P10599 (THIO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	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. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity. Ref.17 Ref.19 Ref.20 Ref.22 Ref.23 ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55). Ref.17 Ref.19 Ref.20 Ref.22 Ref.23
Subunit structure	Homodimer; disulfide-linked. Interacts with TXNIP through the redox-active site. Interacts with MAP3K5 and CASP3. In case of infection, interacts with S.typhimurium protein slrP. Interacts with APEX1; the interaction stimulates the FOS/JUN AP-1 DNA-binding activity in a redox-dependent manner. Ref.19 Ref.21 Ref.25 Ref.34 Ref.35
Subcellular location	Nucleus. Cytoplasm. Secreted. Note: Secreted by a leaderless secretory pathway. Predominantly in the cytoplasm in non irradiated cells. Radiation induces translocation of TRX from the cytoplasm to the nucleus. Ref.18 Ref.19 Ref.20
Induction	Up-regulated by ionizing radiation. Ref.20
Post-translational modification	In the fully reduced protein, both Cys-69 and Cys-73 are nitrosylated in response to nitric oxide (NO). When two disulfide bonds are present in the protein, only Cys-73 is nitrosylated. Cys-73 can serve as donor for nitrosylation of target proteins. In case of infection, ubiquitinated by S.typhimurium protein slrP, leading to its degradation.
Sequence similarities	Belongs to the thioredoxin family. Contains 1 thioredoxin domain.

Ontologies

Keywords
Biological process	Electron transport Transcription Transcription regulation Transport
Cellular component	Cytoplasm Nucleus Secreted
Coding sequence diversity	Alternative splicing
Domain	Redox-active center
Molecular function	Activator
PTM	Acetylation Disulfide bond S-nitrosylation Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	antibiotic metabolic process Inferred from electronic annotation. Source: Compara cell proliferation Traceable author statement Ref.1. Source: ProtInc cell redox homeostasis Inferred from electronic annotation. Source: Compara cell-cell signaling Traceable author statement PubMed 10947064. Source: ProtInc cellular component movement Traceable author statement PubMed 10947064. Source: ProtInc cellular response to drug Inferred from electronic annotation. Source: Compara cellular response to glucose stimulus Inferred from electronic annotation. Source: Compara cellular response to hyperoxia Inferred from electronic annotation. Source: Compara electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW glycerol ether metabolic process Inferred from electronic annotation. Source: InterPro innate immune response Traceable author statement. Source: Reactome negative regulation of protein export from nucleus Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara nucleobase-containing small molecule interconversion Traceable author statement. Source: Reactome nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway Traceable author statement. Source: Reactome oxidation-reduction process Inferred from direct assay Ref.20. Source: UniProtKB positive regulation of DNA binding Inferred from direct assay Ref.20. Source: UniProtKB regulation of protein import into nucleus, translocation Inferred from direct assay Ref.20. Source: UniProtKB response to activity Inferred from electronic annotation. Source: Compara response to axon injury Inferred from electronic annotation. Source: Compara response to dexamethasone stimulus Inferred from electronic annotation. Source: Compara response to radiation Inferred from direct assay Ref.20. Source: UniProtKB response to selenium ion Inferred from electronic annotation. Source: Compara response to thyroxine stimulus Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	axon Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome dendrite Inferred from electronic annotation. Source: Compara extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	electron carrier activity Inferred from electronic annotation. Source: InterPro peptide disulfide oxidoreductase activity Inferred from electronic annotation. Source: Compara protein disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
COPS5	Q92905	8	EBI-594644,EBI-594661
MAP3K5	Q99683	2	EBI-594644,EBI-476263
MYD88	Q99836	4	EBI-594644,EBI-447677

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P10599-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P10599-2)

The sequence of this isoform differs from the canonical sequence as follows:
     44-63: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.14 Ref.15

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

3

1

N6-acetyllysine Ref.26

Modified residue

39

1

N6-acetyllysine Ref.26

Modified residue

62

1

S-nitrosocysteine Ref.35

Modified residue

69

1

S-nitrosocysteine Ref.35

Modified residue

73

1

S-nitrosocysteine Ref.22 Ref.23

Disulfide bond

32 ↔ 35

Redox-active Ref.29 Ref.35

Disulfide bond

73

Interchain; alternate Ref.35

Natural variations

Alternative sequence

44 – 63

20

Missing in isoform 2.

