ID LCK_HUMAN Reviewed; 509 AA. AC P06239; D3DPP8; P07100; Q12850; Q13152; Q5TDH8; Q5TDH9; Q7RTZ3; AC Q96DW4; Q9NYT8; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 6. DT 11-NOV-2015, entry version 214. DE RecName: Full=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=Protein YT16; DE AltName: Full=Proto-oncogene Lck; DE AltName: Full=T cell-specific protein-tyrosine kinase; DE AltName: Full=p56-LCK; GN Name=LCK; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3493153; DOI=10.1002/eji.1830161229; RA Koga Y., Caccia N., Toyonaga B., Spolski R., Yanagi Y., Yoshikai Y., RA Mak T.W.; RT "A human T cell-specific cDNA clone (YT16) encodes a protein with RT extensive homology to a family of protein-tyrosine kinases."; RL Eur. J. Immunol. 16:1643-1646(1986). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3265417; DOI=10.1002/jcb.240380206; RA Perlmutter R.M., Marth J.D., Lewis D.B., Peet R., Ziegler S.F., RA Wilson C.B.; RT "Structure and expression of lck transcripts in human lymphoid RT cells."; RL J. Cell. Biochem. 38:117-126(1988). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2558056; DOI=10.1016/0378-1119(89)90144-3; RA Rouer E., van Huynh T., de Souza S.L., Lang M.C., Fischer S., RA Benarous R.; RT "Structure of the human lck gene: differences in genomic organisation RT within src-related genes affect only N-terminal exons."; RL Gene 84:105-113(1989). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-28; GLN-LYS-PRO-232 INS; RP VAL-353 AND LEU-447, AND PHOSPHORYLATION AT TYR-394 AND TYR-505. RC TISSUE=Leukemia; RX PubMed=8139546; DOI=10.1128/MCB.14.4.2429; RA Wright D.D., Sefton B.M., Kamps M.P.; RT "Oncogenic activation of the Lck protein accompanies translocation of RT the LCK gene in the human HSB2 T-cell leukemia."; RL Mol. Cell. Biol. 14:2429-2437(1994). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND ALTERNATIVE SPLICING. RC TISSUE=Leukemic T-cell; RX PubMed=7495859; DOI=10.1016/0167-4781(95)00162-A; RA Vogel L.B., Arthur R., Fujita D.J.; RT "An aberrant lck mRNA in two human T-cell lines."; RL Biochim. Biophys. Acta 1264:168-172(1995). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=12401726; DOI=10.2337/diabetes.51.11.3326; RA Nervi S., Nicodeme S., Gartioux C., Atlan C., Lathrop M., Reviron D., RA Naquet P., Matsuda F., Imbert J., Vialettes B.; RT "No association between lck gene polymorphisms and protein level in RT type 1 diabetes."; RL Diabetes 51:3326-3330(2002). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Lymph; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35. RX PubMed=2850479; 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 [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35. RX PubMed=2787474; RA Takadera T., Leung S., Gernone A., Koga Y., Takihara Y., RA Miyamoto N.G., Mak T.W.; RT "Structure of the two promoters of the human lck gene: differential RT accumulation of two classes of lck transcripts in T cells."; RL Mol. Cell. Biol. 9:2173-2180(1989). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-509. RC TISSUE=Peripheral blood lymphocyte; RX PubMed=11009097; RX DOI=10.1002/1521-4141(200009)30:9<2632::AID-IMMU2632>3.0.CO;2-C; RA Boncristiano M., Majolini M.B., D'Elios M.M., Pacini S., Valensin S., RA Ulivieri C., Amedei A., Falini B., Del Prete G., Telford J.L., RA Baldari C.T.; RT "Defective recruitment and activation of ZAP-70 in common variable RT immunodeficiency patients with T cell defects."; RL Eur. J. Immunol. 30:2632-2638(2000). RN [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 368-509. RX PubMed=2835736; RA Veillette A., Foss F.M., Sausville E.A., Bolen J.B., Rosen N.; RT "Expression of the lck tyrosine kinase gene in human colon carcinoma RT and other non-lymphoid human tumor cell lines."; RL Oncogene Res. 1:357-374(1987). