LCK_MOUSE
ID LCK_MOUSE Reviewed; 509 AA.
AC P06240; Q61794; Q61795; Q62320; Q91X65;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 236.
DE RecName: Full=Proto-oncogene tyrosine-protein kinase LCK;
DE EC=2.7.10.2;
DE AltName: Full=Leukocyte C-terminal Src kinase;
DE Short=LSK;
DE AltName: Full=Lymphocyte cell-specific protein-tyrosine kinase;
DE AltName: Full=p56-LCK;
GN Name=Lck; Synonyms=Lsk-t;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2416464; DOI=10.1016/0092-8674(85)90169-2;
RA Marth J.D., Peet R., Krebs E.G., Perlmutter R.M.;
RT "A lymphocyte-specific protein-tyrosine kinase gene is rearranged and
RT overexpressed in the murine T cell lymphoma LSTRA.";
RL Cell 43:393-404(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3081813; DOI=10.1038/319682a0;
RA Voronova A.F., Sefton B.M.;
RT "Expression of a new tyrosine protein kinase is stimulated by retrovirus
RT promoter insertion.";
RL Nature 319:682-685(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
RX PubMed=2850479; DOI=10.1128/mcb.8.8.3058-3064.1988;
RA Garvin A.M., Pawar S., Marth J.D., Perlmutter R.M.;
RT "Structure of the murine lck gene and its rearrangement in a murine
RT lymphoma cell line.";
RL Mol. Cell. Biol. 8:3058-3064(1988).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
RX PubMed=3501824; DOI=10.1128/mcb.7.12.4407-4413.1987;
RA Voronova A.F., Adler H.T., Sefton B.M.;
RT "Two lck transcripts containing different 5' untranslated regions are
RT present in T cells.";
RL Mol. Cell. Biol. 7:4407-4413(1987).
RN [7]
RP MUTAGENESIS OF TYR-505.
RX PubMed=3380790; DOI=10.1073/pnas.85.12.4257;
RA Amrein K.E., Sefton B.M.;
RT "Avian reovirus mRNAs are nonfunctional in infected mouse cells:
RT translational basis for virus host-range restriction.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:4257-4261(1988).
RN [8]
RP INTERACTION WITH CD4 AND CD8, AND MUTAGENESIS OF 3-CYS--CYS-5; CYS-20 AND
RP CYS-23.
RX PubMed=2107025; DOI=10.1016/0092-8674(90)90090-2;
RA Turner J.M., Brodsky M.H., Irving B.A., Levin S.D., Perlmutter R.M.,
RA Littman D.R.;
RT "Interaction of the unique N-terminal region of tyrosine kinase p56lck with
RT cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs.";
RL Cell 60:755-765(1990).
RN [9]
RP MUTAGENESIS.
RX PubMed=1279202; DOI=10.1128/jvi.66.12.7406-7413.1992;
RA Hurley T.R., Amrein K.E., Sefton B.M.;
RT "Creation and characterization of temperature-sensitive mutants of the lck
RT tyrosine protein kinase.";
RL J. Virol. 66:7406-7413(1992).
RN [10]
RP MUTAGENESIS OF LYS-273.
RX PubMed=1706070; DOI=10.1038/350062a0;
RA Abraham N., Miceli M.C., Parnes J.C., Veillette A.;
RT "Enhancement of T-cell responsiveness by the lymphocyte-specific tyrosine
RT protein kinase p56lck.";
RL Nature 350:62-66(1991).
RN [11]
RP PHOSPHORYLATION AT TYR-505, AND MUTAGENESIS OF TYR-505.
RX PubMed=1708890; DOI=10.1073/pnas.88.9.3977;
RA Abraham K.M., Levin S.D., Marth J.D., Forbush K.A., Perlmutter R.M.;
RT "Thymic tumorigenesis induced by overexpression of p56lck.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:3977-3981(1991).
RN [12]
RP DISRUPTION PHENOTYPE.
RX PubMed=1579166; DOI=10.1038/357161a0;
RA Molina T.J., Kishihara K., Siderovski D.P., van Ewijk W., Narendran A.,
RA Timms E., Wakeham A., Paige C.J., Hartmann K.U., Veillette A.;
RT "Profound block in thymocyte development in mice lacking p56lck.";
RL Nature 357:161-164(1992).
RN [13]
RP PHOSPHORYLATION BY CSK.
RX PubMed=8371758; DOI=10.1038/365156a0;
RA Chow L.M., Fournel M., Davidson D., Veillette A.;
RT "Negative regulation of T-cell receptor signalling by tyrosine protein
RT kinase p50csk.";
RL Nature 365:156-160(1993).
