PRDX1_HUMAN
ID PRDX1_HUMAN Reviewed; 199 AA.
AC Q06830; B5BU26; D3DPZ8; P35703; Q2V576; Q5T154; Q5T155;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 232.
DE RecName: Full=Peroxiredoxin-1;
DE EC=1.11.1.24 {ECO:0000269|PubMed:11986303, ECO:0000269|PubMed:9497357};
DE AltName: Full=Natural killer cell-enhancing factor A;
DE Short=NKEF-A;
DE AltName: Full=Proliferation-associated gene protein;
DE Short=PAG;
DE AltName: Full=Thioredoxin peroxidase 2;
DE AltName: Full=Thioredoxin-dependent peroxide reductase 2;
DE AltName: Full=Thioredoxin-dependent peroxiredoxin 1 {ECO:0000305};
GN Name=PRDX1; Synonyms=PAGA, PAGB, TDPX2;
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].
RX PubMed=8496166; DOI=10.1016/s0021-9258(18)82090-7;
RA Prosperi M.T., Ferbus D., Karczinski I., Goubin G.;
RT "A human cDNA corresponding to a gene overexpressed during cell
RT proliferation encodes a product sharing homology with amoebic and bacterial
RT proteins.";
RL J. Biol. Chem. 268:11050-11056(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8026862; DOI=10.1007/bf00188176;
RA Shau H., Butterfield L.H., Chiu R., Kim A.;
RT "Cloning and sequence analysis of candidate human natural killer-enhancing
RT factor genes.";
RL Immunogenetics 40:129-134(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-62.
RG NIEHS SNPs program;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Urinary bladder;
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 [10]
RP PROTEIN SEQUENCE OF 17-35; 93-136; 141-151 AND 159-190, AND IDENTIFICATION
RP 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 [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=9497357; DOI=10.1074/jbc.273.11.6297;
RA Kang S.W., Chae H.Z., Seo M.S., Kim K., Baines I.C., Rhee S.G.;
RT "Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in
RT response to growth factors and tumor necrosis factor-alpha.";
RL J. Biol. Chem. 273:6297-6302(1998).
RN [12]
RP OVEROXIDATION AT CYS-52.
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 [13]
RP CATALYTIC ACTIVITY, PHOSPHORYLATION AT THR-90, AND MUTAGENESIS OF THR-90.
RX PubMed=11986303; DOI=10.1074/jbc.m110432200;
RA Chang T.-S., Jeong W., Choi S.Y., Yu S., Kang S.W., Rhee S.G.;
RT "Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation.";
RL J. Biol. Chem. 277:25370-25376(2002).
RN [14]
RP OVEROXIDATION AT CYS-52.
RX PubMed=12161445; DOI=10.1074/jbc.m206626200;
RA Yang K.S., Kang S.W., Woo H.A., Hwang S.C., Chae H.Z., Kim K., Rhee S.G.;
RT "Inactivation of human peroxiredoxin I during catalysis as the result of
RT the oxidation of the catalytic site cysteine to cysteine-sulfinic acid.";
RL J. Biol. Chem. 277:38029-38036(2002).
RN [15]
RP RETROREDUCTION OF CYS-52, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12853451; DOI=10.1074/jbc.m305161200;
RA Chevallet M., Wagner E., Luche S., van Dorsselaer A., Leize-Wagner E.,
RA Rabilloud T.;
RT "Regeneration of peroxiredoxins during recovery after oxidative stress:
RT only some overoxidized peroxiredoxins can be reduced during recovery after
RT oxidative stress.";
RL J. Biol. Chem. 278:37146-37153(2003).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [17]
RP RETROREDUCTION OF CYS-52, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12714748; DOI=10.1126/science.1080273;
RA Woo H.A., Chae H.Z., Hwang S.C., Yang K.S., Kang S.W., Kim K., Rhee S.G.;
RT "Reversing the inactivation of peroxiredoxins caused by cysteine sulfinic
RT acid formation.";
RL Science 300:653-656(2003).
