Proto-oncogene tyrosine-protein kinase LCK

Names and origin

Protein names

Recommended name:
    Proto-oncogene tyrosine-protein kinase LCK
    EC=2.7.10.2
Alternative name(s):
    Lymphocyte cell-specific protein-tyrosine kinase
    p56-LCK
    LSK
    T cell-specific protein-tyrosine kinase

Gene names

Name:

LCK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	509 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Tyrosine kinase that plays an essential role for the selection and maturation of developing T-cell in the thymus and in mature T-cell function. Is constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors and plays a key role in T-cell antigen receptor(TCR)-linked signal transduction pathways. 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, and thereby recruits the associated LCK to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosines-based activation motifs (ITAMs) in the cytoplasmic tails of the TCRgamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. In addition, contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, and upon engagement of the CD2 molecule, LCK undergoes hyperphosphorylation and activation. Also plays a role in the IL2 receptor-linked signaling pathway that controls 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.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Inhibited by tyrosine phosphorylation.
Subunit structure	Binds to the cytoplasmic domain of cell surface receptors, such as CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB and to other protein kinases including CDC2, RAF1, ZAP70 and SYK. Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of KHDRBS1/p70 through its SH2 domain. Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with SQSTM1. Interacts with phosphorylated LIME1. Interacts with CBLB and PTPRH.
Subcellular location	Cytoplasm. Cell membrane; Lipid-anchor; Cytoplasmic side. Note= Present in lipid rafts in an unactive form.
Tissue specificity	Expressed specifically in lymphoid cells.
Domain	The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation.
Post-translational modification	Phosphorylated on Tyr-394, which increases enzymatic activity By similarity. Phosphorylated on Tyr-505, which decreases activity.
Involvement in disease	A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.
Mass spectrometry	Molecular weight is 57869.42 Da from positions 2 - 509. Determined by MALDI. Ref.20

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Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Disease mutation Proto-oncogene
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Palmitate Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	Ras protein signal transduction Traceable author statement. Source: ProtInc T cell differentiation Inferred from mutant phenotype. Source: UniProtKB caspase activation Inferred from direct assay. Source: UniProtKB cellular zinc ion homeostasis Inferred from expression pattern. Source: UniProtKB induction of apoptosis Inferred from mutant phenotype. Source: UniProtKB positive regulation of T cell activation Inferred from direct assay. Source: UniProtKB positive regulation of T cell receptor signaling pathway Non-traceable author statement. Source: UniProtKB protein amino acid phosphorylation Ref.2 Traceable author statement. Source: ProtInc release of sequestered calcium ion into cytosol Inferred from sequence or structural similarity. Source: UniProtKB response to drug Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Inferred from Experiment. Source: Reactome membrane raft Inferred from direct assay. Source: UniProtKB pericentriolar material Inferred from direct assay. Source: UniProtKB plasma membrane Non-traceable author statement. Source: UniProtKB
Molecular function	ATPase binding Inferred from physical interaction. Source: UniProtKB CD4 receptor binding Inferred from physical interaction. Source: UniProtKB CD8 receptor binding Inferred from physical interaction. Source: UniProtKB SH2 domain binding Ref.15 Ref.17 Inferred from physical interaction. Source: UniProtKB glycoprotein binding Inferred from physical interaction. Source: UniProtKB phosphoinositide 3-kinase binding Ref.14 Inferred from physical interaction. Source: UniProtKB protein C-terminus binding Inferred from physical interaction. Source: UniProtKB protein kinase binding Ref.16 Inferred from physical interaction. Source: UniProtKB protein serine/threonine phosphatase activity Inferred from direct assay. Source: UniProtKB protein tyrosine kinase activity Ref.4 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
	P27958	1	EBI-1348,EBI-706378	From a different organism.
	Q9WMX2	1	EBI-1348,EBI-710918	From a different organism.
CD247	P20963	1	EBI-1348,EBI-1165705
KHDRBS1	Q07666	3	EBI-1348,EBI-1364
LAT	O43561	1	EBI-1348,EBI-1222766
MED28	Q9H204	2	EBI-1348,EBI-514199
PTPN22	Q9Y2R2	2	EBI-1348,EBI-1211241
SH2D2A	Q9NP31	1	EBI-1348,EBI-490630
WASL	O00401	1	EBI-1348,EBI-957615
ZAP70	P43403	1	EBI-1348,EBI-1211276

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Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P06239-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: P06239-2) The sequence of this isoform differs from the canonical sequence as follows: 348-363: IAEGMAFIEERNYIHR → VRRLGRGAGQGNRPVT 364-509: Missing.
Notes: No experimental confirmation available.

Isoform 3 (identifier: P06239-3) The sequence of this isoform differs from the canonical sequence as follows: 321-321: N → NDTLLDSQLEEKGLGASPWGNLGQQLLLLPT
Notes: No experimental confirmation available.