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Q86VQ6 (TRXR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thioredoxin reductase 3

EC=1.8.1.9
Alternative name(s):
Thioredoxin and glutathione reductase
Thioredoxin reductase TR2
Gene names
Name:TXNRD3
Synonyms:TGR, TRXR3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length643 AA.
Sequence statusComplete.
Protein existenceEvidence 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 By similarity. UniProtKB Q99MD6

Catalytic activity

Thioredoxin + NADP+ = thioredoxin disulfide + NADPH. UniProtKB Q99MD6

Cofactor

Binds 1 FAD per subunit By similarity. UniProtKB O89049

Subunit structure

Homodimer By similarity. UniProtKB O89049

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Microsome By similarity. Endoplasmic reticulum By similarity. Note: Detected in cytoplasm and nucleus in late spermatids By similarity. UniProtKB Q99MD6

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 By similarity. UniProtKB Q99MD6

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.

Caution

This sequence initiates at a CTG codon (Ref.6).

Sequence caution

The sequence AAH30028.1 differs from that shown. Reason: Erroneous termination at position 642. Translated as Sec.

The sequence AAH30028.1 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

The sequence AAH50032.1 differs from that shown. Reason: Erroneous termination at position 642. Translated as Sec.

The sequence AAH50032.1 differs from that shown. Reason: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 643643Thioredoxin reductase 3
PRO_0000320695

Regions

Domain56 – 156101Glutaredoxin
Nucleotide binding158 – 18730FAD By similarity

Sites

Active site6161Proton acceptor By similarity

Amino acid modifications

Non-standard residue6421Selenocysteine
Modified residue411Phosphoserine Ref.5
Modified residue421Phosphoserine Ref.5
Modified residue3791N6-succinyllysine By similarity
Disulfide bond203 ↔ 208Redox-active By similarity
Cross-link641 ↔ 642Cysteinyl-selenocysteine (Cys-Sec) By similarity

Experimental info

Sequence conflict65 – 662RS → AE in AAD51325. Ref.3
Sequence conflict2461T → I in AAH30028. Ref.2
Sequence conflict3371T → P in AAD39929. Ref.4

Secondary structure

................... 643
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q86VQ6 [UniParc].

Last modified May 29, 2013. Version 4.
Checksum: 6FB04128943A4017

FASTA64370,683
        10         20         30         40         50         60 
MERSPPQSPG PGKAGDAPNR RSGHVRGARV LSPPGRRARL SSPGPSRSSE AREELRRHLV 

        70         80         90        100        110        120 
GLIERSRVVI FSKSYCPHST RVKELFSSLG VECNVLELDQ VDDGARVQEV LSEITNQKTV 

       130        140        150        160        170        180 
PNIFVNKVHV GGCDQTFQAY QSGLLQKLLQ EDLAYDYDLI IIGGGSGGLS CAKEAAILGK 

       190        200        210        220        230        240 
KVMVLDFVVP SPQGTSWGLG GTCVNVGCIP KKLMHQAALL GQALCDSRKF GWEYNQQVRH 

       250        260        270        280        290        300 
NWETMTKAIQ NHISSLNWGY RLSLREKAVA YVNSYGEFVE HHKIKATNKK GQETYYTAAQ 

       310        320        330        340        350        360 
FVIATGERPR YLGIQGDKEY CITSDDLFSL PYCPGKTLVV GASYVALECA GFLAGFGLDV 

       370        380        390        400        410        420 
TVMVRSILLR GFDQEMAEKV GSYMEQHGVK FLRKFIPVMV QQLEKGSPGK LKVLAKSTEG 

       430        440        450        460        470        480 
TETIEGVYNT VLLAIGRDSC TRKIGLEKIG VKINEKSGKI PVNDVEQTNV PYVYAVGDIL 

       490        500        510        520        530        540 
EDKPELTPVA IQSGKLLAQR LFGASLEKCD YINVPTTVFT PLEYGCCGLS EEKAIEVYKK 