VSP_045607

Experimental info

Mutagenesis

32

1

C → S: Loses its reducing activity, interaction with APEX1 and transcription activation; when associated with S-35. Ref.19

Mutagenesis

35

1

C → S: Loses its reducing activity, interaction with APEX1 and transcription activation; when associated with S-32. Ref.19

Mutagenesis

60

1

D → N: Loss of pH-dependence of dimerization.

Mutagenesis

62

1

C → S: Retains its reducing activity. Retains interaction with APEX1 and transcription activation; when associated with S-69 and S-73. Ref.19

Mutagenesis

69

1

C → S: No effect on reducing activity, interaction with APEX1 and on S-nitrosylation of C-73. Retains interaction with APEX1 and transcription activation; when associated with S-62 and S-73. Ref.19 Ref.23

Mutagenesis

70

1

E → A: Strongly reduced interaction with CASP3; when associated with A-72. Ref.23

Mutagenesis

72

1

K → A: Strongly reduced interaction with CASP3; when associated with A-70. Ref.23

Mutagenesis

73

1

C → D: Strongly reduced S-nitrosylation of CASP3. Ref.19 Ref.22 Ref.23

Mutagenesis

73

1

C → S: Loss of nitrosylation, and loss of S-nitrosylating activity towards CASP3. Retains interaction with APEX1 and transcription activation; when associated with S-62 and S-69. Ref.19 Ref.22 Ref.23

