Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001615
UniProt IDP06239
Primary gene name(s)LCK
Synonym gene name(s)unknown
Protein nameTyrosine-protein kinase Lck
Protein functionNon-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor, TCR-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs, ITAM of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:12218089}. Cell membrane {ECO:0000269|PubMed:12218089};
Lipid-anchor {ECO:0000269|PubMed:12218089};
Cytoplasmic side {ECO:0000269|PubMed:12218089}. Note=Present in lipid rafts in an inactive form.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P06239
Gene Ontology
(Biological Process)
Complete annatation
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919];
B cell receptor signaling pathway [GO:0050853];
cellular zinc ion homeostasis [GO:0006882];
hemopoiesis [GO:0030097];
innate immune response [GO:0045087];
leukocyte migration [GO:0050900];
peptidyl-tyrosine autophosphorylation [GO:0038083];
phosphatidylinositol-mediated signaling [GO:0048015];
platelet activation [GO:0030168];
positive regulation of intrinsic apoptotic signaling pathway [GO:2001244];
positive regulation of T cell activation [GO:0050870];
positive regulation of T cell receptor signaling pathway [GO:0050862];
protein phosphorylation [GO:0006468];
regulation of cell proliferation [GO:0042127];
regulation of defense response to virus by virus [GO:0050690];
regulation of lymphocyte activation [GO:0051249];
regulation of phosphatidylinositol 3-kinase signaling [GO:0014066];
release of sequestered calcium ion into cytosol [GO:0051209];
response to drug [GO:0042493];
T cell costimulation [GO:0031295];
T cell differentiation [GO:0030217];
T cell receptor signaling pathway [GO:0050852];
transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
ATPase binding [GO:0051117];
ATP binding [GO:0005524];
CD4 receptor binding [GO:0042609];
CD8 receptor binding [GO:0042610];
glycoprotein binding [GO:0001948];
identical protein binding [GO:0042802];
kinase activity [GO:0016301];
non-membrane spanning protein tyrosine kinase activity [GO:0004715];
phosphatidylinositol 3-kinase binding [GO:0043548];
phosphatidylinositol-4,5-bisphosphate 3-kinase activity [GO:0046934];
protein C-terminus binding [GO:0008022];
protein kinase binding [GO:0019901];
protein phosphatase binding [GO:0019903];
protein serine/threonine phosphatase activity [GO:0004722];
protein tyrosine kinase activity [GO:0004713];
SH2 domain binding [GO:0042169]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
extracellular exosome [GO:0070062];
extrinsic component of cytoplasmic side of plasma membrane [GO:0031234];
immunological synapse [GO:0001772];
membrane raft [GO:0045121];
pericentriolar material [GO:0000242];
plasma membrane [GO:0005886]
Protein-protein interaction110124
Phylogenetic treeP06239
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. CD3-1.524476789378855.43859034907168e-063.57169645931191e-05
AZA vs. DISU0.04641018338704860.8546165766762210.989951370113767
AZA vs. IL70.01894480176952210.9211964122611820.999311006273513
AZA vs. SAHA-0.5147403776011640.03620498293133320.223212234235958
DISU vs. CD31.559060097574892.52867361577591e-050.000168436703863041
DISU vs. IL7-0.03698162078495270.8832583440243840.978147487995092
DISU vs. SAHA-0.5589297477174980.05538904426653190.295741595680196
DMSO vs. AZA0.06774853885298390.6844217395301451
DMSO vs. CD31.579896356205061.40424764838443e-069.80305413480602e-06
DMSO vs. DISU0.01932009422696590.9368790974095650.991745651505415
DMSO vs. IL7-0.04141062620062340.8170905954079530.962956477091318
DMSO vs. SAHA-0.5877704078630560.01320321159615090.10812404262696
HIV vs. Mock in Activation-0.02722842804578460.9651295969822830.999983755607037
HIV vs. Mock in Latency0.01027485707592740.9501646426763040.999834320637052
IL7 vs. CD31.54969040613642.39863931272843e-062.14440630846712e-05
SAHA vs. CD30.9865310670429210.005601292955086930.0157220124479717
SAHA vs. IL7-0.5359654227014030.02851377237080540.126156913624162
(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 -0.725158 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
1.024 1.042 0.855 0.688 1.463
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
0.07 0.3263 -0.1 0.2226 -0.47 0.0016 T-cell activation at 20 hpi
(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
DB01254 Dasatinib approved, investigational yes multitarget
DB01830 {4-[2-Acetylamino-2-(3-Carbamoyl-2-Cyclohexylmethoxy-6,7,8,9-Tetrahydro-5h-Benzocyclohepten-5ylcarbamoyl)-Ethyl]-2-Phosphono-Phenyl}-Phosphonic Acid experimental unknown unknown
DB02010 Staurosporine experimental unknown unknown
DB03023 1-Tert-Butyl-3-(4-Chloro-Phenyl)-1h-Pyrazolo[3,4-D]Pyrimidin-4-Ylamine experimental unknown unknown
DB04003 (4-{2-Acetylamino-2-[1-(3-Carbamoyl-4-Cyclohexylmethoxy-Phenyl)-Ethylcarbamoyl}-Ethyl}-2-Phosphono-Phenoxy)-Acetic Acid experimental unknown unknown
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester experimental unknown unknown
DB06925 3-(2-AMINOQUINAZOLIN-6-YL)-4-METHYL-N-[3-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE experimental unknown unknown
DB07146 2,3-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-B]PYRIDIN-4-AMINE experimental unknown unknown
DB07297 5,6-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-D]PYRIMIDIN-4-AMINE experimental unknown unknown
DB08055 N-(2-chlorophenyl)-5-phenylimidazo[1,5-a]pyrazin-8-amine experimental unknown unknown
DB08056 N-(2,6-dimethylphenyl)-5-phenylimidazo[1,5-a]pyrazin-8-amine experimental unknown unknown
DB08057 N-(2-chloro-6-methylphenyl)-8-[(3S)-3-methylpiperazin-1-yl]imidazo[1,5-a]quinoxalin-4-amine experimental 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
1BHF X-ray 1.8Å A=119-226.
