ID   TRXR2_HUMAN             Reviewed;         524 AA.
AC   Q9NNW7; O95840; Q96IJ2; Q9H2Z5; Q9NZV3; Q9NZV4; Q9P2Y0; Q9P2Y1; Q9UQU8;
DT   19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT   26-FEB-2008, sequence version 3.
DT   27-MAR-2024, entry version 212.
DE   RecName: Full=Thioredoxin reductase 2, mitochondrial {ECO:0000305};
DE            EC=1.8.1.9 {ECO:0000250|UniProtKB:Q9N2I8, ECO:0000250|UniProtKB:Q9Z0J5};
DE   AltName: Full=Selenoprotein Z;
DE            Short=SelZ;
DE   AltName: Full=TR-beta;
DE   AltName: Full=Thioredoxin reductase TR3;
DE   Flags: Precursor;
GN   Name=TXNRD2 {ECO:0000312|HGNC:HGNC:18155}; Synonyms=KIAA1652, TRXR2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606 {ECO:0000312|EMBL:AAD51324.1};
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=10455115; DOI=10.1074/jbc.274.35.24522;
RA   Sun Q.-A., Wu Y., Zappacosta F., Jeang K.-T., Lee B.J., Hatfield D.L.,
RA   Gladyshev V.N.;
RT   "Redox regulation of cell signaling by selenocysteine in mammalian
RT   thioredoxin reductases.";
RL   J. Biol. Chem. 274:24522-24530(1999).
RN   [2] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT
RP   SER-66.
RC   TISSUE=Fetal heart, and Placenta;
RX   PubMed=9923614; DOI=10.1016/s0014-5793(98)01638-x;
RA   Gasdaska P.Y., Berggren M.M., Berry M.J., Powis G.;
RT   "Cloning, sequencing and functional expression of a novel human thioredoxin
RT   reductase.";
RL   FEBS Lett. 442:105-111(1999).
RN   [3] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Adrenal gland, and Testis;
RX   PubMed=10215850; DOI=10.1046/j.1432-1327.1999.00286.x;
RA   Miranda-Vizuete A., Damdimopoulos A.E., Pedrajas J.R., Gustafsson J.-A.,
RA   Spyrou G.;
RT   "Human mitochondrial thioredoxin reductase: cDNA cloning, expression and
RT   genomic organization.";
RL   Eur. J. Biochem. 261:405-412(1999).
RN   [4] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2), AND VARIANT THR-370.
RA   Toji S., Yano M., Tamai K.;
RL   Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN   [5] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), ALTERNATIVE SPLICING, TISSUE
RP   SPECIFICITY, AND VARIANT THR-370.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=10608886; DOI=10.1074/jbc.274.53.38147;
RA   Lescure A., Gautheret D., Carbon P., Krol A.;
RT   "Novel selenoproteins identified in silico and in vivo by using a conserved
RT   RNA structural motif.";
RL   J. Biol. Chem. 274:38147-38154(1999).
RN   [6] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE (ISOFORM 1), AND VARIANTS SER-66 AND THR-370.
RA   Kim J.-R., Lee Y.H., Lee S.-R., Kim B.H., Rhee S.G., Kim J.H.;
RL   Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10591208; DOI=10.1038/990031;
RA   Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA   Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA   Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA   Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA   Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA   Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA   Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA   Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA   Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA   Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA   Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA   Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA   Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA   Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA   Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA   Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA   Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA   Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA   Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA   Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA   Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA   Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA   Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA   Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA   Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA   Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA   Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA   Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA   Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA   Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA   Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA   Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA   Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA   McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA   Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA   Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA   Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA   Wright H.;
RT   "The DNA sequence of human chromosome 22.";
RL   Nature 402:489-495(1999).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 40-524, AND VARIANT SER-66.
RC   TISSUE=Skin;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   ALTERNATIVE SPLICING.
RX   PubMed=11060283; DOI=10.1074/jbc.m004750200;
RA   Sun Q.-A., Zappacosta F., Factor V.M., Wirth P.J., Hatfield D.L.,
RA   Gladyshev V.N.;
RT   "Heterogeneity within animal thioredoxin reductases: evidence for
RT   alternative first exon splicing.";
RL   J. Biol. Chem. 276:3106-3114(2001).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [12]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [13]
RP   FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN GCCD5, VARIANT GCCD5
RP   447-TYR--GLY-524 DEL, CHARACTERIZATION OF VARIANT GCCD5 447-TYR--GLY-524
RP   DEL, AND VARIANTS SER-66; ARG-299 AND THR-370.
