[1]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Neuroblastoma; DOI=10.1074/jbc.273.15.8581; PubMed=9535831 [NCBI, ExPASy, EBI, Israel, Japan] Zhong L., Arner E.S.J., Ljung J., Aaslund F., Holmgren A.; "Rat and calf thioredoxin reductase are homologous to glutathione reductase with a carboxyl-terminal elongation containing a conserved catalytically active penultimate selenocysteine residue."; J. Biol. Chem. 273:8581-8591(1998).
[2]	NUCLEOTIDE SEQUENCE [MRNA], AND SELENOCYSTEINE AT SEC-497. TISSUE=Kidney, and Liver; DOI=10.1042/0264-6021:3400439; PubMed=10333487 [NCBI, ExPASy, EBI, Israel, Japan] Fujiwara N., Fujii T., Fujii J., Taniguchi N.; "Functional expression of rat thioredoxin reductase: selenocysteine insertion sequence element is essential for the active enzyme."; Biochem. J. 340:439-444(1999).
[3]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Liver; Rundlof A., Arner E.S.J.; "Molecular cloning of thioredoxin reductase 1 from rat liver."; Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
[4]	PROTEIN SEQUENCE OF 450-456 AND 487-498, FUNCTION, MUTAGENESIS OF SEC-497, AND CHARACTERIZATION. DOI=10.1074/jbc.M000690200; PubMed=10849437 [NCBI, ExPASy, EBI, Israel, Japan] Zhong L., Holmgren A.; "Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations."; J. Biol. Chem. 275:18121-18128(2000).
[5]	X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF MUTANT CYS-497 IN COMPLEX WITH NADP, DISULFIDE BOND, AND HOMODIMERIZATION. DOI=10.1073/pnas.171178698; PubMed=11481439 [NCBI, ExPASy, EBI, Israel, Japan] Sandalova T., Zhong L., Lindqvist Y., Holmgren A., Schneider G.; "Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme."; Proc. Natl. Acad. Sci. U.S.A. 98:9533-9538(2001).

Comments

CATALYTIC ACTIVITY: Thioredoxin + NADP⁺ = thioredoxin disulfide + NADPH.
COFACTOR: Binds 1 FAD per subunit.
SUBUNIT: Homodimer.
SUBCELLULAR LOCATION: Cytoplasm (By similarity).
MISCELLANEOUS: The 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.
SEQUENCE CAUTION:
- Sequence=AAD43039.1; Type=Erroneous termination; Positions=497; 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

U63923; AAC35244.2; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF108213; AAD43039.1; ALT_SEQ; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF220760; AAF32362.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF220761; AAF32363.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

UniGene

Rn.67581

3D structure databases

PDB

1H6V; X-ray; 3.00 A; A/B/C/D/E/F=1-498.

[ExPASy / RCSB / EBI]

PDBsum

1H6V; -.

ModBase

O89049.

Organism-specific databases

RGD

61959; Txnrd1.

Gene expression databases

ArrayExpress

O89049; -.

Ontologies

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:0008430;	Molecular function: selenium binding (inferred from electronic annotation from UniProtKB-KW).
GO:0004791;	Molecular function: thioredoxin-disulfide reductase activity (inferred from electronic annotation from EC).
GO:0045454;	Biological process: cell redox homeostasis (inferred from electronic annotation from InterPro).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR013027; FAD_pyr_nucl-diS_OxRdtase.
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.
Graphical view of domain structure.

Gene3D

G3DSA:3.30.390.30; Pyr_redox_dim; 1.

PANTHER

PTHR22912:SF23; Reduct_Se; 1.

Pfam

PF00070; Pyr_redox; 1.
PF07992; Pyr_redox_2; 1.
PF02852; Pyr_redox_dim; 1.
Pfam graphical view of domain structure.

PRINTS

PR00368; FADPNR.
PR00945; HGRDTASE.
PR00411; PNDRDTASEI.

ProDom

PD000139; FAD_pyr_redox; 1.
[Domain structure / List of seq. sharing at least 1 domain]

TIGRFAMs

TIGR01438; TGR; 1.

PROSITE

PS00076; PYRIDINE_REDOX_1; 1.

Genome annotation databases

Ensembl

ENSRNOG00000009088; Rattus norvegicus. [Contig view]

Phylogenomic databases

HOVERGEN

O89049; -.

