Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003536
UniProt IDP00519
Primary gene name(s)ABL1
Synonym gene name(s)ABL, JTK7
Protein nameTyrosine-protein kinase ABL1
Protein functionNon-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3, involved in branch formation; ANXA1, involved in membrane anchoring; DBN1, DBNL, CTTN, RAPH1 and ENAH, involved in signaling; or MAPT and PXN, microtubule-binding proteins. Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin, CAV1 and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir, translocated intimin receptor of pathogenic E.coli and possibly Citrobacter, CagA, cytotoxin-associated gene A of H.pylori, or AnkA, ankyrin repeat-containing protein A of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. {ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}.
Subcellular locationCytoplasm, cytoskeleton. Nucleus. Mitochondrion {ECO:0000250}. Note=Shuttles between the nucleus and cytoplasm depending on environmental signals. Sequestered into the cytoplasm through interaction with 14-3-3 proteins. Localizes to mitochondria in response to oxidative stress, By similarity. {ECO:0000250}.;
SUBCELLULAR LOCATION: Isoform IB: Nucleus membrane;
Lipid-anchor. Note=The myristoylated c-ABL protein is reported to be nuclear.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P00519
Gene Ontology
(Biological Process)
Complete annatation
actin cytoskeleton organization [GO:0030036];
actin filament branching [GO:0090135];
activated T cell proliferation [GO:0050798];
activation of protein kinase C activity [GO:1990051];
alpha-beta T cell differentiation [GO:0046632];
autophagy [GO:0006914];
B-1 B cell homeostasis [GO:0001922];
B cell proliferation involved in immune response [GO:0002322];
B cell receptor signaling pathway [GO:0050853];
Bergmann glial cell differentiation [GO:0060020];
cell cycle arrest [GO:0007050];
cellular protein modification process [GO:0006464];
cellular response to DNA damage stimulus [GO:0006974];
cellular response to dopamine [GO:1903351];
cellular response to hydrogen peroxide [GO:0070301];
cellular response to lipopolysaccharide [GO:0071222];
cellular response to oxidative stress [GO:0034599];
cerebellum morphogenesis [GO:0021587];
collateral sprouting [GO:0048668];
DNA damage induced protein phosphorylation [GO:0006975];
epidermal growth factor receptor signaling pathway [GO:0007173];
establishment of protein localization [GO:0045184];
Fc-gamma receptor signaling pathway involved in phagocytosis [GO:0038096];
innate immune response [GO:0045087];
intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630];
microspike assembly [GO:0030035];
mismatch repair [GO:0006298];
mitochondrial depolarization [GO:0051882];
mitotic nuclear division [GO:0007067];
negative regulation of BMP signaling pathway [GO:0030514];
negative regulation of cell-cell adhesion [GO:0022408];
negative regulation of cellular senescence [GO:2000773];
negative regulation of endothelial cell apoptotic process [GO:2000352];
negative regulation of ERK1 and ERK2 cascade [GO:0070373];
negative regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043124];
negative regulation of mitotic cell cycle [GO:0045930];
negative regulation of phospholipase C activity [GO:1900275];
negative regulation of protein serine/threonine kinase activity [GO:0071901];
negative regulation of ubiquitin-protein transferase activity [GO:0051444];
neuromuscular process controlling balance [GO:0050885];
peptidyl-tyrosine autophosphorylation [GO:0038083];
peptidyl-tyrosine phosphorylation [GO:0018108];
platelet-derived growth factor receptor-beta signaling pathway [GO:0035791];
positive regulation of actin filament binding [GO:1904531];
positive regulation of apoptotic process [GO:0043065];
positive regulation of cytosolic calcium ion concentration [GO:0007204];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of interferon-gamma secretion [GO:1902715];
positive regulation of interleukin-2 secretion [GO:1900042];
positive regulation of microtubule binding [GO:1904528];
positive regulation of mitotic cell cycle [GO:0045931];
positive regulation of muscle cell differentiation [GO:0051149];
positive regulation of neuron death [GO:1901216];
positive regulation of osteoblast proliferation [GO:0033690];
positive regulation of oxidoreductase activity [GO:0051353];
positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of release of sequestered calcium ion into cytosol [GO:0051281];
positive regulation of Wnt signaling pathway, planar cell polarity pathway [GO:2000096];
protein autophosphorylation [GO:0046777];
regulation of actin cytoskeleton organization [GO:0032956];