RX   PubMed=24601690; DOI=10.1210/jc.2013-3844;
RA   Prasad R., Chan L.F., Hughes C.R., Kaski J.P., Kowalczyk J.C., Savage M.O.,
RA   Peters C.J., Nathwani N., Clark A.J., Storr H.L., Metherell L.A.;
RT   "Thioredoxin Reductase 2 (TXNRD2) mutation associated with familial
RT   glucocorticoid deficiency (FGD).";
RL   J. Clin. Endocrinol. Metab. 99:E1556-E1563(2014).
CC   -!- FUNCTION: Involved in the control of reactive oxygen species levels and
CC       the regulation of mitochondrial redox homeostasis (PubMed:24601690).
CC       Maintains thioredoxin in a reduced state. May play a role in redox-
CC       regulated cell signaling. {ECO:0000250|UniProtKB:Q9Z0J5,
CC       ECO:0000269|PubMed:24601690}.
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:0000250|UniProtKB:Q9N2I8,
CC         ECO:0000250|UniProtKB:Q9Z0J5};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20347;
CC         Evidence={ECO:0000250|UniProtKB:Q9N2I8,
CC         ECO:0000250|UniProtKB:Q9Z0J5};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000255|RuleBase:RU000402, ECO:0000305};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P38816}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10215850}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1; Synonyms=Alpha {ECO:0000305};
CC         IsoId=Q9NNW7-1; Sequence=Displayed;
CC       Name=2; Synonyms=Beta {ECO:0000305};
CC         IsoId=Q9NNW7-2; Sequence=VSP_008304;
CC       Name=3; Synonyms=SelZf2;
CC         IsoId=Q9NNW7-3; Sequence=VSP_008305;
CC       Name=4; Synonyms=SelZf1;
CC         IsoId=Q9NNW7-4; Sequence=VSP_008306;
CC   -!- TISSUE SPECIFICITY: Highly expressed in the prostate, ovary, liver,
CC       testis, uterus, colon and small intestine. Intermediate levels in
CC       brain, skeletal muscle, heart and spleen. Low levels in placenta,
CC       pancreas, thymus and peripheral blood leukocytes. According to
CC       PubMed:10608886, high levels in kidney, whereas according to
CC       PubMed:9923614, levels are low. High expression is observed in the
CC       adrenal cortex (PubMed:24601690). {ECO:0000269|PubMed:10215850,
CC       ECO:0000269|PubMed:10608886, ECO:0000269|PubMed:24601690,
CC       ECO:0000269|PubMed:9923614}.
CC   -!- DISEASE: Glucocorticoid deficiency 5 (GCCD5) [MIM:617825]: A form of
CC       glucocorticoid deficiency, a rare autosomal recessive disorder
CC       characterized by resistance to ACTH action on the adrenal cortex,
CC       adrenal insufficiency and an inability of the adrenal cortex to produce
CC       cortisol. It usually presents in the neonatal period or in early
CC       childhood with episodes of hypoglycemia and other symptoms related to
CC       cortisol deficiency, including failure to thrive, recurrent illnesses
CC       or infections, convulsions, and shock. In a small number of patients
CC       hypoglycemia can be sufficiently severe and persistent that it leads to
CC       serious long-term neurological damage or death. The diagnosis is
CC       readily confirmed with a low plasma cortisol measurement in the
CC       presence of an elevated ACTH level, and normal aldosterone and plasma
CC       renin measurements. {ECO:0000269|PubMed:24601690}. Note=The disease may
CC       be caused by variants affecting the gene represented in this entry.
CC   -!- MISCELLANEOUS: The active site is a redox-active disulfide bond. The
CC       selenocysteine residue is essential for enzymatic activity (By
CC       similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC       oxidoreductase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAD25167.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAG47635.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={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; AF171054; AAD51324.1; -; mRNA.
DR   EMBL; AF106697; AAD19597.1; -; mRNA.
DR   EMBL; AF044212; AAD25167.1; ALT_INIT; mRNA.
DR   EMBL; AB019694; BAA77601.2; -; mRNA.
DR   EMBL; AB019695; BAA77602.2; -; mRNA.
DR   EMBL; AF166126; AAF21431.1; -; mRNA.
