Reviewed, UniProtKB/Swiss-Prot P10599 (THIO_HUMAN)

Names and origin

Protein names

Recommended name:
    Thioredoxin
      Short name=Trx
Alternative name(s):
    ATL-derived factor
      Short name=ADF
    Surface-associated sulphydryl protein
      Short name=SASP

Gene names

Name:	TXN
Synonyms:	TRDX, TRX, TRX1

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	105 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Ref.15 ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55). Ref.15
Subunit structure	Homodimer. Interacts with TXNIP through the redox-active site.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the thioredoxin family. Contains 1 thioredoxin domain.

Ontologies

Keywords
Biological process	Electron transport Transport
Cellular component	Cytoplasm
Domain	Redox-active center
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell motion Traceable author statement. Source: ProtInc cell proliferation Ref.1 Traceable author statement. Source: ProtInc cell redox homeostasis Inferred from electronic annotation. Source: InterPro cell-cell signaling Traceable author statement. Source: ProtInc electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW signal transduction Traceable author statement. Source: ProtInc transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
COPS5	Q92905	5	EBI-594644,EBI-594661
TXNIP	Q9H3M7	2	EBI-594644,EBI-1369170

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.13

Chain

2 – 105

104

Thioredoxin

PRO_0000120005

Regions

Domain

2 – 105

104

Thioredoxin

Sites

Active site

32

1

Nucleophile

Active site

35

1

Nucleophile

Site

26

1

Deprotonates C-terminal active site Cys

Site

33

1

Contributes to redox potential value

Site

34

1

Contributes to redox potential value

Amino acid modifications

Modified residue

94

1

N6-acetyllysine

Modified residue

100

1

Phosphothreonine Ref.16

Disulfide bond

32 ↔ 35

Redox-active Ref.19

Disulfide bond

73

Interchain

Experimental info

Sequence conflict

39

1

K → N in AAA74596. Ref.1

Sequence conflict

39

1

K → N in AAF86466. Ref.4

Sequence conflict

74

1

M → T in AAA74596. Ref.1

Sequence conflict

74

1

M → T in AAF86466. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

105

Helix Strand Turn

Details...

