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.
670  structures 8874  species 0  interactions 73378  sequences 939  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
External IDsOMIM: 187700 MGI: 98874 HomoloGene: 128202 GeneCards: TXN
Gene location (Human)
Chromosome 9 (human)
Chr.Chromosome 9 (human)[1]
Chromosome 9 (human)
Genomic location for TXN
Genomic location for TXN
Band9q31.3Start110,243,810 bp[1]
End110,256,507 bp[1]
RNA expression pattern
PBB GE TXN 208864 s at fs.png
More reference expression data
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 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. They have also recently been found to play a role in cell-to-cell communication.[7]

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.[8][9]

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.[10]

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.[11] Thioredoxins act as electron donors to peroxidases and ribonucleotide reductase.[12] 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[13] — 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[14] 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.[16]

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.[7]

Mechanism of action

The primary function of Thioredoxin (Trx) is the reduction of oxidized cysteine residues and the cleavage of disulfide bonds.[17] 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.[18] 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.[18]

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).[29][30] 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,[31] into the nucleus.[32] Once in the nucleus, reduced HDAC4 downregulates the activity of transcription factors such as NFAT that mediate cardiac hypertrophy.[18] Trx 1 also controls microRNA levels in the heart and has been found to inhibit cardiac hypertrophy by upregulating miR-98/let-7.[33] Trx1 can regulate the expression level of SMYD1, thus may indirectly modulate protein methylation for purpose of cardiac protection.[34]

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. 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. 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. 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. ^ "Entrez Gene: TXN thioredoxin".
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H (August 2007). "Trends in oxidative aging theories". Free Radical Biology & Medicine. 43 (4): 477–503. doi:10.1016/j.freeradbiomed.2007.03.034. PMID 17640558.
  15. ^ 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. 1854 (12): 1816–1822. doi:10.1016/j.bbapap.2015.09.006. PMC 4721509. PMID 26410624.
  16. ^ 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. 1854 (12): 1816–1822. doi:10.1016/j.bbapap.2015.09.006. PMC 4721509. PMID 26410624.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ 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.
  24. ^ 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.
  25. ^ 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.
  26. ^ 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.
  27. ^ 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. doi:10.1073/pnas.94.8.3633. PMC 20492. PMID 9108029.
  28. ^ 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.
  29. ^ 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.
  30. ^ 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.
  31. ^ 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.
  32. ^ 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.
  33. ^ 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.
  34. ^ 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. 1854 (12): 1816–1822. doi:10.1016/j.bbapap.2015.09.006. PMC 4721509. PMID 26410624.

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 1852508. 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. doi:10.1002/j.1460-2075.1989.tb03436.x. PMC 400872. 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

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
SCOPe3trx / 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 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:

