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LCK LCK proto-oncogene, Src family tyrosine kinase [ Homo sapiens (human) ]

Gene ID: 3932, updated on 15-Jun-2019

Summary

Official Symbol
LCKprovided by HGNC
Official Full Name
LCK proto-oncogene, Src family tyrosine kinaseprovided by HGNC
Primary source
HGNC:HGNC:6524
See related
Ensembl:ENSG00000182866 MIM:153390
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
LSK; YT16; IMD22; p56lck; pp58lck
Summary
This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein is a key signaling molecule in the selection and maturation of developing T-cells. It contains N-terminal sites for myristylation and palmitylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. The protein localizes to the plasma membrane and pericentrosomal vesicles, and binds to cell surface receptors, including CD4 and CD8, and other signaling molecules. Multiple alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Aug 2016]
Expression
Biased expression in lymph node (RPKM 46.5), appendix (RPKM 22.7) and 9 other tissues See more
Orthologs

Genomic context

See LCK in Genome Data Viewer
Location:
1p35.2
Exon count:
13
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 1 NC_000001.11 (32251239..32286167)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (32716840..32751766)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene myotubularin related protein 9 like, pseudogene Neighboring gene family with sequence similarity 167 member B Neighboring gene histone deacetylase 1 Neighboring gene MARCKS like 1

