Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001377
UniProt IDP11021
Primary gene name(s)HSPA5
Synonym gene name(s)GRP78
Protein name78 kDa glucose-regulated protein
Protein functionProbably plays a role in facilitating the assembly of multimeric protein complexes inside the endoplasmic reticulum. Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10, probably to facilitate the release of DNAJC10 from its substrate. {ECO:0000269|PubMed:2294010, ECO:0000269|PubMed:23769672, ECO:0000269|PubMed:23990668}.
Subcellular locationEndoplasmic reticulum lumen {ECO:0000269|PubMed:21080038, ECO:0000269|PubMed:21289099, ECO:0000269|PubMed:23990668}. Melanosome. Cytoplasm {ECO:0000250}. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P11021
Gene Ontology
(Biological Process)
Complete annatation
activation of signaling protein activity involved in unfolded protein response [GO:0006987];
ATF6-mediated unfolded protein response [GO:0036500];
cellular response to antibiotic [GO:0071236];
cellular response to glucose starvation [GO:0042149];
cellular response to interleukin-4 [GO:0071353];
cellular response to manganese ion [GO:0071287];
cerebellar Purkinje cell layer development [GO:0021680];
cerebellum structural organization [GO:0021589];
endoplasmic reticulum unfolded protein response [GO:0030968];
ER-associated ubiquitin-dependent protein catabolic process [GO:0030433];
ER overload response [GO:0006983];
IRE1-mediated unfolded protein response [GO:0036498];
maintenance of protein localization in endoplasmic reticulum [GO:0035437];
negative regulation of apoptotic process [GO:0043066];
negative regulation of protein homodimerization activity [GO:0090074];
negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512];
PERK-mediated unfolded protein response [GO:0036499];
positive regulation of cell migration [GO:0030335];
positive regulation of protein ubiquitination [GO:0031398];
positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress [GO:1990440];
protein folding in endoplasmic reticulum [GO:0034975];
regulation of ATF6-mediated unfolded protein response [GO:1903891];
regulation of IRE1-mediated unfolded protein response [GO:1903894];
regulation of PERK-mediated unfolded protein response [GO:1903897];
regulation of protein folding in endoplasmic reticulum [GO:0060904];
substantia nigra development [GO:0021762];
toxin transport [GO:1901998]
Gene Ontology
(Molecular Function)
Complete annatation
ATPase activity [GO:0016887];
ATP binding [GO:0005524];
calcium ion binding [GO:0005509];
chaperone binding [GO:0051087];
enzyme binding [GO:0019899];
glycoprotein binding [GO:0001948];
misfolded protein binding [GO:0051787];
protein domain specific binding [GO:0019904];
ribosome binding [GO:0043022];
ubiquitin protein ligase binding [GO:0031625];
unfolded protein binding [GO:0051082]
Gene Ontology
(Cellular Component)
Complete annatation
cell surface [GO:0009986];
endoplasmic reticulum [GO:0005783];
endoplasmic reticulum chaperone complex [GO:0034663];
endoplasmic reticulum-Golgi intermediate compartment [GO:0005793];
endoplasmic reticulum lumen [GO:0005788];
endoplasmic reticulum membrane [GO:0005789];
extracellular exosome [GO:0070062];
focal adhesion [GO:0005925];
integral component of endoplasmic reticulum membrane [GO:0030176];
melanosome [GO:0042470];
membrane [GO:0016020];
midbody [GO:0030496];
mitochondrion [GO:0005739];
myelin sheath [GO:0043209];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
smooth endoplasmic reticulum [GO:0005790]
Protein-protein interaction109541
Phylogenetic treeP11021
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD31.004593585502490.002326716688218040.00754318647554794
AZA vs. DISU0.2434984190671180.440784411860450.91814655876178
AZA vs. IL70.1200308629036940.530988721321520.999311006273513
AZA vs. SAHA-0.673005659787820.01776279232048740.142441590613034
DISU vs. CD3-0.7724090745977250.03610581296034120.0831086267589712
DISU vs. IL7-0.1326135318763110.6752282979898170.911530992405883
DISU vs. SAHA-0.9153268152097560.02699147908726560.193892319150669
DMSO vs. AZA-0.009055928225144530.9566918400580571
DMSO vs. CD3-1.025156428328640.001474887592133430.00479274839850953
DMSO vs. DISU-0.254416623451520.430854067038290.881718877024027
DMSO vs. IL70.1363933351523360.4467852951617120.867967476478598
DMSO vs. SAHA-0.6704048002792540.02118386254183490.147036582235524
HIV vs. Mock in Activation-0.0352587080859890.954728598049630.999983755607037
HIV vs. Mock in Latency-0.233587733646570.2460144694788880.999834320637052
IL7 vs. CD3-0.8768988183331810.006617787318980770.0212053376400929
SAHA vs. CD3-1.701612639701833.22829954502168e-062.31779295585883e-05
SAHA vs. IL7-0.7963314031586420.004538029069044770.0360778849151592
(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) FALSE
(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 0.664222 0.000305467
(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
1.047 0.967 1.198 1.168 0.837
(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
DB00025 Antihemophilic Factor (Recombinant) approved, investigational unknown chaperone
DB00945 Acetylsalicylic acid approved, vet_approved unknown binding

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
3IUC X-ray 2.4Å A/C=26-410.
3LDL X-ray 2.3Å A/B=26-407.
3LDN X-ray 2.2Å A/B=26-407.
3LDO X-ray 1.9Å A/B=26-407.
3LDP X-ray 2.2Å A/B=26-407.
5E84 X-ray 2.9Å A/B/C/D/E/F=25-633.
5E85 X-ray 2.5Å A=418-637.
5E86 X-ray 2.6Å A=418-637.
5EVZ X-ray 1.8Å A/B=26-407.
5EX5 X-ray 1.9Å A/B=26-407.
5EXW X-ray 1.9Å A/B=26-407.
5EY4 X-ray 1.8Å A/B=26-407.
5F0X X-ray 1.6Å A/B=26-407.
5F1X X-ray 1.9Å A/B=26-407.
5F2R X-ray 2.1Å A/B=26-407.

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

HIV Partner Interaction Type PubMed
Pr55(Gag) incorporates 11932435
11932435
21738476
Gag-Pol complexes with 23125841
Nef interacts with 21763498
Tat activates 20457808
Nef complexes with 23125841
Vpr interacts with 21763498
Envelope surface glycoprotein gp120 complexes with 23125841
Envelope surface glycoprotein gp160; precursor interacts with 1900540
10514465
Envelope surface glycoprotein gp120 inhibited by 12832005
Vpr upregulates 22438978
23874603
Pr55(Gag) complexes with 23125841
Vpr competes with 10964507
19275587
Tat regulated by 10617616
Envelope surface glycoprotein gp120 upregulates 7906708
matrix stimulated by 10964507

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03060 Protein export - Homo sapiens (human)
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)
hsa04612 Antigen processing and presentation - Homo sapiens (human)
hsa04918 Thyroid hormone synthesis - Homo sapiens (human)
hsa05020 Prion diseases - Homo sapiens (human)
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