  • 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

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 63 members:

2Fe-2S_thioredx AhpC-TSA AhpC-TSA_2 ArsC ArsD Calsequestrin DIM1 DSBA DUF1223 DUF1462 DUF1525 DUF1687 DUF2703 DUF2847 DUF4174 DUF6436 DUF899 DUF953 ERp29_N GILT Glrx-like Glutaredoxin GSHPx GST_N GST_N_2 GST_N_3 GST_N_4 GST_N_5 HyaE KaiB L51_S25_CI-B8 MRP-S23 MRP-S25 OST3_OST6 Phe_hydrox_dim Phosducin QSOX_Trx1 Rdx Redoxin SCO1-SenC SelP_N Sep15_SelM SH3BGR T4_deiodinase Thioredox_DsbH Thioredoxin Thioredoxin_11 Thioredoxin_12 Thioredoxin_13 Thioredoxin_14 Thioredoxin_15 Thioredoxin_16 Thioredoxin_2 Thioredoxin_3 Thioredoxin_4 Thioredoxin_5 Thioredoxin_6 Thioredoxin_7 Thioredoxin_8 Thioredoxin_9 Tom37 TraF YtfJ_HI0045

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
(73378)
Representative proteomes UniProt
(211285)
RP15
(12541)
RP35
(34897)
RP55
(65469)
RP75
(97947)
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
(73378)
Representative proteomes UniProt
(211285)
RP15
(12541)
RP35
(34897)
RP55
(65469)
RP75
(97947)
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
(73378)
Representative proteomes UniProt
(211285)
RP15
(12541)
RP35
(34897)
RP55
(65469)
RP75
(97947)
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: 73378
Average length of the domain: 101.10 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 41.96 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -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: 22
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 670 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
A0A0R0ERR6 View 3D Structure Click here
A0A0R0GST5 View 3D Structure Click here
A0A0R0HDA3 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
A0A0R0JFJ6 View 3D Structure Click here
A0A0R0JK73 View 3D Structure Click here
A0A0R0JK73 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
A0A0R4IGN3 View 3D Structure Click here
A0A0R4IPV5 View 3D Structure Click here
A0A0R4IPV5 View 3D Structure Click here
A0A0R4IQE1 View 3D Structure Click here
A0A0R4IQE1 View 3D Structure Click here
A0A0R4J537 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
A0A1D6ERC1 View 3D Structure Click here
A0A1D6EWS4 View 3D Structure Click here
A0A1D6F5B9 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
A0A1D6I5N8 View 3D Structure Click here
A0A1D6ICL3 View 3D Structure Click here
A0A1D6ILW6 View 3D Structure Click here
A0A1D6IWC0 View 3D Structure Click here
A0A1D6J2L1 View 3D Structure Click here
A0A1D6JS39 View 3D Structure Click here
A0A1D6JZ22 View 3D Structure Click here
A0A1D6K5T9 View 3D Structure Click here
A0A1D6L636 View 3D Structure Click here
A0A1D6LH59 View 3D Structure Click here
A0A1D6LZ74 View 3D Structure Click here
A0A1D6LZ74 View 3D Structure Click here
A0A1D6M6M3 View 3D Structure Click here
A0A1D6MBW0 View 3D Structure Click here
A0A1D6MKP7 View 3D Structure Click here
A0A1D6NMA4 View 3D Structure Click here
A0A1D6P0H0 View 3D Structure Click here
A0A1D6PE55 View 3D Structure Click here
A0A1D6PSC0 View 3D Structure Click here
A0A1D6PSC0 View 3D Structure Click here
A0A1D6Q0H2 View 3D Structure Click here
A0A1D6QJW5 View 3D Structure Click here
A0A1D6QVF9 View 3D Structure Click here
A0A1D6QVF9 View 3D Structure Click here
A0A1D8PII5 View 3D Structure Click here
A0A1D8PJ36 View 3D Structure Click here
A0A1D8PJ36 View 3D Structure Click here
A0A1D8PLK0 View 3D Structure Click here
A0A1D8PNX4 View 3D Structure Click here
A0A1D8PR99 View 3D Structure Click here
A0A1D8PR99 View 3D Structure Click here
A0A1D8PU69 View 3D Structure Click here
A0A1L1SUL6 View 3D Structure Click here
A0A1P8AX25 View 3D Structure Click here
A0A2R8Q3R2 View 3D Structure Click here
A0A2R8QHZ9 View 3D Structure Click here
A0A2R8QUS4 View 3D Structure Click here
A0A2R8QUS4 View 3D Structure Click here
A0A368UI20 View 3D Structure Click here
A0A368UIF8 View 3D Structure Click here
A0A368UIF8 View 3D Structure Click here
A3KPF5 View 3D Structure Click here
A3KPF5 View 3D Structure Click here
A4HRE8 View 3D Structure Click here
A4HSZ7 View 3D Structure Click here
A4HT10 View 3D Structure Click here