RN [18]
RP INTERACTION WITH SESN1 AND SESN2.
RX PubMed=15105503; DOI=10.1126/science.1095569;
RA Budanov A.V., Sablina A.A., Feinstein E., Koonin E.V., Chumakov P.M.;
RT "Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of
RT bacterial AhpD.";
RL Science 304:596-600(2004).
RN [19]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-7; LYS-16; LYS-27 AND LYS-35, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [21]
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 [22]
RP INTERACTION WITH FAM107A.
RX PubMed=21969592; DOI=10.1073/pnas.1103318108;
RA Schmidt M.V., Schuelke J.P., Liebl C., Stiess M., Avrabos C., Bock J.,
RA Wochnik G.M., Davies H.A., Zimmermann N., Scharf S.H., Truembach D.,
RA Wurst W., Zieglgaensberger W., Turck C., Holsboer F., Stewart M.G.,
RA Bradke F., Eder M., Mueller M.B., Rein T.;
RT "Tumor suppressor down-regulated in renal cell carcinoma 1 (DRR1) is a
RT stress-induced actin bundling factor that modulates synaptic efficacy and
RT cognition.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:17213-17218(2011).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32, AND IDENTIFICATION BY
RP 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 [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-185, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-7 AND LYS-120, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH SRXN1, AND SUBUNIT.
RX PubMed=18172504; DOI=10.1038/nature06415;
RA Joensson T.J., Johnson L.C., Lowther W.T.;
RT "Structure of the sulphiredoxin-peroxiredoxin complex reveals an essential
RT repair embrace.";
RL Nature 451:98-101(2008).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS).
RX PubMed=19812042; DOI=10.1074/jbc.m109.036400;
RA Joensson T.J., Johnson L.C., Lowther W.T.;
RT "Protein engineering of the quaternary sulfiredoxin.peroxiredoxin
RT enzyme.substrate complex reveals the molecular basis for cysteine sulfinic
RT acid phosphorylation.";
RL J. Biol. Chem. 284:33305-33310(2009).
RN [31] {ECO:0007744|PDB:4XCS}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS), AND DISULFIDE BONDS.
RX DOI=10.1002/bkcs.10284;
RA Cho K.J., Park Y., Khan T.G., Lee J.-H., Kim S., Seok J.H., Chung Y.B.,
RA Cho A.E., Choi Y., Chang T.-S., Kim K.H.;
RT "Crystal structure of dimeric human peroxiredoxin-1 C83S mutant.";
RL Bull. Korean Chem. Soc. 36:1543-1545(2015).
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. Might participate in the signaling cascades of growth
CC factors and tumor necrosis factor-alpha by regulating the intracellular
CC concentrations of H(2)O(2) (PubMed:9497357). Reduces an intramolecular
CC disulfide bond in GDPD5 that gates the ability to GDPD5 to drive
CC postmitotic motor neuron differentiation (By similarity).
CC {ECO:0000250|UniProtKB:P0CB50, ECO:0000269|PubMed:9497357}.
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:11986303, ECO:0000269|PubMed:9497357};
CC -!- SUBUNIT: Homodimer; disulfide-linked, upon oxidation. 5 homodimers
CC assemble to form a ring-like decamer (PubMed:18172504). Interacts with
CC GDPD5; forms a mixed-disulfide with GDPD5 (By similarity). Interacts
CC with SESN1 and SESN2 (PubMed:15105503). Interacts with FAM107A
CC (PubMed:21969592). {ECO:0000250|UniProtKB:P0CB50,
CC ECO:0000269|PubMed:15105503, ECO:0000269|PubMed:18172504,
CC ECO:0000269|PubMed:21969592}.