RN [14]
RP MUTAGENESIS.
RX PubMed=8421674; DOI=10.1073/pnas.90.2.442;
RA Carrera A.C., Alexandrov K., Roberts T.M.;
RT "The conserved lysine of the catalytic domain of protein kinases is
RT actively involved in the phosphotransfer reaction and not required for
RT anchoring ATP.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:442-446(1993).
RN [15]
RP PALMITOYLATION AT CYS-3 AND CYS-5, AND MUTAGENESIS OF CYS-3 AND CYS-5.
RX PubMed=8413237; DOI=10.1128/mcb.13.10.6385-6392.1993;
RA Shenoy-Scaria A.M., Timson L.K., Kwong J., Shaw A.S., Lublin D.M.;
RT "Palmitylation of an amino-terminal cysteine motif of protein tyrosine
RT kinases p56lck and p59fyn mediates interaction with glycosyl-
RT phosphatidylinositol-anchored proteins.";
RL Mol. Cell. Biol. 13:6385-6392(1993).
RN [16]
RP PALMITOYLATION AT CYS-3 AND CYS-5, MYRISTOYLATION AT GLY-2, AND MUTAGENESIS
RP OF GLY-2; CYS-3 AND CYS-5.
RX PubMed=7980442; DOI=10.1042/bj3030749;
RA Koegl M., Zlatkine P., Ley S.C., Courtneidge S.A., Magee A.I.;
RT "Palmitoylation of multiple Src-family kinases at a homologous N-terminal
RT motif.";
RL Biochem. J. 303:749-753(1994).
RN [17]
RP INTERACTION WITH CBLB.
RX PubMed=10646608; DOI=10.1038/35003228;
RA Bachmaier K., Krawczyk C., Kozieradzki I., Kong Y.-Y., Sasaki T.,
RA Oliveira-dos-Santos A., Mariathasan S., Bouchard D., Wakeham A., Itie A.,
RA Le J., Ohashi P.S., Sarosi I., Nishina H., Lipkowitz S., Penninger J.M.;
RT "Negative regulation of lymphocyte activation and autoimmunity by the
RT molecular adaptor Cbl-b.";
RL Nature 403:211-216(2000).
RN [18]
RP SUBCELLULAR LOCATION.
RX PubMed=12218089; DOI=10.4049/jimmunol.169.6.2813;
RA Yasuda K., Nagafuku M., Shima T., Okada M., Yagi T., Yamada T., Minaki Y.,
RA Kato A., Tani-Ichi S., Hamaoka T., Kosugi A.;
RT "Fyn is essential for tyrosine phosphorylation of Csk-binding
RT protein/phosphoprotein associated with glycolipid-enriched microdomains in
RT lipid rafts in resting T cells.";
RL J. Immunol. 169:2813-2817(2002).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-192, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that plays an essential
CC role in the selection and maturation of developing T-cells in the
CC thymus and in the function of mature T-cells. Plays a key role in T-
CC cell antigen receptor (TCR)-linked signal transduction pathways.
CC Constitutively associated with the cytoplasmic portions of the CD4 and
CC CD8 surface receptors. Association of the TCR with a peptide antigen-
CC bound MHC complex facilitates the interaction of CD4 and CD8 with MHC
CC class II and class I molecules, respectively, thereby recruiting the
CC associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then
CC phosphorylates tyrosine residues within the immunoreceptor tyrosine-
CC based activation motifs (ITAM) of the cytoplasmic tails of the TCR-
CC gamma chains and CD3 subunits, initiating the TCR/CD3 signaling
CC pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70,
CC that becomes phosphorylated and activated by LCK. Following this, a
CC large number of signaling molecules are recruited, ultimately leading
CC to lymphokine production. LCK also contributes to signaling by other
CC receptor molecules. Associates directly with the cytoplasmic tail of
CC CD2, which leads to hyperphosphorylation and activation of LCK. Also
CC plays a role in the IL2 receptor-linked signaling pathway that controls
CC the T-cell proliferative response. Binding of IL2 to its receptor
CC results in increased activity of LCK. Is expressed at all stages of
CC thymocyte development and is required for the regulation of maturation
CC events that are governed by both pre-TCR and mature alpha beta TCR.
CC Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the
CC microtubule-associated protein MAPT, RHOH or TYROBP (By similarity).