A4I1Z8 View 3D Structure Click here
A4I1Z8 View 3D Structure Click here
A4I316 View 3D Structure Click here
A4I4K5 View 3D Structure Click here
A4I571 View 3D Structure Click here
A4I5D2 View 3D Structure Click here
A4I8Z4 View 3D Structure Click here
A4I9Z2 View 3D Structure Click here
A4IAT8 View 3D Structure Click here
A4IB19 View 3D Structure Click here
A4IB27 View 3D Structure Click here
A4ICD5 View 3D Structure Click here
A4ICD5 View 3D Structure Click here
A4IG45 View 3D Structure Click here
A4IG47 View 3D Structure Click here
A4IG47 View 3D Structure Click here
A4IG47 View 3D Structure Click here
A4IG47 View 3D Structure Click here
A8WG88 View 3D Structure Click here
A9CPA7 View 3D Structure Click here
A9CPA7 View 3D Structure Click here
B0S5S6 View 3D Structure Click here
B0S5S6 View 3D Structure Click here
B0S5S6 View 3D Structure Click here
B0UXN0 View 3D Structure Click here
B2RYB1 View 3D Structure Click here
B2RYB1 View 3D Structure Click here
B4F7S8 View 3D Structure Click here
B4F8Q0 View 3D Structure Click here
B4FB80 View 3D Structure Click here
B4FFQ0 View 3D Structure Click here
B4FH04 View 3D Structure Click here
B4FH44 View 3D Structure Click here
B4FQ54 View 3D Structure Click here
B4FRH1 View 3D Structure Click here
B4FSA2 View 3D Structure Click here
B4FSW8 View 3D Structure Click here
B4FTP2 View 3D Structure Click here
B4FV29 View 3D Structure Click here
B6SL60 View 3D Structure Click here
B6SNA1 View 3D Structure Click here
B6SRE1 View 3D Structure Click here
B6T2E4 View 3D Structure Click here
B6T9S0 View 3D Structure Click here
B6TFF1 View 3D Structure Click here
B6THR4 View 3D Structure Click here
B6TXH7 View 3D Structure Click here
B6TYJ4 View 3D Structure Click here
B6UHV8 View 3D Structure Click here
B8A5D4 View 3D Structure Click here
B8A5M6 View 3D Structure Click here
B8A5M6 View 3D Structure Click here
B9G893 View 3D Structure Click here
C0H4Y6 View 3D Structure Click here
C0H4Y6 View 3D Structure Click here
C0H561 View 3D Structure Click here
C0H5C4 View 3D Structure Click here
C0HF65 View 3D Structure Click here
C0P9S6 View 3D Structure Click here
C0PC75 View 3D Structure Click here
C4J0F5 View 3D Structure Click here
C6KXH6 View 3D Structure Click here
C6KXH6 View 3D Structure Click here
C6SVM5 View 3D Structure Click here
C6SVT5 View 3D Structure Click here
C6SWI0 View 3D Structure Click here
C6SXG3 View 3D Structure Click here
C6SYR6 View 3D Structure Click here
C6SZC0 View 3D Structure Click here
C6SZV5 View 3D Structure Click here
C6SZZ6 View 3D Structure Click here
C6T033 View 3D Structure Click here
C6T1N8 View 3D Structure Click here
C6T2B8 View 3D Structure Click here
C6T2G9 View 3D Structure Click here
C6T3W8 View 3D Structure Click here
C6T543 View 3D Structure Click here
C6T8H9 View 3D Structure Click here
C6T8M7 View 3D Structure Click here
C6TCR7 View 3D Structure Click here
C6TFD4 View 3D Structure Click here
C6TFV5 View 3D Structure Click here
C6TNF4 View 3D Structure Click here
C7G009 View 3D Structure Click here
C7G009 View 3D Structure Click here
C7G009 View 3D Structure Click here
D3Z6P0 View 3D Structure Click here
D3Z6P0 View 3D Structure Click here
D3ZGC8 View 3D Structure Click here
D3ZK65 View 3D Structure Click here
D3ZP13 View 3D Structure Click here
D3ZQK4 View 3D Structure Click here
D3ZZC1 View 3D Structure Click here
D3ZZC1 View 3D Structure Click here
D3ZZC1 View 3D Structure Click here
E1JGY6 View 3D Structure Click here
E1JGY6 View 3D Structure Click here
E7EZP8 View 3D Structure Click here
E7FC06 View 3D Structure Click here
F1Q6B4 View 3D Structure Click here
F1Q755 View 3D Structure Click here
F1QJL3 View 3D Structure Click here
F1QJZ7 View 3D Structure Click here
F1QP99 View 3D Structure Click here
F1QP99 View 3D Structure Click here
F1QTX8 View 3D Structure Click here
F1QTX8 View 3D Structure Click here
F1R184 View 3D Structure Click here
F1R184 View 3D Structure Click here
F1R184 View 3D Structure Click here
F4HPP4 View 3D Structure Click here
F4IXE4 View 3D Structure Click here
F4JQK2 View 3D Structure Click here
G3V912 View 3D Structure Click here
G5EC91 View 3D Structure Click here
G5ED07 View 3D Structure Click here
G5ED07 View 3D Structure Click here
G5EES9 View 3D Structure Click here
H2KZJ5 View 3D Structure Click here
H2KZY5 View 3D Structure Click here
I1J4B6 View 3D Structure Click here
I1J5J3 View 3D Structure Click here
I1J8Q1 View 3D Structure Click here
I1J932 View 3D Structure Click here
I1JBS4 View 3D Structure Click here
I1JBS5 View 3D Structure Click here
I1JD59 View 3D Structure Click here
I1JGA5 View 3D Structure Click here
I1JIH4 View 3D Structure Click here
I1JIH4 View 3D Structure Click here
I1JJZ5 View 3D Structure Click here
I1JR62 View 3D Structure Click here
I1JR62 View 3D Structure Click here
I1JT75 View 3D Structure Click here
I1JVD5 View 3D Structure Click here
I1JVD9 View 3D Structure Click here
I1JVG0 View 3D Structure Click here
I1JW39 View 3D Structure Click here
I1JYY2 View 3D Structure Click here
I1K367 View 3D Structure Click here
I1K7N6 View 3D Structure Click here
I1K7Z7 View 3D Structure Click here
I1KAB7 View 3D Structure Click here
I1KAB7 View 3D Structure Click here
I1KDL9 View 3D Structure Click here
I1KDX9 View 3D Structure Click here
I1KEE9 View 3D Structure Click here
I1KEH2 View 3D Structure Click here
I1KJV9 View 3D Structure Click here
I1KM08 View 3D Structure Click here
I1KNE4 View 3D Structure Click here
I1KQM0 View 3D Structure Click here
I1KRI6 View 3D Structure Click here
I1KXP4 View 3D Structure Click here
I1L0J8 View 3D Structure Click here
I1L605 View 3D Structure Click here
I1L7R5 View 3D Structure Click here
I1L7R5 View 3D Structure Click here
I1L9Y6 View 3D Structure Click here
I1LD87 View 3D Structure Click here
I1LEH0 View 3D Structure Click here
I1LEN2 View 3D Structure Click here
I1LL59 View 3D Structure Click here
I1LL59 View 3D Structure Click here
I1LLG1 View 3D Structure Click here
I1LQV6 View 3D Structure Click here
I1LQV6 View 3D Structure Click here
I1LUQ2 View 3D Structure Click here
I1LUZ9 View 3D Structure Click here
I1LV56 View 3D Structure Click here
I1LVZ4 View 3D Structure Click here
I1M0B5 View 3D Structure Click here
I1M319 View 3D Structure Click here
I1M393 View 3D Structure Click here
I1M3J6 View 3D Structure Click here
I1M3M3 View 3D Structure Click here
I1M4K9 View 3D Structure Click here
I1M4K9 View 3D Structure Click here
I1M5K0 View 3D Structure Click here
I1M5K0 View 3D Structure Click here
I1M877 View 3D Structure Click here
I1MAS5 View 3D Structure Click here
I1MC38 View 3D Structure Click here
I1MDN0 View 3D Structure Click here
I1MFI0 View 3D Structure Click here
I1MID5 View 3D Structure Click here
I1ML12 View 3D Structure Click here
I1ML39 View 3D Structure Click here
I1MQP4 View 3D Structure Click here
I1MXZ6 View 3D Structure Click here
I1N197 View 3D Structure Click here
I1N3A8 View 3D Structure Click here
I1N4A4 View 3D Structure Click here
I1N864 View 3D Structure Click here
I1N897 View 3D Structure Click here
I1NAB4 View 3D Structure Click here
I1NE04 View 3D Structure Click here
I1NF61 View 3D Structure Click here
I1NFT7 View 3D Structure Click here
I1NG02 View 3D Structure Click here
I1NI40 View 3D Structure Click here
I6Y8V2 View 3D Structure Click here
I7FST9 View 3D Structure Click here
I7FST9 View 3D Structure Click here
K7K8P4 View 3D Structure Click here
K7KFU2 View 3D Structure Click here
K7KHY6 View 3D Structure Click here
K7KKM8 View 3D Structure Click here
K7KUC7 View 3D Structure Click here
K7LFS6 View 3D Structure Click here
K7LIC7 View 3D Structure Click here
K7LLZ8 View 3D Structure Click here
K7LW63 View 3D Structure Click here
K7LX68 View 3D Structure Click here
K7LX68 View 3D Structure Click here
K7M6X1 View 3D Structure Click here
K7M6X1 View 3D Structure Click here
K7MUQ3 View 3D Structure Click here
K7MUQ5 View 3D Structure Click here
K7MYG8 View 3D Structure Click here
K7N3A5 View 3D Structure Click here
K7TV12 View 3D Structure Click here
K7TXW7 View 3D Structure Click here
K7TYW1 View 3D Structure Click here
K7UGI3 View 3D Structure Click here
K7V0C3 View 3D Structure Click here
K7VRQ5 View 3D Structure Click here
K7VRQ5 View 3D Structure Click here
K7VZE6 View 3D Structure Click here
L7N664 View 3D Structure Click here
M0R402 View 3D Structure Click here
M9PHK6 View 3D Structure Click here
O00391 View 3D Structure Click here
O13704 View 3D Structure Click here
O13811 View 3D Structure Click here
O13811 View 3D Structure Click here
O14095 View 3D Structure Click here
O14463 View 3D Structure Click here
O14530 View 3D Structure Click here
O22229 View 3D Structure Click here
O22263 View 3D Structure Click here
O22263 View 3D Structure Click here
O22779 View 3D Structure Click here
O23166 View 3D Structure Click here
O43396 View 3D Structure Click here
O44508 View 3D Structure Click here
O45017 View 3D Structure Click here
O48737 View 3D Structure Click here
O48773 View 3D Structure Click here
O48773 View 3D Structure Click here
O53161 View 3D Structure Click here
O64628 View 3D Structure Click here
O64654 View 3D Structure Click here
O64764 View 3D Structure Click here
O65541 View 3D Structure Click here
O74790 View 3D Structure Click here
O76003 View 3D Structure Click here
O76877 View 3D Structure Click here
O94504 View 3D Structure Click here
P04785 View 3D Structure Click here
P04785 View 3D Structure Click here
P07237 View 3D Structure Click here
P07237 View 3D Structure Click here
P08003 View 3D Structure Click here
P08003 View 3D Structure Click here
P08003 View 3D Structure Click here
P09103 View 3D Structure Click here
P09103 View 3D Structure Click here
P0AA25 View 3D Structure Click here
P0AGG4 View 3D Structure Click here
P10599 View 3D Structure Click here
P10639 View 3D Structure Click here
P11232 View 3D Structure Click here
P11598 View 3D Structure Click here
P11598 View 3D Structure Click here
P13667 View 3D Structure Click here
P13667 View 3D Structure Click here
P13667 View 3D Structure Click here
P17967 View 3D Structure Click here
P17967 View 3D Structure Click here
P22217 View 3D Structure Click here
P22803 View 3D Structure Click here
P25372 View 3D Structure Click here
P27773 View 3D Structure Click here
P27773 View 3D Structure Click here
P29447 View 3D Structure Click here
P29448 View 3D Structure Click here
P30101 View 3D Structure Click here
P30101 View 3D Structure Click here
P32474 View 3D Structure Click here
P32474 View 3D Structure Click here
P32642 View 3D Structure Click here
P34329 View 3D Structure Click here
P34329 View 3D Structure Click here
P34329 View 3D Structure Click here
P38659 View 3D Structure Click here
P38659 View 3D Structure Click here
P38659 View 3D Structure Click here
P40557 View 3D Structure Click here
P47938 View 3D Structure Click here
P52588 View 3D Structure Click here
P52588 View 3D Structure Click here
P54399 View 3D Structure Click here
P54399 View 3D Structure Click here
P77395 View 3D Structure Click here
P87178 View 3D Structure Click here
P87178 View 3D Structure Click here
P91442 View 3D Structure Click here
P92979 View 3D Structure Click here
P92980 View 3D Structure Click here
P92981 View 3D Structure Click here
P97493 View 3D Structure Click here
P97615 View 3D Structure Click here
P9WG61 View 3D Structure Click here
P9WG67 View 3D Structure Click here
Q03835 View 3D Structure Click here
Q09433 View 3D Structure Click here
Q0D840 View 3D Structure Click here
Q0DKF1 View 3D Structure Click here
Q0E0I1 View 3D Structure Click here
Q0IWL9 View 3D Structure Click here
Q0IWV7 View 3D Structure Click here
Q0J9V5 View 3D Structure Click here
Q0JD42 View 3D Structure Click here
Q0JL88 View 3D Structure Click here
Q10057 View 3D Structure Click here
Q10057 View 3D Structure Click here
Q10M18 View 3D Structure Click here
Q10N04 View 3D Structure Click here
Q11067 View 3D Structure Click here
Q11067 View 3D Structure Click here
Q11183 View 3D Structure Click here
Q12404 View 3D Structure Click here
Q13087 View 3D Structure Click here
Q13087 View 3D Structure Click here
Q14554 View 3D Structure Click here
Q14554 View 3D Structure Click here
Q14554 View 3D Structure Click here
Q15084 View 3D Structure Click here
Q15084 View 3D Structure Click here
Q17424 View 3D Structure Click here
Q17688 View 3D Structure Click here
Q17770 View 3D Structure Click here
Q17770 View 3D Structure Click here
Q17967 View 3D Structure Click here
Q17967 View 3D Structure Click here
Q18484 View 3D Structure Click here
Q18810 View 3D Structure Click here
Q1ECX9 View 3D Structure Click here
Q1ECX9 View 3D Structure Click here
Q1ECX9 View 3D Structure Click here
Q1ZXE0 View 3D Structure Click here
Q20063 View 3D Structure Click here
Q2FV89 View 3D Structure Click here
Q2FXI6 View 3D Structure Click here
Q2FZD2 View 3D Structure Click here
Q2FZZ3 View 3D Structure Click here
Q2G000 View 3D Structure Click here
Q2QP53 View 3D Structure Click here
Q2QTV8 View 3D Structure Click here
Q2R1U3 View 3D Structure Click here
Q304D5 View 3D Structure Click here
Q38879 View 3D Structure Click here
Q39239 View 3D Structure Click here
Q39241 View 3D Structure Click here
Q3TMX7 View 3D Structure Click here
Q3YMU0 View 3D Structure Click here
Q3YMU0 View 3D Structure Click here
Q41864 View 3D Structure Click here
Q42403 View 3D Structure Click here
Q498R3 View 3D Structure Click here
Q498R3 View 3D Structure Click here
Q498R3 View 3D Structure Click here
Q498R3 View 3D Structure Click here
Q4CMH3 View 3D Structure Click here
Q4CNS3 View 3D Structure Click here
Q4CT88 View 3D Structure Click here
Q4CT93 View 3D Structure Click here
Q4D004 View 3D Structure Click here
Q4D630 View 3D Structure Click here
Q4DBT9 View 3D Structure Click here
Q4DDZ3 View 3D Structure Click here
Q4DFA1 View 3D Structure Click here
Q4DFA5 View 3D Structure Click here
Q4DFA6 View 3D Structure Click here
Q4DFA6 View 3D Structure Click here
Q4DG09 View 3D Structure Click here
Q4DIE2 View 3D Structure Click here
Q4DJ25 View 3D Structure Click here
Q4DM29 View 3D Structure Click here
Q4DP22 View 3D Structure Click here
Q4DPR6 View 3D Structure Click here
Q4DPX5 View 3D Structure Click here
Q4DQI9 View 3D Structure Click here
Q4DRM3 View 3D Structure Click here
Q4DT48 View 3D Structure Click here
Q4DTS6 View 3D Structure Click here
Q4DUG9 View 3D Structure Click here
Q4DV70 View 3D Structure Click here
Q4DV71 View 3D Structure Click here
Q4E0T5 View 3D Structure Click here
Q4E156 View 3D Structure Click here
Q4E252 View 3D Structure Click here
Q4E3F7 View 3D Structure Click here
Q4E3F7 View 3D Structure Click here
Q4E5B1 View 3D Structure Click here
Q4VWQ3 View 3D Structure Click here
Q52KJ9 View 3D Structure Click here
Q53LQ0 View 3D Structure Click here
Q53LQ0 View 3D Structure Click here
Q54BW3 View 3D Structure Click here
Q54CF5 View 3D Structure Click here
Q54EN4 View 3D Structure Click here
Q54EN4 View 3D Structure Click here
Q54IQ1 View 3D Structure Click here
Q54KN7 View 3D Structure Click here
Q54LV2 View 3D Structure Click here
Q54NX2 View 3D Structure Click here
Q54NX3 View 3D Structure Click here
Q54QZ6 View 3D Structure Click here
Q54UW6 View 3D Structure Click here
Q54UW6 View 3D Structure Click here
Q550H9 View 3D Structure Click here
Q55FU1 View 3D Structure Click here
Q5A1L9 View 3D Structure Click here
Q5A915 View 3D Structure Click here
Q5AF81 View 3D Structure Click here
Q5BJT4 View 3D Structure Click here
Q5DJV7 View 3D Structure Click here
Q5EUC1 View 3D Structure Click here
Q5EUC2 View 3D Structure Click here
Q5EUC5 View 3D Structure Click here
Q5EUC6 View 3D Structure Click here
Q5EUC7 View 3D Structure Click here
Q5EUD1 View 3D Structure Click here
Q5EUD2 View 3D Structure Click here
Q5EUD7 View 3D Structure Click here
Q5EUD7 View 3D Structure Click here
Q5EUD8 View 3D Structure Click here
Q5EUD8 View 3D Structure Click here
Q5FVM7 View 3D Structure Click here
Q5I0H9 View 3D Structure Click here
Q5I0H9 View 3D Structure Click here
Q5I0H9 View 3D Structure Click here
Q5JMR9 View 3D Structure Click here
Q5QNE5 View 3D Structure Click here
Q5TKD8 View 3D Structure Click here
Q5VLR5 View 3D Structure Click here
Q5WA72 View 3D Structure Click here
Q5WA72 View 3D Structure Click here
Q5XHX6 View 3D Structure Click here
Q5XI02 View 3D Structure Click here
Q5XIK2 View 3D Structure Click here
Q5XJ54 View 3D Structure Click here
Q60EF8 View 3D Structure Click here
Q63081 View 3D Structure Click here
Q63081 View 3D Structure Click here
Q653R4 View 3D Structure Click here
Q655X0 View 3D Structure Click here
