Summary | |
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Symbol | LCK |
Name | LCK proto-oncogene, Src family tyrosine kinase |
Aliases | lymphocyte-specific protein tyrosine kinase; IMD22; YT16; p56lck; pp58lck; T-lymphocyte specific protein tyr ...... |
Chromosomal Location | 1p34.3 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway |
Subcellular Location | Cytoplasm Cell membrane Lipid-anchor Cytoplasmic side Note=Present in lipid rafts in an inactive form. |
Domain |
PF07714 Protein tyrosine kinase PF00017 SH2 domain PF00018 SH3 domain |
Function |
Non-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 tyrosine 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. Interacts with FYB2 (PubMed:27335501). |
Biological Process |
GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002521 leukocyte differentiation GO:0002694 regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0002697 regulation of immune effector process GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0002831 regulation of response to biotic stimulus GO:0006470 protein dephosphorylation GO:0006644 phospholipid metabolic process GO:0006650 glycerophospholipid metabolic process GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0006882 cellular zinc ion homeostasis GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0007159 leukocyte cell-cell adhesion GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0007596 blood coagulation GO:0007599 hemostasis GO:0009615 response to virus GO:0010950 positive regulation of endopeptidase activity GO:0010952 positive regulation of peptidase activity GO:0014065 phosphatidylinositol 3-kinase signaling GO:0014066 regulation of phosphatidylinositol 3-kinase signaling GO:0016311 dephosphorylation GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0022407 regulation of cell-cell adhesion GO:0022409 positive regulation of cell-cell adhesion GO:0030098 lymphocyte differentiation GO:0030168 platelet activation GO:0030217 T cell differentiation GO:0030258 lipid modification GO:0031294 lymphocyte costimulation GO:0031295 T cell costimulation GO:0032844 regulation of homeostatic process GO:0032845 negative regulation of homeostatic process GO:0038083 peptidyl-tyrosine autophosphorylation GO:0042110 T cell activation GO:0042493 response to drug GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043900 regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0045785 positive regulation of cell adhesion GO:0045862 positive regulation of proteolysis GO:0046486 glycerolipid metabolic process GO:0046488 phosphatidylinositol metabolic process GO:0046777 protein autophosphorylation GO:0046834 lipid phosphorylation GO:0046854 phosphatidylinositol phosphorylation GO:0046916 cellular transition metal ion homeostasis GO:0048015 phosphatidylinositol-mediated signaling GO:0048017 inositol lipid-mediated signaling GO:0050688 regulation of defense response to virus GO:0050690 regulation of defense response to virus by virus GO:0050792 regulation of viral process GO:0050817 coagulation GO:0050851 antigen receptor-mediated signaling pathway GO:0050852 T cell receptor signaling pathway GO:0050853 B cell receptor signaling pathway GO:0050854 regulation of antigen receptor-mediated signaling pathway GO:0050856 regulation of T cell receptor signaling pathway GO:0050857 positive regulation of antigen receptor-mediated signaling pathway GO:0050862 positive regulation of T cell receptor signaling pathway GO:0050863 regulation of T cell activation GO:0050865 regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050870 positive regulation of T cell activation GO:0050878 regulation of body fluid levels GO:0050900 leukocyte migration GO:0051208 sequestering of calcium ion GO:0051209 release of sequestered calcium ion into cytosol GO:0051235 maintenance of location GO:0051238 sequestering of metal ion GO:0051249 regulation of lymphocyte activation GO:0051251 positive regulation of lymphocyte activation GO:0051282 regulation of sequestering of calcium ion GO:0051283 negative regulation of sequestering of calcium ion GO:0051480 regulation of cytosolic calcium ion concentration GO:0051607 defense response to virus GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0055069 zinc ion homeostasis GO:0055074 calcium ion homeostasis GO:0055076 transition metal ion homeostasis GO:0060401 cytosolic calcium ion transport GO:0060402 calcium ion transport into cytosol GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070509 calcium ion import GO:0070588 calcium ion transmembrane transport GO:0070838 divalent metal ion transport GO:0071593 lymphocyte aggregation GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072511 divalent inorganic cation transport GO:0097193 intrinsic apoptotic signaling pathway GO:0097553 calcium ion transmembrane import into cytosol GO:0098542 defense response to other organism GO:1902656 calcium ion import into cytosol GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903039 positive regulation of leukocyte cell-cell adhesion GO:2000021 regulation of ion homeostasis GO:2000116 regulation of cysteine-type endopeptidase activity GO:2001056 positive regulation of cysteine-type endopeptidase activity GO:2001233 regulation of apoptotic signaling pathway GO:2001235 positive regulation of apoptotic signaling pathway GO:2001242 regulation of intrinsic apoptotic signaling pathway GO:2001244 positive regulation of intrinsic apoptotic signaling pathway |