CC Interacts with UNC119; this interaction plays a crucial role in
CC activation of LCK (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: The relative activities of the inhibitory
CC tyrosine-protein kinase CSK and the activating tyrosine-protein
CC phosphatase PTPRC/CD45 determine the level of LCK activity. These
CC interactions allow rapid and efficient activation of LCK in response to
CC TCR stimulation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Binds to the cytoplasmic domain of cell surface receptors,
CC such as AXL, CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to
CC effector molecules, such as PI4K, VAV1, RASA1, FYB1 and to other
CC protein kinases including CDK1, RAF1, ZAP70 and SYK. Binds to
CC phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its
CC SH3 domain and to the tyrosine phosphorylated form of KHDRBS1/p70
CC through its SH2 domain. Interacts with SQSTM1. Interacts with
CC phosphorylated LIME1. Interacts with CBLB and PTPRH. Interacts with
CC RUNX3. Forms a signaling complex with EPHA1, PTK2B AND PI3-KINASE; upon
CC activation by EFNA1 which may regulate T-lymphocytes migration.
CC Associates with ZAP70 and RHOH; these interactions allow LCK-mediated
CC RHOH and CD3 subunit phosphorylation in the presence of functional
CC ZAP70. Interacts with CEACAM1 (via cytoplasmic domain); mediates
CC CEACAM1 phosphorylation resulting in PTPN6 recruitment that
CC dephosphorylates TCR stimulation-induced CD247 and ZAP70. Interacts
CC with FYB2 (By similarity). Interacts with CD160. Interacts with CD48.
CC {ECO:0000250|UniProtKB:P06239}.
CC -!- INTERACTION:
CC P06240; P06332: Cd4; NbExp=3; IntAct=EBI-1401, EBI-1404;
CC P06240; P01731: Cd8a; NbExp=2; IntAct=EBI-1401, EBI-1433;
CC P06240; P06800: Ptprc; NbExp=2; IntAct=EBI-1401, EBI-1672;
CC P06240; Q9QXK9: Sh2d2a; NbExp=3; IntAct=EBI-1401, EBI-1644;
CC P06240; Q07666: KHDRBS1; Xeno; NbExp=2; IntAct=EBI-1401, EBI-1364;
CC P06240; P08575: PTPRC; Xeno; NbExp=2; IntAct=EBI-1401, EBI-1341;
CC P06240; O92972; Xeno; NbExp=2; IntAct=EBI-1401, EBI-710506;
CC P06240; P27958; Xeno; NbExp=3; IntAct=EBI-1401, EBI-706378;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12218089};
CC Lipid-anchor {ECO:0000269|PubMed:12218089}; Cytoplasmic side
CC {ECO:0000269|PubMed:12218089}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:12218089}. Note=Present in lipid rafts in an
CC inactive form. {ECO:0000250|UniProtKB:P06239}.
CC -!- TISSUE SPECIFICITY: Present at a low level in most T-cells, and at an
CC elevated level in LSTRA and Thy19 (T-cell lymphoma) cells.
CC -!- DEVELOPMENTAL STAGE: Levels remain relatively constant throughout T-
CC cell ontogeny.
CC -!- DOMAIN: The SH2 domain mediates interaction with SQSTM1. Interaction is
CC regulated by Ser-59 phosphorylation (By similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylated on Tyr-394, increasing enzymatic activity, this
CC site is dephosphorylated by PTN22. Phosphorylated on Tyr-505 by CSK,
CC decreasing activity. Dephosphorylated by PTPRC/CD45. Dephosphorylation
CC at Tyr-394 by PTPN2 negatively regulates T-cells differentiation (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Myristoylation is required prior to palmitoylation.
CC {ECO:0000269|PubMed:7980442, ECO:0000269|PubMed:8413237}.
CC -!- PTM: Palmitoylation regulates association with the plasma membrane and
CC could be mediated by ZDHHC2. {ECO:0000250|UniProtKB:P06239}.
CC -!- DISRUPTION PHENOTYPE: Mice show a dramatic reduction in the level of
CC peripheral T-cells, with 5-10% of wild-type levels. T-cells also
CC exhibit a 10-fold decrease in proliferative response.
CC {ECO:0000269|PubMed:1579166}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; M12056; AAB59674.1; -; mRNA.
DR EMBL; X03533; CAA27234.1; -; mRNA.
DR EMBL; X03533; CAA27235.1; ALT_SEQ; mRNA.
DR EMBL; X03533; CAA27236.1; ALT_SEQ; mRNA.
DR EMBL; AK088001; BAC40086.1; -; mRNA.
DR EMBL; BC011474; AAH11474.1; -; mRNA.
DR EMBL; M21511; AAA39422.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M18098; AAA39421.1; -; Genomic_DNA.
