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

Gene ID: 3932, updated on 24-Nov-2020

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
109.20201120 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (32251265..32286165)
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 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
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 
innate immune response IBA
Inferred from Biological aspect of Ancestor
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 cell population proliferation IBA
Inferred from Biological aspect of Ancestor
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
    5027..39927
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

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
    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 Updated Annotation Release 109.20201120

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..32286165
    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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