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MGP001803

UniProt Annotations

Entry Information
Gene NameLCK proto-oncogene, Src family tyrosine kinase
Protein EntryLCK_HUMAN
UniProt IDP06239
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=Long; IsoId=P06239-1; Sequence=Displayed; Name=Short; IsoId=P06239-2; Sequence=VSP_005000, VSP_005001; Note=No experimental confirmation available.; Name=3; IsoId=P06239-3; Sequence=VSP_016049; Note=No experimental confirmation available.;
Catalytic ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- ProRule:PRU10028}.
DiseaseImmunodeficiency 22 (IMD22) [MIM:615758]: A primary immunodeficiency characterized by T-cell dysfunction. Affected individuals present with lymphopenia, recurrent infections, severe diarrhea, and failure to thrive. {ECO:0000269|PubMed:22985903}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseNote=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
DomainThe SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation.
Enzyme RegulationThe 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. {ECO:0000269|PubMed:21917715}.
FunctionNon-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. {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863}.
InteractionSelf; NbExp=3; IntAct=EBI-1348, EBI-1348; P22575:- (xeno); NbExp=7; IntAct=EBI-1348, EBI-866709; Q9YJQ8:- (xeno); NbExp=2; IntAct=EBI-1348, EBI-7709835; Q13444:ADAM15; NbExp=3; IntAct=EBI-1348, EBI-77818; P10275:AR; NbExp=7; IntAct=EBI-1348, EBI-608057; P20749:BCL3; NbExp=3; IntAct=EBI-1348, EBI-958997; P01730:CD4; NbExp=2; IntAct=EBI-1348, EBI-353826; Q13480:GAB1; NbExp=10; IntAct=EBI-1348, EBI-517684; P08238:HSP90AB1; NbExp=2; IntAct=EBI-1348, EBI-352572; Q07666:KHDRBS1; NbExp=5; IntAct=EBI-1348, EBI-1364; P10721:KIT; NbExp=8; IntAct=EBI-1348, EBI-1379503; O43561:LAT; NbExp=2; IntAct=EBI-1348, EBI-1222766; Q9H204:MED28; NbExp=4; IntAct=EBI-1348, EBI-514199; P08581:MET; NbExp=3; IntAct=EBI-1348, EBI-1039152; P04150:NR3C1; NbExp=3; IntAct=EBI-1348, EBI-493507; Q04759:PRKCQ; NbExp=2; IntAct=EBI-1348, EBI-374762; Q9Y2R2:PTPN22; NbExp=5; IntAct=EBI-1348, EBI-1211241; P29350:PTPN6; NbExp=5; IntAct=EBI-1348, EBI-78260; P08575:PTPRC; NbExp=7; IntAct=EBI-1348, EBI-1341; Q9NP31:SH2D2A; NbExp=12; IntAct=EBI-1348, EBI-490630; P43405:SYK; NbExp=7; IntAct=EBI-1348, EBI-78302; P0CG48:UBC; NbExp=2; IntAct=EBI-1348, EBI-3390054; P43403:ZAP70; NbExp=2; IntAct=EBI-1348, EBI-1211276;
Mass SpectrometryMass=57869.42; Method=MALDI; Range=2-509; Evidence={ECO:0000269|PubMed:11840567};
PtmAutophosphorylated on Tyr-394, increasing enzymatic activity, this site is dephosphorylated by PTN22. Phosphorylated on Tyr-505 by CSK, decreasing activity. Dephosphorylated by PTPRC/CD45. Dephosphorylation at Tyr-394 by PTPN2 negatively regulates T-cell receptor signaling. {ECO:0000269|PubMed:15592455, ECO:0000269|PubMed:1639064, ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:19369195, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:21406692, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:8139546, ECO:0000269|PubMed:8631775}.
PtmMyristoylation is required prior to palmitoylation. {ECO:0000250}.
PtmPalmitoylation regulates subcellular location. {ECO:0000250}.
Sequence CautionSequence=CAI22320.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAI22321.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityBelongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. {ECO:0000255|PROSITE- ProRule:PRU00159}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
SimilarityContains 1 SH2 domain. {ECO:0000255|PROSITE- ProRule:PRU00191}.
SimilarityContains 1 SH3 domain. {ECO:0000255|PROSITE- ProRule:PRU00192}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:12218089}. Cell membrane {ECO:0000269|PubMed:12218089}; Lipid-anchor {ECO:0000269|PubMed:12218089}; Cytoplasmic side {ECO:0000269|PubMed:12218089}. Note=Present in lipid rafts in an inactive form.
SubunitBinds 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, FYB 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. 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. 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. {ECO:0000269|PubMed:12837766, ECO:0000269|PubMed:14610044, ECO:0000269|PubMed:14610046, ECO:0000269|PubMed:14757743, ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:7504174, ECO:0000269|PubMed:7852312, ECO:0000269|PubMed:8618896, ECO:0000269|PubMed:8794306, ECO:0000269|PubMed:9178760}.
Tissue SpecificityExpressed specifically in lymphoid cells.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/LCKID14ch1p34.html";
Web ResourceName=Wikipedia; Note=Lck entry; URL="http://en.wikipedia.org/wiki/Lck";
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