PXD054716

PXD054716 is an original dataset announced via ProteomeXchange.

Title	Endogenous interactors of the natural trapping mutant TMX5/TXNDC15
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2024-09-27
AnnouncementXML	Submission_2024-09-27_06:38:40.089.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD054716
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Manfredo Quadroni
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-08 08:25:49	ID requested
⏵ 1	2024-09-27 06:38:40	announced

10.6019/PXD054716;

submitter keyword: Endoplasmic reticulum

ERp44

Mixed disulfides

PDI family

TMX5/TXND15

Maurizio Molinari
contact affiliation	Institute for Research in Biomedicine, Via F. Chiesa 5, 6500 Bellinzona
contact email	Maurizio.molinari@irb.usi.ch
lab head
Manfredo Quadroni
contact affiliation	University of Lausanne
contact email	manfredo.quadroni@unil.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054716
     1. Label: PRIDE project
     2. Name: Endogenous interactors of the natural trapping mutant TMX5/TXNDC15