1BHH X-ray 1.9Å A=119-226# B=124-226.
1CWD X-ray 2.2Å L=127-222.
1CWE X-ray 2.3Å A/C=127-222.
1FBZ X-ray 2.4Å A/B=123-226.
1H92 NMR - A=59-120.
1IJR X-ray 2.2Å A=124-226.
1KIK NMR - A=64-120.
1LCJ X-ray 1.8Å A=119-226.
1LCK X-ray 2.5Å A=53-226# B=502-509.
1LKK X-ray 1.0Å A=122-226.
1LKL X-ray 1.8Å A=123-226.
1Q68 NMR - B=7-35.
1Q69 NMR - B=7-35.
1QPC X-ray 1.6Å A=231-509.
1QPD X-ray 2.0Å A=231-509.
1QPE X-ray 2.0Å A=231-509.
1QPJ X-ray 2.2Å A=231-509.
1X27 X-ray 2.7Å A/B/C/D/E/F=64-226.
2IIM X-ray 1.0Å A=59-119.
2OF2 X-ray 2.0Å A=231-501.
2OF4 X-ray 2.7Å A=231-501.
2OFU X-ray 2.0Å A=229-501.
2OFV X-ray 2.0Å A/B=232-498.
2OG8 X-ray 2.3Å A/B=237-499.
2PL0 X-ray 2.8Å A=225-509.
2ZM1 X-ray 2.1Å A=225-509.
2ZM4 X-ray 2.7Å A=225-509.
2ZYB X-ray 2.5Å A=225-509.
3AC1 X-ray 1.9Å A=225-509.
3AC2 X-ray 2.1Å A=225-509.
3AC3 X-ray 2.5Å A=225-509.
3AC4 X-ray 2.7Å A=225-509.
3AC5 X-ray 2.5Å A=225-509.
3AC8 X-ray 2.3Å A=225-509.
3ACJ X-ray 2.2Å A=225-509.
3ACK X-ray 2.6Å A=225-509.
3AD4 X-ray 2.2Å A=225-509.
3AD5 X-ray 2.0Å A=225-509.
3AD6 X-ray 2.1Å A=225-509.
3B2W X-ray 2.3Å A=226-502.
3BRH X-ray 2.2Å C/D=391-397.
3BYM X-ray 2.0Å A=230-501.
3BYO X-ray 2.0Å A=231-501.
3BYS X-ray 2.2Å A=225-501.
3BYU X-ray 2.3Å A=225-501.
3KMM X-ray 2.8Å A=229-509.
3KXZ X-ray 2.3Å A=225-509.
3LCK X-ray 1.7Å A=231-501.
3MPM X-ray 1.9Å A=237-501.
4C3F X-ray 1.7Å A=237-501.
4D8K X-ray 2.3Å A=53-226.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 interacts with 1491632
1535086
1622897
2040625
7774645
8887682
12628756
2084220519019957
208422058887682
Tat activates 10799874
Nef inhibits 22123847
Envelope surface glycoprotein gp160; precursor activates 1535787
1548763
9989602
Pr55(Gag) interacts with 24447338
Envelope transmembrane glycoprotein gp41 activates 8671590
Tat activated by 18854243
Envelope surface glycoprotein gp120 inhibits 7539724
7774645
9043947
20842205
Nef complexes with 18854243
2242206819050260
19050260
23986795
Pr55(Gag) enhanced by 18714047
Envelope surface glycoprotein gp160; precursor interacts with 9341793
Nef binds 7859737
8626429
9705913
20012528
239867958794306
10544125
10642173
14965316
15078178
15638726
15976924
17586321
19149577
217385849075929
10364375
18473783
20594957
Nef relocalizes 22123847
22123847
22345475
23986795
2470675522123847
2527512722537596
Envelope surface glycoprotein gp120 regulated by 1622897
7680610
8648738
8671590
8883579
Vpu relocalizes 25275127
Nef activates 18854243
19050260
Nef induces accumulation of 18030346
22345475
22802418
Envelope surface glycoprotein gp120 cooperates with 20835359
Nef interacts with 11525746
15371598
17266559
7831289
7871751
8871625
10208934
Nef inactivates 7853525
17586321
18473783
20594957
23559827
23986795
Tat interacts with 17266559
Envelope surface glycoprotein gp120 induces phosphorylation of 9123823
10358157
10422873
20842205
Nef co-localizes with 19912576
Nef modulated by 19439470
Nef requires 15892963
Envelope surface glycoprotein gp120 activates 7494315
7522245
8671590
9036944
9043947
9123823
208422058671590
8883579
9043947
9269777
9344703
208422058870842
20842205
Nef upregulates 15186530
17632570
23227982
24187576
Envelope surface glycoprotein gp120 requires 9621091
20842205

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04650 Natural killer cell mediated cytotoxicity - Homo sapiens (human)
hsa04658 Th1 and Th2 cell differentiation - Homo sapiens (human)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05340 Primary immunodeficiency - Homo sapiens (human)
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