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15  structures 1364  species 0  interactions 2494  sequences 87  architectures

Family: Thioredoxin_12 (PF18400)

Summary: Thioredoxin-like domain

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

Thioredoxin domain Edit Wikipedia article

Thioredoxin
Identifiers
SymbolThioredoxin
PfamPF00085
InterProIPR013766
PROSITEPDOC00172
SCOP23trx / SCOPe / SUPFAM

Thioredoxins[1][2][3][4] 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 2 cysteine thiol groups to a disulphide, accompanied by the transfer of 2 electrons and 2 protons. The net result is the covalent interconversion of a disulphide and a dithiol.

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

<reaction>trx-S2 + TR-(SH)2 -> trx-(SH)2 + TR-S2 (2)</reaction>

<reaction>Protein-S2 + trx-(SH)2 -> Protein-(SH)2 + trx-S2 (3)</reaction>

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

Protein disulphide isomerase (PDI), a resident foldase of the endoplasmic recticulum, is a multi-functional protein that catalyses the formation and isomerisation of disulphide 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 disulphide isomerase activity, but are functionally non-equivalent[6]. Interestingly, a mutant PDI, with all 4 of the active cysteines replaced by serine, displays a low but detectable level of disulphide isomerase activity[6]. Moreover, PDI exhibits chaperone-like activity towards proteins that contain no disulphide bonds, i.e. behaving independently of its disulphide 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 disulphide 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 disulphide ring is located on the surface of the protein. A flat hydrophobic surface lies adjacent to the disulphide, 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 disulphide 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; 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;

References

  1. ^ a b Holmgren A (1985). "Thioredoxin". Annu. Rev. Biochem. 54: 237–271. 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. PMID 7788289.
  4. ^ a b Martin JL (1995). "Thioredoxin--a fold for all reasons". Structure. 3 (3): 245–250. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ a b Gleason FK, Eklund H, Saarinen M (1995). "Crystal structure of thioredoxin-2 from Anabaena". Structure. 3 (10): 1097–1108. PMID 8590004.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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 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-like domain Provide feedback

This is one of four TRXL(thioredoxin-like) domains found in UDP-glucose:glycoprotein glucosyltransferase (UGGT)[1].

Literature references

  1. Roversi P, Marti L, Caputo AT, Alonzi DS, Hill JC, Dent KC, Kumar A, Levasseur MD, Lia A, Waksman T, Basu S, Soto Albrecht Y, Qian K, McIvor JP, Lipp CB, Siliqi D, Vasiljevic S, Mohammed S, Lukacik P, Walsh MA, Santino A, Zitzmann N;, Proc Natl Acad Sci U S A. 2017;114:8544-8549.: Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint. PUBMED:28739903 EPMC:28739903


Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR040693

This is one of four TRXL (thioredoxin-like) domains found in UDP-glucose:glycoprotein glucosyltransferase (UGGT) [ PUBMED:28739903 ].

Domain organisation

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

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Pfam Clan

Alignments

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  Seed
(96)
Full
(2494)
Representative proteomes UniProt
(3746)
RP15
(396)
RP35
(899)
RP55
(1847)
RP75
(2521)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

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  Seed
(96)
Full
(2494)
Representative proteomes UniProt
(3746)
RP15
(396)
RP35
(899)
RP55
(1847)
RP75
(2521)
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  Seed
(96)
Full
(2494)
Representative proteomes UniProt
(3746)
RP15
(396)
RP35
(899)
RP55
(1847)
RP75
(2521)
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.

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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: UniProt:G0SB58
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: El-Gebali S
Number in seed: 96
Number in full: 2494
Average length of the domain: 182.9 aa
Average identity of full alignment: 30 %
Average coverage of the sequence by the domain: 12.9 %

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 26.1 26.1
Trusted cut-off 26.1 26.5
Noise cut-off 26.0 26.0
Model length: 193
Family (HMM) version: 4
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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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_12 domain has been found. There are 15 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.

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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
A0A044SP17 View 3D Structure Click here
A0A077YXS6 View 3D Structure Click here
A0A0D2EL79 View 3D Structure Click here
A0A0K0E8S0 View 3D Structure Click here
A0A0N4UDJ8 View 3D Structure Click here
A0A0P0VMS9 View 3D Structure Click here
A0A0R0K2I7 View 3D Structure Click here
A0A175VUN3 View 3D Structure Click here
A0A1C1CHF5 View 3D Structure Click here
A0A1D6HNS8 View 3D Structure Click here
A0A1D8PJN6 View 3D Structure Click here
A0A2R8PZV9 View 3D Structure Click here
A0A3P7EEU4 View 3D Structure Click here
A0A5K4EMD1 View 3D Structure Click here
A0A5K4ENB5 View 3D Structure Click here
A4I4S1 View 3D Structure Click here
C0NGU3 View 3D Structure Click here
C1H9J0 View 3D Structure Click here
E7F6G9 View 3D Structure Click here
E9Q4X2 View 3D Structure Click here
F1R7F6 View 3D Structure Click here
G5EF14 View 3D Structure Click here
I1KSR4 View 3D Structure Click here
I1KUN0 View 3D Structure Click here
Q09140 View 3D Structure Click here
Q09332 View 3D Structure Click here
Q0WL80 View 3D Structure Click here
Q4E3K0 View 3D Structure Click here
Q582S2 View 3D Structure Click here
Q6P5E4 View 3D Structure Click here
Q8T191 View 3D Structure Click here
Q9GPA0 View 3D Structure Click here
Q9JLA3 View 3D Structure Click here
Q9NYU1 View 3D Structure Click here
Q9NYU2 View 3D Structure Click here
U7Q7C7 View 3D Structure Click here