DR   EMBL; AF166127; AAF21432.1; -; mRNA.
DR   EMBL; AF201385; AAG47635.1; ALT_SEQ; mRNA.
DR   EMBL; AC000078; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC000080; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC000090; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC007489; AAH07489.3; -; mRNA.
DR   CCDS; CCDS42981.1; -. [Q9NNW7-1]
DR   CCDS; CCDS86998.1; -. [Q9NNW7-3]
DR   RefSeq; NP_006431.2; NM_006440.4. [Q9NNW7-1]
DR   BioGRID; 115836; 58.
DR   IntAct; Q9NNW7; 9.
DR   MINT; Q9NNW7; -.
DR   STRING; 9606.ENSP00000383365; -.
DR   BindingDB; Q9NNW7; -.
DR   ChEMBL; CHEMBL2403; -.
DR   DrugBank; DB05428; Motexafin gadolinium.
DR   GlyGen; Q9NNW7; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9NNW7; -.
DR   PhosphoSitePlus; Q9NNW7; -.
DR   SwissPalm; Q9NNW7; -.
DR   BioMuta; TXNRD2; -.
DR   DMDM; 182705230; -.
DR   EPD; Q9NNW7; -.
DR   jPOST; Q9NNW7; -.
DR   MassIVE; Q9NNW7; -.
DR   MaxQB; Q9NNW7; -.
DR   PaxDb; 9606-ENSP00000383365; -.
DR   PeptideAtlas; Q9NNW7; -.
DR   ProteomicsDB; 81857; -. [Q9NNW7-1]
DR   ProteomicsDB; 81858; -. [Q9NNW7-2]
DR   ProteomicsDB; 81859; -. [Q9NNW7-3]
DR   ProteomicsDB; 81860; -. [Q9NNW7-4]
DR   Pumba; Q9NNW7; -.
DR   Antibodypedia; 230; 295 antibodies from 34 providers.
DR   DNASU; 10587; -.
DR   Ensembl; ENST00000400521.7; ENSP00000383365.1; ENSG00000184470.21. [Q9NNW7-1]
DR   Ensembl; ENST00000542719.6; ENSP00000485128.2; ENSG00000184470.21. [Q9NNW7-3]
DR   GeneID; 10587; -.
DR   KEGG; hsa:10587; -.
DR   MANE-Select; ENST00000400521.7; ENSP00000383365.1; NM_006440.5; NP_006431.2.
DR   AGR; HGNC:18155; -.
DR   CTD; 10587; -.
DR   DisGeNET; 10587; -.
DR   GeneCards; TXNRD2; -.
DR   HGNC; HGNC:18155; TXNRD2.
DR   HPA; ENSG00000184470; Low tissue specificity.
DR   MalaCards; TXNRD2; -.
DR   MIM; 606448; gene.
DR   MIM; 617825; phenotype.
DR   neXtProt; NX_Q9NNW7; -.
DR   OpenTargets; ENSG00000184470; -.
DR   Orphanet; 361; Familial glucocorticoid deficiency.
DR   Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR   PharmGKB; PA38302; -.
DR   VEuPathDB; HostDB:ENSG00000184470; -.
DR   eggNOG; KOG4716; Eukaryota.
DR   GeneTree; ENSGT00940000158832; -.
DR   InParanoid; Q9NNW7; -.
DR   OMA; CFDYVKP; -.
DR   OrthoDB; 5473641at2759; -.
DR   PhylomeDB; Q9NNW7; -.
DR   TreeFam; TF314782; -.
DR   BRENDA; 1.8.1.9; 2681.
DR   PathwayCommons; Q9NNW7; -.
DR   Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR   SignaLink; Q9NNW7; -.
DR   BioGRID-ORCS; 10587; 29 hits in 1167 CRISPR screens.
DR   ChiTaRS; TXNRD2; human.
DR   GenomeRNAi; 10587; -.
DR   Pharos; Q9NNW7; Tbio.
DR   PRO; PR:Q9NNW7; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; Q9NNW7; Protein.
DR   Bgee; ENSG00000184470; Expressed in right lobe of liver and 188 other cell types or tissues.
DR   ExpressionAtlas; Q9NNW7; baseline and differential.
DR   GO; GO:0030424; C:axon; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR   GO; GO:0004791; F:thioredoxin-disulfide reductase (NADP) activity; ISS:UniProtKB.
