PRDX4_MOUSE
ID PRDX4_MOUSE Reviewed; 274 AA.
AC O08807; B1AZS7; Q3U8E4;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Peroxiredoxin-4;
DE EC=1.11.1.24 {ECO:0000250|UniProtKB:Q13162};
DE AltName: Full=Antioxidant enzyme AOE372;
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=C57BL/6J;
RX PubMed=11229364; DOI=10.1089/15230860050192288;
RA Wong C.M., Chun A.C., Kok K.H., Zhou Y., Fung P.C., Kung H.F., Jeang K.-T.,
RA Jin D.-Y.;
RT "Characterization of human and mouse peroxiredoxin IV: evidence for
RT inhibition by Prx-IV of epidermal growth factor- and p53-induced reactive
RT oxygen species.";
RL Antioxid. Redox Signal. 2:507-518(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and DBA/2J; TISSUE=Bone marrow, and Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NMRI; TISSUE=Mammary gland, and Mammary tumor;
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 [5]
RP PROTEIN SEQUENCE OF 190-203 AND 216-226.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U., Yang J.W., Zigmond M.;
RL Submitted (JUL-2007) to UniProtKB.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS), AND DISULFIDE BONDS.
RX PubMed=23949117; DOI=10.1038/srep02456;
RA Sato Y., Kojima R., Okumura M., Hagiwara M., Masui S., Maegawa K.,
RA Saiki M., Horibe T., Suzuki M., Inaba K.;
RT "Synergistic cooperation of PDI family members in peroxiredoxin 4-driven
RT oxidative protein folding.";
RL Sci. Rep. 3:2456-2456(2013).
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 (PubMed:11229364). Regulates the activation of NF-
CC kappa-B in the cytosol by a modulation of I-kappa-B-alpha
CC phosphorylation (By similarity). {ECO:0000250|UniProtKB:Q13162,
CC ECO:0000269|PubMed:11229364}.
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 -!- INTERACTION:
CC O08807; Q8NBS9-1: TXNDC5; Xeno; NbExp=2; IntAct=EBI-494652, EBI-16091651;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13162}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:Q13162}. Note=Not
CC secreted. {ECO:0000269|PubMed:11229364}.
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:0000250|UniProtKB:Q13162}.
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; U96746; AAB57846.1; -; mRNA.
DR EMBL; AK005031; BAB23758.1; -; mRNA.
DR EMBL; AK146402; BAE27143.1; -; mRNA.
DR EMBL; AK152255; BAE31074.1; -; mRNA.
DR EMBL; BX005263; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003349; AAH03349.1; -; mRNA.
DR EMBL; BC019578; AAH19578.1; -; mRNA.
DR CCDS; CCDS30496.1; -.
DR RefSeq; NP_001300640.1; NM_001313711.1.
DR RefSeq; NP_058044.1; NM_016764.5.
DR PDB; 3VWU; X-ray; 3.30 A; A/B/C/D/E/F/G/H/I/J=41-274.
DR PDB; 3VWV; X-ray; 1.80 A; A/B=87-274.
DR PDB; 3W8J; X-ray; 2.10 A; C/D=244-263.
DR PDB; 3WGX; X-ray; 0.92 A; C/D=244-263.
DR PDBsum; 3VWU; -.
DR PDBsum; 3VWV; -.
DR PDBsum; 3W8J; -.
DR PDBsum; 3WGX; -.
DR AlphaFoldDB; O08807; -.
DR SMR; O08807; -.
DR BioGRID; 207303; 21.
DR DIP; DIP-34137N; -.
DR IntAct; O08807; 9.
DR MINT; O08807; -.
DR STRING; 10090.ENSMUSP00000026328; -.
DR PeroxiBase; 4532; Mm2CysPrx04.
DR iPTMnet; O08807; -.
DR PhosphoSitePlus; O08807; -.
DR SwissPalm; O08807; -.
DR REPRODUCTION-2DPAGE; O08807; -.
DR CPTAC; non-CPTAC-3866; -.
DR EPD; O08807; -.
DR jPOST; O08807; -.
DR MaxQB; O08807; -.
DR PaxDb; O08807; -.
DR PeptideAtlas; O08807; -.
DR PRIDE; O08807; -.
