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DrugBank target: P06239

DrugBank target: P06239 (LCK_HUMAN)     

Example structure of target: 1bhf

( There are 52 structures corresponding to this UniProt sequence in the PDB. Click the orange, plus icon above for a list. )

Tyrosine-protein kinase Lck

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

Function

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..

Enzyme

2.7.10.2   [EC->PDB]   [IntEnz]   [ExPASy]   [KEGG]  

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Disease(s)

Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.

Schematic diagram of Pfam domains in target sequence plus wiring diagrams of PDB structures of target.

1bhf
1bhh
1cwd
1cwe
   more ...

Key:    PfamA domain

Sequence length: 508 a.a.

Approved drugs targeting this protein

The DrugBank database identifies 2 drugs for this target protein:

 

Generic name: DB08901 ponatinib
0LI
Formula: C29H27F3N6O
Structure: There are 4 PDB structures containing this molecule although none are bound to the above target protein.
Generic name: DB01254 dasatinib
1N1
Formula: C22H26Cln7O2S
Structure: There are 10 PDB structures containing this molecule although none are bound to the above target protein.

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