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env The ability of gp120 to inhibit SDF-1alpha-induced chemotaxis is mediated by the CD4 receptor and Lck signaling PubMed
env Interaction of HIV-1 gp120 with CD4 leads to increased levels of phosphorylation of the src-family Lck and Fyn protein tyrosine kinases and enhancement of their activities PubMed
env HIV-1 gp120 induces the dissociation of p56lck from CD4 and the downregulation of CD4 from the cellular surface PubMed
env Binding of HIV-1 gp120 to CD4 induces p56lck activation and zeta-chain (TCR) associated protein kinase 70kDa desensitization independent of TCR tyrosine phosphorylation PubMed
env Engagement of CD4 with HIV-1 gp120 inhibits Lck and F-actin recruitment into the immunological synapse PubMed
env The protein tyrosine kinase p56lck plays an active role in transmitting an HIV-1 gp120-mediated signal that increases the oxidative state of cells and as a consequence amplifies TNF-mediated NF-kappa B DNA binding PubMed
env HIV-1 gp120 induces an increase in tyrosine phosphorylation of two proteins, p56lck and phosphatidylinositol 3-kinase (PI 3-kinase) p85 alpha, that are physically complexed to the CD4 molecule PubMed
env HIV-1 gp120 inhibits CD3-induced Lck activation and cellular tyrosine phosphorylation, particularly of phosphoinositide-specific phospholipase C-gamma-1 PubMed
env CD4-p56Lck interaction is required for HIV-1 gp120-induced nuclear translocation of NF-kappaB in HeLa cells PubMed
env p56lck-positive cells are markedly more susceptible to syncytium formation than p56lck-negative cells, implying a regulatory role for p56lck in the syncytium formation mediated by HIV-1 gp120 envelope interaction with CD4 PubMed
env Binding of HIV-1 gp120 to CD4 molecules results in the association of Lck and Raf-1, which is abolished by preincubation of the virus with soluble CD4 PubMed
env Activation of the CD4-p56lck receptor signal transduction pathway by HIV-1 gp120 does not increase prostaglandin formation PubMed
Envelope surface glycoprotein gp160, precursor env Interaction of HIV-1 gp160 with CD4 increases p56lck autophosphorylation and kinase activity PubMed
env HIV-1 gp160 downregulates lymphocyte function-associated antigen-1 (LFA-1)-dependent adhesion between CD4+ T cells and B cells; this downregulation is shown to be p56lck-dependent PubMed
Envelope transmembrane glycoprotein gp41 env HIV-1 gp120 and gp41-induced cell killing is accompanied by tyrosine phosphorylation and activation of the CD4-associated p56(Lck) kinase, and by activation of a second member of the scr family of protein tyrosine kinases, p59(fyn) kinase PubMed
Nef nef HIV-1 NL4-3 Nef recruits LCK (p56) into endosomes, which is dependent upon the CPG-motif of Nef PubMed
nef HIV-1 Nef-induced relocalization of LCK is correlated with N-Ras activation at recycling endosome/TGN compartments PubMed
nef HIV-1 Nef induces relocalization of LCK away from the plasma membrane to the recycling endosome and the trans-Golgi network, inhibiting recruitment of LCK to the immunological synapse PubMed
nef HIV-1 Nef increases the association of the src family tyrosine kinase, Lck, and TCRzeta with rafts in human T cells, suggesting Nef primes resting T cells for activation by upregulating the levels of signaling molecules within rafts PubMed
nef HIV-1 Nef efficiently interacts with Lck by coimmunoprecipitation and in vitro kinase assays; this interaction is reduced by an R71T mutation in the proline-rich motif of Nef PubMed
nef The formation of Nef/LCK/PKCtheta complex activates the ERK MAPK signaling pathway PubMed
nef HIV-1 Nef interferes with the activation of Lck and as a consequence of signaling via the IL-2 receptor PubMed
nef Cooperation of the Lck SH2 and SH3 domains is required for HIV-1 Nef binding to Lck to a level similar to Nef binding to the Hck SH3 domain PubMed
nef The HIV-1 Nef highly conserved valine-glycine-phenylalanine amino acid triplet (VGF) motif is essential for effects of Nef on actin dynamics and Lck localization PubMed
nef Expression of SH3/SH2 ligand-uncoordinated 119 (UNC119) completely reverses the HIV-1 Nef-mediated inhibition of immunological synapse recruitment of LCK PubMed
nef HIV-1 Nef-induced relocalization of LCK increases phosphorylated ERK1/2 induction in infected and trasduced primary T cells PubMed
nef HIV-1 Nef induces intracellular accumulation of Lck and interferes with its recruitment to sites of TCR engagement. The accumulation of Lck requires the membrane attachment G2 and the SH3 binding motif AXXA of Nef PubMed
nef Human T cells expressing herpes virus saimiri-Tip mediate restriction of late-stage replication of HIV-1 by disrupting Nef interaction with Lck in lipid rafts PubMed
nef Formation of the Nef-associated kinase complex (NAKC) is sufficient to activate LCK and ERK1/2 and causes a strong Tat-dependent increase of HIV-1 transcription in T cells PubMed
nef In the context of Nef-associated kinase complex (NAKC), hnRNP-K interacts with HIV-1 Nef and recruits LCK, PKCdelta, and PI-3 kinase. The proline-rich domain (amino-acids 289-315) of hnRNP-K is required for the recruitment of activated LCK18854243 PubMed
nef PKCtheta is a downstream effector of LCK and is recruited by HIV-1 Nef to form the Nef/LCK/PKCtheta complex, which promotes HIV transcription PubMed
nef HIV-1 Nef-mediated increase of HIV transcription requires the Nef N terminus (amino acids 12-29) and LCK kinase activity by Nef activation PubMed
nef Expression of p56(lck) in nonlymphoid CD4-expressing cells restores the ability of Nef in order to increase the internalization rate of CD4 PubMed
nef HIV-1 Nef increases the production of exosomes, which form at the plasma membrane and co-localizes with plasma membrane-associated proteins ICAM1, CD81, and Lck in Jurkat PubMed
nef Amino acid residues 402-419 of the cytoplasmic tail of CD4 are required for association with Lck and also for the downregulation of CD4 induced by HIV-1 Nef, suggesting a potential interaction between Nef and Lck PubMed
nef HIV-1 and SIV Nef can bind Lck SH2 domains, and their N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation PubMed
nef Assays with phage-displayed Nef from HIV-1 NL4-3 have been used to identify a series of guanidine alkaloid-based inhibitors of Nef interactions with p53, actin, and p56(lck) PubMed
nef A highly conserved proline-rich repeat sequence in Nef between amino acids 69-78 directly binds to the SH2 and SH3 domains of Lck PubMed
nef HIV-1 Nef enhances the phosphorylation of c-Cbl in CD4+ T cells, an effect that requires the Src tyrosine kinase Lck PubMed
Pr55(Gag) gag The amplified luminescent proximity homogeneous assay (AlphaScreen) identifies the interaction of HIV-1 Gag with LCK PubMed
gag Lck enhances HIV-1 Gag assembly and release in T cells. Lck palmitoylation sites at cysteine's 3 and 5 are required for the efficient virus production PubMed
Tat tat Herpes virus saimiri-StpC synergizes with Tat during transcriptional activation of the HIV-1 LTR. This transcriptional synergy between StpC and Tat requires Lck and NF-kappaB consensus binding sequences PubMed
tat Formation of the Nef-associated kinase complex (NAKC) is sufficient to activate LCK and ERK1/2 and causes a strong Tat-dependent increase of HIV-1 transcription in T cells PubMed
tat HIV-1 Tat activates p56lck in Jurkat cells leading to the degradation of IkappaBalpha and activation of NFkappaB, AP-1, JNK, MAPKK, caspases, and apoptosis PubMed
Vpu vpu HIV-1 Vpu affects the subcellular localization of LCK but with reduced efficacy compared to HIV-1 Nef PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Alpha-synuclein signaling, organism-specific biosystem (from Pathway Interaction Database)
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  • Atypical NF-kappaB pathway, organism-specific biosystem (from Pathway Interaction Database)
    Atypical NF-kappaB pathway, organism-specific biosystem
    Atypical NF-kappaB pathway
  • B Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
    B Cell Receptor Signaling Pathway, organism-specific biosystemThe functional B-cell receptor is a multi-protein complex consisting of an antigen binding subunit and a signaling subunit. The antigen binding subunit is the membrane bound immunoglobulin and the si...
  • CD28 co-stimulation, organism-specific biosystem (from REACTOME)
    CD28 co-stimulation, organism-specific biosystemIn naive T cells, CD28 costimulation enhances cell cycle entry, potently stimulates expression of both the mitogenic lymphokine interleukin-2 (IL-2) and its receptor, and stimulates the activation o...
  • CD28 dependent PI3K/Akt signaling, organism-specific biosystem (from REACTOME)
    CD28 dependent PI3K/Akt signaling, organism-specific biosystemPI3Ks can be activated by a number of different receptors, including the TcR (T cell receptor), co-stimulatory receptors (CD28), cytokine receptors and chemokine receptors. However, the specific role...
  • CD28 dependent Vav1 pathway, organism-specific biosystem (from REACTOME)
    CD28 dependent Vav1 pathway, organism-specific biosystemCD28 binds to several intracellular proteins including PI3 kinase, Grb-2, Gads and ITK. Grb-2 specifically co-operates with Vav-1 in the up-regulation of NFAT/AP-1 transcription. CD28 costimulation r...
  • CTLA4 inhibitory signaling, organism-specific biosystem (from REACTOME)
    CTLA4 inhibitory signaling, organism-specific biosystemCTLA4 is one of the best studied inhibitory receptors of the CD28 superfamily. CTLA4 inhibits Tcell activation by reducing IL2 production and IL2 expression, and by arresting T cells at the G1 phase ...
  • CXCR4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    CXCR4-mediated signaling events, organism-specific biosystem
    CXCR4-mediated signaling events
  • Cell surface interactions at the vascular wall, organism-specific biosystem (from REACTOME)
    Cell surface interactions at the vascular wall, organism-specific biosystemLeukocyte extravasation is a rigorously controlled process that guides white cell movement from the vascular lumen to sites of tissue inflammation. The powerful adhesive interactions that are require...
  • Class I PI3K signaling events, organism-specific biosystem (from Pathway Interaction Database)
    Class I PI3K signaling events, organism-specific biosystem
    Class I PI3K signaling events
  • Constitutive Signaling by Aberrant PI3K in Cancer, organism-specific biosystem (from REACTOME)
    Constitutive Signaling by Aberrant PI3K in Cancer, organism-specific biosystemSignaling by PI3K/AKT is frequently constitutively activated in cancer via gain-of-function mutations in one of the two PI3K subunits - PI3KCA (encoding the catalytic subunit p110alpha) or PIK3R1 (en...
  • Costimulation by the CD28 family, organism-specific biosystem (from REACTOME)
    Costimulation by the CD28 family, organism-specific biosystemOptimal activation of T-lymphocytes requires at least two signals. A primary one is delivered by the T-cell receptor (TCR) complex after antigen recognition and additional costimulatory signals are d...
  • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
    Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
  • DAP12 interactions, organism-specific biosystem (from REACTOME)
    DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
  • DAP12 signaling, organism-specific biosystem (from REACTOME)
    DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
    Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
  • Downstream TCR signaling, organism-specific biosystem (from REACTOME)
    Downstream TCR signaling, organism-specific biosystemChanges in gene expression are required for the T cell to gain full proliferative competence and to produce effector cytokines. Three transcription factors in particular have been found to play a key...
  • Downstream signal transduction, organism-specific biosystem (from REACTOME)
    Downstream signal transduction, organism-specific biosystemThe role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of aro...
  • Downstream signaling events of B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Downstream signaling events of B Cell Receptor (BCR), organism-specific biosystemSecond messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidyinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RA...
  • EPHA forward signaling, organism-specific biosystem (from Pathway Interaction Database)
    EPHA forward signaling, organism-specific biosystem
    EPHA forward signaling
  • Ephrin B reverse signaling, organism-specific biosystem (from Pathway Interaction Database)
    Ephrin B reverse signaling, organism-specific biosystem
    Ephrin B reverse signaling
  • Fc epsilon receptor (FCERI) signaling, organism-specific biosystem (from REACTOME)
    Fc epsilon receptor (FCERI) signaling, organism-specific biosystemMast cells (MC) are distributed in tissues throughout the human body and have long been recognized as key cells of type I hypersensitivity reactions. They also play important roles in inflammatory an...
  • GAB1 signalosome, organism-specific biosystem (from REACTOME)
    GAB1 signalosome, organism-specific biosystemGAB1 is recruited to the activated EGFR indirectly, through GRB2. GAB1 acts as an adaptor protein that enables formation of an active PIK3, through recruitment of PIK3 regulatory subunit PIK3R1 (also...
  • GPVI-mediated activation cascade, organism-specific biosystem (from REACTOME)
    GPVI-mediated activation cascade, organism-specific biosystemThe GPVI receptor is a complex of the GPVI protein with Fc epsilon R1 gamma (FcR). The Src family kinases Fyn and Lyn constitutively associate with the GPVI-FcR complex in platelets and initiate plat...
  • Generation of second messenger molecules, organism-specific biosystem (from REACTOME)
    Generation of second messenger molecules, organism-specific biosystemIn addition to serving as a scaffold via auto-phosphorylation, ZAP-70 also phosphorylates a restricted set of substrates following TCR stimulation - including LAT and SLP-76. These substrates have be...
  • Glypican 1 network, organism-specific biosystem (from Pathway Interaction Database)
    Glypican 1 network, organism-specific biosystem
    Glypican 1 network
  • HIV Infection, organism-specific biosystem (from REACTOME)
    HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
  • HTLV-I infection, organism-specific biosystem (from KEGG)
    HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
  • HTLV-I infection, conserved biosystem (from KEGG)
    HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
  • Hemostasis, organism-specific biosystem (from REACTOME)
    Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
  • Host Interactions of HIV factors, organism-specific biosystem (from REACTOME)
    Host Interactions of HIV factors, organism-specific biosystemLike all viruses, HIV-1 must co-opt the host cell macromolecular transport and processing machinery. HIV-1 Vpr and Rev proteins play key roles in this co-optation. Efficient HIV-1 replication likewis...
  • IL-2 Signaling Pathway, organism-specific biosystem (from WikiPathways)
    IL-2 Signaling Pathway, organism-specific biosystemIL-2 is a multifunctional cytokine with pleiotropic effects on several cells of the immune system. IL-2 was originally discovered as a T cell growth factor, but it was also found to have actions rela...
  • IL12-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    IL12-mediated signaling events, organism-specific biosystem
    IL12-mediated signaling events
  • IL2 signaling events mediated by PI3K, organism-specific biosystem (from Pathway Interaction Database)
    IL2 signaling events mediated by PI3K, organism-specific biosystem
    IL2 signaling events mediated by PI3K
  • IL2 signaling events mediated by STAT5, organism-specific biosystem (from Pathway Interaction Database)
    IL2 signaling events mediated by STAT5, organism-specific biosystem
    IL2 signaling events mediated by STAT5
  • IL2-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    IL2-mediated signaling events, organism-specific biosystem
    IL2-mediated signaling events
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Infectious disease, organism-specific biosystem (from REACTOME)
    Infectious disease, organism-specific biosystem
    Infectious disease
  • Inflammatory Response Pathway, organism-specific biosystem (from WikiPathways)
    Inflammatory Response Pathway, organism-specific biosystem
    Inflammatory Response Pathway
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Interferon type I signaling pathways, organism-specific biosystem (from WikiPathways)
    Interferon type I signaling pathways, organism-specific biosystemThe type I IFNs (IFN? family, IFN?, IFN?, IFN? and IFN?) all bind to and signal via the type I IFN receptor complex. The type I receptor consists of two main IFNAR1, IFNAR2c receptor chains and other...
  • Interleukin-2 signaling, organism-specific biosystem (from REACTOME)
    Interleukin-2 signaling, organism-specific biosystemInterleukin-2 (IL-2) is a cytokine that is produced by T cells in response to antigen stimulation. Originally, IL-2 was discovered because of its potent growth factor activity on activated T cells in...
  • NF-kappa B signaling pathway, organism-specific biosystem (from KEGG)