Other

ProtoNet

O89049.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Cytoplasm; Direct protein sequencing; FAD; Flavoprotein; NADP; Oxidoreductase; Phosphoprotein; Redox-active center; Selenium; Selenocysteine.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 498`	`498`	`Thioredoxin reductase 1, cytoplasmic.`	`PRO_0000067985`
`NP_BIND`	`42 59`	`18`	`FAD (By similarity).`
`ACT_SITE`	`471 471`		`Proton acceptor.`
`NON_STD`	`497 497`		`Selenocysteine.`
`MOD_RES`	`11 11`		`Phosphotyrosine (By similarity).`
`MOD_RES`	`131 131`		`Phosphotyrosine (By similarity).`
`MOD_RES`	`422 422`		`Phosphotyrosine (By similarity).`
`DISULFID`	`59 64`		`Redox-active.`
`CROSSLNK`	`496 497`		`Cysteinyl-selenocysteine (Cys-Sec).`
`MUTAGEN`	`497 497`		`U->S: Loss of activity.`
`MUTAGEN`	`497 497`		`Missing: Loss of activity.`
`CONFLICT`	`52 53`		`NG -> RW (in Ref. 3; AAF32363).`
`CONFLICT`	`451 455`		`GFAAA -> ALQP (in Ref. 2 and 3; AAF32362).`
`STRAND`	`12 18`	`7`
`HELIX`	`22 31`	`10`
`HELIX`	`32 34`	`3`
`STRAND`	`38 41`	`4`
`HELIX`	`57 62`	`6`
`HELIX`	`64 82`	`19`
`TURN`	`83 87`	`5`
`HELIX`	`98 123`	`26`
`STRAND`	`126 128`	`3`
`STRAND`	`131 136`	`6`
`STRAND`	`139 143`	`5`
`STRAND`	`149 159`	`11`
`STRAND`	`163 165`	`3`
`HELIX`	`173 176`	`4`
`HELIX`	`180 183`	`4`
`STRAND`	`192 196`	`5`
`HELIX`	`200 211`	`12`
`STRAND`	`216 225`	`10`
`HELIX`	`230 242`	`13`
`STRAND`	`245 250`	`6`
`STRAND`	`252 260`	`9`
`STRAND`	`266 272`	`7`
`STRAND`	`278 288`	`11`
`STRAND`	`293 296`	`4`
`TURN`	`303 305`	`3`
`STRAND`	`311 313`	`3`
`STRAND`	`329 331`	`3`
`HELIX`	`333 335`	`3`
`HELIX`	`343 359`	`17`
`STRAND`	`372 374`	`3`
`STRAND`	`376 378`	`3`
`STRAND`	`380 384`	`5`
`HELIX`	`387 394`	`8`
`HELIX`	`396 398`	`3`
`STRAND`	`399 406`	`8`
`HELIX`	`409 412`	`4`
`TURN`	`413 415`	`3`
`STRAND`	`421 428`	`8`
`HELIX`	`429 431`	`3`
`STRAND`	`434 442`	`9`
`HELIX`	`445 456`	`12`
`HELIX`	`461 466`	`6`
`HELIX`	`474 480`	`7`
`HELIX`	`485 487`	`3`

Sequence information

Length: 498 AA [This is the length of the unprocessed precursor]

Molecular weight: 54386 Da [This is the MW of the unprocessed precursor]

CRC64: 2F1EC2A8EAE7BF3E [This is a checksum on the sequence]

        10         20         30         40         50         60 
MNDSKDAPKS YDFDLIIIGG GSGGLAAAKE AAKFDKKVMV LDFVTPTPLG TNGGLGGTCV 

        70         80         90        100        110        120 
NVGCIPKKLM HQAALLGQAL KDSRNYGWKL EDTVKHDWEK MTESVQNHIG SLNWGYRVAL 

       130        140        150        160        170        180 
REKKVVYENA YGKFIGPHKI MATNNKGKEK VYSAERFLIA TGERPRYLGI PGDKEYCISS 

       190        200        210        220        230        240 
DDLFSLPYCP GKTLVVGASY VALECAGFLA GIGLDVTVMV RSILLRGFDQ DMANKIGEHM 

       250        260        270        280        290        300 
EEHGIKFIRQ FVPTKIEQIE AGTPGRLKVT AKSTNSEETI EDEFNTVLLA VGRDSCTRTI 

       310        320        330        340        350        360 
GLETVGVKIN EKTGKIPVTD EEQTNVPYIY AIGDILEGKL ELTPVAIQAG RLLAQRLYGG 

       370        380        390        400        410        420 
STVKCDYDNV PTTVFTPLEY GCCGLSEEKA VEKFGEENIE VYHSFFWPLE WTVPSRDNNK 

       430        440        450        460        470        480 
CYAKVICNLK DNERVVGFHV LGPNAGEVTQ GFAAAKCGLT KQQLDSTIGI HPVCAEIFTT 

       490 
LSVTKRSGGD ILQSGCUG

O89049 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools