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5  structures 955  species 0  interactions 1303  sequences 71  architectures

Family: Thioredoxin_14 (PF18402)

Summary: Thioredoxin-like domain

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

Thioredoxin domain Edit Wikipedia article

Thioredoxin
Identifiers
Symbol Thioredoxin
Pfam PF00085
InterPro IPR013766
PROSITE PDOC00172
SCOP 3trx
SUPERFAMILY 3trx
CDD cd01659

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 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 the third out 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.

No InterPro data for this Pfam family.

Domain organisation

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

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Pfam Clan

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

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

The clan contains the following 62 members:

2Fe-2S_thioredx AhpC-TSA AhpC-TSA_2 ArsC ArsD Calsequestrin DIM1 DSBA DUF1223 DUF1462 DUF1525 DUF1687 DUF2703 DUF2847 DUF4174 DUF836 DUF899 DUF953 ERp29_N GILT Glutaredoxin GSHPx GST_N GST_N_2 GST_N_3 GST_N_4 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

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  Seed
(151)
Full
(1303)
Representative proteomes UniProt
(1882)
NCBI
(2725)
Meta
(3)
RP15
(346)
RP35
(675)
RP55
(987)
RP75
(1196)
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  Seed
(151)
Full
(1303)
Representative proteomes UniProt
(1882)
NCBI
(2725)
Meta
(3)
RP15
(346)
RP35
(675)
RP55
(987)
RP75
(1196)
Alignment:
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  Seed
(151)
Full
(1303)
Representative proteomes UniProt
(1882)
NCBI
(2725)
Meta
(3)
RP15
(346)
RP35
(675)
RP55
(987)
RP75
(1196)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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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.

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This family is new in this Pfam release.

Seed source: UniProt:G0SB58
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: El-Gebali S
Number in seed: 151
Number in full: 1303
Average length of the domain: 239.00 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 16.70 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 30.0 30.0
Trusted cut-off 30.1 30.1
Noise cut-off 29.4 29.9
Model length: 254
Family (HMM) version: 1
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

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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_14 domain has been found. There are 5 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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