Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
676  structures 9088  species 0  interactions 80736  sequences 970  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
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTXN, TRDX, TRX, TRX1, thioredoxin, Trx80
External IDsOMIM: 187700 MGI: 98874 HomoloGene: 128202 GeneCards: TXN
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003329
NM_001244938

NM_011660

RefSeq (protein)

NP_001231867
NP_003320

NP_035790

Location (UCSC)Chr 9: 110.24 – 110.26 MbChr 4: 57.94 – 57.96 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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.[5][6] 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 is 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. Thioredoxins play a role in cell-to-cell communication.[7]

Occurrence

They are found in nearly all known organisms and are essential for life in mammals.[8][9]

Function

The primary function of Thioredoxin (Trx) is the reduction of oxidized cysteine residues and the cleavage of disulfide bonds.[10] 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.[11] The thioredoxins are maintained in their reduced state by the flavoenzyme thioredoxin reductase, in a NADPH-dependent reaction.[12] Thioredoxins act as electron donors to peroxidases and ribonucleotide reductase.[13] The related glutaredoxins share many of the functions of thioredoxins, but are reduced by glutathione rather than a specific reductase.

Structure and mechanism

Thioredoxin is a 12-kD oxidoreductase protein. Thioredoxin proteins also have a characteristic tertiary structure termed the thioredoxin fold. The active site contains a dithiols in a CXXC motif. These two cysteines are the key to the ability of thioredoxin to reduce other proteins.

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

Trx1 can regulate non-redox post-translational modifications.[15] In the mice with cardiac-specific overexpression of Trx1, the proteomics study found that SET and MYND domain-containing protein 1 (SMYD1), a lysine methyltransferase highly expressed in cardiac and other muscle tissues, is also upregulated. This suggests that Trx1 may also play an role in protein methylation via regulating SMYD1 expression, which is independent of its oxidoreductase activity.[15]

Plants have an unusually complex complement of Trx's composed of six well-defined types (Trxs f, m, x, y, h, and o) that reside in diverse cell compartments and function in an array of processes. Thioredoxin proteins move from cell to cell, representing a novel form of cellular communication in plants.[7]

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).[26][27] 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,[28] into the nucleus.[29] 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.[30] Trx1 can regulate the expression level of SMYD1, thus may indirectly modulate protein methylation for purpose of cardiac protection.[15]

Thioredoxin in skin care

Thioredoxin is used in skin care products as an antioxidant in conjunction with glutaredoxin and glutathione.[citation needed]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000136810 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028367 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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. doi:10.1016/S0021-9258(19)37617-3. PMID 3170595.
  6. ^ "Entrez Gene: TXN2 thioredoxin 2".
  7. ^ 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. Bibcode:2010PNAS..107.3900M. doi:10.1073/pnas.0913759107. PMC 2840455. PMID 20133584.
  8. ^ Holmgren A (August 1989). "Thioredoxin and glutaredoxin systems" (PDF). The Journal of Biological Chemistry. 264 (24): 13963–6. doi:10.1016/S0021-9258(18)71625-6. PMID 2668278.
  9. ^ 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.
  10. ^ 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.
  11. ^ "Entrez Gene: TXN thioredoxin".
  12. ^ Mustacich D, Powis G (February 2000). "Thioredoxin reductase". The Biochemical Journal. 346 (1): 1–8. doi:10.1042/0264-6021:3460001. PMC 1220815. PMID 10657232.
  13. ^ 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.
  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. 109: 125–131. doi:10.1016/j.freeradbiomed.2016.12.020. PMC 5462876. PMID 27993729.
  15. ^ a b c Liu T, Wu C, Jain MR, Nagarajan N, Yan L, Dai H, Cui C, Baykal A, Pan S, Ago T, Sadoshima J, Li H (December 2015). "Master redox regulator Trx1 upregulates SMYD1 & modulates lysine methylation". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1854 (12): 1816–1822. doi:10.1016/j.bbapap.2015.09.006. PMC 4721509. PMID 26410624.
  16. ^ 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.
  17. ^ 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 125685. PMID 11689443.
  18. ^ 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 1170601. PMID 9564042.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ 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. doi:10.1093/nar/20.15.3821. PMC 334054. PMID 1508666.
  24. ^ 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. Bibcode:1997PNAS...94.3633H. doi:10.1073/pnas.94.8.3633. PMC 20492. PMID 9108029.
  25. ^ 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 3937768. PMID 24506865.
  26. ^ Ago T, Yeh I, Yamamoto M, Schinke-Braun M, Brown JA, Tian B, Sadoshima J (2006). "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.
  27. ^ 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 228400. PMID 14597765.
  28. ^ 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 3574183. PMID 23271793.
  29. ^ 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. S2CID 2678474.
  30. ^ 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 3249645. PMID 21183740.

