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UniProtKB/Swiss-Prot entry Q99MD6


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name TRXR3_MOUSE
Primary accession number Q99MD6
Secondary accession number Q9CZE5
Integrated into Swiss-Prot on February 26, 2008
Sequence was last modified on February 26, 2008 (Sequence version 2)
Annotations were last modified on    November 25, 2008 (Entry version 45)
Name and origin of the protein
Protein name Thioredoxin reductase 3 [Fragment]
Synonyms EC 1.8.1.9
Thioredoxin reductase TR2
Thioredoxin and glutathione reductase
Gene name
Name: Txnrd3
Synonyms: Tgr, Trxr3
From
Mus musculus (Mouse) [TaxID: 10090] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Mus.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J;
TISSUE=Embryo, and Thymus;
DOI=10.1126/science.1112014; PubMed=16141072 [NCBI, ExPASy, EBI, Israel, Japan]
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-697.
STRAIN=C57BL/6;
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
NUCLEOTIDE SEQUENCE [MRNA] OF 28-697, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, DOMAIN, 3D-STRUCTURE MODELING, AND SELENOCYSTEINE AT SEC-696.
DOI=10.1073/pnas.051454398; PubMed=11259642 [NCBI, ExPASy, EBI, Israel, Japan]
Sun Q.-A., Kirnarsky L., Sherman S., Gladyshev V.N.;
"Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems.";
Proc. Natl. Acad. Sci. U.S.A. 98:3673-3678(2001).
[4]
PROTEIN SEQUENCE OF 236-247 AND 595-606, AND TISSUE SPECIFICITY.
DOI=10.1074/jbc.274.35.24522; PubMed=10455115 [NCBI, ExPASy, EBI, Israel, Japan]
Sun Q.-A., Wu Y., Zappacosta F., Jeang K.-T., Lee B.J., Hatfield D.L., Gladyshev V.N.;
"Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases.";
J. Biol. Chem. 274:24522-24530(1999).
[5]
DOMAIN, AND MUTAGENESIS OF SEC-696 AND 696-SEC-GLY-697.
DOI=10.1021/bi051321w; PubMed=16262253 [NCBI, ExPASy, EBI, Israel, Japan]
Sun Q.-A., Su D., Novoselov S.V., Carlson B.A., Hatfield D.L., Gladyshev V.N.;
"Reaction mechanism and regulation of mammalian thioredoxin/glutathione reductase.";
Biochemistry 44:14528-14537(2005).
[6]
FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
DOI=10.1074/jbc.M503638200; PubMed=15901730 [NCBI, ExPASy, EBI, Israel, Japan]
Su D., Novoselov S.V., Sun Q.-A., Moustafa M.E., Zhou Y., Oko R., Hatfield D.L., Gladyshev V.N.;
"Mammalian selenoprotein thioredoxin-glutathione reductase. Roles in disulfide bond formation and sperm maturation.";
J. Biol. Chem. 280:26491-26498(2005).
Comments
  • FUNCTION: Displays thioredoxin reductase, glutaredoxin and glutathione reductase activities. Catalyzes disulfide bond isomerization. Promotes disulfide bond formation between GPX4 and various sperm proteins and may play a role in sperm maturation by promoting formation of sperm structural components.
  • CATALYTIC ACTIVITY: Thioredoxin + NADP+ = thioredoxin disulfide + NADPH.
  • COFACTOR: Binds 1 FAD per subunit (By similarity).
  • BIOPHYSICOCHEMICAL PROPERTIES:
    Kinetic parameters:   KM=14.7 µM for 5,5'-dithiobis(2-nitrobenzoic acid);
    KM=10.7 µM for NADPH;
    KM=3.0 µM for thioredoxin;
    KM=8.84 µM for oxidized glutathione;
    KM=45.2 µM for beta-hydroxyethyl disulfide;
  • SUBUNIT: Homodimer (By similarity).
  • SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Microsome. Endoplasmic reticulum. Note=Detected in cytoplasm and nucleus in late spermatids.
  • TISSUE SPECIFICITY: Expressed preferentially in testis where it is found in spermatids and spermatocytes but not in sperm. In elongating spermatids, expressed at the site of mitochondrial sheath formation. Low levels in other tissues including heart, lung, liver, kidney, brain, muscle and prostate.
  • DEVELOPMENTAL STAGE: Accumulates in the testis after puberty. Not detected in 20-day-old mice but highly expressed in testes of 7-month-old mice.
  • DOMAIN: The N-terminal glutaredoxin domain does not contain the C-X-X-C redox-active motif normally found in glutaredoxins but activity may be mediated through a single cysteine. The C-terminal Cys-Sec motif of one subunit of the homodimer may transfer electrons from the thiol-disulfide center to the glutaredoxin domain of the other subunit.
  • MISCELLANEOUS: The thioredoxin reductase active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity (By similarity).
  • SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
  • SIMILARITY: Contains 1 glutaredoxin domain.
  • SEQUENCE CAUTION:
    • Sequence=AAH76605.1; Type=Erroneous initiation; Note=Translation N-terminally extended
    • Sequence=AAH76605.1; Type=Erroneous termination; Positions=696; Note=Translated as Sec
    • Sequence=BAB28419.1; Type=Erroneous initiation; Note=Translation N-terminally extended
    • Sequence=BAB28419.1; Type=Erroneous termination; Positions=696; Note=Translated as Sec
    • Sequence=BAB28419.1; Type=Frameshift; Positions=74, 83;
    • Sequence=BAC37890.1; Type=Erroneous initiation; Note=Translation N-terminally extended
    • Sequence=BAC37890.1; Type=Erroneous termination; Positions=696; Note=Translated as Sec
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AK012699; BAB28419.1; ALT_SEQ; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK080362; BAC37890.1; ALT_SEQ; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC076605; AAH76605.1; ALT_SEQ; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF349659; AAK31172.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_694802.2; -.