DR CCDS; CCDS18697.1; -.
DR PIR; I48845; I48845.
DR RefSeq; NP_001155905.1; NM_001162433.1.
DR RefSeq; NP_034823.1; NM_010693.3.
DR RefSeq; XP_006502881.1; XM_006502818.3.
DR AlphaFoldDB; P06240; -.
DR BMRB; P06240; -.
DR SMR; P06240; -.
DR BioGRID; 201120; 30.
DR CORUM; P06240; -.
DR ELM; P06240; -.
DR IntAct; P06240; 33.
DR MINT; P06240; -.
DR STRING; 10090.ENSMUSP00000066209; -.
DR BindingDB; P06240; -.
DR ChEMBL; CHEMBL2480; -.
DR DrugCentral; P06240; -.
DR iPTMnet; P06240; -.
DR PhosphoSitePlus; P06240; -.
DR SwissPalm; P06240; -.
DR EPD; P06240; -.
DR jPOST; P06240; -.
DR MaxQB; P06240; -.
DR PaxDb; P06240; -.
DR PRIDE; P06240; -.
DR ProteomicsDB; 265047; -.
DR Antibodypedia; 735; 1730 antibodies from 45 providers.
DR DNASU; 16818; -.
DR Ensembl; ENSMUST00000067240; ENSMUSP00000066209; ENSMUSG00000000409.
DR Ensembl; ENSMUST00000102596; ENSMUSP00000099656; ENSMUSG00000000409.
DR GeneID; 16818; -.
DR KEGG; mmu:16818; -.
DR UCSC; uc008uxi.2; mouse.
DR CTD; 3932; -.
DR MGI; MGI:96756; Lck.
DR VEuPathDB; HostDB:ENSMUSG00000000409; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000161163; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P06240; -.
DR OMA; ICEHCNY; -.
DR PhylomeDB; P06240; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-1433559; Regulation of KIT signaling.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-202427; Phosphorylation of CD3 and TCR zeta chains.
DR Reactome; R-MMU-202430; Translocation of ZAP-70 to Immunological synapse.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-210990; PECAM1 interactions.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-389356; CD28 co-stimulation.
DR Reactome; R-MMU-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-MMU-389359; CD28 dependent Vav1 pathway.
DR Reactome; R-MMU-389513; CTLA4 inhibitory signaling.
DR Reactome; R-MMU-389948; PD-1 signaling.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-9013407; RHOH GTPase cycle.
DR Reactome; R-MMU-9020558; Interleukin-2 signaling.
DR Reactome; R-MMU-9706374; FLT3 signaling through SRC family kinases.
DR BioGRID-ORCS; 16818; 6 hits in 74 CRISPR screens.
DR ChiTaRS; Lck; mouse.
DR PRO; PR:P06240; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P06240; protein.
DR Bgee; ENSMUSG00000000409; Expressed in thymus and 154 other tissues.
DR ExpressionAtlas; P06240; baseline and differential.
DR Genevisible; P06240; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030139; C:endocytic vesicle; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0001772; C:immunological synapse; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0000242; C:pericentriolar material; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0099091; C:postsynaptic specialization, intracellular component; ISO:MGI.
DR GO; GO:0003823; F:antigen binding; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0042609; F:CD4 receptor binding; IPI:UniProtKB.
DR GO; GO:0042610; F:CD8 receptor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISO:MGI.
DR GO; GO:0016004; F:phospholipase activator activity; ISO:MGI.
DR GO; GO:0043274; F:phospholipase binding; ISO:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
DR GO; GO:1990405; F:protein antigen binding; IPI:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:ARUK-UCL.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0042169; F:SH2 domain binding; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0042608; F:T cell receptor binding; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IDA:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; ISS:UniProtKB.
DR GO; GO:0038094; P:Fc-gamma receptor signaling pathway; ISO:MGI.
DR GO; GO:0042492; P:gamma-delta T cell differentiation; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISO:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; ISO:MGI.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:1903039; P:positive regulation of leukocyte cell-cell adhesion; ISO:MGI.
DR GO; GO:0050870; P:positive regulation of T cell activation; ISS:UniProtKB.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:MGI.
DR GO; GO:0070474; P:positive regulation of uterine smooth muscle contraction; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; IGI:MGI.
DR GO; GO:0050856; P:regulation of T cell receptor signaling pathway; IDA:MGI.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:UniProtKB.
DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0009612; P:response to mechanical stimulus; ISO:MGI.
DR GO; GO:0010038; P:response to metal ion; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISS:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10362; SH2_Src_Lck; 1.