       550        560        570        580        590        600 
ENLEIYHTLF WPLEWTVAGR ENNTCYAKII CNKFDHDRVI GFHILGPNAG EVTQGFAAAM 

       610        620        630        640 
KCGLTKQLLD DTIGIHPTCG EVFTTLEITK SSGLDITQKG CUG 

« Hide

References

« Hide 'large scale' references
[1]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[3]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 65-643, SELENOCYSTEINE AT SEC-642.
[4]"TrxR3, a novel human thioredoxin reductase."
Miranda-Vizuete A.
Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 67-643.
[5]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41 AND SER-42, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"CUG start codon generates thioredoxin/glutathione reductase isoforms in mouse testes."
Gerashchenko M.V., Su D., Gladyshev V.N.
J. Biol. Chem. 285:4595-4602(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PROBABLE NON-AUG INITIATOR START CODON.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC024558 Genomic DNA. No translation available.
BC030028 mRNA. Translation: AAH30028.1. Sequence problems.
BC050032 mRNA. Translation: AAH50032.1. Sequence problems.
AF171055 mRNA. Translation: AAD51325.1.
AF133519 mRNA. Translation: AAD39929.1.
RefSeqNP_001166984.1. NM_001173513.1.
NP_443115.1. NM_052883.1.
UniGeneHs.477475.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3H8QX-ray2.21A/B51-156[»]
ProteinModelPortalQ86VQ6.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125281. 1 interaction.

Chemistry

BindingDBQ86VQ6.
ChEMBLCHEMBL2096978.

PTM databases

PhosphoSiteQ86VQ6.

Polymorphism databases

DMDM510120859.

Proteomic databases

PaxDbQ86VQ6.
PRIDEQ86VQ6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID114112.
KEGGhsa:114112.
UCSCuc003ejd.2. human.

Organism-specific databases

CTD114112.
GeneCardsGC03M126292.
HGNCHGNC:20667. TXNRD3.
HPACAB020802.
HPA036109.
MIM606235. gene.
neXtProtNX_Q86VQ6.
PharmGKBPA134920642.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1249.
HOGENOMHOG000276712.
HOVERGENHBG004959.
InParanoidQ86VQ6.
KOK00384.

Gene expression databases

ArrayExpressQ86VQ6.
CleanExHS_TXNRD3.
GenevestigatorQ86VQ6.

Family and domain databases

Gene3D3.30.390.30. 1 hit.
3.40.30.10. 1 hit.
InterProIPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR002109. Glutaredoxin.
IPR011899. Glutaredoxin_euk/vir.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
IPR023753. Pyr_nucl-diS_OxRdtase_FAD/NAD.
IPR012999. Pyr_OxRdtase_I_AS.
IPR001327. Pyr_OxRdtase_NAD-bd_dom.
IPR012336. Thioredoxin-like_fold.
IPR006338. Thioredoxin/glutathione_Rdtase.
[Graphical view]
PANTHERPTHR22912:SF23. PTHR22912:SF23. 1 hit.
PfamPF00462. Glutaredoxin. 1 hit.
PF00070. Pyr_redox. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
PF02852. Pyr_redox_dim. 1 hit.
[Graphical view]
PRINTSPR00368. FADPNR.
SUPFAMSSF52833. SSF52833. 1 hit.
SSF55424. SSF55424. 1 hit.
TIGRFAMsTIGR02180. GRX_euk. 1 hit.
TIGR01438. TGR. 1 hit.
PROSITEPS51354. GLUTAREDOXIN_2. 1 hit.
PS00076. PYRIDINE_REDOX_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTXNRD3. human.
EvolutionaryTraceQ86VQ6.
GenomeRNAi114112.
NextBio78986.
PROQ86VQ6.
SOURCESearch...

Entry information

Entry nameTRXR3_HUMAN
AccessionPrimary (citable) accession number: Q86VQ6
Secondary accession number(s): Q6PIS8, Q9NNW6, Q9P101
Entry history
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: May 29, 2013
Last modified: April 16, 2014
This is version 112 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM