Thioredoxin domain
Encyclopedia
Thioredoxins 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).
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. 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. Interestingly, a mutant PDI, with all 4 of the active cysteines replaced by serine, displays a low but detectable level of disulfide isomerase activity. Moreover, PDI exhibits chaperone-like activity towards proteins that contain no disulfide bonds, i.e. behaving independently of its disulfide isomerase activity.
A number of endoplasmic reticulum proteins that differ from the PDI major isozyme contain 2 (ERp60, ERp5) or 3 (ERp72) thioredoxin domains; all of them seem to be PDIs. 3D-structures have been determined for a number of thioredoxins. 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. Thioredoxin belongs to a structural family that includes glutaredoxin, glutathione peroxidase, bacterial protein disulfide isomerase DsbA, and the N-terminal domain of glutathione transferase. Thioredoxins have a beta-alpha unit preceding the motif common to all these proteins.
; ERP70; GLRX3
; P4HB
; P5
; 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;
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).
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. 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. Interestingly, a mutant PDI, with all 4 of the active cysteines replaced by serine, displays a low but detectable level of disulfide isomerase activity. Moreover, PDI exhibits chaperone-like activity towards proteins that contain no disulfide bonds, i.e. behaving independently of its disulfide isomerase activity.
A number of endoplasmic reticulum proteins that differ from the PDI major isozyme contain 2 (ERp60, ERp5) or 3 (ERp72) thioredoxin domains; all of them seem to be PDIs. 3D-structures have been determined for a number of thioredoxins. 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. Thioredoxin belongs to a structural family that includes glutaredoxin, glutathione peroxidase, bacterial protein disulfide isomerase DsbA, and the N-terminal domain of glutathione transferase. Thioredoxins have a beta-alpha unit preceding the motif common to all these proteins.
Human proteins containing thioredoxin domain
DNAJC10DNAJC10
DnaJ homolog subfamily C member 10 is a protein that in humans is encoded by the DNAJC10 gene.-Further reading:...
; ERP70; GLRX3
GLRX3
Glutaredoxin-3 is a protein that in humans is encoded by the GLRX3 gene.-Further reading:...
; P4HB
P4HB
Protein disulfide-isomerase is an enzyme that in humans is encoded by the P4HB gene.-Interactions:P4HB has been shown to interact with UBQLN1, ERO1LB and ERO1L.-Further reading:...
; P5
P5
P5 may refer to:Transportation* P-5 Hawk, a 1923 aircraft* Martin P5M Marlin, flying boat* Rover P5, series was a group of saloon and coupé automobiles produced from 1958 until 1973...
; PDIA2; PDIA3
PDIA3
Protein disulfide isomerase family A, member 3 also known as glucose-regulated protein, 58-kD is an isomerase enzyme.-Function:The PDIA3 protein has protein disulfide isomerase activity...
; PDIA4;
PDIA5; PDIA6; PDILT; PDIP; QSOX1
QSOX1
Sulfhydryl oxidase 1 is an enzyme that in humans is encoded by the QSOX1 gene.-Further reading:...
; QSOX2; STRF8; TXN
TXN
- TV Tokyo Network stations :-External links:*...
;
TXN2
TXN2
Thioredoxin, mitochondrial is a protein that in humans is encoded by the TXN2 gene.-Further reading:...
; TXNDC1
TXNDC1
Thioredoxin-related transmembrane protein 1 is a protein that in humans is encoded by the TMX1 gene.-Further reading:...
; TXNDC10
TXNDC10
Protein disulfide-isomerase TMX3 is an enzyme that in humans is encoded by the TMX3 gene.-Further reading:...
; TXNDC11; TXNDC13
TXNDC13
Thioredoxin-related transmembrane protein 4 also known as thioredoxin domain-containing protein 13 is a protein that in humans is encoded by the TMX4 gene....
; TXNDC14; TXNDC15; TXNDC16;
TXNDC2
TXNDC2
Thioredoxin domain-containing protein 2 is a protein that in humans is encoded by the TXNDC2 gene.-Further reading:...
; TXNDC3
TXNDC3
Thioredoxin domain-containing protein 3 , also known as spermatid-specific thioredoxin-2 , is a protein that in humans is encoded by the TXNDC3 gene.- Function :...
; TXNDC4
TXNDC4
Endoplasmic reticulum resident protein 44 also known as thioredoxin domain-containing protein 4 is a protein that in humans is encoded by the ERP44 gene....
; TXNDC5
TXNDC5
Thioredoxin domain-containing protein 5 is a protein that in humans is encoded by the TXNDC5 gene.- Function :This gene encodes a protein disulfide-isomerase. Its expression is induced by hypoxia and its role may be to protect hypoxic cells from apoptosis. This gene can be co-transcribed with the...
; TXNDC6; TXNDC8; TXNL1
TXNL1
Thioredoxin-like protein 1 is a protein that in humans is encoded by the TXNL1 gene.-Further reading:...
; TXNL3;