DR CDD; cd12005; SH3_Lck; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR035850; Lck_SH2.
DR InterPro; IPR035749; Lck_SH3.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Cytoplasm; Kinase; Lipoprotein; Membrane;
KW Myristate; Nucleotide-binding; Palmitate; Phosphoprotein; Proto-oncogene;
KW Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tyrosine-protein kinase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305"
FT CHAIN 2..509
FT /note="Proto-oncogene tyrosine-protein kinase LCK"
FT /id="PRO_0000088125"
FT DOMAIN 61..121
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 127..224
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 245..498
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 2..72
FT /note="Interactions with CD4 and CD8"
FT REGION 154..242
FT /note="Interaction with PTPRH"
FT /evidence="ECO:0000250"
FT ACT_SITE 364
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 251..259
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 273
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 102
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06239"
FT MOD_RES 159
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P06239"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06239"
FT MOD_RES 192
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06239"
FT MOD_RES 394
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P06239"
FT MOD_RES 505
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000250|UniProtKB:P06239"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000305|PubMed:7980442"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:7980442,
FT ECO:0000269|PubMed:8413237"
FT LIPID 5
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:7980442,
FT ECO:0000269|PubMed:8413237"
FT MUTAGEN 2
FT /note="G->A: Abolishes myristoylation and palmitoylation."
FT /evidence="ECO:0000269|PubMed:7980442"
FT MUTAGEN 3..5
FT /note="CVC->SVK: Complete loss of interaction with CD4 or
FT CD8."
FT /evidence="ECO:0000269|PubMed:2107025"
FT MUTAGEN 3
FT /note="C->S: Abolishes plasma membrane association; when
FT associated with S-41. Reduced palmitoylation level."
FT /evidence="ECO:0000269|PubMed:7980442,
FT ECO:0000269|PubMed:8413237"
FT MUTAGEN 5
FT /note="C->K: Reduced palmitoylation level."
FT /evidence="ECO:0000269|PubMed:7980442,
FT ECO:0000269|PubMed:8413237"
FT MUTAGEN 5
FT /note="C->S: Abolishes plasma membrane association; when
FT associated with S-21."
FT /evidence="ECO:0000269|PubMed:7980442,
FT ECO:0000269|PubMed:8413237"
FT MUTAGEN 20
FT /note="C->S: Complete loss of interaction with CD4 or CD8."
FT /evidence="ECO:0000269|PubMed:2107025"
FT MUTAGEN 23
FT /note="C->S: Complete loss of interaction with CD4 or CD8."
FT /evidence="ECO:0000269|PubMed:2107025"
FT MUTAGEN 269
FT /note="K->N: Reduced activity."
FT MUTAGEN 270
FT /note="V->L: Reduced activity."
FT MUTAGEN 271
FT /note="A->S: Reduced activity."
FT MUTAGEN 272
FT /note="V->A: Reduced activity."
FT MUTAGEN 273
FT /note="K->R: Loss of activity."
FT /evidence="ECO:0000269|PubMed:1706070"
FT MUTAGEN 274
FT /note="S->N: Reduced activity."
FT MUTAGEN 275
FT /note="L->M: Reduced activity."
FT MUTAGEN 276
FT /note="K->V: Reduced activity."
FT MUTAGEN 505
FT /note="Y->F: Causes thymic tumors."
FT /evidence="ECO:0000269|PubMed:1708890,
FT ECO:0000269|PubMed:3380790"
SQ SEQUENCE 509 AA; 57943 MW; 3513102F49A7FD0B CRC64;
MGCVCSSNPE DDWMENIDVC ENCHYPIVPL DSKISLPIRN GSEVRDPLVT YEGSLPPASP
LQDNLVIALH SYEPSHDGDL GFEKGEQLRI LEQSGEWWKA QSLTTGQEGF IPFNFVAKAN
SLEPEPWFFK NLSRKDAERQ LLAPGNTHGS FLIRESESTA GSFSLSVRDF DQNQGEVVKH
YKIRNLDNGG FYISPRITFP GLHDLVRHYT NASDGLCTKL SRPCQTQKPQ KPWWEDEWEV
PRETLKLVER LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHPRL
VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLNVNK LLDMAAQIAE GMAFIEEQNY
IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA KFPIKWTAPE AINYGTFTIK
SDVWSFGILL TEIVTHGRIP YPGMTNPEVI QNLERGYRMV RPDNCPEELY HLMMLCWKER
PEDRPTFDYL RSVLDDFFTA TEGQYQPQP