Mutagenesis

73

1

C → S: Retains its reducing activity. Ref.19 Ref.22 Ref.23

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

3 – 5

3

Helix

8 – 17

10

Turn

18 – 20

3

Beta strand

23 – 28

6

Beta strand

30 – 32

3

Helix

33 – 48

16

Turn

49 – 51

3

Beta strand

52 – 58

7

Turn

59 – 61

3

Helix

63 – 68

6

Beta strand

73 – 81

9

Beta strand

84 – 92

9

Helix

94 – 104

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 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
	Isoform 2 [UniParc]. Checksum: 3CC6254BD6A1D66F	FASTA	85	9,452
	10 20 30 40 50 60 MVKQIESKTA FQEALDAAGD KLVVVDFSAT WCGPCKMIKP FFHDVASECE VKCMPTFQFF 70 80 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Isolation and characterization of human thioredoxin-encoding genes." Tonissen K.F., Wells J.R.E. Gene 102:221-228(1991) [PubMed] [Europe PMC] [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] (ISOFORM 1). 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] (ISOFORM 1). 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] (ISOFORM 1). 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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] (ISOFORM 1).
[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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Cervix.
[13]	"An alternative splice variant of human thioredoxin." Wang Y., Wang Y.G., Zhang Y., Yuan Y., Ma D. Chin. Sci. Bull. 43:292-295(1998) Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-85 (ISOFORM 2), ALTERNATIVE SPLICING. Tissue: Liver.
[14]	"Characterization of a thioredoxin-related surface protein." Dean M.F., Martin H., Sansom P.A. Biochem. J. 304:861-867(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-21 AND 38-57. Tissue: Monocyte.
[15]	"Identification of a thioredoxin-related protein associated with plasma membranes." Martin H., Dean M. Biochem. Biophys. Res. Commun. 175:123-128(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-15.
[16]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 9-48; 73-81 AND 95-105, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[17]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[18]	"Secretion of thioredoxin by normal and neoplastic cells through a leaderless secretory pathway." Rubartelli A., Bajetto A., Allavena G., Wollman E., Sitia R. J. Biol. Chem. 267:24161-24164(1992) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[19]	"AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1." Hirota K., Matsui M., Iwata S., Nishiyama A., Mori K., Yodoi J. Proc. Natl. Acad. Sci. U.S.A. 94:3633-3638(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, INTERACTION WITH APEX1, MUTAGENESIS OF CYS-32; CYS-35; CYS-62; CYS-69 AND CYS-73, SUBCELLULAR LOCATION.
[20]	"Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation." Wei S.J., Botero A., Hirota K., Bradbury C.M., Markovina S., Laszlo A., Spitz D.R., Goswami P.C., Yodoi J., Gius D. Cancer Res. 60:6688-6695(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION.
[21]	"S-nitrosation of thioredoxin in the nitrogen monoxide/superoxide system activates apoptosis signal-regulating kinase 1." Yasinska I.M., Kozhukhar A.V., Sumbayev V.V. Arch. Biochem. Biophys. 428:198-203(2004) [PubMed] [Europe PMC] [Abstract] Cited for: S-NITROSYLATION, INTERACTION WITH MAP3K5.
[22]	"Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine." Mitchell D.A., Marletta M.A. Nat. Chem. Biol. 1:154-158(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-73, S-NITROSYLATION AT CYS-73.
[23]	"Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells." Mitchell D.A., Morton S.U., Fernhoff N.B., Marletta M.A. Proc. Natl. Acad. Sci. U.S.A. 104:11609-11614(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-69; GLU-70; LYS-72 AND CYS-73, S-NITROSYLATION AT CYS-73 IN RESPONSE TO NITRIC OXIDE.
[24]	"Abnormal proteins in primary breast cancer tissues from 25 Sudanese patients." Ahamed M.E., Ahmed M.E., Eltoum A.M., Altahir G.O., Ahmed K.M., Harbi S.O., Stansalas J., Mohamed A.O. Eur. J. Inflamm. 6:115-121(2008) Cited for: IDENTIFICATION BY MASS SPECTROMETRY. Tissue: Mammary cancer.
[25]	"Salmonella type III secretion effector SlrP is an E3 ubiquitin ligase for mammalian thioredoxin." Bernal-Bayard J., Ramos-Morales F. J. Biol. Chem. 284:27587-27595(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH S.TYPHIMURIUM SLRP, UBIQUITINATION.
[26]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-3 AND LYS-39, MASS SPECTROMETRY.
[27]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]	"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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[29]	"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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[30]	"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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[31]	"Solution structure of human thioredoxin in a mixed disulfide intermediate complex with its target peptide from the transcription factor NF kappa B." Qin J., Clore G.M., Kennedy W.M., Huth J.R., Gronenborn A.M. Structure 3:289-297(1995) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[32]	"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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[33]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
[34]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANT ASN-60, SUBUNIT.
[35]	"Buried S-nitrosocysteine revealed in crystal structures of human thioredoxin." Weichsel A., Brailey J.L., Montfort W.R. Biochemistry 46:1219-1227(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS), SUBUNIT, DISULFIDE BONDS, S-NITROSYLATION AT CYS-62 AND CYS-69.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
AL158158 Genomic DNA. Translation: CAI14067.1.
CH471105 Genomic DNA. Translation: EAW59059.1.
CH471105 Genomic DNA. Translation: EAW59060.1.
BC003377 mRNA. Translation: AAH03377.1.
BC054866 mRNA. Translation: AAH54866.1.
AF065241 mRNA. Translation: AAC17430.1.

IPI

IPI00216298.
IPI00552768.

PIR

JH0568.

RefSeq

NP_001231867.1. NM_001244938.1.
NP_003320.2. NM_003329.3.

UniGene

Hs.435136.