regulation of actin cytoskeleton reorganization [GO:2000249];
regulation of autophagy [GO:0010506];
regulation of axon extension [GO:0030516];
regulation of cell adhesion [GO:0030155];
regulation of cell motility [GO:2000145];
regulation of cell proliferation [GO:0042127];
regulation of endocytosis [GO:0030100];
regulation of extracellular matrix organization [GO:1903053];
regulation of microtubule polymerization [GO:0031113];
regulation of response to DNA damage stimulus [GO:2001020];
regulation of transcription, DNA-templated [GO:0006355];
response to oxidative stress [GO:0006979];
signal transduction in response to DNA damage [GO:0042770];
spleen development [GO:0048536];
substrate adhesion-dependent cell spreading [GO:0034446];
thymus development [GO:0048538];
transitional one stage B cell differentiation [GO:0002333]
Gene Ontology
(Molecular Function)
Complete annatation
actin monomer binding [GO:0003785];
ATP binding [GO:0005524];
DNA binding [GO:0003677];
magnesium ion binding [GO:0000287];
manganese ion binding [GO:0030145];
mitogen-activated protein kinase binding [GO:0051019];
nicotinate-nucleotide adenylyltransferase activity [GO:0004515];
non-membrane spanning protein tyrosine kinase activity [GO:0004715];
proline-rich region binding [GO:0070064];
protein C-terminus binding [GO:0008022];
protein kinase activity [GO:0004672];
protein kinase C binding [GO:0005080];
protein tyrosine kinase activity [GO:0004713];
SH3 domain binding [GO:0017124];
syntaxin binding [GO:0019905]
Gene Ontology
(Cellular Component)
Complete annatation
actin cytoskeleton [GO:0015629];
cell leading edge [GO:0031252];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
extrinsic component of cytoplasmic side of plasma membrane [GO:0031234];
mitochondrion [GO:0005739];
nuclear membrane [GO:0031965];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471]
Protein-protein interaction106543
Phylogenetic treeP00519
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. CD30.1709978388422230.602356815373010.706680308344517
AZA vs. DISU-0.1234340026442570.6273561806407830.960057478314726
AZA vs. IL7-0.02365949470229250.9030416825767210.999311006273513
AZA vs. SAHA-0.1849346809517140.4519498232114120.792954613290521
DISU vs. CD3-0.3060153310499320.4003694731009860.533849574305552
DISU vs. IL70.09029146877498790.721184675881350.929900869949146
DISU vs. SAHA-0.06000899643286110.8374161618681630.957937888454383
DMSO vs. AZA0.1046820761547280.5372022892805691
DMSO vs. CD3-0.08151510808939710.7994378267199070.858461236733766
DMSO vs. DISU0.2250123747550880.3586276763834540.846705167334898
DMSO vs. IL7-0.1203855917846510.5070673100157720.887294219209258
DMSO vs. SAHA-0.294644559674320.2142997058340710.557904796445895
HIV vs. Mock in Activation0.1439880626122140.8171923160158820.999983755607037
HIV vs. Mock in Latency-0.01197968699779750.9426642767136780.999834320637052
IL7 vs. CD3-0.1880167476137650.5604902132840590.682137180850272
SAHA vs. CD3-0.3801750060022630.2850960555479590.398206176636513
SAHA vs. IL7-0.1643243939488920.5022214551915680.730318948056887
(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 -0.0349418 0.856083
(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
0.943 0.863 0.965 1.063 1.156
(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
DB00171 Adenosine triphosphate approved, nutraceutical unknown inhibitor
DB00619 Imatinib approved unknown inhibitor
DB01254 Dasatinib approved, investigational yes multitarget
DB04868 Nilotinib approved, investigational yes inhibitor
DB05184 XL228 investigational unknown unknown
DB07831 2-{[(6-OXO-1,6-DIHYDROPYRIDIN-3-YL)METHYL]AMINO}-N-[4-PROPYL-3-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE experimental unknown unknown
DB08043 1-[4-(PYRIDIN-4-YLOXY)PHENYL]-3-[3-(TRIFLUOROMETHYL)PHENYL]UREA experimental unknown unknown
DB08231 MYRISTIC ACID experimental unknown unknown
DB08339 6-(2,6-DICHLOROPHENYL)-2-{[3-(HYDROXYMETHYL)PHENYL]AMINO}-8-METHYLPYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONE experimental unknown unknown
DB08350 5-[3-(2-METHOXYPHENYL)-1H-PYRROLO[2,3-B]PYRIDIN-5-YL]-N,N-DIMETHYLPYRIDINE-3-CARBOXAMIDE experimental unknown unknown
DB03878 N-[4-Methyl-3-[[4-(3-Pyridinyl)-2-Pyrimidinyl]Amino]Phenyl]-3-Pyridinecarboxamide experimental unknown unknown
DB08583 2-amino-5-[3-(1-ethyl-1H-pyrazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethylbenzamide experimental unknown unknown
DB08896 Regorafenib approved yes inhibitor
DB06616 Bosutinib approved yes inhibitor
DB08901 Ponatinib approved yes inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1AB2 NMR - A=120-220.
