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Details on Person UniProt:P06239 LCK
| Class:Id | ReferenceGeneProduct:58457 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Sat February 7 2015;chain:2-509 added on Sat February 7 2015;initiator methionine:1 for 58457 removed on Fri Nov 03 2023;initiator methionine: for 58457 added on Fri Nov 03 2023;initiator methionine: for 58457 removed on Fri Aug 15 2025;initiator methionine:1 for 58457 added on Fri Aug 15 2025 |
| _displayName | UniProt:P06239 LCK |
| _timestamp | 2026-02-20 21:50:32 |
| chain | initiator methionine:1 chain:2-509 |
| checksum | 44BFF0D43FFB420D |
| comment | 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 (PubMed:2470098). Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways (PubMed:2470098). Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors (PubMed:2470098). 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 (PubMed:2470098). 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 (PubMed:2470098, PubMed:40592325). 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).CATALYTIC ACTIVITY L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)ACTIVITY REGULATION The relative activities of the inhibitory tyrosine-protein kinase CSK and the activating tyrosine-protein phosphatase PTPRC/CD45 determine the level of LCK activity. These interactions allow rapid and efficient activation of LCK in response to TCR stimulation.SUBUNIT Binds to the cytoplasmic domain of cell surface receptors, such as AXL, CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB1 and to other protein kinases including CDK1, 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. This interaction inhibits its tyrosine-kinase activity. Interacts with SQSTM1. Interacts with phosphorylated LIME1. Interacts with CBLB and PTPRH. Interacts with RUNX3. Forms a signaling complex with EPHA1, PTK2B and PI3-KINASE; upon activation by EFNA1 which may regulate T-lymphocyte migration. Associates with ZAP70 and RHOH; these interactions allow LCK-mediated RHOH and CD3 subunit phosphorylation in the presence of functional ZAP70. Interacts with UNC119; this interaction plays a crucial role in activation of LCK. Interacts with CEACAM1 (via cytoplasmic domain); mediates CEACAM1 phosphorylation resulting in PTPN6 recruitment that dephosphorylates TCR stimulation-induced CD247 and ZAP70 (PubMed:18424730). Interacts with CD160. Interacts with CD48 (PubMed:12007789).SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1 UL46; this interaction activates LCK.SUBUNIT (Microbial infection) Interacts with HIV-1 Nef through its SH3 domain.INTERACTION Present in lipid rafts in an inactive form.ALTERNATIVE PRODUCTS Expressed specifically in lymphoid cells.DOMAIN The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation.PTM Autophosphorylated on Tyr-394, increasing enzymatic activity, this site is dephosphorylated by PTN22. Phosphorylated on Tyr-505 by CSK, decreasing activity (PubMed:40592325). Dephosphorylated by PTPRC/CD45. Dephosphorylation at Tyr-394 by PTPN2 negatively regulates T-cell receptor signaling. Dephosphorylation at Tyr-394 by DUSP22 negatively regulates T-cell receptor signaling (PubMed:24714587, PubMed:38225265).PTM Myristoylation is required prior to palmitoylation.PTM Palmitoylation regulates association with the plasma membrane and could be mediated by ZDHHC2.PTM 'Lys-63'-linked ubiquitinated at Lys-99 and Lys-276 by UBR2; this modification is required for autophosphorylation at Tyr-394.MASS SPECTROMETRY A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.ONLINE INFORMATION Lck entry |
| description | recommendedName: Tyrosine-protein kinase Lck ecNumber evidence="29"2.7.10.2 alternativeName: Leukocyte C-terminal Src kinase shortName: LSK alternativeName: Lymphocyte cell-specific protein-tyrosine kinase alternativeName: Protein YT16 alternativeName: Proto-oncogene Lck alternativeName: T cell-specific protein-tyrosine kinase alternativeName: p56-LCK |
| geneName | LCK |
| identifier | P06239 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing ATP-binding Cell membrane Chromosomal rearrangement Cytoplasm Disease variant Host-virus interaction Isopeptide bond Kinase Lipoprotein Membrane Myristate Nucleotide-binding Palmitate Phosphoprotein Proteomics identification Proto-oncogene Reference proteome SH2 domain SH3 domain Transferase Tyrosine-protein kinase Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | LCK |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8994904] ENSEMBL:ENSG00000182866 LCK [Homo sapiens] |
| secondaryIdentifier | LCK_HUMAN D3DPP8 P07100 Q12850 Q13152 Q5TDH8 Q5TDH9 Q7RTZ3 Q96DW4 Q9NYT8 |
| sequenceLength | 509 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:149587] UniProt:P06239-2 LCK [Homo sapiens] [ReferenceIsoform:234928] UniProt:P06239-3 LCK [Homo sapiens] [ReferenceIsoform:402499] UniProt:P06239-1 LCK [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:167609] LCK [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:202159] p-Y505-LCK [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:202308] p-Y394-LCK [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:8857940] p-Y394-LCK [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:8982825] p-LCK [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:202383] O4'-phospho-L-tyrosine at 505 [ModifiedResidue:202418] O4'-phospho-L-tyrosine at 394 [ModifiedResidue:8982778] phosphorylated residue at unknown position |
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No pathways have been reviewed or authored by UniProt:P06239 LCK (58457)
