UniProt Accession

 THIO_HUMAN; P10599; B1ALW1; O60744; Q53X69; Q96KI3; Q9UDG5 

Genbank Protein ID

 J04026; X77584; X54539; X54540; X54541; AF276919; AY004872; AF313911; AK289508; CR407665; AF548001; AL158158; AL158158; CH471105; CH471105; BC003377; BC054866; AF065241 

Genbank Nucleotide ID

 AAA74596.1; CAA54687.1; CAA38410.1; CAA38410.1; CAA38410.1; AAF86466.1; AAF87085.1; AAG34699.1; BAF82197.1; CAG28593.1; AAN33187.1; CAI14066.1; CAI14067.1; EAW59059.1; EAW59060.1; AAH03377.1; AAH54866.1; AAC17430.1 

Protein Name

 Thioredoxin 

Protein Synonyms/Alias

 Trx; ATL-derived factor; ADF; Surface-associated sulphydryl protein; SASP 

Gene Name

 TXN 

Gene Synonyms/Alias

 TRDX; TRX; TRX1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
3	*****MVKQIESKTA	acetylation	[1]
8	MVKQIESKTAFQEAL	ubiquitination	[2]
39	CGPCKMIKPFFHSLS	acetylation	[1, 3, 4, 5]
39	CGPCKMIKPFFHSLS	ubiquitination	[2, 6, 7, 8]
94	GEFSGANKEKLEATI	acetylation	[5, 9, 10]
94	GEFSGANKEKLEATI	ubiquitination	[2, 5, 8]
96	FSGANKEKLEATINE	ubiquitination	[2, 8, 11]

Reference

 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [4] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [6] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [7] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [8] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [9] Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
 Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y.
 Mol Cell. 2006 Aug;23(4):607-18. [PMID: 16916647]
 [10] Proteome-wide prediction of acetylation substrates.
 Basu A, Rose KL, Zhang J, Beavis RC, Ueberheide B, Garcia BA, Chait B, Zhao Y, Hunt DF, Segal E, Allis CD, Hake SB.
 Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13785-90. [PMID: 19666589]
 [11] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 2 105 Thioredoxin.
 ACT_SITE 32 32 Nucleophile.
 ACT_SITE 35 35 Nucleophile.
 MOD_RES 3 3 N6-acetyllysine.
 MOD_RES 39 39 N6-acetyllysine.
 MOD_RES 62 62 S-nitrosocysteine.
 MOD_RES 69 69 S-nitrosocysteine.
 MOD_RES 73 73 S-nitrosocysteine; alternate.
 DISULFID 32 35 Redox-active.
 DISULFID 73 73 Interchain; alternate.  

Keyword

 3D-structure; Acetylation; Activator; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; Disulfide bond; Electron transport; Nucleus; Redox-active center; Reference proteome; S-nitrosylation; Secreted; Transcription; Transcription regulation; Transport; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 105 AA 

Protein Sequence

Gene Ontology

 GO:0030424; C:axon; IEA:Compara.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0030425; C:dendrite; IEA:Compara.
 GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0009055; F:electron carrier activity; IEA:InterPro.
 GO:0015037; F:peptide disulfide oxidoreductase activity; IEA:Compara.
 GO:0015035; F:protein disulfide oxidoreductase activity; IEA:InterPro.
 GO:0016999; P:antibiotic metabolic process; IEA:Compara.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0045454; P:cell redox homeostasis; IEA:Compara.
 GO:0007267; P:cell-cell signaling; TAS:ProtInc.
 GO:0006928; P:cellular component movement; TAS:ProtInc.
 GO:0035690; P:cellular response to drug; IEA:Compara.
 GO:0071333; P:cellular response to glucose stimulus; IEA:Compara.
 GO:0071455; P:cellular response to hyperoxia; IEA:Compara.
 GO:0022900; P:electron transport chain; IEA:UniProtKB-KW.
 GO:0006662; P:glycerol ether metabolic process; IEA:InterPro.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0046826; P:negative regulation of protein export from nucleus; IEA:Compara.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
 GO:0035872; P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway; TAS:Reactome.
 GO:0055114; P:oxidation-reduction process; IDA:UniProtKB.
 GO:0043388; P:positive regulation of DNA binding; IDA:UniProtKB.
 GO:0033158; P:regulation of protein import into nucleus, translocation; IDA:UniProtKB.
 GO:0014823; P:response to activity; IEA:Compara.
 GO:0048678; P:response to axon injury; IEA:Compara.
 GO:0071548; P:response to dexamethasone stimulus; IEA:Compara.
 GO:0009314; P:response to radiation; IDA:UniProtKB.
 GO:0010269; P:response to selenium ion; IEA:Compara.
 GO:0097068; P:response to thyroxine stimulus; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 

Interpro

 IPR005746; Thioredoxin.
 IPR012336; Thioredoxin-like_fold.
 IPR017937; Thioredoxin_CS.
 IPR013766; Thioredoxin_domain. 

Pfam

 PF00085; Thioredoxin 

SMART

  

PROSITE

 PS00194; THIOREDOXIN_1
 PS51352; THIOREDOXIN_2 

PRINTS

 PR00421; THIOREDOXIN.