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509  structures 5131  species 20  interactions 34820  sequences 493  architectures

Family: Thioredoxin (PF00085)

Summary: Thioredoxin

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Thioredoxin". More...

Thioredoxin Edit Wikipedia article

TXN
Тиоредоксин, гомодимер.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TXN, TRDX, TRX, TRX1, thioredoxin
External IDs OMIM: 187700 MGI: 98874 HomoloGene: 128202 GeneCards: TXN
RNA expression pattern
PBB GE TXN 208864 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003329
NM_001244938

NM_011660

RefSeq (protein)

NP_001231867
NP_003320

NP_035790.1
NP_035790

Location (UCSC) Chr 9: 110.24 – 110.26 Mb Chr 4: 57.94 – 57.96 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes, including redox signaling. In humans, thioredoxins are encoded by TXN and TXN2 genes.[3][4] Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the developing embryo. Although not entirely understood, thioredoxin plays a central role in humans and is increasingly linked to medicine through their response to reactive oxygen species (ROS). In plants, thioredoxins regulate a spectrum of critical functions, ranging from photosynthesis to growth, flowering and the development and germination of seeds. It has also recently been found to play a role in cell-to-cell communication.[5]

Function

Thioredoxins are proteins that act as antioxidants by facilitating the reduction of other proteins by cysteine thiol-disulfide exchange. Thioredoxins are found in nearly all known organisms and are essential for life in mammals.[6][7]

Thioredoxin is a 12-kD oxidoreductase enzyme containing a dithiol-disulfide active site. It is ubiquitous and found in many organisms from plants and bacteria to mammals. Multiple in vitro substrates for thioredoxin have been identified, including ribonuclease, choriogonadotropins, coagulation factors, glucocorticoid receptor, and insulin. Reduction of insulin is classically used as an activity test.[8]

Thioredoxins are characterized at the level of their amino acid sequence by the presence of two vicinal cysteines in a CXXC motif. These two cysteines are the key to the ability of thioredoxin to reduce other proteins. Thioredoxin proteins also have a characteristic tertiary structure termed the thioredoxin fold.

The thioredoxins are kept in the reduced state by the flavoenzyme thioredoxin reductase, in a NADPH-dependent reaction.[9] Thioredoxins act as electron donors to peroxidases and ribonucleotide reductase.[10] The related glutaredoxins share many of the functions of thioredoxins, but are reduced by glutathione rather than a specific reductase.

The benefit of thioredoxins to reduce oxidative stress is shown by transgenic mice that overexpress thioredoxin, are more resistant to inflammation, and live 35% longer[11] — supporting the free radical theory of aging. However, the controls of this study were short lived, which may have contributed to the apparent increase in longevity.[12]

Plants have an unusually complex complement of Trxs composed of six well-defined types (Trxs f, m, x, y, h, and o) that reside in different cell compartments and function in an array of processes. In 2010 it was discovered for the first time that thioredoxin proteins are able to move from cell to cell, representing a novel form of cellular communication in plants.[5]

Mechanism of action

The primary function of Thioredoxin (Trx) is the reduction of oxidized cysteine residues and the cleavage of disulfide bonds.[13] For Trx1, this process begins by attack of Cys32, one of the residues conserved in the thioredoxin CXXC motif, onto the oxidized group of the substrate.[14] Almost immediately after this event Cys35, the other conserved Cys residue in Trx1, forms a disulfide bond with Cys32, thereby transferring 2 electrons to the substrate which is now in its reduced form. Oxidized Trx1 is then reduced by thioredoxin reductase, which in turn is reduced by NADPH as described above.[14]

Mechanism of Trx1 reducing a substrate

Interactions

Thioredoxin has been shown to interact with:

Effect on cardiac hypertrophy

Trx1 has been shown to downregulate cardiac hypertrophy, the thickening of the walls of the lower heart chambers, by interactions with several different targets. Trx1 upregulates the transcriptional activity of nuclear respiratory factors 1 and 2 (NRF1 and NRF2) and stimulates the expression of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α).[25][26] Furthermore, Trx1 reduces two cysteine residues in histone deacetylase 4 (HDAC4), which allows HDAC4 to be imported from the cytosol, where the oxidized form resides,[27] into the nucleus.[28] Once in the nucleus, reduced HDAC4 downregulates the activity of transcription factors such as NFAT that mediate cardiac hypertrophy.[14] Trx 1 also controls microRNA levels in the heart and has been found to inhibit cardiac hypertrophy by upregulating miR-98/let-7.[29]

