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 02-OCT-2024, entry version 218. 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; Q06830: PRDX1; NbExp=2; IntAct=EBI-2211957, EBI-353193; 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 PDB; 8EKW; EM; 2.83 A; A/B/C/D/E/F/G/H/I/J=1-271. DR PDB; 8EKY; EM; 3.47 A; A/B/C/D/E/F/G/H/I/J=1-271. 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 PDBsum; 8EKW; -. DR PDBsum; 8EKY; -. DR AlphaFoldDB; Q13162; -. DR EMDB; EMD-28214; -. DR EMDB; EMD-28217; -. DR SMR; Q13162; -. DR BioGRID; 115800; 233. DR IntAct; Q13162; 82. 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 CPTAC; CPTAC-1448; -. DR CPTAC; CPTAC-1449; -. DR CPTAC; CPTAC-1450; -. DR CPTAC; CPTAC-1451; -. DR CPTAC; CPTAC-713; -. DR CPTAC; CPTAC-714; -. DR jPOST; Q13162; -. DR MassIVE; Q13162; -. DR PaxDb; 9606-ENSP00000368646; -. DR PeptideAtlas; Q13162; -. DR ProteomicsDB; 59198; -. DR Pumba; Q13162; -. DR TopDownProteomics; Q13162; -. DR ABCD; Q13162; 2 sequenced antibodies. DR Antibodypedia; 3275; 526 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 AGR; HGNC:17169; -. 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; KPAPEWE; -. DR OrthoDB; 47465at2759; -. 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; 21 hits in 782 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 214 other cell types or tissues. DR ExpressionAtlas; Q13162; baseline and differential. 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:0060090; F:molecular adaptor activity; EXP:DisProt. DR GO; GO:0140313; F:molecular sequestering activity; IDA:DisProt. DR GO; GO:0008379; F:thioredoxin peroxidase activity; IBA:GO_Central. DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central. DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl. DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IBA:GO_Central. 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:0022417; P:protein maturation by protein folding; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; IBA:GO_Central. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR CDD; cd03015; PRX_Typ2cys; 1. DR DisProt; DP02764; -. DR Gene3D; 3.40.30.10; Glutaredoxin; 1. DR InterPro; IPR000866; AhpC/TSA. DR InterPro; IPR050217; Peroxiredoxin. DR InterPro; IPR019479; Peroxiredoxin_C. DR InterPro; IPR036249; Thioredoxin-like_sf. DR InterPro; IPR013766; Thioredoxin_domain. DR PANTHER; PTHR10681:SF173; PEROXIREDOXIN-4; 1. DR PANTHER; PTHR10681; THIOREDOXIN PEROXIDASE; 1. DR Pfam; PF10417; 1-cysPrx_C; 1. DR Pfam; PF00578; AhpC-TSA; 1. DR SUPFAM; SSF52833; Thioredoxin-like; 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 Proteomics identification; 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 STRAND 256..258 FT /evidence="ECO:0007829|PDB:8EKY" 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 //