Further reading

External links

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

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

Thioredoxin domain Edit Wikipedia article

Thioredoxin
Identifiers
SymbolThioredoxin
PfamPF00085
InterProIPR013766
PROSITEPDOC00172
SCOP23trx / SCOPe / SUPFAM
CDDcd01659
Membranome337

Thioredoxins[1][2][3][4] are small disulfide-containing redox proteins that have been found in all the kingdoms of living organisms. Thioredoxin serves as a general protein disulfide oxidoreductase. It interacts with a broad range of proteins by a redox mechanism based on reversible oxidation of 2 cysteine thiol groups to a disulfide, accompanied by the transfer of 2 electrons and 2 protons. The net result is the covalent interconversion of a disulfide and a dithiol.

TR-S2 + NADPH + H+ -> TR-(SH)2 + NADP+ (1)

trx-S2 + TR-(SH)2 -> trx-(SH)2 + TR-S2 (2)

Protein-S2 + trx-(SH)2 -> Protein-(SH)2 + trx-S2 (3)

In the NADPH-dependent protein disulfide reduction, thioredoxin reductase (TR) catalyses reduction of oxidised thioredoxin (trx) by NADPH using FAD and its redox-active disulfide (steps 1 and 2). Reduced thioredoxin then directly reduces the disulfide in the substrate protein (step 3).[1]

Protein disulfide isomerase (PDI), a resident foldase of the endoplasmic recticulum, is a multi-functional protein that catalyses the formation and isomerisation of disulfide bonds during protein folding.[5][6] PDI contains 2 redox active domains, near the N- and C-termini, that are similar to thioredoxin: both contribute to disulfide isomerase activity, but are functionally non-equivalent.[6] A mutant PDI, with all 4 of the active cysteines replaced by serine, displays a low but detectable level of disulfide isomerase activity.[6] Moreover, PDI exhibits chaperone-like activity towards proteins that contain no disulfide bonds, i.e. behaving independently of its disulfide isomerase activity.[7]

A number of endoplasmic reticulum proteins that differ from the PDI major isozyme contain 2 (ERp60, ERp5) or 3 (ERp72[8]) thioredoxin domains; all of them seem to be PDIs. 3D-structures have been determined for a number of thioredoxins.[9] The molecule has a doubly wound alternating alpha/beta fold, consisting of a 5-stranded parallel beta-sheet core, enclosed by 4 alpha-helices. The active site disulfide is located at the N-terminus of helix 2 in a short segment that is separated from the rest of the helix by a kink caused by a conserved proline. The 4-membered disulfide ring is located on the surface of the protein. A flat hydrophobic surface lies adjacent to the disulfide, which presumably facilitates interaction with other proteins.

One invariant feature of all thioredoxins is a cis-proline located in a loop preceding beta-strand 4. This residue is positioned in van der Waals contact with the active site cysteines and is important both for stability and function.[9] Thioredoxin belongs to a structural family that includes glutaredoxin, glutathione peroxidase, bacterial protein disulfide isomerase DsbA, and the N-terminal domain of glutathione transferase.[4] Thioredoxins have a beta-alpha unit preceding the motif common to all these proteins.

Human proteins containing thioredoxin domain

DNAJC10; ERP70; GLRX3; P4HB; PDIA2; PDIA3; PDIA4; PDIA5; PDIA6; PDILT; PDIP; QSOX1; QSOX2; STRF8; TXN; TXN2; TXNDC1; TXNDC10; TXNDC11; TXNDC13; TXNDC14; TXNDC15; TXNDC16; TXNDC2; TXNDC3; TXNDC4; TXNDC5; TXNDC6; TXNDC8; TXNL1; TXNL3;

References

  1. ^ a b Holmgren A (1985). "Thioredoxin". Annu. Rev. Biochem. 54: 237–271. doi:10.1146/annurev.bi.54.070185.001321. PMID 3896121.
  2. ^ Holmgren A (1989). "Thioredoxin and glutaredoxin systems". J. Biol. Chem. 264 (24): 13963–13966. PMID 2668278.
  3. ^ Holmgren A (1995). "Thioredoxin structure and mechanism: conformational changes on oxidation of the active-site sulfhydryls to a disulfide". Structure. 3 (3): 239–243. doi:10.1016/s0969-2126(01)00153-8. PMID 7788289.
  4. ^ a b Martin JL (1995). "Thioredoxin--a fold for all reasons". Structure. 3 (3): 245–250. doi:10.1016/S0969-2126(01)00154-X. PMID 7788290.
  5. ^ Puig A, Lyles MM, Noiva R, Gilbert HF (1994). "The role of the thiol/disulfide centers and peptide binding site in the chaperone and anti-chaperone activities of protein disulfide isomerase". J. Biol. Chem. 269 (29): 19128–19135. PMID 7913469.
  6. ^ a b c Lyles MM, Gilbert HF (1994). "Mutations in the thioredoxin sites of protein disulfide isomerase reveal functional nonequivalence of the N- and C-terminal domains". J. Biol. Chem. 269 (49): 30946–30952. PMID 7983029.
  7. ^ Wang CC, Song JL (1995). "Chaperone-like activity of protein disulfide-isomerase in the refolding of rhodanese". Eur. J. Biochem. 231 (2): 312–316. doi:10.1111/j.1432-1033.1995.tb20702.x. PMID 7635143.
  8. ^ Mazzarella RA, Srinivasan M, Haugejorden SM, Green M (1990). "ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase". J. Biol. Chem. 265 (2): 1094–1101. PMID 2295602.
  9. ^ a b Gleason FK, Eklund H, Saarinen M (1995). "Crystal structure of thioredoxin-2 from Anabaena". Structure. 3 (10): 1097–1108. doi:10.1016/s0969-2126(01)00245-3. PMID 8590004.
This article incorporates text from the public domain Pfam and InterPro: IPR013766

