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

    Gene ID: 3932, updated on 7-Feb-2023

    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; AllianceGenome:HGNC:6524
    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See LCK in Genome Data Viewer
    Location:
    1p35.2
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    110 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (32251265..32286165)
    110 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (32109169..32144081)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (32716866..32751766)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene eukaryotic translation initiation factor 3 subunit I Neighboring gene myotubularin related protein 9 like, pseudogene Neighboring gene family with sequence similarity 167 member B Neighboring gene histone deacetylase 1 Neighboring gene uncharacterized LOC124903949 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 Functions

    What'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 PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables ATPase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables CD4 receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables CD8 receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables SH2 domain binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables T cell receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables non-membrane spanning protein tyrosine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables non-membrane spanning protein tyrosine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables phosphatidylinositol 3-kinase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables phospholipase activator activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables phospholipase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables phosphotyrosine residue binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein phosphatase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein serine/threonine phosphatase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein tyrosine kinase activity EXP
    Inferred from Experiment
    more info
    PubMed 
    enables protein tyrosine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein tyrosine kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables protein tyrosine kinase activity TAS
    Traceable Author Statement
    more info
     
    enables signaling receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in B cell receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in Fc-gamma receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in T cell costimulation TAS
    Traceable Author Statement
    more info
     
    involved_in T cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in T cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in T cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in hemopoiesis NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in innate immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in intracellular zinc ion homeostasis IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in leukocyte migration TAS
    Traceable Author Statement
    more info
     
    involved_in peptidyl-tyrosine autophosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in peptidyl-tyrosine phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in platelet activation TAS
    Traceable Author Statement
    more info
     
    involved_in positive regulation of T cell activation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of T cell receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of heterotypic cell-cell adhesion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of intrinsic apoptotic signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of leukocyte cell-cell adhesion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of lymphocyte activation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in release of sequestered calcium ion into cytosol ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in response to xenobiotic stimulus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in transmembrane receptor protein tyrosine kinase signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in extracellular exosome HDA PubMed 
    is_active_in extrinsic component of cytoplasmic side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in immunological synapse IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in membrane raft IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in pericentriolar material IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in 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
    XP_047276355.1
    XP_047276359.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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
      5027..39927
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_153

    mRNA and Protein(s)

    1. NM_001042771.3NP_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
      Consensus CDS
      CCDS359.1
      UniProtKB/Swiss-Prot
      P06239, Q9NYT8
      UniProtKB/TrEMBL
      A0A0S2Z3Y8
      Related
      ENSP00000328213.4, ENST00000333070.4
      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
      Consensus CDS
      CCDS90908.1
      UniProtKB/TrEMBL
      A0A0S2Z3Y4
      Related
      ENSP00000435605.2, ENST00000495610.7
      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, Q9NYT8
      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 110 details...Open this link in a new tab

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      32251265..32286165
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      UniProtKB/TrEMBL
      E9PKQ8
      Related
      ENSP00000431517.2, ENST00000482949.6
      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 X3

      See identical proteins and their annotated locations for XP_011539755.1

      UniProtKB/TrEMBL
      Q573B4
      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_047420399.1XP_047276355.1  tyrosine-protein kinase Lck isoform X2

    4. XM_024447047.2XP_024302815.1  tyrosine-protein kinase Lck isoform X1

      UniProtKB/TrEMBL
      E9PKQ8
      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
    5. XM_047420403.1XP_047276359.1  tyrosine-protein kinase Lck isoform X4

      UniProtKB/TrEMBL
      A0A0S2Z3Y4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      32109169..32144081
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)