THIO1_PLAF7
ID THIO1_PLAF7 Reviewed; 104 AA.
AC Q7KQL8; A0A144A4E0; Q9NIR2;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Thioredoxin 1 {ECO:0000303|PubMed:11013257};
DE Short=PfTRX1 {ECO:0000303|PubMed:11013257};
GN Name=TRX1 {ECO:0000303|PubMed:11013257}; ORFNames=PF14_0545, PF3D7_1457200;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11013257; DOI=10.1074/jbc.m007633200;
RA Kanzok S.M., Schirmer R.H., Turbachova I., Iozef R., Becker K.;
RT "The thioredoxin system of the malaria parasite Plasmodium falciparum.
RT Glutathione reduction revisited.";
RL J. Biol. Chem. 275:40180-40186(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [3]
RP FUNCTION.
RX PubMed=14962358; DOI=10.1179/135100003225002844;
RA Rahlfs S., Nickel C., Deponte M., Schirmer R.H., Becker K.;
RT "Plasmodium falciparum thioredoxins and glutaredoxins as central players in
RT redox metabolism.";
RL Redox Rep. 8:246-250(2003).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF CYS-30 AND CYS-33.
RX PubMed=19360125; DOI=10.1371/journal.ppat.1000383;
RA Sturm N., Jortzik E., Mailu B.M., Koncarevic S., Deponte M.,
RA Forchhammer K., Rahlfs S., Becker K.;
RT "Identification of proteins targeted by the thioredoxin superfamily in
RT Plasmodium falciparum.";
RL PLoS Pathog. 5:e1000383-e1000383(2009).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF CYS-30; CYS-33 AND CYS-43.
RX PubMed=20673832; DOI=10.1016/j.jmb.2010.07.039;
RA Jortzik E., Fritz-Wolf K., Sturm N., Hipp M., Rahlfs S., Becker K.;
RT "Redox regulation of Plasmodium falciparum ornithine delta-
RT aminotransferase.";
RL J. Mol. Biol. 402:445-459(2010).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=21203490; DOI=10.1371/journal.ppat.1001242;
RA Kehr S., Sturm N., Rahlfs S., Przyborski J.M., Becker K.;
RT "Compartmentation of redox metabolism in malaria parasites.";
RL PLoS Pathog. 6:e1001242-e1001242(2010).
RN [7] {ECO:0007744|PDB:1SYR}
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS), AND DISULFIDE BOND.
RA Robien M.A., Hol W.G.J.;
RT "Structural genomics of pathogenic protozoa initial structural analysis of
RT Plasmodium falciparum thioredoxin.";
RL Submitted (APR-2004) to the PDB data bank.
RN [8] {ECO:0007744|PDB:4J56, ECO:0007744|PDB:4J57}
RP X-RAY CRYSTALLOGRAPHY (2.37 ANGSTROMS) OF 2-104 OF MUTANT SER-30 IN COMPLEX
RP WITH TRXR, AND DISULFIDE BOND.
RX PubMed=23845423; DOI=10.1016/j.jmb.2013.06.037;
RA Fritz-Wolf K., Jortzik E., Stumpf M., Preuss J., Iozef R., Rahlfs S.,
RA Becker K.;
RT "Crystal structure of the Plasmodium falciparum thioredoxin reductase-
RT thioredoxin complex.";
RL J. Mol. Biol. 425:3446-3460(2013).
RN [9] {ECO:0007744|PDB:2MMN, ECO:0007744|PDB:2MMO}
RP STRUCTURE BY NMR OF 2-104, AND DISULFIDE BOND.
RA Munte C., Kalbitzer H., Schirmer R.;
RT "Solution Structure of Plasmodium falciparum Thioredoxin.";
RL Submitted (MAR-2014) to the PDB data bank.