Beta strand

2 – 5

4

Helix

8 – 17

10

Turn

18 – 20

3

Beta strand

23 – 28

6

Helix

33 – 48

16

Beta strand

52 – 58

7

Turn

59 – 61

3

Helix

63 – 68

6

Beta strand

73 – 81

9

Beta strand

84 – 91

8

Helix

94 – 104

11

Sequences

	Sequence		Length	Mass (Da)
	P10599-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 256F4E3C8A187693	FASTA	105	11,737
	10 20 30 40 50 60 MVKQIESKTA FQEALDAAGD KLVVVDFSAT WCGPCKMIKP FFHSLSEKYS NVIFLEVDVD 70 80 90 100 DCQDVASECE VKCMPTFQFF KKGQKVGEFS GANKEKLEAT INELV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of a cDNA for human thioredoxin." Wollman E.E., D'Auriol L., Rimsky L., Shaw A., Jacquot J.-P., Wingfield P., Graber P., Dessarps F. J. Biol. Chem. 263:15506-15512(1988) [PubMed: 3170595] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction." Tagaya Y., Maeda Y., Mitsui A., Kndo N., Matsui H., Hamuro J., Brown N., Arai K., Yokota T., Wakasugi H., Yodoi J. EMBO J. 8:757-764(1989) [PubMed: 2785919] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Isolation and characterization of human thioredoxin-encoding genes." Tonissen K.F., Wells J.R.E. Gene 102:221-228(1991) [PubMed: 1874447] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	Reddy P.G., Bhuyan D.K., Bhuyan K.C. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lens.
[5]	"Cloning, purification and characterization of human lens thioredoxin." Liu A., Lou M.F. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lens.
[6]	"Cloning and sequencing of thioredoxin cDNA from human brain." Xu J.Y., Xu L., Li K.S., Dai R. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[8]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	NIEHS SNPs program Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"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]. Tissue: Cervix.
[13]	"Identification of a thioredoxin-related protein associated with plasma membranes." Martin H., Dean M. Biochem. Biophys. Res. Commun. 175:123-128(1991) [PubMed: 1998498] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-15.
[14]	Lubec G., Vishwanath V. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 73-81, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[15]	"Human thioredoxin reactivity-structure/function relationship." Jacquot J.-P., de Lamotte F., Fontecav M., Schuermann P., Decottignies P., Miginiac-Maslow M., Wollman E. Biochem. Biophys. Res. Commun. 173:1375-1381(1990) [PubMed: 2176490] [Abstract] Cited for: FUNCTION.
[16]	"Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC." Gevaert K., Staes A., Van Damme J., De Groot S., Hugelier K., Demol H., Martens L., Goethals M., Vandekerckhove J. Proteomics 5:3589-3599(2005) [PubMed: 16097034] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-100, MASS SPECTROMETRY. Tissue: Hepatocyte.
[17]	"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey." Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y. Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-94, MASS SPECTROMETRY. Tissue: Epithelium.
[18]	"A proton nuclear magnetic resonance assignment and secondary structure determination of recombinant human thioredoxin." Forman-Kay J.D., Clore G.M., Dricoll P.C., Wingfield P., Richards F.M., Gronenborn A.M. Biochemistry 28:7088-7097(1989) [PubMed: 2684271] [Abstract] Cited for: STRUCTURE BY NMR.
[19]	"High-resolution three-dimensional structure of reduced recombinant human thioredoxin in solution." Forman-Kay J.D., Clore G.M., Wingfield P., Gronenborn A.M. Biochemistry 30:2685-2698(1991) [PubMed: 2001356] [Abstract] Cited for: STRUCTURE BY NMR.
[20]	"The high-resolution three-dimensional solution structures of the oxidized and reduced states of human thioredoxin." Qin J., Clore G.M., Gronenborn A.M. Structure 2:503-522(1994) [PubMed: 7922028] [Abstract] Cited for: STRUCTURE BY NMR.
[21]	"The solution structure of human thioredoxin complexed with its target from Ref-1 reveals peptide chain reversal." Qin J., Clore G.M., Kennedy W.P., Kuszewski J., Gronenborn A.M. Structure 4:613-620(1996) [PubMed: 8736558] [Abstract] Cited for: STRUCTURE BY NMR.
[22]	"Crystal structures of reduced, oxidized, and mutated human thioredoxins: evidence for a regulatory homodimer." Weichsel A., Gasdaska J.R., Powis G., Montfort W.R. Structure 4:735-751(1996) [PubMed: 8805557] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
[23]	"Human thioredoxin homodimers: regulation by pH, role of aspartate 60, and crystal structure of the aspartate 60 --> asparagine mutant." Andersen J.F., Sanders D.A., Gasdaska J.R., Weichsel A., Powis G., Montfort W.R. Biochemistry 36:13979-13988(1997) [PubMed: 9369469] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANT ASN-61.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

J04026 mRNA. Translation: AAA74596.1.
X77584 mRNA. Translation: CAA54687.1.
X54539, X54540, X54541 Genomic DNA. Translation: CAA38410.1.
AF276919 mRNA. Translation: AAF86466.1.
AY004872 mRNA. Translation: AAF87085.1.
AF313911 mRNA. Translation: AAG34699.1.
AK289508 mRNA. Translation: BAF82197.1.
CR407665 mRNA. Translation: CAG28593.1.
AF548001 Genomic DNA. Translation: AAN33187.1.
AL158158 Genomic DNA. Translation: CAI14066.1.
CH471105 Genomic DNA. Translation: EAW59059.1.
BC003377 mRNA. Translation: AAH03377.1.
BC054866 mRNA. Translation: AAH54866.1.

PIR

JH0568.

RefSeq

NP_003320.2.

UniGene

Hs.435136

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AIU	X-ray	2.00	A	1-105	[»]
1AUC	X-ray	2.10	A	1-105	[»]
1CQG	NMR	-	A	1-105	[»]
1CQH	NMR	-	A	1-105	[»]
1ERT	X-ray	1.70	A	1-105	[»]
1ERU	X-ray	2.10	A