UniGene Mm.229332
3D structure databases
HSSP O89049; 1H6V. [HSSP ENTRY / PDB]
SMR Q99MD6; 126-608.
ModBase Q99MD6.
PTM databases
PhosphoSite Q99MD6; -.
Organism-specific databases
MGI MGI:2386711; Txnrd3.
Gene expression databases
ArrayExpress Q99MD6; -.
CleanEx MM_TXNRD3; -.
Ontologies
GO
GO:0005783; Cellular component: endoplasmic reticulum (inferred from electronic annotation from UniProtKB-KW).
GO:0005792; Cellular component: microsome (inferred from direct assay from MGI).
GO:0005634; Cellular component: nucleus (inferred from electronic annotation from UniProtKB-KW).
GO:0009055; Molecular function: electron carrier activity (inferred from electronic annotation from InterPro).
GO:0050660; Molecular function: FAD binding (inferred from electronic annotation from InterPro).
GO:0050661; Molecular function: NADP binding (inferred from electronic annotation from InterPro).
GO:0016654; Molecular function: oxidoreductase activity, acting on NADH or NADPH, disulfide as acceptor (inferred from electronic annotation from InterPro).
GO:0015035; Molecular function: protein disulfide oxidoreductase activity (inferred from electronic annotation from InterPro).
GO:0008430; Molecular function: selenium binding (inferred from electronic annotation from UniProtKB-KW).
GO:0004791; Molecular function: thioredoxin-disulfide reductase activity (inferred from direct assay from MGI).
GO:0030154; Biological process: cell differentiation (inferred from electronic annotation from UniProtKB-KW).
GO:0045454; Biological process: cell redox homeostasis (inferred from electronic annotation from InterPro).
GO:0022900; Biological process: electron transport chain (inferred from electronic annotation from UniProtKB-KW).
GO:0006749; Biological process: glutathione metabolic process (inferred from direct assay from MGI).
GO:0007275; Biological process: multicellular organismal development (inferred from electronic annotation from UniProtKB-KW).
GO:0007283; Biological process: spermatogenesis (inferred from electronic annotation from UniProtKB-KW).
GO:0006810; Biological process: transport (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.
Family and domain databases
InterPro IPR013027; FAD_pyr_nucl-diS_OxRdtase.
IPR011767; GLR_AS.
IPR002109; Glutaredoxin.
IPR014025; Glutaredoxin_sub.
IPR011899; GRX_euk.
IPR000815; Hg_reductase.
IPR001100; Pyr_nuc-diS_OxRdtase.
IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
IPR012999; Pyr_OxRdtase_I_AS.
IPR001327; Pyr_OxRdtase_NAD_bd.
IPR006338; Reduct_Se.
IPR012335; Thioredoxin_fold.
Graphical view of domain structure.
Gene3D G3DSA:3.30.390.30; Pyr_redox_dim; 1.
G3DSA:3.40.30.10; Thioredoxin_fold; 1.
PANTHER PTHR22912:SF23; Reduct_Se; 1.
Pfam PF00462; Glutaredoxin; 1.
PF00070; Pyr_redox; 1.
PF07992; Pyr_redox_2; 1.
PF02852; Pyr_redox_dim; 1.
Pfam graphical view of domain structure.
PRINTS PR00368; FADPNR.
PR00160; GLUTAREDOXIN.
PR00945; HGRDTASE.
PR00411; PNDRDTASEI.
ProDom PD000139; FAD_pyr_redox; 1.
[Domain structure / List of seq. sharing at least 1 domain]
TIGRFAMs TIGR02180; GRX_euk; 1.
TIGR01438; TGR; 1.
PROSITE PS00195; GLUTAREDOXIN_1; FALSE_NEG.
PS51354; GLUTAREDOXIN_2; 1.
PS00076; PYRIDINE_REDOX_1; 1.
PROSITE graphical view of domain structure (profiles).
Genome annotation databases
Ensembl ENSMUSG00000000811; Mus musculus. [Contig view]
GeneID 232223; -.
KEGG mmu:232223; -.
Phylogenomic databases
HOGENOM Q99MD6; -.
HOVERGEN Q99MD6; -.
Other
NextBio 380996; -.
SOURCE Txnrd3; Mus musculus.
ProtoNet Q99MD6.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Cytoplasm; Developmental protein; Differentiation; Direct protein sequencing; Electron transport; Endoplasmic reticulum; FAD; Flavoprotein; Microsome; NADP; Nucleus; Oxidoreductase; Phosphoprotein; Redox-active center; Selenium; Selenocysteine; Spermatogenesis; Transport.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   <1   697  >697     Thioredoxin reductase 3. PRO_0000320696
DOMAIN   110   210  101     Glutaredoxin. 
NP_BIND   212   241  30     FAD (By similarity). 
ACT_SITE   670   670        Proton acceptor (By similarity). 
NON_STD   696   696        Selenocysteine. 
MOD_RES   95    95        Phosphoserine (By similarity). 
DISULFID   257   262        Redox-active (By similarity). 
CROSSLNK   695   696        Cysteinyl-selenocysteine (Cys-Sec) (By similarity). 
MUTAGEN   696   697        Missing: Abolishes thioredoxin reductase, glutaredoxin and gluthioine reductase activities. 
MUTAGEN   696   696        U->C: Thioredoxin reductase activity reduced to 21%. Glutaredoxin activity reduced to 14%. Glutathione reductase activity reduced to 18%. 
MUTAGEN   696   696        U->S: Abolishes thioredoxin reductase, glutaredoxin and gluthioine reductase activities. 
CONFLICT   41    41        S -> N (in Ref. 1; BAB28419). 
CONFLICT   53    53        P -> R (in Ref. 1; BAB28419). 
CONFLICT   61    61        S -> W (in Ref. 1; BAB28419). 
NON_TER   1     1         
Sequence information
Length: 697 AA [This is the length of the partial sequence of the unprocessed precursor] Molecular weight: 76114 Da [This is the MW of the partial sequence of the unprocessed precursor] CRC64: 0BFDBF1B99F45D08 [This is a checksum on the sequence]
        10         20         30         40         50         60 
SCPVRPRPVR SVLKFSAALP ASSPRRPPAS RFLSRPGSAR SDNKALEKPP SPPPPPRAQT 