See also

References

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Wollman EE, d'Auriol L, Rimsky L, Shaw A, Jacquot JP, Wingfield P, Graber P, Dessarps F, Robin P, Galibert F (October 1988). "Cloning and expression of a cDNA for human thioredoxin". The Journal of Biological Chemistry. 263 (30): 15506–12. PMID 3170595. 
  4. ^ "Entrez Gene: TXN2 thioredoxin 2". 
  5. ^ a b Meng L, Wong JH, Feldman LJ, Lemaux PG, Buchanan BB (February 2010). "A membrane-associated thioredoxin required for plant growth moves from cell to cell, suggestive of a role in intercellular communication". Proceedings of the National Academy of Sciences of the United States of America. 107 (8): 3900–5. doi:10.1073/pnas.0913759107. PMC 2840455Freely accessible. PMID 20133584. 
  6. ^ Holmgren A (August 1989). "Thioredoxin and glutaredoxin systems" (PDF). The Journal of Biological Chemistry. 264 (24): 13963–6. PMID 2668278. 
  7. ^ Nordberg J, Arnér ES (December 2001). "Reactive oxygen species, antioxidants, and the mammalian thioredoxin system". Free Radical Biology & Medicine. 31 (11): 1287–312. doi:10.1016/S0891-5849(01)00724-9. PMID 11728801. 
  8. ^ "Entrez Gene: TXN thioredoxin". 
  9. ^ Mustacich D, Powis G (February 2000). "Thioredoxin reductase". The Biochemical Journal. 346 Pt 1 (Pt 1): 1–8. doi:10.1042/0264-6021:3460001. PMC 1220815Freely accessible. PMID 10657232. 
  10. ^ Arnér ES, Holmgren A (October 2000). "Physiological functions of thioredoxin and thioredoxin reductase". European Journal of Biochemistry. 267 (20): 6102–9. doi:10.1046/j.1432-1327.2000.01701.x. PMID 11012661. 
  11. ^ Yoshida T, Nakamura H, Masutani H, Yodoi J (December 2005). "The involvement of thioredoxin and thioredoxin binding protein-2 on cellular proliferation and aging process". Annals of the New York Academy of Sciences. 1055: 1–12. doi:10.1196/annals.1323.002. PMID 16387713. 
  12. ^ Muller, F.L., Lustgarten, M.S., Jang, Y., Richardson, A. & Van Remmen, H. Trends in oxidative aging theories. Free Radic Biol Med 43, 477-503 (2007).
  13. ^ Nakamura H, Nakamura K, Yodoi J (1997-01-01). "Redox regulation of cellular activation". Annual Review of Immunology. 15 (1): 351–69. doi:10.1146/annurev.immunol.15.1.351. PMID 9143692. 
  14. ^ a b c Nagarajan N, Oka S, Sadoshima J (December 2016). "Modulation of signaling mechanisms in the heart by thioredoxin 1". Free Radical Biology & Medicine. doi:10.1016/j.freeradbiomed.2016.12.020. PMID 27993729. 
  15. ^ Liu Y, Min W (June 2002). "Thioredoxin promotes ASK1 ubiquitination and degradation to inhibit ASK1-mediated apoptosis in a redox activity-independent manner". Circulation Research. 90 (12): 1259–66. doi:10.1161/01.res.0000022160.64355.62. PMID 12089063. 
  16. ^ Morita K, Saitoh M, Tobiume K, Matsuura H, Enomoto S, Nishitoh H, Ichijo H (November 2001). "Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress". The EMBO Journal. 20 (21): 6028–36. doi:10.1093/emboj/20.21.6028. PMC 125685Freely accessible. PMID 11689443. 
  17. ^ Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, Kawabata M, Miyazono K, Ichijo H (May 1998). "Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1". The EMBO Journal. 17 (9): 2596–606. doi:10.1093/emboj/17.9.2596. PMC 1170601Freely accessible. PMID 9564042. 
  18. ^ Matsumoto K, Masutani H, Nishiyama A, Hashimoto S, Gon Y, Horie T, Yodoi J (July 2002). "C-propeptide region of human pro alpha 1 type 1 collagen interacts with thioredoxin". Biochemical and Biophysical Research Communications. 295 (3): 663–7. doi:10.1016/s0006-291x(02)00727-1. PMID 12099690. 
  19. ^ Makino Y, Yoshikawa N, Okamoto K, Hirota K, Yodoi J, Makino I, Tanaka H (January 1999). "Direct association with thioredoxin allows redox regulation of glucocorticoid receptor function". The Journal of Biological Chemistry. 274 (5): 3182–8. doi:10.1074/jbc.274.5.3182. PMID 9915858. 
  20. ^ Li X, Luo Y, Yu L, Lin Y, Luo D, Zhang H, He Y, Kim YO, Kim Y, Tang S, Min W (April 2008). "SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis". Cell Death and Differentiation. 15 (4): 739–50. doi:10.1038/sj.cdd.4402303. PMID 18219322. 
  21. ^ Nishiyama A, Matsui M, Iwata S, Hirota K, Masutani H, Nakamura H, Takagi Y, Sono H, Gon Y, Yodoi J (July 1999). "Identification of thioredoxin-binding protein-2/vitamin D(3) up-regulated protein 1 as a negative regulator of thioredoxin function and expression". The Journal of Biological Chemistry. 274 (31): 21645–50. doi:10.1074/jbc.274.31.21645. PMID 10419473. 
  22. ^ Matthews JR, Wakasugi N, Virelizier JL, Yodoi J, Hay RT (August 1992). "Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62". Nucleic Acids Research. 20 (15): 3821–30. PMC 334054Freely accessible. PMID 1508666. 
  23. ^ Hirota K, Matsui M, Iwata S, Nishiyama A, Mori K, Yodoi J (April 1997). "AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1". Proceedings of the National Academy of Sciences of the United States of America. 94 (8): 3633–8. PMC 20492Freely accessible. PMID 9108029. 
  24. ^ Shao D, Oka S, Liu T, Zhai P, Ago T, Sciarretta S, Li H, Sadoshima J (February 2014). "A redox-dependent mechanism for regulation of AMPK activation by Thioredoxin1 during energy starvation". Cell Metabolism. 19 (2): 232–45. doi:10.1016/j.cmet.2013.12.013. PMC 3937768Freely accessible. PMID 24506865. 
  25. ^ Ago T, Yeh I, Yamamoto M, Schinke-Braun M, Brown JA, Tian B, Sadoshima J. "Thioredoxin1 upregulates mitochondrial proteins related to oxidative phosphorylation and TCA cycle in the heart". Antioxidants & Redox Signaling. 8 (9-10): 1635–50. doi:10.1089/ars.2006.8.1635. PMID 16987018. 
  26. ^ Yamamoto M, Yang G, Hong C, Liu J, Holle E, Yu X, Wagner T, Vatner SF, Sadoshima J (November 2003). "Inhibition of endogenous thioredoxin in the heart increases oxidative stress and cardiac hypertrophy". The Journal of Clinical Investigation. 112 (9): 1395–406. doi:10.1172/JCI17700. PMC 228400Freely accessible. PMID 14597765. 
  27. ^ Matsushima S, Kuroda J, Ago T, Zhai P, Park JY, Xie LH, Tian B, Sadoshima J (February 2013). "Increased oxidative stress in the nucleus caused by Nox4 mediates oxidation of HDAC4 and cardiac hypertrophy". Circulation Research. 112 (4): 651–63. doi:10.1161/CIRCRESAHA.112.279760. PMC 3574183Freely accessible. PMID 23271793. 
  28. ^ Ago T, Liu T, Zhai P, Chen W, Li H, Molkentin JD, Vatner SF, Sadoshima J (June 2008). "A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy". Cell. 133 (6): 978–93. doi:10.1016/j.cell.2008.04.041. PMID 18555775. 
  29. ^ Yang Y, Ago T, Zhai P, Abdellatif M, Sadoshima J (February 2011). "Thioredoxin 1 negatively regulates angiotensin II-induced cardiac hypertrophy through upregulation of miR-98/let-7". Circulation Research. 108 (3): 305–13. doi:10.1161/CIRCRESAHA.110.228437. PMC 3249645Freely accessible. PMID 21183740. 

Further reading

  • Arnér ES, Holmgren A (October 2000). "Physiological functions of thioredoxin and thioredoxin reductase". European Journal of Biochemistry. 267 (20): 6102–9. doi:10.1046/j.1432-1327.2000.01701.x. PMID 11012661. 
  • Nishinaka Y, Masutani H, Nakamura H, Yodoi J (2002). "Regulatory roles of thioredoxin in oxidative stress-induced cellular responses". Redox Report. 6 (5): 289–95. doi:10.1179/135100001101536427. PMID 11778846. 
  • Ago T, Sadoshima J (November 2006). "Thioredoxin and ventricular remodeling". Journal of Molecular and Cellular Cardiology. 41 (5): 762–73. doi:10.1016/j.yjmcc.2006.08.006. PMC 1852508Freely accessible. PMID 17007870. 
  • Tonissen KF, Wells JR (June 1991). "Isolation and characterization of human thioredoxin-encoding genes". Gene. 102 (2): 221–8. doi:10.1016/0378-1119(91)90081-L. PMID 1874447. 
  • Martin H, Dean M (February 1991). "Identification of a thioredoxin-related protein associated with plasma membranes". Biochemical and Biophysical Research Communications. 175 (1): 123–8. doi:10.1016/S0006-291X(05)81209-4. PMID 1998498. 
  • Forman-Kay JD, Clore GM, Wingfield PT, Gronenborn AM (March 1991). "High-resolution three-dimensional structure of reduced recombinant human thioredoxin in solution". Biochemistry. 30 (10): 2685–98. doi:10.1021/bi00224a017. PMID 2001356. 
  • Jacquot JP, de Lamotte F, Fontecave M, Schürmann P, Decottignies P, Miginiac-Maslow M, Wollman E (December 1990). "Human thioredoxin reactivity-structure/function relationship". Biochemical and Biophysical Research Communications. 173 (3): 1375–81. doi:10.1016/S0006-291X(05)80940-4. PMID 2176490. 
  • Forman-Kay JD, Clore GM, Driscoll PC, Wingfield P, Richards FM, Gronenborn AM (August 1989). "A proton nuclear magnetic resonance assignment and secondary structure determination of recombinant human thioredoxin". Biochemistry. 28 (17): 7088–97. doi:10.1021/bi00443a045. PMID 2684271. 
  • Tagaya Y, Maeda Y, Mitsui A, Kondo N, Matsui H, Hamuro J, Brown N, Arai K, Yokota T, Wakasugi H (March 1989). "ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction". The EMBO Journal. 8 (3): 757–64. PMC 400872Freely accessible. PMID 2785919. 
  • Wollman EE, d'Auriol L, Rimsky L, Shaw A, Jacquot JP, Wingfield P, Graber P, Dessarps F, Robin P, Galibert F (October 1988). "Cloning and expression of a cDNA for human thioredoxin". The Journal of Biological Chemistry. 263 (30): 15506–12. PMID 3170595. 
  • Heppell-Parton A, Cahn A, Bench A, Lowe N, Lehrach H, Zehetner G, Rabbitts P (March 1995). "Thioredoxin, a mediator of growth inhibition, maps to 9q31". Genomics. 26 (2): 379–81. doi:10.1016/0888-7543(95)80223-9. PMID 7601465. 
  • Qin J, Clore GM, Kennedy WM, Huth JR, Gronenborn AM (March 1995). "Solution structure of human thioredoxin in a mixed disulfide intermediate complex with its target peptide from the transcription factor NF kappa B". Structure. 3 (3): 289–97. doi:10.1016/S0969-2126(01)00159-9. PMID 7788295. 
  • Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, Yokoyama-Kobayashi M, Aoki T (December 1994). "Construction of a human full-length cDNA bank". Gene. 150 (2): 243–50. doi:10.1016/0378-1119(94)90433-2. PMID 7821789. 
  • Qin J, Clore GM, Gronenborn AM (June 1994). "The high-resolution three-dimensional solution structures of the oxidized and reduced states of human thioredoxin". Structure. 2 (6): 503–22. doi:10.1016/S0969-2126(00)00051-4. PMID 7922028. 
  • Gasdaska PY, Oblong JE, Cotgreave IA, Powis G (August 1994). "The predicted amino acid sequence of human thioredoxin is identical to that of the autocrine growth factor human adult T-cell derived factor (ADF): thioredoxin mRNA is elevated in some human tumors". Biochimica et Biophysica Acta. 1218 (3): 292–6. doi:10.1016/0167-4781(94)90180-5. PMID 8049254. 
  • Qin J, Clore GM, Kennedy WP, Kuszewski J, Gronenborn AM (May 1996). "The solution structure of human thioredoxin complexed with its target from Ref-1 reveals peptide chain reversal". Structure. 4 (5): 613–20. doi:10.1016/S0969-2126(96)00065-2. PMID 8736558. 
  • Weichsel A, Gasdaska JR, Powis G, Montfort WR (June 1996). "Crystal structures of reduced, oxidized, and mutated human thioredoxins: evidence for a regulatory homodimer". Structure. 4 (6): 735–51. doi:10.1016/S0969-2126(96)00079-2. PMID 8805557. 
  • Andersen JF, Sanders DA, Gasdaska JR, Weichsel A, Powis G, Montfort WR (November 1997). "Human thioredoxin homodimers: regulation by pH, role of aspartate 60, and crystal structure of the aspartate 60 --> asparagine mutant". Biochemistry. 36 (46): 13979–88. doi:10.1021/bi971004s. PMID 9369469. 
  • Maruyama T, Kitaoka Y, Sachi Y, Nakanoin K, Hirota K, Shiozawa T, Yoshimura Y, Fujii S, Yodoi J (November 1997). "Thioredoxin expression in the human endometrium during the menstrual cycle". Molecular Human Reproduction. 3 (11): 989–93. doi:10.1093/molehr/3.11.989. PMID 9433926. 
  • Sahlin L, Stjernholm Y, Holmgren A, Ekman G, Eriksson H (December 1997). "The expression of thioredoxin mRNA is increased in the human cervix during pregnancy". Molecular Human Reproduction. 3 (12): 1113–7. doi:10.1093/molehr/3.12.1113. PMID 9464857. 
  • Maeda K, Hägglund P, Finnie C, Svensson B, Henriksen A (November 2006). "Structural basis for target protein recognition by the protein disulfide reductase thioredoxin". Structure. 14 (11): 1701–10. doi:10.1016/j.str.2006.09.012. PMID 17098195. 

External links

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This is the Wikipedia entry entitled "Thioredoxin fold". More...

Thioredoxin fold Edit Wikipedia article

Thioredoxin
Thioredoxin-fold-1ert.png
One molecule of human thioredoxin (PDB ID 1ERT), a canonical example of the thioredoxin fold class.
Identifiers
Symbol Thioredoxin
Pfam PF00085
Pfam clan CL0172
InterPro IPR013766
PROSITE PDOC00172
SCOP 3trx
SUPERFAMILY 3trx
CDD cd01659

The thioredoxin fold is a protein fold common to enzymes that catalyze disulfide bond formation and isomerization. The fold is named for the canonical example thioredoxin and is found in both prokaryotic and eukaryotic proteins. It is an example of an alpha/beta protein fold that has oxidoreductase activity. The fold's spatial topology consists of a four-stranded antiparallel beta sheet sandwiched between three alpha helices. The strand topology is 2134 with 3 antiparallel to the rest.

Sequence conservation

Despite sequence variability in many regions of the fold, thioredoxin proteins share a common active site sequence with two reactive cysteine residues: Cys-X-Y-Cys, where X and Y are often but not necessarily hydrophobic amino acids. The reduced form of the protein contains two free thiol groups at the cysteine residues, whereas the oxidized form contains a disulfide bond between them.

Disulfide bond formation

Different thioredoxin fold-containing proteins vary greatly in their reactivity and in the pKa of their free thiols, which derives from the ability of the overall protein structure to stabilize the activated thiolate. Although the structure is fairly consistent among proteins containing the thioredoxin fold, the pKa is extremely sensitive to small variations in structure, especially in the placement of protein backbone atoms near the first cysteine.

Examples

Human proteins containing this domain include:

References

  • Creighton TE. (2000). Protein folding coupled to disulphide-bond formation. In Mechanisms of Protein Folding 2nd ed. Editor RH Pain. Oxford University Press.

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Thioredoxin Provide feedback

Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013766

Thioredoxins [PUBMED:3896121, PUBMED:2668278, PUBMED:7788289, PUBMED:7788290] are small disulphide-containing redox proteins that have been found in all the kingdoms of living organisms. Thioredoxin serves as a general protein disulphide oxidoreductase. It interacts with a broad range of proteins by a redox mechanism based on reversible oxidation of two cysteine thiol groups to a disulphide, accompanied by the transfer of two electrons and two protons. The net result is the covalent interconversion of a disulphide and a dithiol. In the NADPH-dependent protein disulphide reduction, thioredoxin reductase (TR) catalyses the reduction of oxidised thioredoxin (trx) by NADPH using FAD and its redox-active disulphide; reduced thioredoxin then directly reduces the disulphide in the substrate protein [PUBMED:3896121].

