Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000039
UniProt IDP00813
Primary gene name(s)ADA
Synonym gene name(s)ADA1
Protein nameAdenosine deaminase
Protein functionCatalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine, PubMed:8452534, PubMed:16670267. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4, PubMed:20959412. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion, PubMed:11772392. Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion, By similarity. Enhances CD4+ T-cell differentiation and proliferation, PubMed:20959412. Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change, PubMed:23193172. Stimulates plasminogen activation, PubMed:15016824. Plays a role in male fertility, PubMed:21919946, PubMed:26166670. Plays a protective role in early postimplantation embryonic development, By similarity. {ECO:0000250|UniProtKB:P03958, ECO:0000250|UniProtKB:P56658, ECO:0000269|PubMed:11772392, ECO:0000269|PubMed:15016824, ECO:0000269|PubMed:16670267, ECO:0000269|PubMed:20959412, ECO:0000269|PubMed:21919946, ECO:0000269|PubMed:23193172, ECO:0000269|PubMed:26166670, ECO:0000269|PubMed:8452534}.
Subcellular locationCell membrane {ECO:0000269|PubMed:11772392, ECO:0000269|PubMed:8101391};
Peripheral membrane protein;
Extracellular side. Cell junction {ECO:0000269|PubMed:11772392}. Cytoplasmic vesicle lumen {ECO:0000250|UniProtKB:P03958}. Cytoplasm {ECO:0000250}. Lysosome {ECO:0000269|PubMed:8452534}. Note=Colocalized with DPP4 at the cell surface. {ECO:0000269|PubMed:11772392}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P00813
Gene Ontology
(Biological Process)
Complete annatation
adenosine catabolic process [GO:0006154];
aging [GO:0007568];
dATP catabolic process [GO:0046061];
deoxyadenosine catabolic process [GO:0006157];
embryonic digestive tract development [GO:0048566];
germinal center B cell differentiation [GO:0002314];
histamine secretion [GO:0001821];
hypoxanthine salvage [GO:0043103];
inosine biosynthetic process [GO:0046103];
liver development [GO:0001889];
lung alveolus development [GO:0048286];
negative regulation of adenosine receptor signaling pathway [GO:0060169];
negative regulation of circadian sleep/wake cycle, non-REM sleep [GO:0042323];
negative regulation of inflammatory response [GO:0050728];
negative regulation of leukocyte migration [GO:0002686];
negative regulation of mature B cell apoptotic process [GO:0002906];
negative regulation of mucus secretion [GO:0070256];
negative regulation of penile erection [GO:0060407];
negative regulation of thymocyte apoptotic process [GO:0070244];
Peyer's patch development [GO:0048541];
placenta development [GO:0001890];
positive regulation of alpha-beta T cell differentiation [GO:0046638];
positive regulation of B cell proliferation [GO:0030890];
positive regulation of calcium-mediated signaling [GO:0050850];
positive regulation of germinal center formation [GO:0002636];
positive regulation of heart rate [GO:0010460];
positive regulation of smooth muscle contraction [GO:0045987];
positive regulation of T cell differentiation in thymus [GO:0033089];
positive regulation of T cell receptor signaling pathway [GO:0050862];
purine-containing compound salvage [GO:0043101];
purine nucleotide salvage [GO:0032261];
purine ribonucleoside monophosphate biosynthetic process [GO:0009168];
regulation of cell-cell adhesion mediated by integrin [GO:0033632];
response to drug [GO:0042493];
response to hydrogen peroxide [GO:0042542];
response to hypoxia [GO:0001666];
response to morphine [GO:0043278];
response to vitamin E [GO:0033197];
T cell activation [GO:0042110];
trophectodermal cell differentiation [GO:0001829];
xanthine biosynthetic process [GO:0046111]
Gene Ontology
(Molecular Function)
Complete annatation
adenosine deaminase activity [GO:0004000];
purine nucleoside binding [GO:0001883];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cell junction [GO:0030054];
cell surface [GO:0009986];
cytoplasm [GO:0005737];
cytoplasmic membrane-bounded vesicle lumen [GO:0060205];