Q66GQ3 View 3D Structure Click here
Q66GQ3 View 3D Structure Click here
Q67IX6 View 3D Structure Click here
Q67IX6 View 3D Structure Click here
Q67UF5 View 3D Structure Click here
Q67UF5 View 3D Structure Click here
Q67VZ8 View 3D Structure Click here
Q69AB1 View 3D Structure Click here
Q69AB2 View 3D Structure Click here
Q69SA9 View 3D Structure Click here
Q69ST6 View 3D Structure Click here
Q69ST6 View 3D Structure Click here
Q6A555 View 3D Structure Click here
Q6AUC6 View 3D Structure Click here
Q6DGI6 View 3D Structure Click here
Q6ES52 View 3D Structure Click here
Q6H7E4 View 3D Structure Click here
Q6IQC7 View 3D Structure Click here
Q6IUU3 View 3D Structure Click here
Q6K9R2 View 3D Structure Click here
Q6NPF9 View 3D Structure Click here
Q6NPL9 View 3D Structure Click here
Q6P131 View 3D Structure Click here
Q6P3G9 View 3D Structure Click here
Q6P6J9 View 3D Structure Click here
Q6P902 View 3D Structure Click here
Q6PKC3 View 3D Structure Click here
Q6PKC3 View 3D Structure Click here
Q6YTI3 View 3D Structure Click here
Q6YW09 View 3D Structure Click here
Q6Z4A7 View 3D Structure Click here
Q6Z4I3 View 3D Structure Click here
Q6Z4N3 View 3D Structure Click here
Q6Z7L3 View 3D Structure Click here
Q6ZRP7 View 3D Structure Click here
Q70G58 View 3D Structure Click here
Q715S9 View 3D Structure Click here
Q715T0 View 3D Structure Click here
Q71A37 View 3D Structure Click here
Q75GM1 View 3D Structure Click here
Q75JM6 View 3D Structure Click here
Q75M08 View 3D Structure Click here
Q75M08 View 3D Structure Click here
Q7JQR3 View 3D Structure Click here
Q7JW12 View 3D Structure Click here
Q7K037 View 3D Structure Click here
Q7PLG1 View 3D Structure Click here
Q7TN22 View 3D Structure Click here
Q7X8R5 View 3D Structure Click here
Q7XKD0 View 3D Structure Click here
Q7XQQ2 View 3D Structure Click here
Q7XRB5 View 3D Structure Click here
Q7XRB5 View 3D Structure Click here
Q7XSQ7 View 3D Structure Click here
Q7Y0D4 View 3D Structure Click here
Q7ZUI4 View 3D Structure Click here
Q7ZVX9 View 3D Structure Click here
Q80TN4 View 3D Structure Click here
Q84JR9 View 3D Structure Click here
Q84M47 View 3D Structure Click here
Q84NN4 View 3D Structure Click here
Q84NN4 View 3D Structure Click here
Q84P95 View 3D Structure Click here
Q851R5 View 3D Structure Click here
Q869Q9 View 3D Structure Click here
Q869Q9 View 3D Structure Click here
Q869Z0 View 3D Structure Click here
Q86H62 View 3D Structure Click here
Q86HI2 View 3D Structure Click here
Q86IA3 View 3D Structure Click here
Q86IA3 View 3D Structure Click here
Q86VQ3 View 3D Structure Click here
Q86XW9 View 3D Structure Click here
Q8BND5 View 3D Structure Click here
Q8BXZ1 View 3D Structure Click here
Q8C0L0 View 3D Structure Click here
Q8CDN6 View 3D Structure Click here
Q8GXV2 View 3D Structure Click here
Q8GYD1 View 3D Structure Click here
Q8H2V6 View 3D Structure Click here
Q8H6X5 View 3D Structure Click here
Q8I2V9 View 3D Structure Click here
Q8I2V9 View 3D Structure Click here
Q8IB72 View 3D Structure Click here
Q8IBS1 View 3D Structure Click here
Q8IDH5 View 3D Structure Click here
Q8IDP4 View 3D Structure Click here
Q8IFW4 View 3D Structure Click here
Q8II23 View 3D Structure Click here
Q8II23 View 3D Structure Click here
Q8II88 View 3D Structure Click here
Q8IIR6 View 3D Structure Click here
Q8IIV8 View 3D Structure Click here
Q8IJX5 View 3D Structure Click here
Q8IKB2 View 3D Structure Click here
Q8IKL4 View 3D Structure Click here
Q8IMY4 View 3D Structure Click here
Q8IXB1 View 3D Structure Click here
Q8IXB1 View 3D Structure Click here
Q8IXB1 View 3D Structure Click here
Q8IXB1 View 3D Structure Click here
Q8K2W3 View 3D Structure Click here
Q8K2W3 View 3D Structure Click here
Q8K581 View 3D Structure Click here
Q8L7S9 View 3D Structure Click here
Q8LCH9 View 3D Structure Click here
Q8LCT3 View 3D Structure Click here
Q8LCV1 View 3D Structure Click here
Q8LD49 View 3D Structure Click here
Q8LDI5 View 3D Structure Click here
Q8LEK4 View 3D Structure Click here
Q8N427 View 3D Structure Click here
Q8N807 View 3D Structure Click here
Q8N807 View 3D Structure Click here