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 375-509. RX PubMed=3489486; DOI=10.1016/0167-4889(86)90228-4; RA Trevillyan J.M., Lin Y., Chen S.J., Phillips C.A., Canna C., RA Linna T.J.; RT "Human T lymphocytes express a protein-tyrosine kinase homologous to RT p56LSTRA."; RL Biochim. Biophys. Acta 888:286-295(1986). RN [15] RP PHOSPHORYLATION AT TYR-505. RX PubMed=1639064; RA Bergman M., Mustelin T., Oetken C., Partanen J., Flint N.A., RA Amrein K.E., Autero M., Burn P., Alitalo K.; RT "The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and RT down regulates its catalytic activity."; RL EMBO J. 11:2919-2924(1992). RN [16] RP INTERACTION WITH PI3K. RX PubMed=7504174; RA Vogel L.B., Fujita D.J.; RT "The SH3 domain of p56lck is involved in binding to RT phosphatidylinositol 3'-kinase from T lymphocytes."; RL Mol. Cell. Biol. 13:7408-7417(1993). RN [17] RP INTERACTION WITH KHDRBS1. RX PubMed=7852312; DOI=10.1074/jbc.270.6.2506; RA Vogel L.B., Fujita D.J.; RT "p70 phosphorylation and binding to p56lck is an early event in RT interleukin-2-induced onset of cell cycle progression in T- RT lymphocytes."; RL J. Biol. Chem. 270:2506-2511(1995). RN [18] RP INTERACTION WITH SQSTM1, AND MUTAGENESIS OF SER-59 AND ARG-154. RX PubMed=8618896; DOI=10.1073/pnas.92.26.12338; RA Park I., Chung J., Walsh C.T., Yun Y., Strominger J.L., Shin J.; RT "Phosphotyrosine-independent binding of a 62-kDa protein to the src RT homology 2 (SH2) domain of p56lck and its regulation by RT phosphorylation of Ser-59 in the lck unique N-terminal region."; RL Proc. Natl. Acad. Sci. U.S.A. 92:12338-12342(1995). RN [19] RP PHOSPHORYLATION AT TYR-505 BY CSK, AND AUTOPHOSPHORYLATION. RX PubMed=8631775; DOI=10.1074/jbc.271.13.7465; RA Bougeret C., Delaunay T., Romero F., Jullien P., Sabe H., Hanafusa H., RA Benarous R., Fischer S.; RT "Detection of a physical and functional interaction between Csk and RT Lck which involves the SH2 domain of Csk and is mediated by RT autophosphorylation of Lck on tyrosine 394."; RL J. Biol. Chem. 271:7465-7472(1996). RN [20] RP INTERACTION WITH HIV-1 NEF. RX PubMed=8794306; RA Greenway A.L., Azad A., Mills J., McPhee D.A.; RT "Human immunodeficiency virus type 1 Nef binds directly to LCK and RT mitogen-activated protein kinase, inhibiting kinase activity."; RL J. Virol. 70:6701-6708(1996). RN [21] RP INTERACTION WITH AXL. RX PubMed=9178760; DOI=10.1038/sj.onc.1201123; RA Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R., RA Ullrich A., Bartram C.R., Janssen J.W.; RT "Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is RT mediated mainly by a multi-substrate docking-site."; RL Oncogene 14:2619-2631(1997). RN [22] RP REVIEW. RX PubMed=10848956; DOI=10.1046/j.1432-1327.2000.01412.x; RA Isakov N., Biesinger B.; RT "Lck protein tyrosine kinase is a key regulator of T-cell activation RT and a target for signal intervention by Herpesvirus saimiri and other RT viral gene products."; RL Eur. J. Biochem. 267:3413-3421(2000). RN [23] 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., RA Minaki Y., 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 RT microdomains in lipid rafts in resting T cells."; RL J. Immunol. 