1ABL Model - A=65-121.
1AWO NMR - A=65-119.
1BBZ X-ray 1.6Å A/C/E/G=64-121.
1JU5 NMR - C=62-122.
1OPL X-ray 3.4Å A/B=27-512.
1ZZP NMR - A=1007-1130.
2ABL X-ray 2.5Å A=57-218.
2E2B X-ray 2.2Å A/B=229-515.
2F4J X-ray 1.9Å A=229-513.
2FO0 X-ray 2.2Å A=38-512.
2G1T X-ray 1.8Å A/B/C/D=229-512.
2G2F X-ray 2.7Å A/B=229-512.
2G2H X-ray 2.0Å A/B=229-512.
2G2I X-ray 3.1Å A/B=229-512.
2GQG X-ray 2.4Å A/B=229-500.
2HIW X-ray 2.2Å A/B=230-512.
2HYY X-ray 2.4Å A/B/C/D=228-500.
2HZ0 X-ray 2.1Å A/B=228-497.
2HZ4 X-ray 2.8Å A/B/C=228-500.
2HZI X-ray 1.7Å A/B=229-500.
2O88 X-ray 1.7Å A/B=64-121.
2V7A X-ray 2.5Å A/B=229-512.
3CS9 X-ray 2.2Å A/B/C/D=229-500.
3EG0 X-ray 2.3Å A=60-121.
3EG1 X-ray 1.8Å A/B=60-121.
3EG2 X-ray 1.8Å A=60-121.
3EG3 X-ray 1.4Å A=60-121.
3EGU X-ray 2.2Å A=60-121.
3K2M X-ray 1.7Å A/B=121-232.
3PYY X-ray 1.8Å A/B=229-512.
3QRI X-ray 2.1Å A/B=229-499.
3QRJ X-ray 1.8Å A/B=229-499.
3QRK X-ray 2.3Å A=229-499.
3T04 X-ray 2.1Å A=112-232.
3UE4 X-ray 2.4Å A/B=229-512.
3UYO X-ray 1.8Å A=112-232.
4J9B X-ray 1.7Å A=60-121.
4J9C X-ray 1.0Å A=60-121.
4J9D X-ray 1.5Å A/C/E=60-121.
4J9E X-ray 1.4Å A/C/E=60-121.
4J9F X-ray 1.0Å A/C/E=60-121.
4J9G X-ray 1.8Å A/C/E=60-121.
4J9H X-ray 1.7Å A/B/C/D/E/F=60-121.
4J9I X-ray 2.2Å A/C/E=60-121.
4JJB X-ray 1.6Å A=60-121.
4JJC X-ray 1.6Å A=60-121.
4JJD X-ray 1.6Å A=60-121.
4TWP X-ray 2.4Å A/B=233-503.
4WA9 X-ray 2.2Å A/B=246-512.
4XEY X-ray 2.8Å A/B=119-515.
4YC8 X-ray 2.9Å A/B=229-512.
4ZOG X-ray 2.3Å A/B=229-511.
5DC0 X-ray 2.2Å B=112-232.
5DC4 X-ray 1.4Å A=112-232.
5DC9 X-ray 1.5Å A=112-232.
5HU9 X-ray 1.5Å A=229-500.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 cooperates with 20585556
Tat upregulates 24872081
Tat downregulates 22632162

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04012 ErbB signaling pathway - Homo sapiens (human)
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04110 Cell cycle - Homo sapiens (human)
hsa04360 Axon guidance - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa05130 Pathogenic Escherichia coli infection - Homo sapiens (human)
hsa05131 Shigellosis - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05416 Viral myocarditis - Homo sapiens (human)
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