3D structure databases

PDBe
RCSB PDB
PDBj

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	1-105	[»]
1ERV	X-ray	1.65	A	1-105	[»]
1ERW	X-ray	1.80	A	1-105	[»]
1M7T	NMR	-	A	1-65	[»]
1MDI	NMR	-	A	2-104	[»]
1MDJ	NMR	-	A	2-104	[»]
1MDK	NMR	-	A	2-104	[»]
1TRS	NMR	-	A	1-105	[»]
1TRU	NMR	-	A	1-105	[»]
1TRV	NMR	-	A	1-105	[»]
1TRW	NMR	-	A	1-105	[»]
1W1C	model	-	C	1-105	[»]
1W1E	model	-	C	1-105	[»]
2HSH	X-ray	1.35	A	1-105	[»]
2HXK	X-ray	1.65	A/B/C	1-105	[»]
2IFQ	X-ray	1.20	A/B/C	1-105	[»]
2IIY	X-ray	1.70	A	1-105	[»]
3E3E	X-ray	2.01	A/B	1-105	[»]
3KD0	X-ray	1.70	A	1-105	[»]
3M9J	X-ray	1.10	A/B	1-105	[»]
3M9K	X-ray	1.50	A/B	1-105	[»]
3QFA	X-ray	2.20	C/D	2-105	[»]
3QFB	X-ray	2.60	C/D	2-105	[»]
3TRX	NMR	-	A	1-105	[»]
4TRX	NMR	-	A	1-105	[»]

ProteinModelPortal

P10599.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6129N.

IntAct

P10599. 23 interactions.

MINT

MINT-1522967.

STRING

9606.ENSP00000363641.

Protein family/group databases

Allergome

3543. Hom s Trx.

PTM databases

PhosphoSite

P10599.

Polymorphism databases

DMDM

135773.

2D gel databases

DOSAC-COBS-2DPAGE

P10599.

REPRODUCTION-2DPAGE

IPI00216298.

SWISS-2DPAGE

P10599.

Proteomic databases

PaxDb

P10599.

PeptideAtlas

P10599.

PRIDE

P10599.

Protocols and materials databases

DNASU

7295.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000374515; ENSP00000363639; ENSG00000136810.
ENST00000374517; ENSP00000363641; ENSG00000136810.

GeneID

7295.

KEGG

hsa:7295.

UCSC

uc004bep.2. human.

Organism-specific databases

CTD

7295.

GeneCards

GC09M113006.

HGNC

HGNC:12435. TXN.

HPA

CAB008678.

MIM

187700. gene.

neXtProt

NX_P10599.

PharmGKB

PA37091.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0526.

HOGENOM

HOG000292977.

HOVERGEN

HBG009243.

InParanoid

P10599.

KO

K03671.

OMA

DYEGKAI.

OrthoDB

EOG47PX7J.

PhylomeDB

P10599.

Enzyme and pathway databases

Pathway_Interaction_DB

p38_mkk3_6pathway. p38 MAPK signaling pathway.
ptp1bpathway. Signaling events mediated by PTP1B.
tnfpathway. TNF receptor signaling pathway.

Reactome

REACT_111217. Metabolism.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P10599.

Bgee

P10599.

CleanEx

HS_TXN.

Genevestigator

P10599.

GermOnline

ENSG00000136810. Homo sapiens.

Family and domain databases

Gene3D

3.40.30.10. 1 hit.

InterPro

IPR005746. Thioredoxin.
IPR012336. Thioredoxin-like_fold.
IPR017937. Thioredoxin_CS.
IPR013766. Thioredoxin_domain.
[Graphical view]

PANTHER

PTHR10438. PTHR10438. 1 hit.

Pfam

PF00085. Thioredoxin. 1 hit.
[Graphical view]

PIRSF

PIRSF000077. Thioredoxin. 1 hit.

PRINTS

PR00421. THIOREDOXIN.

SUPFAM

SSF52833. Thiordxn-like_fd. 1 hit.

PROSITE

PS00194. THIOREDOXIN_1. 1 hit.
PS51352. THIOREDOXIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TXN. human.

EvolutionaryTrace

P10599.

GenomeRNAi

7295.

NextBio

28523.

SOURCE

Search...

Entry information

Entry name

THIO_HUMAN

Accession

Primary (citable) accession number: P10599
Secondary accession number(s): B1ALW1 , O60744, Q53X69, Q96KI3, Q9UDG5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 163 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.