Q8NBS9 View 3D Structure Click here
Q8NBS9 View 3D Structure Click here
Q8NBS9 View 3D Structure Click here
Q8S091 View 3D Structure Click here
Q8VBT0 View 3D Structure Click here
Q8VWG7 View 3D Structure Click here
Q8VX13 View 3D Structure Click here
Q8VX13 View 3D Structure Click here
Q8VZT6 View 3D Structure Click here
Q8W1A1 View 3D Structure Click here
Q8W4J3 View 3D Structure Click here
Q90WA5 View 3D Structure Click here
Q90WA5 View 3D Structure Click here
Q91W90 View 3D Structure Click here
Q91W90 View 3D Structure Click here
Q91W90 View 3D Structure Click here
Q920J4 View 3D Structure Click here
Q921X9 View 3D Structure Click here
Q921X9 View 3D Structure Click here
Q921X9 View 3D Structure Click here
Q922R8 View 3D Structure Click here
Q922R8 View 3D Structure Click here
Q93VQ9 View 3D Structure Click here
Q93YX4 View 3D Structure Click here
Q942L2 View 3D Structure Click here
Q942L2 View 3D Structure Click here
Q94F09 View 3D Structure Click here
Q95QQ1 View 3D Structure Click here
Q95TL8 View 3D Structure Click here
Q961B9 View 3D Structure Click here
Q96J42 View 3D Structure Click here
Q96JJ7 View 3D Structure Click here
Q99316 View 3D Structure Click here
Q99757 View 3D Structure Click here
Q9AS75 View 3D Structure Click here
Q9BS26 View 3D Structure Click here
Q9C5C5 View 3D Structure Click here
Q9C9Y6 View 3D Structure Click here
Q9CAS1 View 3D Structure Click here
Q9CQ79 View 3D Structure Click here
Q9CQM9 View 3D Structure Click here
Q9D1Q6 View 3D Structure Click here
Q9D710 View 3D Structure Click here
Q9DAN1 View 3D Structure Click here
Q9DC23 View 3D Structure Click here
Q9DC23 View 3D Structure Click here
Q9DC23 View 3D Structure Click here
Q9DC23 View 3D Structure Click here
Q9FF55 View 3D Structure Click here
Q9FF55 View 3D Structure Click here
Q9FG36 View 3D Structure Click here
Q9FNG5 View 3D Structure Click here
Q9GUG7 View 3D Structure Click here
Q9H1E5 View 3D Structure Click here
Q9H3N1 View 3D Structure Click here
Q9JLZ1 View 3D Structure Click here
Q9LJU2 View 3D Structure Click here
Q9LSU4 View 3D Structure Click here
Q9LXZ8 View 3D Structure Click here
Q9M7X9 View 3D Structure Click here
Q9MAH1 View 3D Structure Click here
Q9MAU6 View 3D Structure Click here
Q9MAU6 View 3D Structure Click here
Q9N357 View 3D Structure Click here
Q9N4L6 View 3D Structure Click here
Q9P2K2 View 3D Structure Click here
Q9P4X1 View 3D Structure Click here
Q9SA00 View 3D Structure Click here
Q9SEU6 View 3D Structure Click here
Q9SEU7 View 3D Structure Click here
Q9SEU8 View 3D Structure Click here
Q9SGS4 View 3D Structure Click here
Q9SGS4 View 3D Structure Click here
Q9SIN1 View 3D Structure Click here
Q9SRG3 View 3D Structure Click here
Q9SRG3 View 3D Structure Click here
Q9T042 View 3D Structure Click here
Q9TW67 View 3D Structure Click here
Q9TXY8 View 3D Structure Click here
Q9USR1 View 3D Structure Click here
Q9V429 View 3D Structure Click here
Q9V438 View 3D Structure Click here
Q9V438 View 3D Structure Click here
Q9VD61 View 3D Structure Click here
Q9VD62 View 3D Structure Click here
Q9VI96 View 3D Structure Click here
Q9VJZ1 View 3D Structure Click here
Q9VJZ1 View 3D Structure Click here
Q9VJZ1 View 3D Structure Click here
Q9VJZ6 View 3D Structure Click here
Q9VQ17 View 3D Structure Click here
Q9VRP3 View 3D Structure Click here
Q9VUG9 View 3D Structure Click here
Q9VYV3 View 3D Structure Click here
Q9VYV3 View 3D Structure Click here
Q9VYV3 View 3D Structure Click here
Q9W022 View 3D Structure Click here
Q9XFH8 View 3D Structure Click here
Q9XFH9 View 3D Structure Click here
Q9XFI1 View 3D Structure Click here
Q9XI01 View 3D Structure Click here
Q9XI01 View 3D Structure Click here
Q9XIF4 View 3D Structure Click here
Q9XTU8 View 3D Structure Click here
Q9XTU8 View 3D Structure Click here
Q9XWE1 View 3D Structure Click here
Q9XWE1 View 3D Structure Click here
Q9XWE1 View 3D Structure Click here
Q9XWE1 View 3D Structure Click here
Q9Y2G8 View 3D Structure Click here
Q9Y320 View 3D Structure Click here
Q9ZP20 View 3D Structure Click here
Q9ZPE9 View 3D Structure Click here
Q9ZPH2 View 3D Structure Click here
Q9ZU40 View 3D Structure Click here