TRXR_PLAF5
ID TRXR_PLAF5 Reviewed; 541 AA.
AC Q25861; Q25864;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Thioredoxin reductase {ECO:0000303|PubMed:8892299};
DE Short=PfTrxR {ECO:0000303|PubMed:8892299};
DE EC=1.8.1.9 {ECO:0000269|PubMed:8892299};
GN Name=TRXR {ECO:0000303|PubMed:8892299};
GN Synonyms=GR {ECO:0000303|PubMed:8719241};
OS Plasmodium falciparum (isolate FCH-5).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=132416;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=8719241; DOI=10.1016/0166-6851(95)02476-x;
RA Mueller S., Becker K., Bergmann B., Schirmer R.H., Walter R.D.;
RT "Plasmodium falciparum glutathione reductase exhibits sequence similarities
RT with the human host enzyme in the core structure but differs at the ligand-
RT binding sites.";
RL Mol. Biochem. Parasitol. 74:11-18(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 47-517, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=8892299; DOI=10.1016/0166-6851(96)02694-1;
RA Mueller S., Gilberger T.-W., Faerber P.M., Becker K., Schirmer R.H.,
RA Walter R.D.;
RT "Recombinant putative glutathione reductase of Plasmodium falciparum
RT exhibits thioredoxin reductase activity.";
RL Mol. Biochem. Parasitol. 80:215-219(1996).
CC -!- FUNCTION: Catalyzes the transfer of electrons from NADPH to
CC thioredoxins TRX1, TRX2 and TRX3, which in turn act as reductants of
CC disulfide containing proteins (PubMed:8892299). Able to reduce
CC nitroglutathione (GSNO), a compound involved in the transport of nitric
CC oxide (NO); however, TRX1 is more efficient in reducing GSNO. Has no
CC catalytic activity towards oxidized glutathione (GSSG) (By similarity).
CC {ECO:0000250|UniProtKB:P61076, ECO:0000269|PubMed:8892299}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide +
CC H(+) + NADPH; Xref=Rhea:RHEA:20345, Rhea:RHEA-COMP:10698, Rhea:RHEA-
CC COMP:10700, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.8.1.9;
CC Evidence={ECO:0000269|PubMed:8892299};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20347;
CC Evidence={ECO:0000269|PubMed:8892299};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P61076};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:P61076};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.1 uM for NADPH (at 20 degrees Celsius and pH 7.4)
CC {ECO:0000269|PubMed:8892299};
CC KM=66 uM for E.coli thioredoxin (at 37 degrees Celsius and pH 7.6)
CC {ECO:0000269|PubMed:8892299};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:8892299}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P61076}.
CC -!- MISCELLANEOUS: There are 2 isoforms resulting from alternative
CC translation initiation. The displayed sequence is likely to represent
CC the shorter isoform. {ECO:0000305}.
CC -!- MISCELLANEOUS: In Plasmodium, the C-terminal redox center, which acts
CC as the active site, is formed by two cysteines while in mammalian TRXR
CC this redox center is composed of a cysteine-selenocysteine active site.
CC {ECO:0000250|UniProtKB:P61076}.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a glutathione reductase.
CC {ECO:0000305|PubMed:8719241}.
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DR EMBL; X87095; CAA60574.1; -; mRNA.
DR EMBL; X83603; CAA58583.1; -; Genomic_DNA.
DR PIR; S57658; S57658.
DR AlphaFoldDB; Q25861; -.
DR SMR; Q25861; -.
DR SABIO-RK; Q25861; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004791; F:thioredoxin-disulfide reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf.
DR InterPro; IPR001100; Pyr_nuc-diS_OxRdtase.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR InterPro; IPR006338; Thioredoxin/glutathione_Rdtase.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR PIRSF; PIRSF000350; Mercury_reductase_MerA; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF55424; SSF55424; 1.
DR TIGRFAMs; TIGR01438; TGR; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Disulfide bond; FAD; Flavoprotein; NADP; Oxidoreductase;
KW Redox-active center.
FT CHAIN 1..541
FT /note="Thioredoxin reductase"
FT /id="PRO_0000067986"
FT REGION 438..452
FT /note="Loop important for the interaction with TRX1"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT ACT_SITE 509
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT BINDING 51..52
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT BINDING 71..74
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT BINDING 87..88
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT BINDING 92..96
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT BINDING 161
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT BINDING 357
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT BINDING 364..366
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT BINDING 509
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT DISULFID 88..93
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT DISULFID 535..540
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:P61076"
FT CONFLICT 49..51
FT /note="GGP -> AGS (in Ref. 2; CAA58583)"
FT /evidence="ECO:0000305"
FT CONFLICT 512..517
FT /note="DAESFM -> AAEELS (in Ref. 2; CAA58583)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 541 AA; 59686 MW; 5449D50D7BA5BD9D CRC64;
MCKDKNEKKN YEHVNANEKN GYLASEKNEL TKNKVEEHTY DYDYVVIGGG PGGMASAKEA
AAHGARVLLF DYVKPSSQGT KWGIGGTCVN VGCVPKKLMH YAGHMGSIFK LDSKAYGWKF
DNLKHDWKKL VTTVQSHIRS LNFSYMTGLR SSKVKYINGL AKLKDKNTVS YYLKGDLSKE
ETVTGKYILI ATGCRPHIPD DVEGAKELSI TSDDIFSLKK DPGKTLVVGA SYVALECSGF
LNSLGYDVTV AVRSIVLRGF DQQCAVKVKL YMEEQGVMFK NGILPKKLTK MDDKILVEFS
DKTSELYDTV LYAIGRKGDI DGLNLESLNM NVNKSNNKII ADHLSCTNIP SIFAVGDVAE
NVPELAPVAI KAGEILARRL FKDSDEIMDY SYIPTSIYTP IEYGACGYSE EKAYELYGKS
NVEVFLQEFN NLEISAVHRQ KHIRAQKDEY DLDVSSTCLA KLVCLKNEDN RVIGFHYVGP
NAGEVTQGMA LALRLKVKKK DFDNCIGIHP TDAESFMNLF VTISSGLSYA AKGGCGGGKC
G
