Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0008493
UniProt IDP07948
Primary gene name(s)LYN
Synonym gene name(s)JTK8
Protein nameTyrosine-protein kinase Lyn
Protein functionNon-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs, ITIM, that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, PTK2B/PYK2, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR, erythropoietin receptor in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. {ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:10748115, ECO:0000269|PubMed:10891478, ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11825908, ECO:0000269|PubMed:14726379, ECO:0000269|PubMed:15795233, ECO:0000269|PubMed:16467205, ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:17977829, ECO:0000269|PubMed:18056483, ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18235045, ECO:0000269|PubMed:18577747, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19290919, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:7687428}.
Subcellular locationCell membrane. Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Golgi apparatus. Membrane {ECO:0000305};
Lipid-anchor {ECO:0000305}. Note=Accumulates in the nucleus by inhibition of CRM1-mediated nuclear export. Nuclear accumulation is increased by inhibition of its kinase activity. The trafficking from the Golgi apparatus to the plasma membrane occurs in a kinase domain-dependent but kinase activity independent manner and is mediated by exocytic vesicular transport. Detected on plasma membrane lipid rafts.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P07948
Gene Ontology
(Biological Process)
Complete annatation
adaptive immune response [GO:0002250];
B cell homeostasis [GO:0001782];
B cell receptor signaling pathway [GO:0050853];
blood coagulation [GO:0007596];
cellular response to DNA damage stimulus [GO:0006974];
cellular response to extracellular stimulus [GO:0031668];
cellular response to heat [GO:0034605];
cellular response to retinoic acid [GO:0071300];
central nervous system development [GO:0007417];
cytokine secretion [GO:0050663];
dendritic cell differentiation [GO:0097028];
ephrin receptor signaling pathway [GO:0048013];
erythrocyte differentiation [GO:0030218];
Fc-epsilon receptor signaling pathway [GO:0038095];
Fc-gamma receptor signaling pathway involved in phagocytosis [GO:0038096];
Fc receptor mediated inhibitory signaling pathway [GO:0002774];
Fc receptor mediated stimulatory signaling pathway [GO:0002431];
histamine secretion by mast cell [GO:0002553];
immune response-regulating cell surface receptor signaling pathway [GO:0002768];
inflammatory response [GO:0006954];
innate immune response [GO:0045087];
JAK-STAT cascade involved in growth hormone signaling pathway [GO:0060397];
leukocyte migration [GO:0050900];
lipopolysaccharide-mediated signaling pathway [GO:0031663];
negative regulation of B cell proliferation [GO:0030889];
negative regulation of cell proliferation [GO:0008285];
negative regulation of ERK1 and ERK2 cascade [GO:0070373];
negative regulation of immune response [GO:0050777];
negative regulation of intracellular signal transduction [GO:1902532];
negative regulation of MAP kinase activity [GO:0043407];
negative regulation of mast cell proliferation [GO:0070667];
negative regulation of myeloid leukocyte differentiation [GO:0002762];
negative regulation of protein phosphorylation [GO:0001933];
negative regulation of toll-like receptor 2 signaling pathway [GO:0034136];
negative regulation of toll-like receptor 4 signaling pathway [GO:0034144];
neuron projection development [GO:0031175];
oligodendrocyte development [GO:0014003];
peptidyl-tyrosine autophosphorylation [GO:0038083];
peptidyl-tyrosine phosphorylation [GO:0018108];
platelet activation [GO:0030168];
platelet degranulation [GO:0002576];
positive regulation of B cell receptor signaling pathway [GO:0050861];
positive regulation of cell migration [GO:0030335];
positive regulation of cell proliferation [GO:0008284];
positive regulation of cellular component movement [GO:0051272];
positive regulation of dendritic cell apoptotic process [GO:2000670];
positive regulation of Fc receptor mediated stimulatory signaling pathway [GO:0060369];
positive regulation of glial cell proliferation [GO:0060252];
positive regulation of mast cell proliferation [GO:0070668];
positive regulation of neuron projection development [GO:0010976];
positive regulation of oligodendrocyte progenitor proliferation [GO:0070447];
positive regulation of phosphatidylinositol 3-kinase activity [GO:0043552];
positive regulation of stress-activated protein kinase signaling cascade [GO:0070304];
positive regulation of tyrosine phosphorylation of STAT protein [GO:0042531];
protein autophosphorylation [GO:0046777];
protein phosphorylation [GO:0006468];
regulation of B cell apoptotic process [GO:0002902];
regulation of B cell receptor signaling pathway [GO:0050855];
regulation of cell adhesion mediated by integrin [GO:0033628];
regulation of cytokine production [GO:0001817];
regulation of cytokine secretion [GO:0050707];
regulation of ERK1 and ERK2 cascade [GO:0070372];
regulation of erythrocyte differentiation [GO:0045646];
regulation of inflammatory response [GO:0050727];
regulation of mast cell activation [GO:0033003];
regulation of mast cell degranulation [GO:0043304];
regulation of monocyte chemotaxis [GO:0090025];
regulation of platelet aggregation [GO:0090330];
regulation of protein phosphorylation [GO:0001932];
regulation of release of sequestered calcium ion into cytosol [GO:0051279];
response to amino acid [GO:0043200];
response to axon injury [GO:0048678];
response to carbohydrate [GO:0009743];
response to drug [GO:0042493];
response to hormone [GO:0009725];
response to insulin [GO:0032868];
response to organic cyclic compound [GO:0014070];
response to sterol depletion [GO:0006991];
response to toxic substance [GO:0009636];
signal transduction [GO:0007165];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
T cell costimulation [GO:0031295];
tolerance induction to self antigen [GO:0002513];
transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
enzyme binding [GO:0019899];
glycosphingolipid binding [GO:0043208];
ion channel binding [GO:0044325];
non-membrane spanning protein tyrosine kinase activity [GO:0004715];
protein tyrosine kinase activity [GO:0004713];
receptor binding [GO:0005102];
receptor signaling protein tyrosine kinase activity [GO:0004716]
Gene Ontology
(Cellular Component)
Complete annatation
cell-cell adherens junction [GO:0005913];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
extracellular exosome [GO:0070062];
extrinsic component of cytoplasmic side of plasma membrane [GO:0031234];
Golgi apparatus [GO:0005794];
integrin alpha2-beta1 complex [GO:0034666];
mast cell granule [GO:0042629];
membrane raft [GO:0045121];
mitochondrial crista [GO:0030061];
mitochondrial intermembrane space [GO:0005758];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
plasma membrane [GO:0005886];
postsynaptic density [GO:0014069]
Protein-protein interaction110245
Phylogenetic treeP07948
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. CD32.218693931136861.03074056401198e-079.92038427891988e-07
AZA vs. DISU0.05146848652756270.9081254674939930.994169411479968
AZA vs. IL7-0.02455005517659790.9525420242855040.999311006273513
AZA vs. SAHA0.03419230820155240.9370845552412050.986599683266836
DISU vs. CD3-2.177676202489939.02372984001865e-078.77705086189823e-06
DISU vs. IL7-0.08729602755939530.8424206143432130.967173404182981
DISU vs. SAHA-0.01348191407126050.9763960510267540.995922620191181
DMSO vs. AZA-0.1209182810106320.7876470309195721
DMSO vs. CD3-2.339096846639955.51546650573442e-074.15629141949814e-06
DMSO vs. DISU-0.1707377330086770.7215020831309360.963669976056625
DMSO vs. IL70.1018636888313070.8194855569549540.962956477091318
DMSO vs. SAHA0.148532525811720.750071868696030.927241300088349
HIV vs. Mock in Activation0.6770241649603690.2797222094469550.999983755607037
HIV vs. Mock in Latency1.0940622471641.94257898655792e-098.87346534647699e-07
IL7 vs. CD3-2.241239595788393.17548043415883e-084.3315852112286e-07
SAHA vs. CD3-2.204366490471842.49900111715107e-072.37004070707782e-06
SAHA vs. IL70.05891516306248660.8903772604526860.956735111735158
(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
-0.5368 0.03139

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 1.30544 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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB03023 1-Tert-Butyl-3-(4-Chloro-Phenyl)-1h-Pyrazolo[3,4-D]Pyrimidin-4-Ylamine experimental unknown unknown
DB06616 Bosutinib approved unknown unknown
DB08901 Ponatinib approved unknown inhibitor
DB09079 Nintedanib approved unknown Inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1W1F NMR - A=61-123.
1WA7 NMR - A=61-123.
3A4O X-ray 3.0Å X=233-512.

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

HIV Partner Interaction Type PubMed
Nef interacts with 10544125
10642173
12734410
15078178
15638726
16454711
Envelope surface glycoprotein gp120 relocalizes 18453587
Envelope surface glycoprotein gp120 activates 16621960
18453587
Nef activates 16849330
2239341522393415

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04611 Platelet activation - Homo sapiens (human)
hsa04662 B cell receptor signaling pathway - Homo sapiens (human)
hsa04664 Fc epsilon RI signaling pathway - Homo sapiens (human)
hsa04666 Fc gamma R-mediated phagocytosis - Homo sapiens (human)
hsa04730 Long-term depression - Homo sapiens (human)
hsa05120 Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
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