TRXR3_HUMAN
ID TRXR3_HUMAN Reviewed; 643 AA.
AC Q86VQ6; Q6PIS8; Q9NNW6; Q9P101;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2013, sequence version 4.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Thioredoxin reductase 3;
DE EC=1.8.1.9;
DE AltName: Full=Thioredoxin and glutathione reductase;
DE AltName: Full=Thioredoxin reductase TR2;
GN Name=TXNRD3 {ECO:0000312|EMBL:AAH50032.1};
GN Synonyms=TGR {ECO:0000250|UniProtKB:Q99MD6},
GN TRXR3 {ECO:0000312|EMBL:AAD39929.1};
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;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAH50032.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis {ECO:0000312|EMBL:AAH50032.1};
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 [3] {ECO:0000305, ECO:0000312|EMBL:AAD51325.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 65-643, AND SELENOCYSTEINE AT SEC-642.
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 [4] {ECO:0000305, ECO:0000312|EMBL:AAD39929.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 67-643.
RA Miranda-Vizuete A.;
RT "TrxR3, a novel human thioredoxin reductase.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41 AND SER-42, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP PROBABLE NON-AUG INITIATOR START CODON.
RX PubMed=20018845; DOI=10.1074/jbc.m109.070532;
RA Gerashchenko M.V., Su D., Gladyshev V.N.;
RT "CUG start codon generates thioredoxin/glutathione reductase isoforms in
RT mouse testes.";
RL J. Biol. Chem. 285:4595-4602(2010).
CC -!- FUNCTION: Displays thioredoxin reductase, glutaredoxin and glutathione
CC reductase activities. Catalyzes disulfide bond isomerization. Promotes
CC disulfide bond formation between GPX4 and various sperm proteins and
CC may play a role in sperm maturation by promoting formation of sperm
CC structural components (By similarity). {ECO:0000250|UniProtKB:Q99MD6}.
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:Q99MD6};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:O89049};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:O89049};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:O89049}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q99MD6}. Nucleus
CC {ECO:0000250|UniProtKB:Q99MD6}. Microsome
CC {ECO:0000250|UniProtKB:Q99MD6}. Endoplasmic reticulum {ECO:0000250}.
CC Note=Detected in cytoplasm and nucleus in late spermatids.
CC {ECO:0000250|UniProtKB:Q99MD6}.
CC -!- DOMAIN: The N-terminal glutaredoxin domain does not contain the C-X-X-C
CC redox-active motif normally found in glutaredoxins but activity may be
CC mediated through a single cysteine. The C-terminal Cys-Sec motif of one
CC subunit of the homodimer may transfer electrons from the thiol-
CC disulfide center to the glutaredoxin domain of the other subunit (By
CC similarity). {ECO:0000250|UniProtKB:Q99MD6}.
CC -!- MISCELLANEOUS: The thioredoxin reductase active site is a redox-active
CC disulfide bond. The selenocysteine residue is also essential for
CC catalytic activity (By similarity). {ECO:0000250|UniProtKB:Q16881}.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
CC -!- CAUTION: This sequence initiates at a CTG codon.
CC {ECO:0000305|PubMed:20018845}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH30028.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH30028.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC Sequence=AAH50032.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH50032.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
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DR EMBL; AC024558; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030028; AAH30028.1; ALT_SEQ; mRNA.
DR EMBL; BC050032; AAH50032.1; ALT_SEQ; mRNA.
DR EMBL; AF171055; AAD51325.1; -; mRNA.
DR EMBL; AF133519; AAD39929.1; -; mRNA.
DR CCDS; CCDS77811.1; -.
DR RefSeq; NP_001166984.1; NM_001173513.1.
DR RefSeq; NP_443115.1; NM_052883.1.
DR PDB; 3H8Q; X-ray; 2.21 A; A/B=51-156.
DR PDBsum; 3H8Q; -.
DR SMR; Q86VQ6; -.
DR BioGRID; 125281; 19.
DR IntAct; Q86VQ6; 1.
DR BindingDB; Q86VQ6; -.
DR ChEMBL; CHEMBL2096978; -.
DR iPTMnet; Q86VQ6; -.
DR PhosphoSitePlus; Q86VQ6; -.
DR BioMuta; TXNRD3; -.
DR DMDM; 510120859; -.
DR EPD; Q86VQ6; -.
DR jPOST; Q86VQ6; -.
DR MassIVE; Q86VQ6; -.
DR MaxQB; Q86VQ6; -.
DR PaxDb; Q86VQ6; -.
DR PeptideAtlas; Q86VQ6; -.
DR PRIDE; Q86VQ6; -.
DR ProteomicsDB; 70059; -.
DR Antibodypedia; 60139; 149 antibodies from 17 providers.
DR DNASU; 114112; -.
DR Ensembl; ENST00000524230.9; ENSP00000430031.4; ENSG00000197763.20.
DR GeneID; 114112; -.
DR KEGG; hsa:114112; -.
DR MANE-Select; ENST00000524230.9; ENSP00000430031.4; NM_052883.3; NP_443115.1.
DR CTD; 114112; -.
DR DisGeNET; 114112; -.
DR GeneCards; TXNRD3; -.
DR HGNC; HGNC:20667; TXNRD3.
DR HPA; ENSG00000197763; Tissue enhanced (testis).
DR MIM; 606235; gene.