DR ProteomicsDB; 291790; -.
DR Antibodypedia; 3275; 463 antibodies from 38 providers.
DR DNASU; 53381; -.
DR Ensembl; ENSMUST00000026328; ENSMUSP00000026328; ENSMUSG00000025289.
DR GeneID; 53381; -.
DR KEGG; mmu:53381; -.
DR UCSC; uc009uru.1; mouse.
DR CTD; 10549; -.
DR MGI; MGI:1859815; Prdx4.
DR VEuPathDB; HostDB:ENSMUSG00000025289; -.
DR eggNOG; KOG0852; Eukaryota.
DR GeneTree; ENSGT00940000153430; -.
DR HOGENOM; CLU_042529_21_1_1; -.
DR InParanoid; O08807; -.
DR OMA; EDSESCY; -.
DR OrthoDB; 1326484at2759; -.
DR PhylomeDB; O08807; -.
DR TreeFam; TF105181; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 53381; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Prdx4; mouse.
DR PRO; PR:O08807; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; O08807; protein.
DR Bgee; ENSMUSG00000025289; Expressed in saccule of membranous labyrinth and 258 other tissues.
DR ExpressionAtlas; O08807; baseline and differential.
DR Genevisible; O08807; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
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; IGI:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IGI:MGI.
DR GO; GO:0008584; P:male gonad development; IMP:MGI.
DR GO; GO:2000255; P:negative regulation of male germ cell proliferation; IMP:MGI.
DR GO; GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; IGI:MGI.
DR GO; GO:0022417; P:protein maturation by protein folding; IGI:MGI.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IDA:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR DisProt; DP02001; -.
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..40
FT /evidence="ECO:0000250"
FT CHAIN 41..274
FT /note="Peroxiredoxin-4"
FT /id="PRO_0000135099"
FT DOMAIN 82..240
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT ACT_SITE 127
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q13162"
FT DISULFID 127
FT /note="Interchain (with C-248); in linked form"
FT /evidence="ECO:0000269|PubMed:23949117,
FT ECO:0007744|PDB:3VWU, ECO:0007744|PDB:3VWV"
FT DISULFID 248
FT /note="Interchain (with C-127); in linked form"
FT /evidence="ECO:0000269|PubMed:23949117,
FT ECO:0007744|PDB:3VWU, ECO:0007744|PDB:3VWV"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:3VWV"
FT STRAND 100..105
FT /evidence="ECO:0007829|PDB:3VWV"
FT HELIX 106..109
FT /evidence="ECO:0007829|PDB:3VWV"
FT STRAND 112..118
FT /evidence="ECO:0007829|PDB:3VWV"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:3VWV"
FT HELIX 129..136
FT /evidence="ECO:0007829|PDB:3VWV"
FT HELIX 138..143
FT /evidence="ECO:0007829|PDB:3VWV"
FT STRAND 146..154
FT /evidence="ECO:0007829|PDB:3VWV"
FT HELIX 156..163
FT /evidence="ECO:0007829|PDB:3VWV"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:3VWV"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:3VWV"
FT HELIX 186..190
FT /evidence="ECO:0007829|PDB:3VWV"
FT TURN 196..199
FT /evidence="ECO:0007829|PDB:3VWV"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:3VWV"
FT STRAND 212..219
FT /evidence="ECO:0007829|PDB:3VWV"
FT HELIX 226..244
FT /evidence="ECO:0007829|PDB:3VWV"
SQ SEQUENCE 274 AA; 31053 MW; 73DB5374EC46241C CRC64;
MEARSKLLDG TTASRRWTRK LVLLLPPLLL FLLRTESLQG LESDERFRTR ENECHFYAGG
QVYPGEASRV SVADHSLHLS KAKISKPAPY WEGTAVINGE FKELKLTDYR GKYLVFFFYP
LDFTFVCPTE IIAFGDRIEE FKSINTEVVA CSVDSQFTHL AWINTPRRQG GLGPIRIPLL
SDLNHQISKD YGVYLEDSGH TLRGLFIIDD KGVLRQITLN DLPVGRSVDE TLRLVQAFQY
TDKHGEVCPA GWKPGSETII PDPAGKLKYF DKLN
