LipidDB ID

LipidDB-9606-00575

Entry Name

UniProt Accession

P06239; D3DPP8; P07100; Q12850; Q13152; Q5TDH8; Q5TDH9; Q7RTZ3; Q96DW4; Q9NYT8;

Theoretical PI

5.23

Molecular Weight

58000.61

Genbank Protein ID

CAA28691.1; CAA31884.1; AAA59502.1; CAA32211.1; CAA32211.1; CAA32211.1; AAA18225.1; AAC50287.1; CAD55807.1; CAI22320.1; CAI22321.1; EAX07543.1; EAX07546.1; AAH13200.1; AAA59501.1; AAA59503.1; AAF34794.1; CAA29667.1; CAA28165.1;

Genbank Nucleotide ID

X05027; X13529; M36881; X14055; X14053; X14054; U07236; U23852; BN000073; AL121991; AL121991; CH471059; CH471059; BC013200; M21510; M26692; AF228313; X06369; X04476;

Protein Name

Tyrosine-protein kinase Lck

Protein Synonyms/Alias

2.7.10.2; Leukocyte C-terminal Src kinase; LSK; Lymphocyte cell-specific protein-tyrosine kinase; Protein YT16; Proto-oncogene Lck; T cell-specific protein-tyrosine kinase; p56-LCK;

Gene Name

LCK

Gene Synonyms/Alias

Created Date

01-JAN-1988

Organism

Homo sapiens (Human)

NCBI Taxa ID

9606

Reference

[1] Kabouridis PS, Magee AI, Ley SC. S-acylation of LCK protein tyrosine kinase isessential for its signalling function in T lymphocytes. EMBO J. 1997 Aug15;16(16):4983-98.[PMID:9305640]

Functional Description

Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T- cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.

Sequence Annotation

Domain: 61 121 SH3.
Domain: 127 224 SH2.
Domain: 245 498 Protein kinase.
Nucleotide-binding: 251 259 ATP.
Region: 2 72 Interactions with CD4 and CD8.
Region: 154 242 Interaction with PTPRH.
Active site: 364 364 Proton acceptor.
Binding site: 273 273 ATP.
Modified residue: 102 102 Phosphoserine.
Modified residue: 159 159 Phosphothreonine.
Modified residue: 162 162 Phosphoserine.
Modified residue: 194 194 Phosphoserine.
Modified residue: 394 394 Phosphotyrosine; by autocatalysis.
Modified residue: 505 505 Phosphotyrosine; by CSK.

Protein Length

509 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0005911; C:cell-cell junction; IEA:Ensembl
GO:0005829; C:cytosol; TAS:Reactome
GO:0030139; C:endocytic vesicle; IEA:Ensembl
GO:0070062; C:extracellular vesicular exosome; IDA:UniProt
GO:0001772; C:immunological synapse; IDA:MGI
GO:0045121; C:membrane raft; IDA:UniProtKB
GO:0000242; C:pericentriolar material; IDA:UniProtKB
GO:0005886; C:plasma membrane; IDA:BHF-UCL
GO:0003823; F:antigen binding; IEA:Ensembl
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0051117; F:ATPase binding; IPI:UniProtKB
GO:0042609; F:CD4 receptor binding; IPI:UniProtKB
GO:0042610; F:CD8 receptor binding; IPI:UniProtKB
GO:0001948; F:glycoprotein binding; IPI:UniProtKB
GO:0042802; F:identical protein binding; IPI:IntAct
GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC
GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:UniProtKB
GO:0008022; F:protein C-terminus binding; IPI:UniProtKB
GO:0019901; F:protein kinase binding; IPI:UniProtKB
GO:0019903; F:protein phosphatase binding; IPI:UniProtKB
GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB
GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB
GO:0042169; F:SH2 domain binding; IPI:UniProtKB
GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB
GO:0007568; P:aging; IEA:Ensembl
GO:0050853; P:B cell receptor signaling pathway; IEA:Ensembl
GO:0007596; P:blood coagulation; TAS:Reactome
GO:0006882; P:cellular zinc ion homeostasis; IEP:UniProtKB
GO:0016311; P:dephosphorylation; IDA:GOC
GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome
GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome
GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome
GO:0030097; P:hemopoiesis; NAS:UniProtKB
GO:0045087; P:innate immune response; TAS:Reactome
GO:0050900; P:leukocyte migration; TAS:Reactome
GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome
GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome
GO:0030168; P:platelet activation; TAS:Reactome
GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IEA:Ensembl
GO:0010628; P:positive regulation of gene expression; IEA:Ensembl
GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB
GO:0050870; P:positive regulation of T cell activation; IDA:UniProtKB
GO:0050862; P:positive regulation of T cell receptor signaling pathway; NAS:UniProtKB
GO:0042523; P:positive regulation of tyrosine phosphorylation of Stat5 protein; IEA:Ensembl
GO:0070474; P:positive regulation of uterine smooth muscle contraction; IEA:Ensembl
GO:0046777; P:protein autophosphorylation; IEA:Ensembl
GO:0006468; P:protein phosphorylation; IDA:UniProtKB
GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome
GO:0051249; P:regulation of lymphocyte activation; NAS:UniProtKB
GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:UniProtKB
GO:0042493; P:response to drug; IDA:UniProtKB
GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl
GO:0009612; P:response to mechanical stimulus; IEA:Ensembl
GO:0010043; P:response to zinc ion; IEA:Ensembl
GO:0031295; P:T cell costimulation; TAS:Reactome
GO:0030217; P:T cell differentiation; IMP:UniProtKB
GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome
GO:0016032; P:viral process; TAS:Reactome

Interpro

InterPro; IPR011009; Kinase-like_dom
InterPro; IPR000719; Prot_kinase_dom
InterPro; IPR017441; Protein_kinase_ATP_BS
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom
InterPro; IPR000980; SH2
InterPro; IPR001452; SH3_domain
InterPro; IPR008266; Tyr_kinase_AS
InterPro; IPR020635; Tyr_kinase_cat_dom

Pfam

Pfam; PF07714; Pkinase_Tyr;
Pfam; PF00017; SH2;
Pfam; PF00018; SH3_1;

SMART

SMART; SM00252; SH2;
SMART; SM00326; SH3;
SMART; SM00219; TyrKc;

PROSITE

PROSITE; PS00107; PROTEIN_KINASE_ATP;
PROSITE; PS50011; PROTEIN_KINASE_DOM;
PROSITE; PS00109; PROTEIN_KINASE_TYR;
PROSITE; PS50001; SH2;
PROSITE; PS50002; SH3;

PRINTS

PRINTS; PR00401; SH2DOMAIN;
PRINTS; PR00452; SH3DOMAIN;
PRINTS; PR00109; TYRKINASE;