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

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
SymbolThioredoxin, Trx
PfamPF00085
Pfam clanCL0172
InterProIPR013766
PROSITEPDOC00172
SCOP23trx / SCOPe / SUPFAM
CDDcd01659
Membranome337
Thioredoxin
Identifiers
SymbolTrx
Membranome260

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 Pain RH (ed.). Mechanisms of Protein Folding (2nd ed.). 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:

  • Escherichia coli DsbA (or PrfA) and its orthologs in Vibrio cholerae (TtcpG) and Haemophilus influenzae (Por).
  • E. coli DsbC (or XpRA) and its orthologues in Erwinia chrysanthemi and H. influenzae.
  • E. coli DsbD (or DipZ) and its H. influenzae orthologue.
  • E. coli DsbE (or CcmG) and orthologues in H. influenzae.
  • Rhodobacter capsulatus (Rhodopseudomonas capsulata) (HelX), Rhiziobiacae (CycY and TlpA).

This entry represents the thioredoxin domain.

Domain organisation

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

Loading domain graphics...

Pfam Clan

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(34)
Full
(80736)
Representative proteomes UniProt
(219851)
RP15
(14392)
RP35
(37473)
RP55
(70868)
RP75
(106116)
Jalview View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(34)
Full
(80736)
Representative proteomes UniProt
(219851)
RP15
(14392)
RP35
(37473)
RP55
(70868)
RP75
(106116)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(34)
Full
(80736)
Representative proteomes UniProt
(219851)
RP15
(14392)
RP35
(37473)
RP55
(70868)
RP75
(106116)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

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
Sequence Ontology: SO:0000417
Author: Sonnhammer ELL , Eddy SR
Number in seed: 34
Number in full: 80736
Average length of the domain: 101.20 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 41.25 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.5 23.5
Trusted cut-off 23.5 23.5
Noise cut-off 23.4 23.4
Model length: 103
Family (HMM) version: 23
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

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

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

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...

Loading sunburst data...

Tree controls

Hide

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

Loading...

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.

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 676 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 sequence.

Loading structure mapping...

AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A096QB26 View 3D Structure Click here
A0A0B4LHC9 View 3D Structure Click here
A0A0P0VTI6 View 3D Structure Click here
A0A0P0Y945 View 3D Structure Click here
A0A0R0ERR6 View 3D Structure Click here
A0A0R0GST5 View 3D Structure Click here
A0A0R0HDA3 View 3D Structure Click here
A0A0R0HFK6 View 3D Structure Click here
A0A0R0HHA4 View 3D Structure Click here
A0A0R0HJB6 View 3D Structure Click here
A0A0R0ID39 View 3D Structure Click here
A0A0R0IHU4 View 3D Structure Click here
A0A0R0JFJ6 View 3D Structure Click here
A0A0R0JK73 View 3D Structure Click here
A0A0R0K134 View 3D Structure Click here
A0A0R0KCB6 View 3D Structure Click here
A0A0R4IGN3 View 3D Structure Click here
A0A0R4IPV5 View 3D Structure Click here
A0A0R4IQE1 View 3D Structure Click here
A0A0R4J537 View 3D Structure Click here
A0A144A4E0 View 3D Structure Click here
A0A1D6E3G4 View 3D Structure Click here
A0A1D6EAJ9 View 3D Structure Click here
A0A1D6EAQ4 View 3D Structure Click here
A0A1D6ERC1 View 3D Structure Click here
A0A1D6EWS4 View 3D Structure Click here
A0A1D6F5B9 View 3D Structure Click here
A0A1D6FKX0 View 3D Structure Click here
A0A1D6FLB1 View 3D Structure Click here
A0A1D6GUH5 View 3D Structure Click here
A0A1D6H3L5 View 3D Structure Click here
A0A1D6H544 View 3D Structure Click here
A0A1D6HAA2 View 3D Structure Click here
A0A1D6HB10 View 3D Structure Click here
A0A1D6HLS2 View 3D Structure Click here
A0A1D6HPP0 View 3D Structure Click here
A0A1D6I5N8 View 3D Structure Click here
A0A1D6ICL3 View 3D Structure Click here
A0A1D6ILW6 View 3D Structure Click here
A0A1D6IWC0 View 3D Structure Click here