Molecular Function |
GO:0001948 glycoprotein binding GO:0004713 protein tyrosine kinase activity GO:0004715 non-membrane spanning protein tyrosine kinase activity GO:0004721 phosphoprotein phosphatase activity GO:0004722 protein serine/threonine phosphatase activity GO:0008022 protein C-terminus binding GO:0016791 phosphatase activity GO:0019902 phosphatase binding GO:0019903 protein phosphatase binding GO:0035004 phosphatidylinositol 3-kinase activity GO:0042169 SH2 domain binding GO:0042578 phosphoric ester hydrolase activity GO:0042609 CD4 receptor binding GO:0042610 CD8 receptor binding GO:0043548 phosphatidylinositol 3-kinase binding GO:0046934 phosphatidylinositol-4,5-bisphosphate 3-kinase activity GO:0051117 ATPase binding GO:0052813 phosphatidylinositol bisphosphate kinase activity |
Cellular Component |
GO:0000242 pericentriolar material GO:0001772 immunological synapse GO:0005813 centrosome GO:0009898 cytoplasmic side of plasma membrane GO:0019897 extrinsic component of plasma membrane GO:0019898 extrinsic component of membrane GO:0031234 extrinsic component of cytoplasmic side of plasma membrane GO:0044450 microtubule organizing center part GO:0045121 membrane raft GO:0098552 side of membrane GO:0098562 cytoplasmic side of membrane GO:0098589 membrane region GO:0098857 membrane microdomain |
KEGG |
hsa04064 NF-kappa B signaling pathway hsa04380 Osteoclast differentiation hsa04650 Natural killer cell mediated cytotoxicity hsa04660 T cell receptor signaling pathway |
Reactome |
R-HSA-1280218: Adaptive Immune System R-HSA-389356: CD28 co-stimulation R-HSA-389357: CD28 dependent PI3K/Akt signaling R-HSA-389359: CD28 dependent Vav1 pathway R-HSA-389513: CTLA4 inhibitory signaling R-HSA-202733: Cell surface interactions at the vascular wall R-HSA-2219530: Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-388841: Costimulation by the CD28 family R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-2172127: DAP12 interactions R-HSA-2424491: DAP12 signaling R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-202424: Downstream TCR signaling R-HSA-186763: Downstream signal transduction R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR) R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-180292: GAB1 signalosome R-HSA-114604: GPVI-mediated activation cascade R-HSA-202433: Generation of second messenger molecules R-HSA-162906: HIV Infection R-HSA-109582: Hemostasis R-HSA-162909: Host Interactions of HIV factors R-HSA-168256: Immune System R-HSA-5663205: Infectious disease R-HSA-168249: Innate Immune System R-HSA-451927: Interleukin-2 signaling R-HSA-187037: NGF signalling via TRKA from the plasma membrane R-HSA-167590: Nef Mediated CD4 Down-regulation R-HSA-164944: Nef and signal transduction R-HSA-164938: Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters R-HSA-199418: Negative regulation of the PI3K/AKT network R-HSA-389948: PD-1 signaling R-HSA-210990: PECAM1 interactions R-HSA-2219528: PI3K/AKT Signaling in Cancer R-HSA-198203: PI3K/AKT activation R-HSA-6811558: PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-1257604: PIP3 activates AKT signaling R-HSA-202427: Phosphorylation of CD3 and TCR zeta chains R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-1433559: Regulation of KIT signaling R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization R-HSA-162582: Signal Transduction R-HSA-177929: Signaling by EGFR R-HSA-449147: Signaling by Interleukins R-HSA-186797: Signaling by PDGF R-HSA-1433557: Signaling by SCF-KIT R-HSA-983705: Signaling by the B Cell Receptor (BCR) R-HSA-166520: Signalling by NGF R-HSA-202403: TCR signaling R-HSA-164952: The role of Nef in HIV-1 replication and disease pathogenesis R-HSA-202430: Translocation of ZAP-70 to Immunological synapse |
Summary | |
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Symbol | LCK |
Name | LCK proto-oncogene, Src family tyrosine kinase |
Aliases | lymphocyte-specific protein tyrosine kinase; IMD22; YT16; p56lck; pp58lck; T-lymphocyte specific protein tyr ...... |
Chromosomal Location | 1p34.3 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Literatures that report relations between LCK and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells. |
Literatures describing the relation between LCK and anti-tumor immunity in human cancer.