    NF-kappa B signaling pathway, organism-specific biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
  • NF-kappa B signaling pathway, conserved biosystem (from KEGG)
    NF-kappa B signaling pathway, conserved biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
  • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
    NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
  • Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
    Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
  • Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
    Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
  • Nef Mediated CD4 Down-regulation, organism-specific biosystem (from REACTOME)
    Nef Mediated CD4 Down-regulation, organism-specific biosystemThe presence of Nef accelerates endocytosis and lysosomal degradation of the transmembrane glycoprotein CD4. CD4 has its own internalization motif, though this motif is normally concealed by CD4 inte...
  • Nef and signal transduction, organism-specific biosystem (from REACTOME)
    Nef and signal transduction, organism-specific biosystemNef interferes with cellular signal transduction pathways in a number of ways. Nef is associated with lipid rafts through its amino-terminal myristoylation and a proline-rich SH3-binding domain. Thes...
  • Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters, organism-specific biosystem (from REACTOME)
    Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters, organism-specific biosystemThe maximal virulence of HIV-1 requires Nef, a virally encoded peripheral membrane protein. Nef binds to the adaptor protein (AP) complexes of coated vesicles, inducing an expansion of the endosomal ...
  • Negative regulation of the PI3K/AKT network, organism-specific biosystem (from REACTOME)
    Negative regulation of the PI3K/AKT network, organism-specific biosystemThe PI3K/AKT network is negatively regulated by phosphatases that dephosphorylate PIP3, thus hampering AKT activation.
  • Notch Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Notch Signaling Pathway, organism-specific biosystemThe Notch pathway is an evolutionally conserved signaling pathway which plays an important role in diverse developmental and physiological processes. These include cell-fate determination, tissue pat...
  • Osteoclast differentiation, organism-specific biosystem (from KEGG)
    Osteoclast differentiation, organism-specific biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
  • Osteoclast differentiation, conserved biosystem (from KEGG)
    Osteoclast differentiation, conserved biosystemThe osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways...
  • PD-1 signaling, organism-specific biosystem (from REACTOME)
    PD-1 signaling, organism-specific biosystemThe Programmed cell death protein 1 (PD-1) is one of the negative regulators of TCR signaling. PD-1 may exert its effects on cell differentiation and survival directly by inhibiting early activation ...
  • PDGFR-beta signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    PDGFR-beta signaling pathway, organism-specific biosystem
    PDGFR-beta signaling pathway
  • PECAM1 interactions, organism-specific biosystem (from REACTOME)
    PECAM1 interactions, organism-specific biosystemPECAM-1/CD31 is a member of the immunoglobulin superfamily (IgSF) and has been implicated to mediate the adhesion and trans-endothelial migration of T-lymphocytes into the vascular wall, T cell activ...
  • PI3K/AKT Signaling in Cancer, organism-specific biosystem (from REACTOME)
    PI3K/AKT Signaling in Cancer, organism-specific biosystemClass IA PI3K is a heterodimer of a p85 regulatory subunit (encoded by PIK3R1, PIK3R2 or PIK3R3) and a p110 catalytic subunit (encoded by PIK3CA, PIK3CB or PIK3CD). In the absence of activating signa...
  • PI3K/AKT activation, organism-specific biosystem (from REACTOME)
    PI3K/AKT activation, organism-specific biosystemPI3K/AKT signalling is a major regulator of neuron survival. It blocks cell death by both impinging on the cytoplasmic cell death machinery and by regulating the expression of genes involved in cell...
  • PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling, organism-specific biosystem (from REACTOME)
    PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling, organism-specific biosystemPhosphatidylinositol-5-phosphate (PI5P) may modulate PI3K/AKT signaling in several ways. PI5P is used as a substrate for production of phosphatidylinositol-4,5-bisphosphate, PI(4,5)P2 (Rameh et al. 1...
  • PIP3 activates AKT signaling, organism-specific biosystem (from REACTOME)
    PIP3 activates AKT signaling, organism-specific biosystemSignaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimula...
  • Phosphorylation of CD3 and TCR zeta chains, organism-specific biosystem (from REACTOME)
    Phosphorylation of CD3 and TCR zeta chains, organism-specific biosystemPrior to T cell receptor (TCR) stimulation, CD4/CD8 associated Lck remains seperated from the TCR and is maintained in an inactive state by the action of Csk. Csk phosphorylates the negative regulato...
  • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
    Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
  • Primary immunodeficiency, organism-specific biosystem (from KEGG)
    Primary immunodeficiency, organism-specific biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
  • Primary immunodeficiency, conserved biosystem (from KEGG)
    Primary immunodeficiency, conserved biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
  • Regulation of KIT signaling, organism-specific biosystem (from REACTOME)
    Regulation of KIT signaling, organism-specific biosystemSCF induced proliferation is negatively regulated by various proteins including SHP1, PKC, CBL, SOCS1, SOCS6 and LNK.
  • Regulation of p38-alpha and p38-beta, organism-specific biosystem (from Pathway Interaction Database)
    Regulation of p38-alpha and p38-beta, organism-specific biosystem
    Regulation of p38-alpha and p38-beta
  • Role of LAT2/NTAL/LAB on calcium mobilization, organism-specific biosystem (from REACTOME)
    Role of LAT2/NTAL/LAB on calcium mobilization, organism-specific biosystemThe lipid raft resident adaptor molecules LAT1 and Non-T cell activation linker (NTAL), also known as linker for activation of B cells (LAB)/LAT2 are known participants in the regulation of mast cell...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by EGFR, organism-specific biosystem (from REACTOME)
    Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
  • Signaling by Interleukins, organism-specific biosystem (from REACTOME)
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  • Signaling by PDGF, organism-specific biosystem (from REACTOME)
    Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
  • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
    Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
  • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
  • Signaling events mediated by PTP1B, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by PTP1B, organism-specific biosystem
    Signaling events mediated by PTP1B
  • Signalling by NGF, organism-specific biosystem (from REACTOME)
    Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
  • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
    T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
  • T cell receptor signaling pathway, conserved biosystem (from KEGG)
    T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
  • T-Cell Receptor and Co-stimulatory Signaling, organism-specific biosystem (from WikiPathways)
    T-Cell Receptor and Co-stimulatory Signaling, organism-specific biosystemThe activation and translocation of transcription factors NFAT, AP-1 and NF-kappa-B via the co-stimulatory signaling cascade triggered by MHC peptide, B7 proteins and PD-L1. The activation of NFAT in...
  • T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection, organism-specific biosystem (from WikiPathways)
    T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection, organism-specific biosystemThis pathway is based on Figure 4 of "A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus au...
  • TCR signaling, organism-specific biosystem (from REACTOME)
    TCR signaling, organism-specific biosystemThe TCR is a multisubunit complex that consists of clonotypic alpha/beta chains noncovalently associated with the invariant CD3 delta/epsilon/gamma and TCR zeta chains. T cell activation by antigen p...
  • TCR signaling in naive CD4+ T cells, organism-specific biosystem (from Pathway Interaction Database)
    TCR signaling in naive CD4+ T cells, organism-specific biosystem
    TCR signaling in naive CD4+ T cells
  • TCR signaling in naive CD8+ T cells, organism-specific biosystem (from Pathway Interaction Database)
    TCR signaling in naive CD8+ T cells, organism-specific biosystem
    TCR signaling in naive CD8+ T cells
  • Th1 and Th2 cell differentiation, organism-specific biosystem (from KEGG)
    Th1 and Th2 cell differentiation, organism-specific biosystemImmunity to different classes of microorganisms is orchestrated by separate lineages of effector T helper (TH)-cells, which differentiate from naive CD4+ precursor cells in response to cues provided ...
  • Th1 and Th2 cell differentiation, conserved biosystem (from KEGG)
    Th1 and Th2 cell differentiation, conserved biosystemImmunity to different classes of microorganisms is orchestrated by separate lineages of effector T helper (TH)-cells, which differentiate from naive CD4+ precursor cells in response to cues provided ...
  • Th17 cell differentiation, organism-specific biosystem (from KEGG)
    Th17 cell differentiation, organism-specific biosystemInterleukin (IL)-17-producing helper T (Th17) cells serve as a subset of CD4+ T cells involved in epithelial cell- and neutrophil mediated immune responses against extracellular microbes and in the p...
  • Th17 cell differentiation, conserved biosystem (from KEGG)
    Th17 cell differentiation, conserved biosystemInterleukin (IL)-17-producing helper T (Th17) cells serve as a subset of CD4+ T cells involved in epithelial cell- and neutrophil mediated immune responses against extracellular microbes and in the p...
  • The role of Nef in HIV-1 replication and disease pathogenesis, organism-specific biosystem (from REACTOME)
    The role of Nef in HIV-1 replication and disease pathogenesis, organism-specific biosystemThe HIV-1 Nef protein is a 27-kDa myristoylated protein that is abundantly produced during the early phase of viral replication cycle. It is highly conserved in all primate lentiviruses, suggesting t...
  • Thromboxane A2 receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
    Thromboxane A2 receptor signaling, organism-specific biosystem
    Thromboxane A2 receptor signaling
  • Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway, organism-specific biosystem
    Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway
  • Translocation of ZAP-70 to Immunological synapse, organism-specific biosystem (from REACTOME)
    Translocation of ZAP-70 to Immunological synapse, organism-specific biosystemThe dual phosphorylated ITAMs recruit Syk kinase ZAP-70 via their tandem SH2 domains (step 4). ZAP-70 subsequently undergoes phosphorylation on multiple tyrosine residues for further activation. ZAP-...
  • amb2 Integrin signaling, organism-specific biosystem (from Pathway Interaction Database)
    amb2 Integrin signaling, organism-specific biosystem
    amb2 Integrin signaling