cytosol [GO:0005829];
dendrite cytoplasm [GO:0032839];
external side of plasma membrane [GO:0009897];
extracellular space [GO:0005615];
lysosome [GO:0005764];
membrane [GO:0016020];
neuronal cell body [GO:0043025];
plasma membrane [GO:0005886]
Protein-protein interaction106614
Phylogenetic treeP00813
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: HCV(r; HDV [enhances CHIKV; HIV-1; MV; VEEV; VSV; WNV; YFV]
      Viral life cycle: replication
      Mechanism related to antiviral activity: viral RNA editing; suppress PKR
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. CD3-0.7034358115102310.0347313461195030.0735521777031262
AZA vs. DISU-0.7280824127894010.004527820776409120.174113189754059
AZA vs. IL70.1116878167535610.5659975111870950.999311006273513
AZA vs. SAHA-0.09407675279687730.7032148406504520.916243135612562
DISU vs. CD3-0.03596951410073390.9224383705564730.949406826481166
DISU vs. IL70.8299548728759280.001209274411034240.031158112544613
DISU vs. SAHA0.6361791927285810.03079700888185750.210411054539188
DMSO vs. AZA0.01061373051043370.95027009508081
DMSO vs. CD30.6994343265489680.03164996544629720.065675858050753
DMSO vs. DISU0.7360316384372040.00291861854318420.116358681073508
DMSO vs. IL70.1085755697531170.5510252987604350.898292059447065
DMSO vs. SAHA-0.1092271584059310.6468357338630720.88678807832715
HIV vs. Mock in Activation-0.1146761652710490.8543120020291660.999983755607037
HIV vs. Mock in Latency-0.2416293818530810.1484871432502630.999834320637052
IL7 vs. CD30.8216249371551240.01156637683417380.0335565356595127
SAHA vs. CD30.5857253495645980.1088045930743710.186497408738714
SAHA vs. IL7-0.2076768223587090.4024511066786170.648996226758157
(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
2 0.002749142 1.4 0.052820169 1.7 0.00480724
(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 2.81642 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
1.045 1.009 1.097 1.115 1.26
(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
204639_at 1.88 No upregulated in CD8+ cells
216705_s_at 1.89 No upregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB02472 6-Hydroxy-7,8-Dihydro Purine Nucleoside experimental unknown unknown
DB03015 6-Hydroxy-1,6-Dihydro Purine Nucleoside experimental unknown unknown
DB04218 1-Deaza-Adenosine experimental unknown unknown
DB04440 Purine Riboside experimental unknown unknown
DB00975 Dipyridamole approved yes inhibitor
DB00552 Pentostatin approved, investigational yes inhibitor
DB00640 Adenosine approved, investigational unknown substrate
DB00194 Vidarabine approved unknown substrate
DB00277 Theophylline approved unknown inhibitor
DB01280 Nelarabine approved, investigational unknown substrate
DB07711 (2S,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol experimental unknown unknown
DB02616 FR117016 experimental unknown unknown
DB02096 FR221647 experimental unknown unknown
DB03572 FR230513 experimental unknown unknown
DB07783 1-((1R)-1-(HYDROXYMETHYL)-3-{6-[(3-PHENYLPROPANOYL)AMINO]-1H-INDOL-1-YL}PROPYL)-1H-IMIDAZOLE-4-CARBOXAMIDE experimental unknown unknown
DB03220 FR233623 experimental unknown unknown
DB03370 FR239087 experimental unknown unknown
DB02830 FR236913 experimental unknown unknown
DB07785 1-{(1R,2S)-2-HYDROXY-1-[2-(2-NAPHTHYLOXY)ETHYL]PROPYL}-1H-IMIDAZONE-4-CARBOXAMIDE experimental unknown unknown
DB07786 1-((1R,2S)-1-{2-[2-(4-CHLOROPHENYL)-1,3-BENZOXAZOL-7-YL]ETHYL}-2-HYDROXYPROPYL)-1H-IMIDAZOLE-4-CARBOXAMIDE experimental unknown unknown
DB00974 Edetic Acid approved, vet_approved unknown inhibitor
DB05057 Erdosteine investigational unknown inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1M7M Model - A=1-363.
3IAR X-ray 1.5Å A=5-363.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 upregulates 24162774
Envelope surface glycoprotein gp120 inhibits 9103436

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00230 Purine metabolism - Homo sapiens (human)
hsa01100 Metabolic pathways - Homo sapiens (human)
hsa05340 Primary immunodeficiency - Homo sapiens (human)