GPX3_CANAL
ID GPX3_CANAL Reviewed; 171 AA.
AC Q59WD3;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 25-MAY-2022, entry version 129.
DE RecName: Full=Glutathione peroxidase-like peroxiredoxin GPX3 {ECO:0000305};
DE EC=1.11.1.24 {ECO:0000250|UniProtKB:P40581};
DE AltName: Full=Glutathione peroxidase homolog 3 {ECO:0000303|PubMed:23706023};
DE Short=GPx 3;
GN Name=GPX3 {ECO:0000303|PubMed:23706023};
GN OrderedLocusNames=CAALFM_C107350CA; ORFNames=orf19.4436;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23706023; DOI=10.1089/ars.2013.5199;
RA Patterson M.J., McKenzie C.G., Smith D.A., da Silva Dantas A., Sherston S.,
RA Veal E.A., Morgan B.A., MacCallum D.M., Erwig L.P., Quinn J.;
RT "Ybp1 and Gpx3 signaling in Candida albicans govern hydrogen peroxide-
RT induced oxidation of the Cap1 transcription factor and macrophage escape.";
RL Antioxid. Redox Signal. 19:2244-2260(2013).
CC -!- FUNCTION: Involved in oxidative stress response and redox homeostasis.
CC Functions as a sensor and transducer of hydroperoxide stress. In
CC response to hydroperoxide stress it oxidizes (activates) the
CC transcription activator CAP1, which is involved in transcription
CC activation of genes of the oxidative stress response pathway
CC (PubMed:23706023). May also play a direct role in hydroperoxide
CC scavenging. The enzyme is not required for the glutaredoxin-mediated
CC antioxidant function. In the presence of peroxides, GPX3 is directly
CC oxidized at Cys-43 to form a cysteine sulfenic acid (-SOH). Cys-43-SOH
CC then forms either an intramolecular disulfide bond (Cys-43 with Cys-89)
CC or a transient, intermolecular disulfide bond with 'Cys-446' of CAP1,
CC which is further resolved into a CAP1 intramolecular disulfide bond
CC ('Cys-303' with 'Cys-598'), which causes its nuclear accumulation and
CC activation, and a reduced Cys-43 in GPX3 (By similarity). Required for
CC C.albicans-mediated macrophage killing (PubMed:23706023).
CC {ECO:0000250|UniProtKB:P40581, ECO:0000269|PubMed:23706023}.
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:P40581};
CC -!- SUBUNIT: Interacts with CAP1 and probably YBP1.
CC {ECO:0000250|UniProtKB:P40581}.
CC -!- DISRUPTION PHENOTYPE: Sensitive to hydrogen peroxide. Unable to
CC filament and thus, escape from murine macrophages after phagocytosis.
CC Also displays defective virulence in the Galleria mellonella infection
CC model. {ECO:0000269|PubMed:23706023}.
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 atypical 2-Cys
CC peroxiredoxin, C(R) is present in the same subunit to form an
CC intramolecular disulfide. {ECO:0000250|UniProtKB:P40581}.
CC -!- SIMILARITY: Belongs to the glutathione peroxidase family.
CC {ECO:0000305}.
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DR EMBL; CP017623; AOW26383.1; -; Genomic_DNA.
DR RefSeq; XP_713880.1; XM_708787.2.
DR AlphaFoldDB; Q59WD3; -.
DR SMR; Q59WD3; -.
DR STRING; 237561.Q59WD3; -.
DR EnsemblFungi; KHC83493; KHC83493; W5Q_00712.
DR EnsemblFungi; KHC89529; KHC89529; I503_00716.
DR GeneID; 3644471; -.
DR KEGG; cal:CAALFM_C107350CA; -.
DR CGD; CAL0000190813; GPX3.
DR VEuPathDB; FungiDB:C1_07350C_A; -.
DR eggNOG; KOG1651; Eukaryota.
DR HOGENOM; CLU_029507_2_2_1; -.
DR InParanoid; Q59WD3; -.
DR OMA; LAPFKGQ; -.
DR OrthoDB; 1483113at2759; -.
DR PHI-base; PHI:3807; -.
DR Proteomes; UP000000559; Chromosome 1.
DR GO; GO:0031315; C:extrinsic component of mitochondrial outer membrane; IEA:EnsemblFungi.
DR GO; GO:0005782; C:peroxisomal matrix; IEA:EnsemblFungi.
DR GO; GO:0004602; F:glutathione peroxidase activity; IEA:EnsemblFungi.
DR GO; GO:0004601; F:peroxidase activity; IBA:GO_Central.
DR GO; GO:0051920; F:peroxiredoxin activity; IEA:UniProtKB-EC.
DR GO; GO:0047066; F:phospholipid-hydroperoxide glutathione peroxidase activity; IEA:EnsemblFungi.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:CGD.
DR GO; GO:0018171; P:peptidyl-cysteine oxidation; IMP:CGD.
DR GO; GO:0007031; P:peroxisome organization; IEA:EnsemblFungi.
DR GO; GO:0061407; P:positive regulation of transcription from RNA polymerase II promoter in response to hydrogen peroxide; IMP:CGD.
DR CDD; cd00340; GSH_Peroxidase; 1.
DR InterPro; IPR000889; Glutathione_peroxidase.
DR InterPro; IPR029759; GPX_AS.
DR InterPro; IPR029760; GPX_CS.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR PANTHER; PTHR11592; PTHR11592; 1.
DR Pfam; PF00255; GSHPx; 1.
DR PIRSF; PIRSF000303; Glutathion_perox; 1.
DR PRINTS; PR01011; GLUTPROXDASE.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS00460; GLUTATHIONE_PEROXID_1; 1.
DR PROSITE; PS00763; GLUTATHIONE_PEROXID_2; 1.
DR PROSITE; PS51355; GLUTATHIONE_PEROXID_3; 1.
PE 3: Inferred from homology;
KW Antioxidant; Disulfide bond; Oxidoreductase; Peroxidase;
KW Redox-active center; Reference proteome.
FT CHAIN 1..171
FT /note="Glutathione peroxidase-like peroxiredoxin GPX3"
FT /id="PRO_0000441072"
FT ACT_SITE 43
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000250|UniProtKB:P40581"
FT DISULFID 43..89
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:P40581"
FT DISULFID 43
FT /note="Interchain (with C-446 in CAP1); transient"
FT /evidence="ECO:0000250|UniProtKB:P40581"
SQ SEQUENCE 171 AA; 19842 MW; C8C2428F8D0BBEDC CRC64;
MGNELLSTAR IYTFKIPDAY NNVIDFDQFK NKVILIVNVA SLCGFTPQYK ELQLLYEKYH
ERGLEILGFP CNQFGNQEPL QEEEIVESCR RNFGVSFPIM KKTKVNIDCD GHESELYKYL
KSEKPGEVGF KGVRWNFEKF IVNRKGEVVA RFNSLITPLQ LEGFIEQLLS E
