Tclin LCK Tyrosine-protein kinase Lck

Protein Summary

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 tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. Interacts with FYB2 (PubMed:27335501). 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]

Uniprot Accession IDs

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

Gene Name

• LCK

Ensembl ID

• ENST00000333070
• ENSP00000328213
• ENSG00000182866
• ENST00000336890
• ENSP00000337825
• ENST00000619559
• ENSP00000477713

Symbol

• LSK
• YT16
• IMD22
• p56lck
• pp58lck

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
molecular function	1
small molecule	1
protein domain	0.97

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Src Family / Tyrosine-protein Kinase Lck

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1928.67   (req: < 5)

Gene RIFs: 171   (req: <= 3)

Antibodies: 1561   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1928.67   (req: >= 5)

Gene RIFs: 171   (req: > 3)

Antibodies: 1561   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 42

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 569

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 10