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
ATPase binding IPI
Inferred from Physical Interaction
more info
PubMed 
CD4 receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
CD8 receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
SH2 domain binding IPI
Inferred from Physical Interaction
more info
PubMed 
T cell receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
non-membrane spanning protein tyrosine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
phosphatidylinositol 3-kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
phosphotyrosine residue binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein C-terminus binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein phosphatase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein serine/threonine phosphatase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein tyrosine kinase activity EXP
Inferred from Experiment
more info
PubMed 
protein tyrosine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein tyrosine kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein tyrosine kinase activity TAS
Traceable Author Statement
more info
 
signaling receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
B cell receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
T cell costimulation TAS
Traceable Author Statement
more info
 
T cell differentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
T cell differentiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
T cell receptor signaling pathway TAS
Traceable Author Statement
more info
 
activation of cysteine-type endopeptidase activity involved in apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
cell differentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular zinc ion homeostasis IEP
Inferred from Expression Pattern
more info
PubMed 
hemopoiesis NAS
Non-traceable Author Statement
more info
PubMed 
leukocyte migration TAS
Traceable Author Statement
more info
 
peptidyl-tyrosine autophosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
peptidyl-tyrosine phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
platelet activation TAS
Traceable Author Statement
more info
 
positive regulation of T cell activation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of T cell receptor signaling pathway NAS
Non-traceable Author Statement
more info
PubMed 
positive regulation of heterotypic cell-cell adhesion IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of intrinsic apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of leukocyte cell-cell adhesion IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of protein kinase B signaling TAS
Traceable Author Statement
more info
 
protein dephosphorylation IEA
Inferred from Electronic Annotation
more info
 
protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of defense response to virus by virus TAS
Traceable Author Statement
more info
 
regulation of lymphocyte activation NAS
Non-traceable Author Statement
more info
PubMed 
release of sequestered calcium ion into cytosol ISS
Inferred from Sequence or Structural Similarity
more info
 
response to drug IDA
Inferred from Direct Assay
more info
PubMed 
transmembrane receptor protein tyrosine kinase signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Component Evidence Code Pubs
cytosol TAS
Traceable Author Statement
more info
 
extracellular exosome HDA PubMed 
extrinsic component of cytoplasmic side of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
immunological synapse IDA
Inferred from Direct Assay
more info
PubMed 
membrane raft IDA
Inferred from Direct Assay
more info
PubMed 
pericentriolar material IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
tyrosine-protein kinase Lck
Names
T-lymphocyte specific protein tyrosine kinase p56lck
leukocyte C-terminal Src kinase
lymphocyte cell-specific protein-tyrosine kinase
p56(LSTRA) protein-tyrosine kinase
proto-oncogene tyrosine-protein kinase LCK
t cell-specific protein-tyrosine kinase
NP_001036236.1
NP_001317397.1
NP_005347.3
XP_011539755.1
XP_024302814.1
XP_024302815.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_023387.1 RefSeqGene