DR   GO; GO:0045454; P:cell redox homeostasis; IMP:UniProtKB.
DR   GO; GO:0055093; P:response to hyperoxia; IEA:Ensembl.
DR   GO; GO:0000305; P:response to oxygen radical; TAS:UniProtKB.
DR   GO; GO:0010269; P:response to selenium ion; IEA:Ensembl.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
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:SF6; THIOREDOXIN REDUCTASE 2; 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   1: Evidence at protein level;
KW   Alternative splicing; Disease variant; Disulfide bond; FAD; Flavoprotein;
KW   Mitochondrion; NADP; Oxidoreductase; Redox-active center;
KW   Reference proteome; Selenocysteine; Transit peptide.
FT   TRANSIT         1..36
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           37..524
FT                   /note="Thioredoxin reductase 2, mitochondrial"
FT                   /id="PRO_0000030288"
FT   ACT_SITE        497
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         41..70
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   NON_STD         523
FT                   /note="Selenocysteine"
FT   MOD_RES         175
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JLT4"
FT   MOD_RES         329
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JLT4"
FT   DISULFID        86..91
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250"
FT   CROSSLNK        522..523
FT                   /note="Cysteinyl-selenocysteine (Cys-Sec)"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..247
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:10608886"
FT                   /id="VSP_008306"
FT   VAR_SEQ         1..96
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:10608886"
FT                   /id="VSP_008305"
FT   VAR_SEQ         1..30
FT                   /note="MAAMAVALRGLGGRFRWRTQAVAGGVRGAA -> MEDQ (in isoform
FT                   2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_008304"
FT   VARIANT         14
FT                   /note="R -> L (in dbSNP:rs45593642)"
FT                   /id="VAR_051777"
FT   VARIANT         66
FT                   /note="A -> S (in dbSNP:rs5748469)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:24601690, ECO:0000269|PubMed:9923614,
FT                   ECO:0000269|Ref.6"
FT                   /id="VAR_051778"
FT   VARIANT         299
FT                   /note="S -> R (in dbSNP:rs5992495)"
FT                   /evidence="ECO:0000269|PubMed:24601690"
FT                   /id="VAR_051779"
FT   VARIANT         370
FT                   /note="I -> T (in dbSNP:rs1139793)"
FT                   /evidence="ECO:0000269|PubMed:10608886,
FT                   ECO:0000269|PubMed:24601690, ECO:0000269|Ref.4,
FT                   ECO:0000269|Ref.6"
FT                   /id="VAR_051780"
FT   VARIANT         447..524
FT                   /note="Missing (in GCCD5; the mutant protein is
FT                   undetectable in patient cells)"
FT                   /evidence="ECO:0000269|PubMed:24601690"
FT                   /id="VAR_080529"
FT   CONFLICT        33
FT                   /note="Missing (in Ref. 6; AAG47635)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        285
FT                   /note="R -> K (in Ref. 6; AAG47635)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   524 AA;  56507 MW;  B575A185A2183DAC CRC64;
     MAAMAVALRG LGGRFRWRTQ AVAGGVRGAA RGAAAGQRDY DLLVVGGGSG GLACAKEAAQ
     LGRKVAVVDY VEPSPQGTRW GLGGTCVNVG CIPKKLMHQA ALLGGLIQDA PNYGWEVAQP
     VPHDWRKMAE AVQNHVKSLN WGHRVQLQDR KVKYFNIKAS FVDEHTVCGV AKGGKEILLS
     ADHIIIATGG RPRYPTHIEG ALEYGITSDD IFWLKESPGK TLVVGASYVA LECAGFLTGI
     GLDTTIMMRS IPLRGFDQQM SSMVIEHMAS HGTRFLRGCA PSRVRRLPDG QLQVTWEDST
     TGKEDTGTFD TVLWAIGRVP DTRSLNLEKA GVDTSPDTQK ILVDSREATS VPHIYAIGDV
     VEGRPELTPI AIMAGRLLVQ RLFGGSSDLM DYDNVPTTVF TPLEYGCVGL SEEEAVARHG
     QEHVEVYHAH YKPLEFTVAG RDASQCYVKM VCLREPPQLV LGLHFLGPNA GEVTQGFALG
     IKCGASYAQV MRTVGIHPTC SEEVVKLRIS KRSGLDPTVT GCUG
//