CC -!- INTERACTION:
CC Q06830; P10275: AR; NbExp=3; IntAct=EBI-353193, EBI-608057;
CC Q06830; Q86TI2-2: DPP9; NbExp=3; IntAct=EBI-353193, EBI-21529239;
CC Q06830; Q8N7X4: MAGEB6; NbExp=3; IntAct=EBI-353193, EBI-6447163;
CC Q06830; P04156: PRNP; NbExp=4; IntAct=EBI-353193, EBI-977302;
CC Q06830; P60484: PTEN; NbExp=7; IntAct=EBI-353193, EBI-696162;
CC Q06830; Q9BYN0: SRXN1; NbExp=3; IntAct=EBI-353193, EBI-15678820;
CC Q06830; Q13043: STK4; NbExp=11; IntAct=EBI-353193, EBI-367376;
CC Q06830; P54274: TERF1; NbExp=2; IntAct=EBI-353193, EBI-710997;
CC Q06830; P13693: TPT1; NbExp=4; IntAct=EBI-353193, EBI-1783169;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17081065,
CC ECO:0000269|PubMed:9497357}. Melanosome {ECO:0000269|PubMed:17081065}.
CC Note=Identified by mass spectrometry in melanosome fractions from stage
CC I to stage IV.
CC -!- INDUCTION: Constitutively expressed in most human cells; is induced to
CC higher levels upon serum stimulation in untransformed and transformed
CC cells.
CC -!- PTM: Phosphorylated on Thr-90 during the M-phase, which leads to a more
CC than 80% decrease in enzymatic activity. {ECO:0000269|PubMed:11986303}.
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. It can be reactivated by forming a
CC transient disulfide bond with sulfiredoxin SRXN1, which reduces the
CC cysteine sulfinic acid in an ATP- and Mg-dependent manner.
CC {ECO:0000269|PubMed:12059788, ECO:0000269|PubMed:12161445,
CC ECO:0000269|PubMed:12714748, ECO:0000269|PubMed:12853451,
CC ECO:0000269|PubMed:18172504, ECO:0000269|PubMed:19812042}.
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|Ref.31}.
CC -!- SIMILARITY: Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PAGID266.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/prdx1/";
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DR EMBL; X67951; CAA48137.1; -; mRNA.
DR EMBL; L19184; AAA50464.1; -; mRNA.
DR EMBL; BT019740; AAV38545.1; -; mRNA.
DR EMBL; CR407652; CAG28580.1; -; mRNA.
DR EMBL; DQ297142; ABB84465.1; -; Genomic_DNA.
DR EMBL; AB451262; BAG70076.1; -; mRNA.
DR EMBL; AB451388; BAG70202.1; -; mRNA.
DR EMBL; AL451136; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06975.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06976.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06978.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06979.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06980.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06981.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06982.1; -; Genomic_DNA.
DR EMBL; BC007063; AAH07063.1; -; mRNA.
DR EMBL; BC021683; AAH21683.1; -; mRNA.
DR CCDS; CCDS522.1; -.
DR PIR; A46711; A46711.
DR RefSeq; NP_001189360.1; NM_001202431.1.
DR RefSeq; NP_002565.1; NM_002574.3.
DR RefSeq; NP_859047.1; NM_181696.2.
DR RefSeq; NP_859048.1; NM_181697.2.
DR PDB; 2RII; X-ray; 2.60 A; A/B=1-199.
DR PDB; 3HY2; X-ray; 2.10 A; A/B=1-199.
DR PDB; 4XCS; X-ray; 2.10 A; A/B/C/D/E/F=1-199.
DR PDB; 7LJ1; X-ray; 2.97 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T=1-199.
DR PDBsum; 2RII; -.
DR PDBsum; 3HY2; -.
DR PDBsum; 4XCS; -.
DR PDBsum; 7LJ1; -.
DR AlphaFoldDB; Q06830; -.
DR SMR; Q06830; -.
DR BioGRID; 111089; 275.
DR CORUM; Q06830; -.
DR DIP; DIP-33152N; -.
DR IntAct; Q06830; 108.
DR MINT; Q06830; -.
DR STRING; 9606.ENSP00000262746; -.
