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)

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
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

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
HSSP	HSSP built from PDB template 1H6V based on UniProtKB O89049.
SMR	Q86VQ6. Positions 194-676.
ModBase	Search...
PTM databases
PhosphoSite	Q86VQ6.
Genome annotation databases
Ensembl	ENSG00000197763. Homo sapiens. [Contig view]
Organism-specific databases
GeneCards	GC03M127808.
HGNC	HGNC:20667. TXNRD3.
MIM	606235. gene.
PharmGKB	PA134920642.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q86VQ6.
HOVERGEN	Q86VQ6.
Enzyme and pathway databases
BRENDA	1.8.1.9. 247.
Gene expression databases
ArrayExpress	Q86VQ6.
Bgee	Q86VQ6.
CleanEx	HS_TXNRD3.
Family and domain databases
InterPro	IPR013027. FAD_pyr_nucl-diS_OxRdtase. IPR011767. GLR_AS. IPR002109. Glutaredoxin. IPR011899. GRX_euk. IPR000815. Hg_reductase. IPR004099. Pyr_nucl-diS_OxRdtase_dimer. IPR012999. Pyr_OxRdtase_I_AS. IPR001327. Pyr_OxRdtase_NAD_bd. IPR006338. Reduct_Se. 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:	June 16, 2009
This is version 62 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)