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PXD054716

PXD054716 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEndogenous interactors of the natural trapping mutant TMX5/TXNDC15
DescriptionThe endoplasmic reticulum (ER) is the organelle of nucleated cells that produces lipids, sugars and proteins. More than 20 ER-resident members of the Protein Disulfide Isomerase (PDI) family regulate formation, isomerization and disassembly of covalent bonds in newly synthesized polypeptides. The PDI family includes few membrane-bound members. Among these, TMX1, TMX2, TMX3, TMX4 and TMX5 belong to the thioredoxin-related transmembrane (TMX) protein family. TMX5 is the least known member of the family. Here, we establish that TMX5 covalently engages via its active site cysteine residue at position 220 a subset of secretory proteins, mainly single- and multi-pass Golgi-resident polypeptides. TMX5 also interacts non-covalently, and covalently, via non-catalytic cysteine residues, with the PDI family members PDI, ERp57 and ERp44. The association of TMX5 and ERp44 requires formation of a mixed disulfide between the catalytic cysteine residue 29 of ERp44 and the non-catalytic cysteine residues 114 and/or 124 of TMX5 and controls the ER retention of TMX5. Thus, TMX5 belongs to the family of proteins including Ero1, Ero1, Prx4, ERAP1, SUMF1 that do not display ER retention sequences and rely on ERp44 engagement for proper inter-compartmental distribution. The client-specificity of TMX5 in cellulo was assessed by expressing mutant forms of the enzymes, where the last cysteine residue of the TMX’s CXXC catalytic sites has been mutated to alanine, which stabilizes the mixed disulfide that oxidoreductases establish with clients. Clients remain disulfide-bonded to the oxidoreductase and are identified upon co-immunoprecipitation and mass spectrometry analyses.
HostingRepositoryPRIDE
AnnounceDate2024-09-27
AnnouncementXMLSubmission_2024-09-27_06:38:40.089.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD054716
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterManfredo Quadroni
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-08-08 08:25:49ID requested
12024-09-27 06:38:40announced
Publication List
10.6019/PXD054716;
Keyword List
submitter keyword: Endoplasmic reticulum
ERp44
Mixed disulfides
PDI family
TMX5/TXND15
Contact List
Maurizio Molinari
contact affiliationInstitute for Research in Biomedicine, Via F. Chiesa 5, 6500 Bellinzona
contact emailMaurizio.molinari@irb.usi.ch
lab head
Manfredo Quadroni
contact affiliationUniversity of Lausanne
contact emailmanfredo.quadroni@unil.ch
dataset submitter
Full Dataset Link List
Dataset FTP location
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