DR BindingDB; Q06830; -.
DR ChEMBL; CHEMBL5315; -.
DR DrugBank; DB11638; Artenimol.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB09221; Polaprezinc.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR PeroxiBase; 4501; Hs2CysPrx01.
DR GlyGen; Q06830; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q06830; -.
DR MetOSite; Q06830; -.
DR PhosphoSitePlus; Q06830; -.
DR SwissPalm; Q06830; -.
DR BioMuta; PRDX1; -.
DR DMDM; 548453; -.
DR DOSAC-COBS-2DPAGE; Q06830; -.
DR OGP; Q06830; -.
DR SWISS-2DPAGE; Q06830; -.
DR UCD-2DPAGE; Q06830; -.
DR EPD; Q06830; -.
DR jPOST; Q06830; -.
DR MassIVE; Q06830; -.
DR MaxQB; Q06830; -.
DR PaxDb; Q06830; -.
DR PeptideAtlas; Q06830; -.
DR PRIDE; Q06830; -.
DR ProteomicsDB; 58486; -.
DR TopDownProteomics; Q06830; -.
DR Antibodypedia; 1574; 705 antibodies from 45 providers.
DR DNASU; 5052; -.
DR Ensembl; ENST00000262746.5; ENSP00000262746.1; ENSG00000117450.15.
DR Ensembl; ENST00000319248.13; ENSP00000361152.5; ENSG00000117450.15.
DR Ensembl; ENST00000424390.2; ENSP00000389047.2; ENSG00000117450.15.
DR Ensembl; ENST00000447184.6; ENSP00000407034.2; ENSG00000117450.15.
DR Ensembl; ENST00000676549.1; ENSP00000503140.1; ENSG00000117450.15.
DR GeneID; 5052; -.
DR KEGG; hsa:5052; -.
DR MANE-Select; ENST00000319248.13; ENSP00000361152.5; NM_181697.3; NP_859048.1.
DR UCSC; uc001coa.4; human.
DR CTD; 5052; -.
DR DisGeNET; 5052; -.
DR GeneCards; PRDX1; -.
DR HGNC; HGNC:9352; PRDX1.
DR HPA; ENSG00000117450; Low tissue specificity.
DR MalaCards; PRDX1; -.
DR MIM; 176763; gene.
DR neXtProt; NX_Q06830; -.
DR OpenTargets; ENSG00000117450; -.
DR PharmGKB; PA33722; -.
DR VEuPathDB; HostDB:ENSG00000117450; -.
DR eggNOG; KOG0852; Eukaryota.
DR GeneTree; ENSGT00940000154277; -.
DR InParanoid; Q06830; -.
DR OMA; FWYPKDF; -.
DR OrthoDB; 1326484at2759; -.
DR PhylomeDB; Q06830; -.
DR TreeFam; TF105181; -.
DR BioCyc; MetaCyc:HS04134-MON; -.
DR BRENDA; 1.11.1.24; 2681.
DR PathwayCommons; Q06830; -.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-8862803; Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-HSA-9759194; Nuclear events mediated by NFE2L2.
DR SignaLink; Q06830; -.
DR SIGNOR; Q06830; -.
DR BioGRID-ORCS; 5052; 67 hits in 1091 CRISPR screens.
DR ChiTaRS; PRDX1; human.
DR EvolutionaryTrace; Q06830; -.
DR GeneWiki; Peroxiredoxin_1; -.
DR GenomeRNAi; 5052; -.
DR Pharos; Q06830; Tchem.
DR PRO; PR:Q06830; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q06830; protein.
DR Bgee; ENSG00000117450; Expressed in right lobe of thyroid gland and 205 other tissues.
DR ExpressionAtlas; Q06830; baseline and differential.
DR Genevisible; Q06830; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0004601; F:peroxidase activity; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IDA:BHF-UCL.
DR GO; GO:0008283; P:cell population proliferation; TAS:ProtInc.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0034101; P:erythrocyte homeostasis; IEA:Ensembl.
DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:BHF-UCL.
DR GO; GO:0045321; P:leukocyte activation; IBA:GO_Central.
DR GO; GO:0030101; P:natural killer cell activation; IDA:UniProtKB.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:1901222; P:regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IBA:GO_Central.
DR GO; GO:0001895; P:retina homeostasis; HEP:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
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 3D-structure; Acetylation; Antioxidant; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Isopeptide bond; Oxidoreductase;
KW Peroxidase; Phosphoprotein; Redox-active center; Reference proteome;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:25944712"
FT CHAIN 2..199
FT /note="Peroxiredoxin-1"
FT /id="PRO_0000135076"
FT DOMAIN 6..165
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT REGION 176..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..199
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 52
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000305|PubMed:12059788,
FT ECO:0000305|PubMed:12161445"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:25944712"
FT MOD_RES 7
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 16
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 27
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 35
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 35
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P35700"
FT MOD_RES 90
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000269|PubMed:11986303"
FT MOD_RES 136
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P35700"
FT DISULFID 52
FT /note="Interchain (with C-173); in linked form"
FT /evidence="ECO:0000269|Ref.31, ECO:0007744|PDB:4XCS"
FT DISULFID 173
FT /note="Interchain (with C-52); in linked form"
FT /evidence="ECO:0000269|Ref.31, ECO:0007744|PDB:4XCS"
FT CROSSLNK 7
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 120
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 185
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0007744|PubMed:25114211"
FT VARIANT 62
FT /note="R -> G (in dbSNP:rs34034070)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_025050"
FT MUTAGEN 90
FT /note="T->A: Abolishes phosphorylation by CDK1; 30%
FT reduction in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11986303"
FT MUTAGEN 90
FT /note="T->D: 87% reduction in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:11986303"
FT CONFLICT 147
FT /note="L -> P (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 149..150
FT /note="VG -> CC (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="Q -> P (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="S -> T (in Ref. 2)"
FT /evidence="ECO:0000305"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:4XCS"
FT STRAND 16..20
FT /evidence="ECO:0007829|PDB:3HY2"
FT STRAND 26..30
FT /evidence="ECO:0007829|PDB:3HY2"
FT HELIX 31..34
FT /evidence="ECO:0007829|PDB:3HY2"
FT STRAND 37..43
FT /evidence="ECO:0007829|PDB:3HY2"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:4XCS"
FT HELIX 54..61
FT /evidence="ECO:0007829|PDB:3HY2"
FT HELIX 63..68
FT /evidence="ECO:0007829|PDB:3HY2"
FT STRAND 71..79
FT /evidence="ECO:0007829|PDB:3HY2"
FT HELIX 81..88
FT /evidence="ECO:0007829|PDB:3HY2"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:3HY2"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:3HY2"
FT HELIX 111..115
FT /evidence="ECO:0007829|PDB:3HY2"
FT TURN 121..123
FT /evidence="ECO:0007829|PDB:3HY2"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:3HY2"
FT STRAND 128..133
FT /evidence="ECO:0007829|PDB:3HY2"
FT STRAND 137..145
FT /evidence="ECO:0007829|PDB:3HY2"
FT HELIX 153..168
FT /evidence="ECO:0007829|PDB:3HY2"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:2RII"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:3HY2"
SQ SEQUENCE 199 AA; 22110 MW; 8F68E56D75BF5304 CRC64;
MSSGNAKIGH PAPNFKATAV MPDGQFKDIS LSDYKGKYVV FFFYPLDFTF VCPTEIIAFS
DRAEEFKKLN CQVIGASVDS HFCHLAWVNT PKKQGGLGPM NIPLVSDPKR TIAQDYGVLK
ADEGISFRGL FIIDDKGILR QITVNDLPVG RSVDETLRLV QAFQFTDKHG EVCPAGWKPG
SDTIKPDVQK SKEYFSKQK
