Protein disulfide-isomerase

UniProt P07237 Organism Homo sapiens Gene ERBA2L, P4HB, PDI, PDIA1, PO4DB EC 5.3.4.1

Also known as: ERBA2L, P4HB, PDI, PDIA1, PO4DB

Function

This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration.

Classification

Family (Pfam): PF00085 Thioredoxin, PF13848 Thioredoxin_6
InterPro: PDI_thioredoxin-like_dom, Prot_disulphide_isomerase, Thioredoxin-like_sf, Thioredoxin_CS, Thioredoxin_domain
Functional cluster: Adenylate Kinases & Peroxiredoxins

Experimental structures · PDB · 14

1BJX NMR
1MEK NMR
1X5C NMR
2BJX NMR
2K18 NMR
3BJ5 X-ray 2.20A
3UEM X-ray 2.29A
4EKZ X-ray 2.51A
4EL1 X-ray 2.88A
4JU5 X-ray 2.28A
6I7S X-ray 2.50A
7ZSC X-ray 3.85A
… and 2 more

A predicted model is available from AlphaFold.

Gene Ontology · 36

Disease associations

Cole-Carpenter syndrome 1 MONDO:0007204

Drugs targeting this protein · 3

LOMITAPIDE MESYLATE inhibitor
IMPLITAPIDE inhibitor
SLX-4090 inhibitor

Related proteins · sequence + function similarity

Protein disulfide-isomerase 1.00
Protein disulfide-isomerase 1.00
Protein disulfide-isomerase 0.99
Protein disulfide-isomerase 0.99
Protein disulfide-isomerase 0.99
Protein disulfide-isomerase 0.99
Protein disulfide-isomerase 0.98
Protein disulfide-isomerase 0.98
Protein disulfide-isomerase 2 0.94
Protein disulfide-isomerase 0.91
Protein disulfide isomerase-like 1-1 0.91
Protein disulfide-isomerase 0.91

Co-cited proteins · studied together in the literature

Envelope glycoprotein gp160 4 shared papers
Microsomal triglyceride transfer protein large subunit 3 shared papers
Envelope glycoprotein gp160 1 shared papers
Protein disulfide-isomerase 3 shared papers
Protein disulfide-isomerase A3 1 shared papers
60 kDa heat shock protein, mitochondrial 3 shared papers
Microsomal triacylglycerol transfer protein 1 shared papers
Prolyl 4-hydroxylase subunit alpha-1 1 shared papers
Ubiquilin-1 1 shared papers
Protein disulfide-isomerase A3 4 shared papers
Envelope glycoprotein gp160 1 shared papers
Microsomal triglyceride transfer protein large subunit 1 shared papers

Literature · 39 cited papers

Phosphorylation switches protein disulfide isomerase activity to maintain proteostasis and attenuate ER stress. EMBO J. · 2020
A novel abetalipoproteinemia missense mutation highlights the importance of N-Terminal beta-barrel in microsomal triglyceride transfer protein function. Circ. Cardiovasc. Genet. · 2015
A single kinase generates the majority of the secreted phosphoproteome. Cell · 2015
N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
Cole-Carpenter syndrome is caused by a heterozygous missense mutation in P4HB. Am. J. Hum. Genet. · 2015
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Loss of both phospholipid and triglyceride transfer activities of microsomal triglyceride transfer protein in abetalipoproteinemia. J. Lipid Res. · 2013
Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry. Proc. Natl. Acad. Sci. U.S.A. · 2011
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J. Proteome Res. · 2006
Phospholipid transfer activity of microsomal triacylglycerol transfer protein is sufficient for the assembly and secretion of apolipoprotein B lipoproteins. J. Biol. Chem. · 2006
Glycosaminoglycans and protein disulfide isomerase-mediated reduction of HIV Env. Mol. Pharmacol. · 2005
… and 27 more in the literature graph

A document in the lmmol reference corpus — open public data (UniProt, GO, PDB, the literature graph) rendered as a single cross-linked page. Hover any link to preview its target.