Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0006182
UniProt IDP07237
Primary gene name(s)P4HB
Synonym gene name(s)ERBA2L, PDI, PDIA1, PO4DB
Protein nameProtein disulfide-isomerase
Protein functionThis 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, 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 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, PubMed:21670307. {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307}.
Subcellular locationEndoplasmic reticulum {ECO:0000269|PubMed:23475612}. Endoplasmic reticulum lumen {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:23475612}. Melanosome {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065}. Cell membrane {ECO:0000269|PubMed:21670307};
Peripheral membrane protein {ECO:0000305}. Note=Highly abundant. In some cell types, seems to be also secreted or associated with the plasma membrane, where it undergoes constant shedding and replacement from intracellular sources, Probable. Localizes near CD4-enriched regions on lymphoid cell surfaces, PubMed:11181151. Identified by mass spectrometry in melanosome fractions from stage I to stage IV, PubMed:10636893. Colocalizes with MTTP in the endoplasmic reticulum, PubMed:23475612. {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:11181151, ECO:0000269|PubMed:23475612, ECO:0000305}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P07237
Gene Ontology
(Biological Process)
Complete annatation
cell redox homeostasis [GO:0045454];
cellular response to hypoxia [GO:0071456];
lipoprotein biosynthetic process [GO:0042158];
peptidyl-proline hydroxylation to 4-hydroxy-L-proline [GO:0018401];
positive regulation of viral entry into host cell [GO:0046598];
regulation of oxidative stress-induced intrinsic apoptotic signaling pathway [GO:1902175];
response to endoplasmic reticulum stress [GO:0034976];
response to reactive oxygen species [GO:0000302]
Gene Ontology
(Molecular Function)
Complete annatation
integrin binding [GO:0005178];
poly(A RNA binding [GO:0044822];
procollagen-proline 4-dioxygenase activity [GO:0004656];
protein disulfide isomerase activity [GO:0003756];
protein heterodimerization activity [GO:0046982]
Gene Ontology
(Cellular Component)
Complete annatation
endoplasmic reticulum [GO:0005783];
endoplasmic reticulum chaperone complex [GO:0034663];
endoplasmic reticulum-Golgi intermediate compartment [GO:0005793];
endoplasmic reticulum lumen [GO:0005788];
external side of plasma membrane [GO:0009897];
extracellular exosome [GO:0070062];
extracellular region [GO:0005576];
focal adhesion [GO:0005925];
melanosome [GO:0042470];
procollagen-proline 4-dioxygenase complex [GO:0016222]
Protein-protein interaction111073
Phylogenetic treeP07237
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.09908161930254960.7617920725414660.83497419222929
AZA vs. DISU-0.02106272120214690.9335883862887050.995042856396371
AZA vs. IL7-0.05367191649700720.7793170781823280.999311006273513
AZA vs. SAHA-0.2978605634672820.221229625293970.589713927268377
DISU vs. CD3-0.1316241705925780.7161187813085720.801148342038593
DISU vs. IL7-0.04216611923697820.8669246234251680.974537471944736
DISU vs. SAHA-0.2747384211563660.3455553692061640.723415053383262
DMSO vs. AZA-0.03038060479937920.8554384253319561
DMSO vs. CD3-0.1419573699889860.6564561162153770.7445799872598
DMSO vs. DISU-0.01151942763129460.9622840395469370.994294013509907
DMSO vs. IL7-0.015766132948180.9298600910033030.986185512302997
DMSO vs. SAHA-0.2728038302318660.2462339419759850.594656797374496
HIV vs. Mock in Activation0.1540102558921870.8043774349674390.999983755607037
HIV vs. Mock in Latency0.05684264385063070.7294195490899880.999834320637052
IL7 vs. CD3-0.1465210694511730.6476782096112610.756310323324336
SAHA vs. CD3-0.4202296019103570.2341054153446150.341262198611273
SAHA vs. IL7-0.2466940469855390.3100065817500710.558842288124918
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.262762 0.0541544
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.999 0.925 1.065 1.149 0.877
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB03615 Ribostamycin approved unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1BJX NMR - A=136-245.
1MEK NMR - A=18-137.
1X5C NMR - A=368-475.
2BJX NMR - A=136-245.
2K18 NMR - A=135-357.
3BJ5 X-ray 2.2Å A=230-368.
3UEM X-ray 2.2Å A=137-479.
4EKZ X-ray 2.5Å A=18-479.
4EL1 X-ray 2.8Å A/B=18-479.
4JU5 X-ray 2.2Å A/B=135-367.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 cleaved by 12218051
Rev interacts with 22174317
Envelope surface glycoprotein gp160; precursor interacts with 22190034
Envelope surface glycoprotein gp120 interacts with 20458450
Vpr upregulates 23874603
Envelope surface glycoprotein gp160; precursor processed by 17301129

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)