    Range
    5001..39929
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001042771.2NP_001036236.1  tyrosine-protein kinase Lck isoform a

    See identical proteins and their annotated locations for NP_001036236.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) is transcribed from the proximal type I promoter. Variants 1 and 2 encode the same isoform (a).
    Source sequence(s)
    AA747421, AF228313, DB122062, DB129997, HY261581
    Consensus CDS
    CCDS359.1
    UniProtKB/Swiss-Prot
    P06239
    UniProtKB/TrEMBL
    A0A0S2Z3Y8
    Related
    ENSP00000477713.1, ENST00000619559.4
    Conserved Domains (3) summary
    cd10362
    Location:123223
    SH2_Src_Lck; Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck)
    cd12005
    Location:65118
    SH3_Lck; Src homology 3 domain of Lck Protein Tyrosine Kinase
    cd05067
    Location:237500
    PTKc_Lck_Blk; Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk
  2. NM_001330468.2NP_001317397.1  tyrosine-protein kinase Lck isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) is transcribed from the distal type II promoter, contains a distinct 5' UTR, and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
    Source sequence(s)
    AL109945, AL121991
    UniProtKB/TrEMBL
    A0A0S2Z3Y4
    Conserved Domains (3) summary
    cd10362
    Location:123215
    SH2_Src_Lck; Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck)
    cd12005
    Location:65118
    SH3_Lck; Src homology 3 domain of Lck Protein Tyrosine Kinase
    cl21453
    Location:212449
    PKc_like; Protein Kinases, catalytic domain
  3. NM_005356.5NP_005347.3  tyrosine-protein kinase Lck isoform a

    See identical proteins and their annotated locations for NP_005347.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) is transcribed from the distal type II promoter and contains a distinct 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (a).
    Source sequence(s)
    AA747421, AF228313, DA007906, X13529
    Consensus CDS
    CCDS359.1
    UniProtKB/Swiss-Prot
    P06239
    UniProtKB/TrEMBL
    A0A0S2Z3Y8
    Related
    ENSP00000337825.5, ENST00000336890.10
    Conserved Domains (3) summary
    cd10362
    Location:123223
    SH2_Src_Lck; Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck)
    cd12005
    Location:65118
    SH3_Lck; Src homology 3 domain of Lck Protein Tyrosine Kinase
    cd05067
    Location:237500
    PTKc_Lck_Blk; Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

    Range
    32251265..32286167
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024447046.1XP_024302814.1  tyrosine-protein kinase Lck isoform X1

    Conserved Domains (3) summary
    cd10362
    Location:181281
    SH2_Src_Lck; Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck)
    cd12005
    Location:123176
    SH3_Lck; Src homology 3 domain of Lck Protein Tyrosine Kinase
    cd05067
    Location:295558
    PTKc_Lck_Blk; Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk
  2. XM_011541453.3XP_011539755.1  tyrosine-protein kinase Lck isoform X2

    See identical proteins and their annotated locations for XP_011539755.1

    UniProtKB/TrEMBL
    Q573B4
    Related
    ENSP00000362665.3, ENST00000373564.7
    Conserved Domains (3) summary
    cd10362
    Location:181273
    SH2_Src_Lck; Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck)
    cd12005
    Location:123176
    SH3_Lck; Src homology 3 domain of Lck Protein Tyrosine Kinase
    cl21453
    Location:270507
    PKc_like; Protein Kinases, catalytic domain
  3. XM_024447047.1XP_024302815.1  tyrosine-protein kinase Lck isoform X1

    Conserved Domains (3) summary
    cd10362
    Location:181281
    SH2_Src_Lck; Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck)
    cd12005
    Location:123176
    SH3_Lck; Src homology 3 domain of Lck Protein Tyrosine Kinase
    cd05067
    Location:295558
    PTKc_Lck_Blk; Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk
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