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Summary | |
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Symbol | LCK |
Name | LCK proto-oncogene, Src family tyrosine kinase |
Aliases | lymphocyte-specific protein tyrosine kinase; IMD22; YT16; p56lck; pp58lck; T-lymphocyte specific protein tyr ...... |
Chromosomal Location | 1p34.3 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets. |
> High-throughput Screening
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Statistical results of LCK in screening data sets for detecting immune reponses.
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Summary | |
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Symbol | LCK |
Name | LCK proto-oncogene, Src family tyrosine kinase |
Aliases | lymphocyte-specific protein tyrosine kinase; IMD22; YT16; p56lck; pp58lck; T-lymphocyte specific protein tyr ...... |
Chromosomal Location | 1p34.3 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders |
Points in the above scatter plot represent the expression difference of LCK in various data sets.
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Points in the above scatter plot represent the mutation difference of LCK in various data sets.
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Summary | |
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Symbol | LCK |
Name | LCK proto-oncogene, Src family tyrosine kinase |
Aliases | lymphocyte-specific protein tyrosine kinase; IMD22; YT16; p56lck; pp58lck; T-lymphocyte specific protein tyr ...... |
Chromosomal Location | 1p34.3 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of LCK. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene. |
Summary | |
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Symbol | LCK |
Name | LCK proto-oncogene, Src family tyrosine kinase |
Aliases | lymphocyte-specific protein tyrosine kinase; IMD22; YT16; p56lck; pp58lck; T-lymphocyte specific protein tyr ...... |
Chromosomal Location | 1p34.3 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of LCK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by LCK. > Immunoinhibitor > Immunostimulator > MHC molecule |
Summary | |
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Symbol | LCK |
Name | LCK proto-oncogene, Src family tyrosine kinase |
Aliases | lymphocyte-specific protein tyrosine kinase; IMD22; YT16; p56lck; pp58lck; T-lymphocyte specific protein tyr ...... |
Chromosomal Location | 1p34.3 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of LCK. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor |
Summary | |
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Symbol | LCK |
Name | LCK proto-oncogene, Src family tyrosine kinase |
Aliases | lymphocyte-specific protein tyrosine kinase; IMD22; YT16; p56lck; pp58lck; T-lymphocyte specific protein tyr ...... |
Chromosomal Location | 1p34.3 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Distribution of LCK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype |
Summary | |
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Symbol | LCK |
Name | LCK proto-oncogene, Src family tyrosine kinase |
Aliases | lymphocyte-specific protein tyrosine kinase; IMD22; YT16; p56lck; pp58lck; T-lymphocyte specific protein tyr ...... |
Chromosomal Location | 1p34.3 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Associations between LCK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade |
Summary | |
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Symbol | LCK |
Name | LCK proto-oncogene, Src family tyrosine kinase |
Aliases | lymphocyte-specific protein tyrosine kinase; IMD22; YT16; p56lck; pp58lck; T-lymphocyte specific protein tyr ...... |
Chromosomal Location | 1p34.3 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Drugs targeting LCK collected from DrugBank database. |
Details on drugs targeting LCK.
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