        70         80         90        100        110        120 
SPGLGKVGVL PNRRLGAVRG GLMSSPPGRR ARLASPGTSR PSSEAREELR RRLRDLIEGN 

       130        140        150        160        170        180 
RVMIFSKSYC PHSTRVKELF SSLGVVYNIL ELDQVDDGAS VQEVLTEISN QKTVPNIFVN 

       190        200        210        220        230        240 
KVHVGGCDRT FQAHQNGLLQ KLLQDDSAHD YDLIIIGGGS GGLSCAKEAA NLGKKVMVLD 

       250        260        270        280        290        300 
FVVPSPQGTT WGLGGTCVNV GCIPKKLMHQ AALLGHALQD AKKYGWEYNQ QVKHNWEAMT 

       310        320        330        340        350        360 
EAIQSHIGSL NWGYRVTLRE KGVTYVNSFG EFVDLHKIKA TNKKGQETFY TASKFVIATG 

       370        380        390        400        410        420 
ERPRYLGIQG DKEYCITSDD LFSLPYCPGC TLVVGASYVG LECAGFLAGL GLDVTVMVRS 

       430        440        450        460        470        480 
VLLRGFDQEM AEKVGSYLEQ QGVKFQRKFT PILVQQLEKG LPGKLKVVAK STEGPETVEG 

       490        500        510        520        530        540 
IYNTVLLAIG RDSCTRKIGL EKIGVKINEK NGKIPVNDVE QTNVPHVYAI GDILDGKPEL 

       550        560        570        580        590        600 
TPVAIQAGKL LARRLFGVSL EKCDYINIPT TVFTPLEYGC CGLSEEKAIE MYKKENLEVY 

       610        620        630        640        650        660 
HTLFWPLEWT VAGRDNNTCY AKIICNKFDN ERVVGFHLLG PNAGEITQGF AAAMKCGLTK 

       670        680        690 
QLLDDTIGIH PTCGEVFTTL EITKSSGLDI TQKGCUG 

Q99MD6 in FASTA format

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