Reviewed, UniProtKB/Swiss-Prot Q99MD6 (TRXR3_MOUSE)

Names and origin

Protein names

Recommended name:
    Thioredoxin reductase 3
    EC=1.8.1.9
Alternative name(s):
    Thioredoxin reductase TR2
    Thioredoxin and glutathione reductase

Gene names

Name:	Txnrd3
Synonyms:	Tgr, Trxr3

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	697 AA.
Sequence status	Fragment.
Protein existence	Evidence at protein level.

General annotation (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. Ref.3 Ref.6
Catalytic activity	Thioredoxin + NADP+ = thioredoxin disulfide + NADPH. Ref.3
Cofactor	Binds 1 FAD per subunit By similarity. UniProtKB O89049
Subunit structure	Homodimer By similarity. UniProtKB O89049
Subcellular location	Cytoplasm. Nucleus. Microsome. Endoplasmic reticulum. Note: Detected in cytoplasm and nucleus in late spermatids. Ref.3 Ref.6
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. Ref.6 Ref.4
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. Ref.6
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. Ref.3 Ref.5
Miscellaneous	The thioredoxin reductase active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity By similarity. UniProtKB Q16881
Sequence similarities	Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. Contains 1 glutaredoxin domain.
Biophysicochemical properties	Kinetic parameters: KM=14.7 µM for 5,5'-dithiobis(2-nitrobenzoic acid) Ref.3 KM=10.7 µM for NADPH Ref.3 KM=3.0 µM for thioredoxin Ref.3 KM=8.84 µM for oxidized glutathione Ref.3 KM=45.2 µM for beta-hydroxyethyl disulfide Ref.3
Sequence caution	The sequence AAH76605.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH76605.1 differs from that shown. Reason: Erroneous termination at position 696. Translated as Sec. The sequence BAB28419.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAB28419.1 differs from that shown. Reason: Erroneous termination at position 696. Translated as Sec. The sequence BAB28419.1 differs from that shown. Reason: Frameshift at positions 74 and 83. The sequence BAC37890.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAC37890.1 differs from that shown. Reason: Erroneous termination at position 696. Translated as Sec.

Ontologies

Keywords
Biological process	Differentiation Electron transport Spermatogenesis Transport
Cellular component	Cytoplasm Endoplasmic reticulum Microsome Nucleus
Coding sequence diversity	Selenocysteine
Domain	Redox-active center
Ligand	FAD Flavoprotein NADP Selenium
Molecular function	Developmental protein Oxidoreductase
PTM	Disulfide bond Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell redox homeostasis Inferred from electronic annotation. Source: InterPro electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW glutathione metabolic process Ref.3 Inferred from direct assay. Source: MGI multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW spermatogenesis Inferred from electronic annotation. Source: UniProtKB-KW transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Ref.3 Inferred from direct assay. Source: MGI nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	FAD binding Inferred from electronic annotation. Source: InterPro NADP or NADPH binding Inferred from electronic annotation. Source: InterPro electron carrier activity Inferred from electronic annotation. Source: InterPro protein disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro selenium binding Inferred from electronic annotation. Source: UniProtKB-KW thioredoxin-disulfide reductase activity Ref.3 Inferred from direct assay. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	‹1 – 697	›697	Thioredoxin reductase 3		PRO_0000320696
Regions
	Domain	110 – 210	101	Glutaredoxin
	Nucleotide binding	212 – 241	30	FAD By similarity UniProtKB O89049
Sites
	Active site	670	1	Proton acceptor By similarity UniProtKB O89049
Amino acid modifications
	Non-standard residue	696	1	Selenocysteine Ref.3
	Modified residue	95	1	Phosphoserine By similarity
	Disulfide bond	257 ↔ 262		Redox-active By similarity UniProtKB O89049
	Cross-link	695 ↔ 696		Cysteinyl-selenocysteine (Cys-Sec) By similarity UniProtKB O89049
Experimental info
	Mutagenesis	696 – 697	2	Missing: Abolishes thioredoxin reductase, glutaredoxin and gluthioine reductase activities. Ref.5
	Mutagenesis	696	1	U → C: Thioredoxin reductase activity reduced to 21%. Glutaredoxin activity reduced to 14%. Glutathione reductase activity reduced to 18%. Ref.5
	Mutagenesis	696	1	U → S: Abolishes thioredoxin reductase, glutaredoxin and gluthioine reductase activities. Ref.5
	Sequence conflict	41	1	S → N in BAB28419. Ref.1
	Sequence conflict	53	1	P → R in BAB28419. Ref.1
	Sequence conflict	61	1	S → W in BAB28419. Ref.1
	Non-terminal residue	1	1

