Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000526
UniProt IDP10747
Primary gene name(s)CD28
Synonym gene name(s)unknown
Protein nameT-cell-specific surface glycoprotein CD28
Protein functionInvolved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival. Enhances the production of IL4 and IL10 in T-cells in conjunction with TCR/CD3 ligation and CD40L costimulation, PubMed:8617933. Isoform 3 enhances CD40L-mediated activation of NF-kappa-B and kinases MAPK8 and PAK2 in T-cells, PubMed:15067037. {ECO:0000269|PubMed:15067037, ECO:0000269|PubMed:8617933}.
Subcellular locationMembrane;
Single-pass type I membrane protein.;
SUBCELLULAR LOCATION: Isoform 3: Cell surface {ECO:0000269|PubMed:15067037}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P10747
Gene Ontology
(Biological Process)
Complete annatation
apoptotic signaling pathway [GO:0097190];
cell surface receptor signaling pathway [GO:0007166];
cytokine biosynthetic process [GO:0042089];
humoral immune response [GO:0006959];
negative regulation of gene expression [GO:0010629];
negative thymic T cell selection [GO:0045060];
phosphatidylinositol-mediated signaling [GO:0048015];
positive regulation of alpha-beta T cell proliferation [GO:0046641];
positive regulation of gene expression [GO:0010628];
positive regulation of inflammatory response to antigenic stimulus [GO:0002863];
positive regulation of interleukin-10 production [GO:0032733];
positive regulation of interleukin-2 biosynthetic process [GO:0045086];
positive regulation of interleukin-4 production [GO:0032753];
positive regulation of isotype switching to IgG isotypes [GO:0048304];
positive regulation of mitotic nuclear division [GO:0045840];
positive regulation of phosphatidylinositol 3-kinase signaling [GO:0014068];
positive regulation of protein kinase B signaling [GO:0051897];
positive regulation of T cell proliferation [GO:0042102];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of translation [GO:0045727];
positive regulation of viral genome replication [GO:0045070];
regulation of defense response to virus by virus [GO:0050690];
regulation of phosphatidylinositol 3-kinase signaling [GO:0014066];
regulation of regulatory T cell differentiation [GO:0045589];
regulatory T cell differentiation [GO:0045066];
T cell costimulation [GO:0031295];
T cell receptor signaling pathway [GO:0050852]
Gene Ontology
(Molecular Function)
Complete annatation
coreceptor activity [GO:0015026];
identical protein binding [GO:0042802];
phosphatidylinositol-4,5-bisphosphate 3-kinase activity [GO:0046934];
protease binding [GO:0002020];
SH3/SH2 adaptor activity [GO:0005070]
Gene Ontology
(Cellular Component)
Complete annatation
cell surface [GO:0009986];
cytosol [GO:0005829];
external side of plasma membrane [GO:0009897];
immunological synapse [GO:0001772];
integral component of plasma membrane [GO:0005887];
plasma membrane [GO:0005886]
Protein-protein interaction107378
Phylogenetic treeP10747
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. CD31.01441678243980.05308859842026860.104910365201296
AZA vs. DISU0.2658006048417190.4891874692756970.932188732024563
AZA vs. IL7-0.1006193092359970.8123772795448360.999311006273513
AZA vs. SAHA-0.07483475469599510.8381870117381250.961440456451378
DISU vs. CD3-0.76237704769230.1255524414939090.222761005541336
DISU vs. IL7-0.3739016808190540.3458006800588240.726745469383351
DISU vs. SAHA-0.3416209846400350.3099090011095950.693487536113245
DMSO vs. AZA-0.115732594485910.7487124741318321
DMSO vs. CD3-1.148972645258470.01635752333327740.0377548780474682
DMSO vs. DISU-0.3855381844037460.2341833874976350.751201287694628
DMSO vs. IL70.02337988164144350.949912702865610.990836487125109
DMSO vs. SAHA0.03340661299927850.9123149268836030.979403400357616
HIV vs. Mock in Activation-0.5123558717893320.5877084022405270.999983755607037
HIV vs. Mock in Latency-0.3002575966250850.1481339474878820.999834320637052
IL7 vs. CD3-1.102598968223670.03923302481918070.0901462474237058
SAHA vs. CD3-1.117116270970280.02494926325449550.0554142074053423
SAHA vs. IL70.01943086503237110.9587895712029280.984589821943793
(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
1 0.87796452 -1.4 0.00833792 -2 0.003307401
(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 -1.12773 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
unknown unknown unknown unknown unknown
(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

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1YJD X-ray 2.7Å C=17-152.
3WA4 X-ray 1.3Å B=189-196.
5AUL X-ray 1.1Å B=189-196.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 interacts with 8706326
20380698
matrix upregulates 18570590
Envelope transmembrane glycoprotein gp41 inhibits 1832084
Envelope surface glycoprotein gp120 inhibits 7541827
Tat interacts with 9045614
9510190
Nef co-localizes with 11285224
Envelope surface glycoprotein gp160; precursor interacts with 8450224
9328113
Vpr downregulates 17023015
19275586
23986795
Envelope surface glycoprotein gp120 inhibited by 7589092
Tat inhibited by 12077252
Pr55(Gag) regulated by 22911005
Nef downregulates 11285224
12734410
16091223
16354571
16454711
18438604
18473783
19149577
19327048
19449444
19770068
20012528
20380698
20463068
21068258
21543478
21922073
22013062
22103833
22175768
22844345
22980333
23847689
23986795
24187576
24495362
24904546
25505066
2582753111285224
12836198
15078178
16454711
1847378312836198
18438604
19149577
20638642
2398679515194762
1914957721543478
Envelope surface glycoprotein gp160; precursor regulated by 22911005
Nef upregulates 10618429
23224761

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04514 Cell adhesion molecules (CAMs) - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04672 Intestinal immune network for IgA production - Homo sapiens (human)
hsa04940 Type I diabetes mellitus - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05320 Autoimmune thyroid disease - Homo sapiens (human)
hsa05322 Systemic lupus erythematosus - Homo sapiens (human)
hsa05323 Rheumatoid arthritis - Homo sapiens (human)
hsa05330 Allograft rejection - Homo sapiens (human)
hsa05332 Graft-versus-host disease - Homo sapiens (human)
hsa05416 Viral myocarditis - Homo sapiens (human)
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