CC -!- FUNCTION: Participates in various redox reactions through the
CC reversible oxidation of its active center dithiol to a disulfide and
CC catalyzes dithiol-disulfide exchange reactions (PubMed:11013257,
CC PubMed:20673832). By modifying the redox status of targeted proteins,
CC induces changes in their structure and activity (PubMed:19360125,
CC PubMed:20673832). Reduces oxidized glutathione (GSSG), thereby acting
CC as a backup for the glutathione redox system (PubMed:11013257). Reduces
CC nitroglutathione (GSNO), a compound involved in the transport of nitric
CC oxide (NO) (PubMed:11013257). Also reduces oxidative stress by
CC detoxifying hydrogen peroxide, tert-butyl hydroperoxide and cumene
CC hydroperoxide (PubMed:14962358). Activates ornithine aminotransferase
CC OAT by reducing a disulfide bond in the substrate binding loop, thereby
CC enhancing the affinity of OAT for its substrates (PubMed:20673832). May
CC reduce S-adenosyl-L-homocysteine hydrolase SAHH (PubMed:19360125).
CC {ECO:0000269|PubMed:11013257, ECO:0000269|PubMed:14962358,
CC ECO:0000269|PubMed:19360125, ECO:0000269|PubMed:20673832}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Redox potential:
CC E(0) is -270 mV (at pH 7.4 and 25 degrees Celsius).
CC {ECO:0000269|PubMed:11013257};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21203490}.
CC -!- PTM: The disulfide bond between Cys-30 and Cys-33 acts as a redox-
CC active center and is reduced by thioredoxin reductase TRXR.
CC {ECO:0000269|PubMed:23845423}.
CC -!- SIMILARITY: Belongs to the thioredoxin family. {ECO:0000305}.
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DR EMBL; AF202664; AAF34541.1; -; mRNA.
DR EMBL; LN999946; CZU00268.1; -; Genomic_DNA.
DR RefSeq; XP_001348719.1; XM_001348683.1.
DR PDB; 1SYR; X-ray; 2.95 A; A/B/C/D/E/F/G/H/I/J/K/L=1-104.
DR PDB; 2MMN; NMR; -; A=2-104.
DR PDB; 2MMO; NMR; -; A=2-104.
DR PDB; 4J56; X-ray; 2.37 A; E/F/G/H=2-104.
DR PDB; 4J57; X-ray; 2.50 A; E/F=2-104.
DR PDBsum; 1SYR; -.
DR PDBsum; 2MMN; -.
DR PDBsum; 2MMO; -.
DR PDBsum; 4J56; -.
DR PDBsum; 4J57; -.
DR AlphaFoldDB; Q7KQL8; -.
DR BMRB; Q7KQL8; -.
DR SMR; Q7KQL8; -.
DR BioGRID; 1207479; 1.
DR IntAct; Q7KQL8; 1.
DR STRING; 5833.PF14_0545; -.
DR PRIDE; Q7KQL8; -.
DR EnsemblProtists; CZU00268; CZU00268; PF3D7_1457200.
DR GeneID; 812127; -.
DR KEGG; pfa:PF3D7_1457200; -.
DR VEuPathDB; PlasmoDB:PF3D7_1457200; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000531000; -.
DR VEuPathDB; PlasmoDB:Pf7G8_140062400; -.
DR VEuPathDB; PlasmoDB:PfCD01_140062500; -.
DR VEuPathDB; PlasmoDB:PfDd2_140061600; -.
DR VEuPathDB; PlasmoDB:PfGA01_140062600; -.
DR VEuPathDB; PlasmoDB:PfGB4_140063300; -.
DR VEuPathDB; PlasmoDB:PfGN01_140062500; -.
DR VEuPathDB; PlasmoDB:PfHB3_140062900; -.
DR VEuPathDB; PlasmoDB:PfIT_140063600; -.
DR VEuPathDB; PlasmoDB:PfKE01_140062000; -.
DR VEuPathDB; PlasmoDB:PfKH01_140062700; -.
DR VEuPathDB; PlasmoDB:PfKH02_140062900; -.
DR VEuPathDB; PlasmoDB:PfML01_140062800; -.
DR VEuPathDB; PlasmoDB:PfNF135_140061300; -.
DR VEuPathDB; PlasmoDB:PfNF166_140060100; -.
DR VEuPathDB; PlasmoDB:PfNF54_140060900; -.
DR VEuPathDB; PlasmoDB:PfSD01_140060500; -.
DR VEuPathDB; PlasmoDB:PfSN01_140064400; -.
DR VEuPathDB; PlasmoDB:PfTG01_140062500; -.
