Q86VQ6 (TRXR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	682 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 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 681. Translated as Sec. The sequence AAH50032.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH50032.1 differs from that shown. Reason: Erroneous termination at position 681. 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
Molecular function	Developmental protein Oxidoreductase
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell redox homeostasis Non-traceable author statement Ref.3. 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
Cellular_component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	NADP binding Inferred from electronic annotation. Source: InterPro electron carrier activity Inferred from electronic annotation. Source: InterPro flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro protein disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro thioredoxin-disulfide reductase activity Non-traceable author statement Ref.3. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

‹1 – 682

›682

Thioredoxin reductase 3

PRO_0000320695

Regions

Domain

95 – 195

101

Glutaredoxin

Nucleotide binding

197 – 226

30

FAD By similarity

Sites

Active site

655

1

Proton acceptor By similarity

Amino acid modifications

Non-standard residue

681

1

Selenocysteine

Modified residue

80

1

Phosphoserine Ref.5

Modified residue

81

1

Phosphoserine Ref.5

Disulfide bond

242 ↔ 247

Redox-active By similarity

Cross-link

680 ↔ 681

Cysteinyl-selenocysteine (Cys-Sec) By similarity

Experimental info

Sequence conflict

104 – 105

2

RS → AE in AAD51325. Ref.3

Sequence conflict

285

1

T → I in AAH30028. Ref.2

Sequence conflict

376

1

T → P in AAD39929. Ref.4

Non-terminal residue

1

1

Secondary structure

1

.

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682

Helix Strand Turn

Details...

Helix

92 – 104

13

Beta strand

106 – 111

6

Helix

116 – 127

12

Beta strand

133 – 136

4

Turn

137 – 139

3

Helix

143 – 154

12

Beta strand

161 – 164

4

Beta strand

167 – 171

5

Helix

172 – 181

10

Helix

183 – 189

7

Sequences

	Sequence		Length	Mass (Da)
	Q86VQ6 [UniParc]. Last modified March 23, 2010. Version 3. Checksum: 284F1E9C9FE1EE7B	FASTA	682	74,823
	10 20 30 40 50 60 VRVASEGSVR RPSGPVPAPQ PPAFRFVSRP GRARSESETL ERSPPQSPGP GKAGDAPNRR 70 80 90 100 110 120 SGHVRGARVL SPPGRRARLS SPGPSRSSEA REELRRHLVG LIERSRVVIF SKSYCPHSTR 130 140 150 160 170 180 VKELFSSLGV ECNVLELDQV DDGARVQEVL SEITNQKTVP NIFVNKVHVG GCDQTFQAYQ 190 200 210 220 230 240 SGLLQKLLQE DLAYDYDLII IGGGSGGLSC AKEAAILGKK VMVLDFVVPS PQGTSWGLGG 250 260 270 280 290 300 TCVNVGCIPK KLMHQAALLG QALCDSRKFG WEYNQQVRHN WETMTKAIQN HISSLNWGYR 310 320 330 340 350 360 LSLREKAVAY VNSYGEFVEH HKIKATNKKG QETYYTAAQF VIATGERPRY LGIQGDKEYC 370 380 390 400 410 420 ITSDDLFSLP YCPGKTLVVG ASYVALECAG FLAGFGLDVT VMVRSILLRG FDQEMAEKVG 430 440 450 460 470 480 SYMEQHGVKF LRKFIPVMVQ QLEKGSPGKL KVLAKSTEGT ETIEGVYNTV LLAIGRDSCT 490 500 510 520 530 540 RKIGLEKIGV KINEKSGKIP VNDVEQTNVP YVYAVGDILE DKPELTPVAI QSGKLLAQRL 550 560 570 580 590 600 FGASLEKCDY INVPTTVFTP LEYGCCGLSE EKAIEVYKKE NLEIYHTLFW PLEWTVAGRE 610 620 630 640 650 660 NNTCYAKIIC NKFDHDRVIG FHILGPNAGE VTQGFAAAMK CGLTKQLLDD TIGIHPTCGE 670 680 VFTTLEITKS SGLDITQKGC UG

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] [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 104-682, SELENOCYSTEINE AT SEC-681.
[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 106-682.
[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-80 AND SER-81, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	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.

IPI

IPI00981128.

RefSeq

NP_001166984.1. NM_001173513.1.
NP_443115.1. NM_052883.1.

UniGene

Hs.477475.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3H8Q	X-ray	2.21	A/B	90-195	[»]

ProteinModelPortal

Q86VQ6.

SMR

Q86VQ6. Positions 90-682.

ModBase

Search...

PTM databases

PhosphoSite

Q86VQ6.

Polymorphism databases

DMDM

292495056.

Proteomic databases

PaxDb

Q86VQ6.

PRIDE

Q86VQ6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

114112.

KEGG

hsa:114112.

UCSC

uc003ejd.2. human.

Organism-specific databases

CTD

114112.

GeneCards

GC03M126292.

HGNC

HGNC:20667. TXNRD3.

HPA

CAB020802.

MIM

606235. gene.

neXtProt

NX_Q86VQ6.

PharmGKB

PA134920642.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1249.

HOGENOM

HOG000276712.

HOVERGEN

HBG004959.

InParanoid

Q86VQ6.

KO

K00384.

OrthoDB

EOG4H463K.

Gene expression databases

CleanEx

HS_TXNRD3.

Genevestigator

Q86VQ6.

Family and domain databases

Gene3D

3.30.390.30. 1 hit.
3.40.30.10. 1 hit.

InterPro

IPR016156. 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]

PANTHER

PTHR22912:SF23. PTHR22912:SF23. 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.

SUPFAM

SSF55424. FAD/NAD-linked_reductase_dimer. 1 hit.
SSF52833. Thiordxn-like_fd. 1 hit.

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

BindingDB

Q86VQ6.

ChEMBL

CHEMBL3793.

ChiTaRS

TXNRD3. human.

EvolutionaryTrace

Q86VQ6.

GenomeRNAi

114112.

NextBio

78986.

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:	March 23, 2010
Last modified:	April 3, 2013
This is version 102 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.