q13162; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q13162; protein.
DR Bgee; ENSG00000123131; Expressed in body of pancreas and 212 other tissues.
DR ExpressionAtlas; Q13162; baseline and differential.
DR Genevisible; Q13162; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; TAS:ProtInc.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0007252; P:I-kappaB phosphorylation; TAS:ProtInc.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:2000255; P:negative regulation of male germ cell proliferation; IEA:Ensembl.
DR GO; GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; IEA:Ensembl.
DR GO; GO:0022417; P:protein maturation by protein folding; IEA:Ensembl.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR DisProt; DP02764; -.
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 3D-structure; Antioxidant; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Oxidoreductase; Peroxidase;
KW Redox-active center; Reference proteome; Signal.
FT SIGNAL 1..37
FT /evidence="ECO:0000269|PubMed:19892738,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 38..271
FT /note="Peroxiredoxin-4"
FT /id="PRO_0000135098"
FT DOMAIN 79..237
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT ACT_SITE 124
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000305|PubMed:12059788,
FT ECO:0000305|PubMed:21916849"
FT DISULFID 124
FT /note="Interchain (with C-245); in linked form"
FT /evidence="ECO:0000269|PubMed:21994946,
FT ECO:0007744|PDB:3TJB, ECO:0007744|PDB:3TJG"
FT DISULFID 245
FT /note="Interchain (with C-124); in linked form"
FT /evidence="ECO:0000269|PubMed:21994946,
FT ECO:0007744|PDB:3TJB, ECO:0007744|PDB:3TJG"
FT CONFLICT 12
FT /note="P -> S (in Ref. 3; CAG46469)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="C -> Y (in Ref. 3; CAG46469)"
FT /evidence="ECO:0000305"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:3TJK"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:2PN8"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:2PN8"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:2PN8"
FT STRAND 109..115
FT /evidence="ECO:0007829|PDB:2PN8"
FT HELIX 123..133
FT /evidence="ECO:0007829|PDB:2PN8"
FT HELIX 135..139
FT /evidence="ECO:0007829|PDB:2PN8"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:2PN8"
FT STRAND 143..151
FT /evidence="ECO:0007829|PDB:2PN8"
FT HELIX 153..160
FT /evidence="ECO:0007829|PDB:2PN8"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:2PN8"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:2PN8"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:5HQP"
FT HELIX 183..187
FT /evidence="ECO:0007829|PDB:2PN8"
FT TURN 193..195
FT /evidence="ECO:0007829|PDB:2PN8"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:2PN8"
FT STRAND 200..205
FT /evidence="ECO:0007829|PDB:2PN8"
FT STRAND 209..217
FT /evidence="ECO:0007829|PDB:2PN8"
FT HELIX 225..241
FT /evidence="ECO:0007829|PDB:2PN8"
FT TURN 260..262
FT /evidence="ECO:0007829|PDB:2PN8"
FT HELIX 263..267
FT /evidence="ECO:0007829|PDB:2PN8"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:3TKS"
SQ SEQUENCE 271 AA; 30540 MW; 7E56B580049FC60F CRC64;
MEALPLLAAT TPDHGRHRRL LLLPLLLFLL PAGAVQGWET EERPRTREEE CHFYAGGQVY
PGEASRVSVA DHSLHLSKAK ISKPAPYWEG TAVIDGEFKE LKLTDYRGKY LVFFFYPLDF
TFVCPTEIIA FGDRLEEFRS INTEVVACSV DSQFTHLAWI NTPRRQGGLG PIRIPLLSDL
THQISKDYGV YLEDSGHTLR GLFIIDDKGI LRQITLNDLP VGRSVDETLR LVQAFQYTDK
HGEVCPAGWK PGSETIIPDP AGKLKYFDKL N