Sequences

	Sequence		Length	Mass (Da)
	Q99MD6-1 [UniParc]. Last modified February 26, 2008. Version 2. Checksum: 0BFDBF1B99F45D08	FASTA	697	76,114
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." 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. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Embryo and Thymus.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-697. Strain: C57BL/6. Tissue: Brain.
[3]	"Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems." Sun Q.-A., Kirnarsky L., Sherman S., Gladyshev V.N. Proc. Natl. Acad. Sci. U.S.A. 98:3673-3678(2001) [PubMed: 11259642] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 28-697, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, DOMAIN, 3D-STRUCTURE MODELING, SELENOCYSTEINE AT SEC-696.
[4]	"Redox regulation of cell signaling by selenocysteine in mammalian thioredoxin reductases." Sun Q.-A., Wu Y., Zappacosta F., Jeang K.-T., Lee B.J., Hatfield D.L., Gladyshev V.N. J. Biol. Chem. 274:24522-24530(1999) [PubMed: 10455115] [Abstract] Cited for: PROTEIN SEQUENCE OF 236-247 AND 595-606, TISSUE SPECIFICITY.
[5]	"Reaction mechanism and regulation of mammalian thioredoxin/glutathione reductase." Sun Q.-A., Su D., Novoselov S.V., Carlson B.A., Hatfield D.L., Gladyshev V.N. Biochemistry 44:14528-14537(2005) [PubMed: 16262253] [Abstract] Cited for: DOMAIN, MUTAGENESIS OF SEC-696 AND 696-SEC-GLY-697.
[6]	"Mammalian selenoprotein thioredoxin-glutathione reductase. Roles in disulfide bond formation and sperm maturation." Su D., Novoselov S.V., Sun Q.-A., Moustafa M.E., Zhou Y., Oko R., Hatfield D.L., Gladyshev V.N. J. Biol. Chem. 280:26491-26498(2005) [PubMed: 15901730] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK012699 mRNA. Translation: BAB28419.1. Sequence problems. AK080362 mRNA. Translation: BAC37890.1. Sequence problems. BC076605 mRNA. Translation: AAH76605.1. Sequence problems. AF349659 mRNA. Translation: AAK31172.1. Different initiation.
IPI	IPI00138866.
RefSeq	NP_694802.2.
UniGene	Mm.229332
3D structure databases
HSSP	HSSP built from PDB template 1H6V based on UniProtKB O89049.
ModBase	Search...
Protein-protein interaction databases
STRING	Q99MD6.
PTM databases
PhosphoSite	Q99MD6.
Genome annotation databases
Ensembl	ENSMUST00000000828; ENSMUSP00000000828; ENSMUSG00000000811; Mus musculus. [Genome view]
GeneID	232223.
KEGG	mmu:232223.
Organism-specific databases
CTD	232223.
MGI	MGI:2386711. Txnrd3.
Phylogenomic databases
HOGENOM	HBG515043.
HOVERGEN	Q99MD6.
InParanoid	Q99MD6.
Enzyme and pathway databases
BRENDA	1.8.1.9. 244.
Gene expression databases
ArrayExpress	Q99MD6.
Bgee	Q99MD6.
CleanEx	MM_TXNRD3.
Genevestigator	Q99MD6.
Family and domain databases
InterPro	IPR016156. FAD/NAD-linked_Rdtase_dimer. IPR013027. FAD_pyr_nucl-diS_OxRdtase. IPR002109. Glutaredoxin. IPR011899. Glutaredoxin_euk/vir. IPR000815. Hg_reductase. IPR004099. Pyr_nucl-diS_OxRdtase_dimer. IPR012999. Pyr_OxRdtase_I_AS. IPR001327. Pyr_OxRdtase_NAD_bd. IPR012336. Thioredoxin-like_fold. IPR006338. Thioredoxin/glutathione_Rdtase. IPR012335. Thioredoxin_fold. [Graphical view]
Gene3D	G3DSA:3.30.390.30. Pyr_redox_dim. 1 hit. G3DSA:3.40.30.10. Thioredoxin_fold. 1 hit.
PANTHER	PTHR22912:SF23. Reduct_Se. 1 hit.
Pfam	PF00462. Glutaredoxin. 1 hit. PF00070. Pyr_redox. 1 hit. PF07992. Pyr_redox_2. 1 hit. PF02852. Pyr_redox_dim. 1 hit. [Graphical view]
PRINTS	PR00368. FADPNR. PR00945. HGRDTASE.
TIGRFAMs	TIGR02180. GRX_euk. 1 hit. TIGR01438. TGR. 1 hit.
PROSITE	PS00195. GLUTAREDOXIN_1. False negative. PS51354. GLUTAREDOXIN_2. 1 hit. PS00076. PYRIDINE_REDOX_1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	380996.
SOURCE	Search...

Entry information

Entry name

TRXR3_MOUSE

Accession

Primary (citable) accession number: Q99MD6
Secondary accession number(s): Q9CZE5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	February 26, 2008
Last modified:	February 9, 2010
This is version 58 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)