TPX1_SCHPO
ID TPX1_SCHPO Reviewed; 192 AA.
AC O74887;
DT 23-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Peroxiredoxin tpx1 {ECO:0000303|PubMed:20356456};
DE EC=1.11.1.24 {ECO:0000269|PubMed:20356456};
DE AltName: Full=Thioredoxin peroxidase {ECO:0000303|PubMed:20356456};
DE Short=TPx {ECO:0000303|PubMed:20356456};
DE AltName: Full=Thioredoxin-dependent peroxiredoxin tpx1 {ECO:0000305};
GN Name=tpx1; Synonyms=tsa1; ORFNames=SPCC576.03c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND MUTAGENESIS OF LYS-191
RP AND HIS-192.
RX PubMed=11795888; DOI=10.1006/abbi.2001.2700;
RA Koo K.H., Lee S., Jeong S.Y., Kim E.T., Kim H.J., Kim K., Song K.,
RA Chae H.Z.;
RT "Regulation of thioredoxin peroxidase activity by C-terminal truncation.";
RL Arch. Biochem. Biophys. 397:312-318(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP FUNCTION, INTERACTION WITH SRX1, AND MUTAGENESIS OF CYS-48 AND CYS-169.
RX PubMed=15824112; DOI=10.1074/jbc.m502757200;
RA Bozonet S.M., Findlay V.J., Day A.M., Cameron J., Veal E.A., Morgan B.A.;
RT "Oxidation of a eukaryotic 2-Cys peroxiredoxin is a molecular switch
RT controlling the transcriptional response to increasing levels of hydrogen
RT peroxide.";
RL J. Biol. Chem. 280:23319-23327(2005).
RN [4]
RP FUNCTION.
RX PubMed=15956211; DOI=10.1073/pnas.0503251102;
RA Vivancos A.P., Castillo E.A., Biteau B., Nicot C., Ayte J., Toledano M.B.,
RA Hidalgo E.;
RT "A cysteine-sulfinic acid in peroxiredoxin regulates H2O2-sensing by the
RT antioxidant Pap1 pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8875-8880(2005).
RN [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [6]
RP FUNCTION.
RX PubMed=17409354; DOI=10.1091/mbc.e06-11-1039;
RA Jara M., Vivancos A.P., Calvo I.A., Moldon A., Sanso M., Hidalgo E.;
RT "The peroxiredoxin Tpx1 is essential as a H2O2 scavenger during aerobic
RT growth in fission yeast.";
RL Mol. Biol. Cell 18:2288-2295(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105 AND SER-148, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18257517; DOI=10.1021/pr7006335;
RA Wilson-Grady J.T., Villen J., Gygi S.P.;
RT "Phosphoproteome analysis of fission yeast.";
RL J. Proteome Res. 7:1088-1097(2008).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=20356456; DOI=10.5483/bmbrep.2010.43.3.170;
RA Kim J.S., Bang M.A., Lee S., Chae H.Z., Kim K.;
RT "Distinct functional roles of peroxiredoxin isozymes and glutathione
RT peroxidase from fission yeast, Schizosaccharomyces pombe.";
RL BMB Rep. 43:170-175(2010).
RN [9]
RP FUNCTION, INTERACTION WITH PAP1, SUBCELLULAR LOCATION, SUBUNIT, AND
RP DISULFIDE BONDS.
RX PubMed=24316080; DOI=10.1016/j.celrep.2013.11.027;
RA Calvo I.A., Boronat S., Domenech A., Garcia-Santamarina S., Ayte J.,
RA Hidalgo E.;
RT "Dissection of a redox relay: H2O2-dependent activation of the
RT transcription factor Pap1 through the peroxidatic Tpx1-thioredoxin cycle.";
RL Cell Rep. 5:1413-1424(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:17409354, PubMed:20356456). Relays hydrogen
CC peroxide as a signal to the transcription factor pap1 by inducing the
CC formation of intramolecular disulfide bonds in pap1, which causes its
CC nuclear accumulation and activation (PubMed:15824112, PubMed:24316080).
CC Reduced by srx1 and this regulation acts as a molecular switch
CC controlling the transcriptional response to hydrogen peroxide
CC (PubMed:15956211). {ECO:0000269|PubMed:15824112,
CC ECO:0000269|PubMed:15956211, ECO:0000269|PubMed:17409354,
CC ECO:0000269|PubMed:20356456, ECO:0000269|PubMed:24316080}.
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:20356456};
CC -!- SUBUNIT: Homodimer; disulfide-linked, upon oxidation (PubMed:11795888,
CC PubMed:20356456, PubMed:24316080). Interacts with srx1 in response to
CC oxidative stress (PubMed:15824112). Interacts with pap1 via transient
CC disulfide linkages (PubMed:24316080). {ECO:0000269|PubMed:11795888,
CC ECO:0000269|PubMed:15824112, ECO:0000269|PubMed:20356456,
CC ECO:0000269|PubMed:24316080}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372,
CC ECO:0000269|PubMed:24316080}. Nucleus {ECO:0000269|PubMed:16823372}.
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 srx1, which reduces the
CC cysteine sulfinic acid in an ATP- and Mg-dependent manner.
