ID H0VKC2_CAVPO Unreviewed; 499 AA.
AC H0VKC2;
DT 22-FEB-2012, integrated into UniProtKB/TrEMBL.
DT 22-NOV-2017, sequence version 2.
DT 27-MAR-2024, entry version 73.
DE RecName: Full=Thioredoxin reductase 1, cytoplasmic {ECO:0000256|ARBA:ARBA00044068};
DE EC=1.11.1.2 {ECO:0000256|ARBA:ARBA00044049};
DE EC=1.8.1.9 {ECO:0000256|ARBA:ARBA00012610};
DE AltName: Full=Peroxidase TXNRD1 {ECO:0000256|ARBA:ARBA00044275};
DE AltName: Full=Thioredoxin reductase TR1 {ECO:0000256|ARBA:ARBA00044212};
GN Name=TXNRD1 {ECO:0000313|Ensembl:ENSCPOP00000010744.3};
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141 {ECO:0000313|Ensembl:ENSCPOP00000010744.3, ECO:0000313|Proteomes:UP000005447};
RN [1] {ECO:0000313|Proteomes:UP000005447}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=2N {ECO:0000313|Proteomes:UP000005447};
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2] {ECO:0000313|Ensembl:ENSCPOP00000010744.3}
RP IDENTIFICATION.
RC STRAIN=2N {ECO:0000313|Ensembl:ENSCPOP00000010744.3};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + H2O2 + NADPH = 2 H2O + NADP(+); Xref=Rhea:RHEA:15173,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.11.1.2;
CC Evidence={ECO:0000256|ARBA:ARBA00043653};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15174;
CC Evidence={ECO:0000256|ARBA:ARBA00043653};
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:0000256|ARBA:ARBA00029303};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20347;
CC Evidence={ECO:0000256|ARBA:ARBA00029303};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000256|PIRSR:PIRSR000350-3};
CC Note=Binds 1 FAD per subunit. {ECO:0000256|PIRSR:PIRSR000350-3};
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000256|ARBA:ARBA00007532,
CC ECO:0000256|RuleBase:RU003691}.
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DR EMBL; AAKN02055460; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; H0VKC2; -.
DR STRING; 10141.ENSCPOP00000010744; -.
DR Ensembl; ENSCPOT00000012057.3; ENSCPOP00000010744.3; ENSCPOG00000011941.4.
DR VEuPathDB; HostDB:ENSCPOG00000011941; -.
DR eggNOG; KOG4716; Eukaryota.
DR GeneTree; ENSGT00940000160180; -.
DR HOGENOM; CLU_016755_2_4_1; -.
DR InParanoid; H0VKC2; -.
DR OMA; GTCINWG; -.
DR TreeFam; TF314782; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000011941; Expressed in zone of skin and 12 other cell types or tissues.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0001650; C:fibrillar center; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0071949; F:FAD binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0050137; F:NADPH peroxidase activity; IEA:Ensembl.
DR GO; GO:0004791; F:thioredoxin-disulfide reductase (NADP) activity; IEA:UniProtKB-EC.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0010035; P:response to inorganic substance; IEA:UniProt.
DR GO; GO:0006979; P:response to oxidative stress; IEA:UniProt.
DR Gene3D; 3.30.390.30; -; 1.
DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 2.
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; IPR046952; GSHR/TRXR-like.
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 NCBIfam; TIGR01438; TGR; 1.
DR PANTHER; PTHR42737; GLUTATHIONE REDUCTASE; 1.
DR PANTHER; PTHR42737:SF8; THIOREDOXIN REDUCTASE 1; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR PIRSF; PIRSF000350; Mercury_reductase_MerA; 1.
DR PRINTS; PR00368; FADPNR.
DR PRINTS; PR00411; PNDRDTASEI.
DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1.
DR SUPFAM; SSF55424; FAD/NAD-linked reductases, dimerisation (C-terminal) domain; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 3: Inferred from homology;
KW FAD {ECO:0000256|ARBA:ARBA00022827, ECO:0000256|PIRSR:PIRSR000350-3};
KW Flavoprotein {ECO:0000256|ARBA:ARBA00022630,
KW ECO:0000256|RuleBase:RU003691}; NAD {ECO:0000256|PIRSR:PIRSR000350-3};
KW Nucleotide-binding {ECO:0000256|PIRSR:PIRSR000350-3};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW ECO:0000256|RuleBase:RU003691};
KW Redox-active center {ECO:0000256|ARBA:ARBA00023284,
KW ECO:0000256|RuleBase:RU003691};
KW Reference proteome {ECO:0000313|Proteomes:UP000005447};
KW Selenocysteine {ECO:0000256|ARBA:ARBA00022933}.
FT DOMAIN 14..351
FT /note="FAD/NAD(P)-binding"
FT /evidence="ECO:0000259|Pfam:PF07992"
FT DOMAIN 371..482
FT /note="Pyridine nucleotide-disulphide oxidoreductase
FT dimerisation"
FT /evidence="ECO:0000259|Pfam:PF02852"
FT ACT_SITE 473
FT /note="Proton acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR000350-2"
FT BINDING 69
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR000350-3"
FT BINDING 133
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR000350-3"
FT BINDING 198..205
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|PIRSR:PIRSR000350-3"
FT BINDING 293
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|PIRSR:PIRSR000350-3"
FT BINDING 335
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000256|PIRSR:PIRSR000350-3"
FT DISULFID 60..65
FT /note="Redox-active"
FT /evidence="ECO:0000256|PIRSR:PIRSR000350-4"
SQ SEQUENCE 499 AA; 54554 MW; 0FC967D26EEACA39 CRC64;
MNNSQDSLPE SYDFDLIIIG GGSGGLAASK EAAKYGKKVM VLDFVTPTPL GTRWGLGGTC
VNVGCIPKKL MHQAALLGQA LQDSRNYGWK VEDAVKHDWE KMTEAVQNHI GSLNWGYRVA
LREKKVVYEN AYGQFIGPHR IKATNNKGKE KIYSAERFLI ATGERPRYLG IPGDKEFCIS
SDDLFSLPYC PGKTLVVGAS YVALECAGFL AGIGLDVTVM VRSILLRGFD QDMANKIGEH
MEEHGIKFIK QFVPIKVEQI EPGTPGRLKV TAKSTHSEDI IEGEYNTVLL AIGRDACTRN
IGLETVGVKI NEKTGKIPVT DEEQTNVPYI YAIGDILEGK LELTPVAIQA GRLLAQRLYG
GSTVKCDYEN VPTTVFTPLE YGACGLSEEK AVERFGEDNV EVYHSFFWPL EWTVPSRDLN
KCYAKIVCNL QDDERVVGFH ILGPNAGEVT QGFAAALKCG LTKRQLDSTI GIHPVCAEVF
TTLSVTKRSG ASVLQSGCG
//