DR HOGENOM; CLU_090389_14_6_1; -.
DR InParanoid; Q7KQL8; -.
DR OMA; CRVISPI; -.
DR PhylomeDB; Q7KQL8; -.
DR EvolutionaryTrace; Q7KQL8; -.
DR Proteomes; UP000001450; Chromosome 14.
DR GO; GO:0005829; C:cytosol; IDA:GeneDB.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IDA:UniProtKB.
DR InterPro; IPR005746; Thioredoxin.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR017937; Thioredoxin_CS.
DR InterPro; IPR013766; Thioredoxin_domain.
DR Pfam; PF00085; Thioredoxin; 1.
DR PIRSF; PIRSF000077; Thioredoxin; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR TIGRFAMs; TIGR01068; thioredoxin; 1.
DR PROSITE; PS00194; THIOREDOXIN_1; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Disulfide bond; Electron transport;
KW Redox-active center; Reference proteome; Transport.
FT CHAIN 1..104
FT /note="Thioredoxin 1"
FT /id="PRO_0000233976"
FT DOMAIN 2..104
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT ACT_SITE 30
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P10599"
FT ACT_SITE 33
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P10599"
FT SITE 24
FT /note="Deprotonates C-terminal active site Cys"
FT /evidence="ECO:0000305"
FT SITE 31
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000305"
FT SITE 32
FT /note="Contributes to redox potential value"
FT /evidence="ECO:0000305"
FT DISULFID 30..33
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691,
FT ECO:0000269|PubMed:23845423, ECO:0000269|Ref.7,
FT ECO:0000269|Ref.9, ECO:0007744|PDB:1SYR,
FT ECO:0007744|PDB:2MMO, ECO:0007744|PDB:4J56,
FT ECO:0007744|PDB:4J57"
FT MUTAGEN 30
FT /note="C->S: Does not stably interact with OAT and fails to
FT increase OAT catalytic activity; when associated with S-33
FT or S-33 and S-43. Does not stably interact with SAHH; when
FT associated with S-33."
FT /evidence="ECO:0000269|PubMed:19360125,
FT ECO:0000269|PubMed:20673832"
FT MUTAGEN 33
FT /note="C->S: Forms a stable disulfide intermediate with
FT OAT. Fails to increase OAT catalytic activity. Does not
FT stably interact with OAT and fails to increase OAT
FT catalytic activity; when associated with S-30 and/or S-43.
FT Forms a stable disulfide intermediate with SAHH. Does not
FT stably interact with SAHH; when associated with S-30."
FT /evidence="ECO:0000269|PubMed:19360125,
FT ECO:0000269|PubMed:20673832"
FT MUTAGEN 43
FT /note="C->S: Does not stably interact with OAT and fails to
FT increase OAT catalytic activity; when associated with S-33
FT or S-30 and S-33."
FT /evidence="ECO:0000269|PubMed:20673832"
FT CONFLICT 9
FT /note="A -> S (in Ref. 1; AAF34541)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="K -> I (in Ref. 1; AAF34541)"
FT /evidence="ECO:0000305"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:4J56"
FT HELIX 8..18
FT /evidence="ECO:0007829|PDB:4J56"
FT STRAND 19..26
FT /evidence="ECO:0007829|PDB:4J56"
FT HELIX 31..46
FT /evidence="ECO:0007829|PDB:4J56"
FT STRAND 49..56
FT /evidence="ECO:0007829|PDB:4J56"
FT TURN 57..60
FT /evidence="ECO:0007829|PDB:4J56"
FT HELIX 61..67
FT /evidence="ECO:0007829|PDB:4J56"
FT STRAND 71..79
FT /evidence="ECO:0007829|PDB:4J56"
FT STRAND 82..90
FT /evidence="ECO:0007829|PDB:4J56"
FT HELIX 92..103
FT /evidence="ECO:0007829|PDB:4J56"
SQ SEQUENCE 104 AA; 11716 MW; 0129998AEB88770C CRC64;
MVKIVTSQAE FDSIISQNEL VIVDFFAEWC GPCKRIAPFY EECSKTYTKM VFIKVDVDEV
SEVTEKENIT SMPTFKVYKN GSSVDTLLGA NDSALKQLIE KYAA