CC {ECO:0000269|PubMed:15824112, ECO:0000269|PubMed:15956211}.
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 the typical 2-Cys
CC AhpC/Prx1 family, C(R) is provided by the other dimeric subunit to form
CC an intersubunit disulfide. The disulfide is subsequently reduced by
CC thioredoxin. {ECO:0000305|PubMed:24316080}.
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; AF083335; AAC71013.1; -; mRNA.
DR EMBL; CU329672; CAA21182.1; -; Genomic_DNA.
DR PIR; T41413; T41413.
DR RefSeq; NP_588430.1; NM_001023421.2.
DR AlphaFoldDB; O74887; -.
DR SMR; O74887; -.
DR BioGRID; 276132; 19.
DR IntAct; O74887; 3.
DR MINT; O74887; -.
DR STRING; 4896.SPCC576.03c.1; -.
DR PeroxiBase; 4483; Spom2CysPrx.
DR TCDB; 8.A.147.1.1; the peroxiredoxin heme-binding protein, tpx1 (tpx1) family.
DR iPTMnet; O74887; -.
DR MaxQB; O74887; -.
DR PaxDb; O74887; -.
DR PRIDE; O74887; -.
DR EnsemblFungi; SPCC576.03c.1; SPCC576.03c.1:pep; SPCC576.03c.
DR GeneID; 2539572; -.
DR KEGG; spo:SPCC576.03c; -.
DR PomBase; SPCC576.03c; tpx1.
DR VEuPathDB; FungiDB:SPCC576.03c; -.
DR eggNOG; KOG0852; Eukaryota.
DR HOGENOM; CLU_042529_21_0_1; -.
DR InParanoid; O74887; -.
DR OMA; FWYPKDF; -.
DR PhylomeDB; O74887; -.
DR BRENDA; 1.11.1.24; 5613.
DR Reactome; R-SPO-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-SPO-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-SPO-6798695; Neutrophil degranulation.
DR Reactome; R-SPO-9755511; KEAP1-NFE2L2 pathway.
DR PRO; PR:O74887; -.
DR Proteomes; UP000002485; Chromosome III.
DR GO; GO:0005737; C:cytoplasm; IDA:PomBase.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0005634; C:nucleus; HDA:PomBase.
DR GO; GO:0004601; F:peroxidase activity; IDA:PomBase.
DR GO; GO:0051920; F:peroxiredoxin activity; IDA:PomBase.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IDA:PomBase.
DR GO; GO:0051082; F:unfolded protein binding; IDA:PomBase.
DR GO; GO:0045454; P:cell redox homeostasis; IMP:PomBase.
DR GO; GO:0061692; P:cellular detoxification of hydrogen peroxide; IMP:PomBase.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IMP:PomBase.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:PomBase.
DR GO; GO:0036091; P:positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress; IMP:PomBase.
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 Antioxidant; Cytoplasm; Disulfide bond; Nucleus; Oxidoreductase;
KW Peroxidase; Phosphoprotein; Redox-active center; Reference proteome.
FT CHAIN 1..192
FT /note="Peroxiredoxin tpx1"
FT /id="PRO_0000351076"
FT DOMAIN 3..161
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT ACT_SITE 48
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000305|PubMed:24316080"
FT MOD_RES 105
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT MOD_RES 148
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT DISULFID 48
FT /note="Interchain (with C-169); in linked form"
FT /evidence="ECO:0000269|PubMed:24316080"
FT DISULFID 169
FT /note="Interchain (with C-30 in TRX1); transient"
FT /evidence="ECO:0000269|PubMed:24316080"
FT DISULFID 169
FT /note="Interchain (with C-48); in linked form"
FT /evidence="ECO:0000269|PubMed:24316080"
FT MUTAGEN 48
FT /note="C->S: No nuclear accumulation of pap1."
FT /evidence="ECO:0000269|PubMed:15824112"
FT MUTAGEN 169
FT /note="C->S: No nuclear accumulation of pap1."
FT /evidence="ECO:0000269|PubMed:15824112"
FT MUTAGEN 191
FT /note="K->D: Peroxide reduction reduced."
FT /evidence="ECO:0000269|PubMed:11795888"
FT MUTAGEN 191
FT /note="K->R: Inactivated by 1 mM H(2)O(2)."
FT /evidence="ECO:0000269|PubMed:11795888"
FT MUTAGEN 192
FT /note="H->E,G,K,L,Q,Y: Peroxide reduction reduced."
FT /evidence="ECO:0000269|PubMed:11795888"
SQ SEQUENCE 192 AA; 21191 MW; 0DFE0C757C09A96B CRC64;
MSLQIGKPAP DFKGTAVVNG AFEEIKLADY KGKWVFLGFY PLDFTFVCPT EIVAFSEAAS
KFAERNAQVI LTSTDSEYSH LAFINTPRKE GGLGGINIPL LADPSHKVSR DYGVLIEDAG
VAFRGLFLID PKGVLRQITI NDLPVGRSVD EALRLLDAFQ FVEEHGEVCP ANWHKGSDTI
DTKNPEKYFS KH