DR neXtProt; NX_Q86VQ6; -.
DR OpenTargets; ENSG00000197763; -.
DR PharmGKB; PA134920642; -.
DR VEuPathDB; HostDB:ENSG00000197763; -.
DR GeneTree; ENSGT00940000159178; -.
DR InParanoid; Q86VQ6; -.
DR OMA; HPTCGEI; -.
DR OrthoDB; 581771at2759; -.
DR BRENDA; 1.8.1.9; 2681.
DR PathwayCommons; Q86VQ6; -.
DR SignaLink; Q86VQ6; -.
DR BioGRID-ORCS; 114112; 14 hits in 331 CRISPR screens.
DR ChiTaRS; TXNRD3; human.
DR EvolutionaryTrace; Q86VQ6; -.
DR GenomeRNAi; 114112; -.
DR Pharos; Q86VQ6; Tbio.
DR PRO; PR:Q86VQ6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q86VQ6; protein.
DR Bgee; ENSG00000197763; Expressed in right testis and 125 other tissues.
DR ExpressionAtlas; Q86VQ6; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0097573; F:glutathione oxidoreductase activity; IEA:InterPro.
DR GO; GO:0004791; F:thioredoxin-disulfide reductase activity; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR Gene3D; 3.30.390.30; -; 1.
DR Gene3D; 3.50.50.60; -; 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; IPR002109; Glutaredoxin.
DR InterPro; IPR011899; Glutaredoxin_euk/vir.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR006338; Thioredoxin/glutathione_Rdtase.
DR Pfam; PF00462; Glutaredoxin; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR SUPFAM; SSF55424; SSF55424; 1.
DR TIGRFAMs; TIGR02180; GRX_euk; 1.
DR TIGRFAMs; TIGR01438; TGR; 1.
DR PROSITE; PS51354; GLUTAREDOXIN_2; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Developmental protein; Differentiation;
KW Disulfide bond; Electron transport; Endoplasmic reticulum; FAD;
KW Flavoprotein; Methylation; Microsome; NADP; Nucleus; Oxidoreductase;
KW Phosphoprotein; Redox-active center; Reference proteome; Selenocysteine;
KW Spermatogenesis; Transport.
FT CHAIN 1..643
FT /note="Thioredoxin reductase 3"
FT /id="PRO_0000320695"
FT DOMAIN 56..156
FT /note="Glutaredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00686"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 616
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 158..187
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT NON_STD 642
FT /note="Selenocysteine"
FT MOD_RES 26
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99MD6"
FT MOD_RES 26
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99MD6"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 379
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99MD6"
FT DISULFID 203..208
FT /note="Redox-active"
FT /evidence="ECO:0000250"
FT CROSSLNK 641..642
FT /note="Cysteinyl-selenocysteine (Cys-Sec)"
FT /evidence="ECO:0000250"
FT CONFLICT 65..66
FT /note="RS -> AE (in Ref. 3; AAD51325)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="T -> I (in Ref. 2; AAH30028)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="T -> P (in Ref. 4; AAD39929)"
FT /evidence="ECO:0000305"
FT HELIX 53..65
FT /evidence="ECO:0007829|PDB:3H8Q"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:3H8Q"
FT HELIX 77..88
FT /evidence="ECO:0007829|PDB:3H8Q"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:3H8Q"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:3H8Q"
FT HELIX 104..115
FT /evidence="ECO:0007829|PDB:3H8Q"
FT STRAND 122..125
FT /evidence="ECO:0007829|PDB:3H8Q"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:3H8Q"
FT HELIX 133..142
FT /evidence="ECO:0007829|PDB:3H8Q"
FT HELIX 144..150
FT /evidence="ECO:0007829|PDB:3H8Q"
SQ SEQUENCE 643 AA; 70683 MW; 6FB04128943A4017 CRC64;
MERSPPQSPG PGKAGDAPNR RSGHVRGARV LSPPGRRARL SSPGPSRSSE AREELRRHLV
GLIERSRVVI FSKSYCPHST RVKELFSSLG VECNVLELDQ VDDGARVQEV LSEITNQKTV
PNIFVNKVHV GGCDQTFQAY QSGLLQKLLQ EDLAYDYDLI IIGGGSGGLS CAKEAAILGK
KVMVLDFVVP SPQGTSWGLG GTCVNVGCIP KKLMHQAALL GQALCDSRKF GWEYNQQVRH
NWETMTKAIQ NHISSLNWGY RLSLREKAVA YVNSYGEFVE HHKIKATNKK GQETYYTAAQ
FVIATGERPR YLGIQGDKEY CITSDDLFSL PYCPGKTLVV GASYVALECA GFLAGFGLDV
TVMVRSILLR GFDQEMAEKV GSYMEQHGVK FLRKFIPVMV QQLEKGSPGK LKVLAKSTEG
TETIEGVYNT VLLAIGRDSC TRKIGLEKIG VKINEKSGKI PVNDVEQTNV PYVYAVGDIL
EDKPELTPVA IQSGKLLAQR LFGASLEKCD YINVPTTVFT PLEYGCCGLS EEKAIEVYKK
ENLEIYHTLF WPLEWTVAGR ENNTCYAKII CNKFDHDRVI GFHILGPNAG EVTQGFAAAM
KCGLTKQLLD DTIGIHPTCG EVFTTLEITK SSGLDITQKG CUG