Thioredoxin is present in prokaryotes and eukaryotes and the sequence around the redox-active disulphide bond is well conserved. All thioredoxins contain a cis-proline located in a loop preceding beta-strand 4, which makes contact with the active site cysteines, and is important for stability and function [PUBMED:8590004]. Thioredoxin belongs to a structural family that includes glutaredoxin, glutathione peroxidase, bacterial protein disulphide isomerase DsbA, and the N-terminal domain of glutathione transferase [PUBMED:7788290]. Thioredoxins have a beta-alpha unit preceding the motif common to all these proteins.

A number of eukaryotic proteins contain domains evolutionary related to thioredoxin, most of them are protein disulphide isomerases (PDI). PDI (EC) [PUBMED:3371540, PUBMED:2537773, PUBMED:7940678] is an endoplasmic reticulum multi-functional enzyme that catalyses the formation and rearrangement of disulphide bonds during protein folding [PUBMED:7913469]. All PDI contains two or three (ERp72) copies of the thioredoxin domain, each of which contributes to disulphide isomerase activity, but which are functionally non-equivalent [PUBMED:7983029]. Moreover, PDI exhibits chaperone-like activity towards proteins that contain no disulphide bonds, i.e. behaving independently of its disulphide isomerase activity [PUBMED:7635143]. The various forms of PDI which are currently known are:

  • PDI major isozyme; a multifunctional protein that also function as the beta subunit of prolyl 4-hydroxylase (EC), as a component of oligosaccharyl transferase (EC), as thyroxine deiodinase (EC), as glutathione-insulin transhydrogenase (EC) and as a thyroid hormone-binding protein
  • ERp60 (ER-60; 58 Kd microsomal protein). ERp60 was originally thought to be a phosphoinositide-specific phospholipase C isozyme and later to be a protease.
  • ERp72.
  • ERp5.

Bacterial proteins that act as thiol:disulphide interchange proteins that allows disulphide bond formation in some periplasmic proteins also contain a thioredoxin domain. These proteins include:

This entry represents the thioredoxin domain.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Thioredoxin (CL0172), which has the following description:

This clan contains families related to the thioredoxin family. Thioredoxins are small enzymes that are involved in redox reactions via the reversible oxidation of an active centre disulfide bond. The thioredoxin fold consists of a 3 layer alpha/beta/alpha sandwich and a central beta sheet.

The clan contains the following 54 members:

2Fe-2S_thioredx AhpC-TSA AhpC-TSA_2 ArsC ArsD Calsequestrin DIM1 DSBA DUF1223 DUF1462 DUF1525 DUF1687 DUF2703 DUF2847 DUF4174 DUF836 DUF899 DUF953 ERp29_N GILT Glutaredoxin GSHPx GST_N GST_N_2 GST_N_3 GST_N_4 HyaE KaiB L51_S25_CI-B8 MRP-S23 MRP-S25 OST3_OST6 Phe_hydrox_dim Phosducin Rdx Redoxin SCO1-SenC SelP_N Sep15_SelM SH3BGR T4_deiodinase Thioredox_DsbH Thioredoxin Thioredoxin_2 Thioredoxin_3 Thioredoxin_4 Thioredoxin_5 Thioredoxin_6 Thioredoxin_7 Thioredoxin_8 Thioredoxin_9 Tom37 TraF YtfJ_HI0045

Alignments

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: thiored;
Type: Domain
Author: Sonnhammer ELL, Eddy SR
Number in seed: 37
Number in full: 34820
Average length of the domain: 101.90 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 43.23 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.1 22.1
Trusted cut-off 22.1 22.1
Noise cut-off 22.0 22.0
Model length: 104
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Tree controls

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The tree shows the occurrence of this domain across different species. More...

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Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There are 20 interactions for this family. More...

RHD_DNA_bind LMWPc DNA_pol_A FeThRed_B Thioredoxin_3 Evr1_Alr Pyr_redox Exo_endo_phos Kunitz_legume Thioredoxin_6 PAPS_reduct PMSR Redoxin Thioredoxin DnaJ Tubulin Thioredoxin_6 FeThRed_A DnaJ Pyr_redox_2

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Thioredoxin domain has been found. There are 509 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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