Reviewed, UniProtKB/Swiss-Prot Q86VQ6 (TRXR3_HUMAN)

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

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	754 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 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.
Sequence caution	The sequence AAH30028.1 differs from that shown. Reason: Erroneous termination at position 753. Translated as Sec. The sequence AAH50032.1 differs from that shown. Reason: Erroneous termination at position 753. 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	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell redox homeostasis Ref.3 Non-traceable author statement. Source: UniProtKB electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW 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 Inferred from electronic annotation. Source: UniProtKB-SubCell 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 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 754

754

Thioredoxin reductase 3

PRO_0000320695

Regions

Domain

167 – 267

101

Glutaredoxin

Nucleotide binding

269 – 298

30

FAD By similarity UniProtKB O89049

Sites

Active site

727

1

Proton acceptor By similarity UniProtKB O89049

Amino acid modifications

Non-standard residue

753

1

Selenocysteine Ref.3

Modified residue

152

1

Phosphoserine Ref.5

Modified residue

153

1

Phosphoserine Ref.5

Disulfide bond

314 ↔ 319

Redox-active By similarity UniProtKB O89049

Cross-link

752 ↔ 753

Cysteinyl-selenocysteine (Cys-Sec) By similarity UniProtKB O89049

Experimental info

Sequence conflict

72

1

V → G in AAH50032. Ref.2

Sequence conflict

176 – 177

2

RS → AE in AAD51325. Ref.3

Sequence conflict

357

1

T → I in AAH30028. Ref.2

Sequence conflict

448

1

T → P in AAD39929. Ref.4

Secondary structure

1

.

.

.

.

.

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754

Helix Strand Turn

Details...

Helix

164 – 170

7

Turn

174 – 176

3

Beta strand

179 – 183

5

Helix

188 – 199

12

Beta strand

205 – 208

4

Turn

209 – 211

3

Helix

217 – 226

10

Beta strand

233 – 236

4

Helix

245 – 252

8

Helix

256 – 261

6

Sequences

	Sequence		Length	Mass (Da)
	Q86VQ6-1 [UniParc]. Last modified February 26, 2008. Version 2. Checksum: 189F7C0C435277CF	FASTA	754	82,464
	10 20 30 40 50 60 MGHVHRLVSG KRRMHLTSRP VASTHSPLIL DMCPHLNNGP MTGCGRAGDP ISHARGGAGG 70 80 90 100 110 120 RGERLPRGFA RVVRVASEGS VRRPSGPVPA PQPPAFRFVS RPGRARSESE TLERSPPQSP 130 140 150 160 170 180 GPGKAGDAPN RRSGHVRGAR VLSPPGRRAR LSSPGPSRSS EAREELRRHL VGLIERSRVV 190 200 210 220 230 240 IFSKSYCPHS TRVKELFSSL GVECNVLELD QVDDGARVQE VLSEITNQKT VPNIFVNKVH 250 260 270 280 290 300 VGGCDQTFQA YQSGLLQKLL QEDLAYDYDL IIIGGGSGGL SCAKEAAILG KKVMVLDFVV 310 320 330 340 350 360 PSPQGTSWGL GGTCVNVGCI PKKLMHQAAL LGQALCDSRK FGWEYNQQVR HNWETMTKAI 370 380 390 400 410 420 QNHISSLNWG YRLSLREKAV AYVNSYGEFV EHHKIKATNK KGQETYYTAA QFVIATGERP 430 440 450 460 470 480 RYLGIQGDKE YCITSDDLFS LPYCPGKTLV VGASYVALEC AGFLAGFGLD VTVMVRSILL 490 500 510 520 530 540 RGFDQEMAEK VGSYMEQHGV KFLRKFIPVM VQQLEKGSPG KLKVLAKSTE GTETIEGVYN 550 560 570 580 590 600 TVLLAIGRDS CTRKIGLEKI GVKINEKSGK IPVNDVEQTN VPYVYAVGDI LEDKPELTPV 610 620 630 640 650 660 AIQSGKLLAQ RLFGASLEKC DYINVPTTVF TPLEYGCCGL SEEKAIEVYK KENLEIYHTL 670 680 690 700 710 720 FWPLEWTVAG RENNTCYAKI ICNKFDHDRV IGFHILGPNA GEVTQGFAAA MKCGLTKQLL 730 740 750 DDTIGIHPTC GEVFTTLEIT KSSGLDITQK GCUG

References

	« Hide 'large scale' referencesShow '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. , 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: 16641997] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 72-754. 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: 10455115] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 176-754, SELENOCYSTEINE AT SEC-753.
[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 178-754.
[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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-152 AND SER-153, MASS SPECTROMETRY.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00013954.

UniGene

Hs.477475

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3H8Q	X-ray	2.21	A/B	162-267	[»]

SMR

Q86VQ6. Positions 194-676.

ModBase

Search...

Protein-protein interaction databases

STRING

Q86VQ6.

PTM databases

PhosphoSite

Q86VQ6.

Genome annotation databases

Ensembl

ENST00000360201; ENSP00000353329; ENSG00000197763; Homo sapiens. [Genome view]
ENST00000450785; ENSP00000413404; ENSG00000197763; Homo sapiens. [Genome view]
ENST00000457556; ENSP00000408253; ENSG00000197763; Homo sapiens. [Genome view]

Organism-specific databases

GeneCards

GC03M127808.

HGNC

HGNC:20667. TXNRD3.

HPA

CAB020802.

MIM

606235. gene.

PharmGKB

PA134920642.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q86VQ6.

Enzyme and pathway databases

BRENDA

1.8.1.9. 247.

Gene expression databases

ArrayExpress

Q86VQ6.

Bgee

Q86VQ6.

CleanEx

HS_TXNRD3.

Genevestigator

Q86VQ6.

Family and domain databases

InterPro

IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR011767. GLR_AS.
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.
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.

ProDom

PD000139. FAD_pyr_redox. 1 hit.
[Graphical view] [Entries sharing at least one domain]

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

SOURCE

Search...

Entry information

Entry name

TRXR3_HUMAN

Accession

Primary (citable) accession number: Q86VQ6
Secondary accession number(s): Q6PIS8, Q9NNW6, Q9P101

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	February 26, 2008
Last modified:	November 3, 2009
This is version 68 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.