169:2813-2817(2002). RN [24] RP MASS SPECTROMETRY. RC TISSUE=Mammary cancer; RX PubMed=11840567; RX DOI=10.1002/1615-9861(200202)2:2<212::AID-PROT212>3.0.CO;2-H; RA Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., RA Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., RA Zvelebil M.J.; RT "Cluster analysis of an extensive human breast cancer cell line RT protein expression map database."; RL Proteomics 2:212-223(2002). RN [25] RP INTERACTION WITH LIME1. RX PubMed=14610046; DOI=10.1084/jem.20031484; RA Brdickova N., Brdicka T., Angelisova P., Horvath O., Spicka J., RA Hilgert I., Paces J., Simeoni L., Kliche S., Merten C., Schraven B., RA Horejsi V.; RT "LIME: a new membrane raft-associated adaptor protein involved in CD4 RT and CD8 coreceptor signaling."; RL J. Exp. Med. 198:1453-1462(2003). RN [26] RP INTERACTION WITH LIME1. RX PubMed=14610044; DOI=10.1084/jem.20030232; RA Hur E.M., Son M., Lee O.-H., Choi Y.B., Park C., Lee H., Yun Y.; RT "LIME, a novel transmembrane adaptor protein, associates with p56lck RT and mediates T cell activation."; RL J. Exp. Med. 198:1463-1473(2003). RN [27] RP INTERACTION WITH PTPRH. RX PubMed=12837766; DOI=10.1074/jbc.M300648200; RA Ito T., Okazawa H., Maruyama K., Tomizawa K., Motegi S., Ohnishi H., RA Kuwano H., Kosugi A., Matozaki T.; RT "Interaction of SAP-1, a transmembrane-type protein-tyrosine RT phosphatase, with the tyrosine kinase Lck. Roles in regulation of T RT cell function."; RL J. Biol. Chem. 278:34854-34863(2003). RN [28] RP INTERACTION WITH UNC119. RX PubMed=14757743; DOI=10.1084/jem.20030589; RA Gorska M.M., Stafford S.J., Cen O., Sur S., Alam R.; RT "Unc119, a novel activator of Lck/Fyn, is essential for T cell RT activation."; RL J. Exp. Med. 199:369-379(2004). RN [29] RP FUNCTION IN PHOSPHORYLATION OF ZAP70. RX PubMed=16339550; DOI=10.4049/jimmunol.175.12.8123; RA Gelkop S., Gish G.D., Babichev Y., Pawson T., Isakov N.; RT "T cell activation-induced CrkII binding to the Zap70 protein tyrosine RT kinase is mediated by Lck-dependent phosphorylation of Zap70 tyrosine RT 315."; RL J. Immunol. 175:8123-8132(2005). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer RT cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [31] RP DEPHOSPHORYLATION BY PTN22. RX PubMed=16461343; DOI=10.1074/jbc.M600498200; RA Wu J., Katrekar A., Honigberg L.A., Smith A.M., Conn M.T., Tang J., RA Jeffery D., Mortara K., Sampang J., Williams S.R., Buggy J., RA Clark J.M.; RT "Identification of substrates of human protein-tyrosine phosphatase RT PTPN22."; RL J. Biol. Chem. 281:11002-11010(2006). RN [32] RP FUNCTION IN PHOSPHORYLATION OF TYROBP. RX PubMed=16709819; DOI=10.4049/jimmunol.176.11.6615; RA Mason L.H., Willette-Brown J., Taylor L.S., McVicar D.W.; RT "Regulation of Ly49D/DAP12 signal transduction by Src-family kinases RT and CD45."; RL J. Immunol. 176:6615-6623(2006). RN [33] RP INTERACTION WITH EPHA1; PTK2B AND PI3-KINASE. RX PubMed=17634955; DOI=10.1002/eji.200737111; RA Hjorthaug H.S., Aasheim H.C.; RT "Ephrin-A1 stimulates migration of CD8+CCR7+ T lymphocytes."; RL Eur. J. Immunol. 37:2326-2336(2007). RN [34] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102; THR-159; SER-162; RP SER-194 AND TYR-505, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [37] RP FUNCTION IN PHOSPHORYLATION OF RUNX3. RX PubMed=20100835; DOI=10.1074/jbc.M109.071381; RA Goh Y.M., Cinghu S., Hong E.T., Lee Y.S., Kim J.H., Jang J.W., RA Li Y.H., Chi X.Z., Lee K.S., Wee H., Ito Y., Oh B.C., Bae S.C.; RT "Src kinase phosphorylates RUNX3 at tyrosine residues and localizes RT the protein in the cytoplasm."; RL J. Biol. Chem. 285:10122-10129(2010). RN [38] RP FUNCTION IN PTK2B/PYK2 PHOSPHORYLATION. RX PubMed=20028775; DOI=10.1189/jlb.0409227; RA Collins M., Tremblay M., Chapman N., Curtiss M., Rothman P.B., RA Houtman J.C.; RT "The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 RT and 580 occurs via a distinct mechanism than other receptor systems."; RL J. Leukoc. Biol. 87:691-701(2010). RN [39] RP FUNCTION IN PHOSPHORYLATION OF RHOH. RX PubMed=20851766; DOI=10.1016/j.cellsig.2010.09.009; RA Wang H., Zeng X., Fan Z., Lim B.; RT "RhoH modulates pre-TCR and TCR signalling by regulating LCK."; RL Cell. Signal. 23:249-258(2011). RN [40] RP FUNCTION IN TCR SIGNALING, PHOSPHORYLATION, AND DEPHOSPHORYLATION AT RP TYR-394 BY PTPN2. RX PubMed=22080863; DOI=10.1172/JCI59492; RA Wiede F., Shields B.J., Chew S.H., Kyparissoudis K., van Vliet C., RA Galic S., Tremblay M.L., Russell S.M., Godfrey D.I., Tiganis T.; RT "T cell protein tyrosine phosphatase attenuates T cell signaling to RT maintain tolerance in mice."; RL J. Clin. Invest. 121:4758-4774(2011). RN [41] RP FUNCTION IN PHOSPHORYLATION OF MAPT. RX PubMed=21269457; DOI=10.1186/1750-1326-6-12; RA Scales T.M., Derkinderen P., Leung K.Y., Byers H.L., Ward M.A., RA Price C., Bird I.N., Perera T., Kellie S., Williamson R., RA Anderton B.H., Reynolds C.H.; RT "Tyrosine phosphorylation of tau by the SRC family kinases lck and RT fyn."; RL Mol. Neurodegener. 6:12-12(2011). RN [42] RP ENZYME REGULATION. RX PubMed=21917715; DOI=10.1126/scisignal.2001893; RA Schoenborn J.R., Tan Y.X., Zhang C., Shokat K.M., Weiss A.; RT "Feedback circuits monitor and adjust Basal lck-dependent events in T RT cell receptor signaling."; RL Sci. Signal. 4:RA59-RA59(2011). RN [43] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [44] RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 UL46. RX PubMed=23946459; DOI=10.1128/JVI.01702-13; RA Strunk U., Saffran H.A., Wu F.W., Smiley J.R.; RT "Role of herpes simplex virus VP11/12 tyrosine-based motifs in binding RT and activation of the Src family kinase Lck and recruitment of p85, RT Grb2, and Shc."; RL J. Virol. 87:11276-11286(2013). RN [45] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 53-226. RX PubMed=7512222; DOI=10.1038/368764a0; RA Eck M.J., Atweell S.K., Shoelson S.E., Harrison S.C.; RT "Structure of the regulatory domains of the Src-family tyrosine kinase RT Lck."; RL Nature 368:764-769(1994). RN [46] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 127-221. RX PubMed=7532720; DOI=10.1006/jmbi.1994.0089; RA Mikol V., Baumann G., Keller T.H., Manning U.M., Zurini M.G.M.; RT "The crystal structures of the SH2 domain of p56lck complexed with two RT phosphonopeptides suggest a gated peptide binding site."; RL J. Mol. Biol. 246:344-355(1995). RN [47] RP X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 122-226. RX PubMed=8604142; DOI=10.1006/jmbi.1996.0112; RA Tong L., Warren T.C., King J., Betageri R., Rose J., Jakes S.; RT "Crystal structures of the human p56lck SH2 domain in complex with two RT short phosphotyrosyl peptides at 1.0-A and 1.8-A resolution."; RL J. Mol. Biol. 256:601-610(1996). RN [48] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 231-501. RX PubMed=8945479; DOI=10.1038/384484a0; RA Yamaguchi H., Hendrickson W.A.; RT "Structural basis for activation of human lymphocyte kinase Lck upon RT tyrosine phosphorylation."; RL Nature 384:484-489(1996). RN [49] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 119-226. RX PubMed=9685372; DOI=10.1074/jbc.273.32.20238; RA Tong L., Warren T.C., Lukas S., Schembri-King J., Betageri R., RA Proudfoot J.R., Jakes S.; RT "Carboxymethyl-phenylalanine as a replacement for phosphotyrosine in RT SH2 domain binding."; RL J. Biol. Chem. 273:20238-20242(1998). RN [50] RP VARIANT IMD22 PRO-341. RX PubMed=22985903; DOI=10.1016/j.jaci.2012.07.029; RA Hauck F., Randriamampita C., Martin E., Gerart S., Lambert N., Lim A., RA Soulier J., Maciorowski Z., Touzot F., Moshous D., Quartier P., RA Heritier S., Blanche S., Rieux-Laucat F., Brousse N., Callebaut I., RA Veillette A., Hivroz C., Fischer A., Latour S., Picard C.; RT "Primary T-cell immunodeficiency with immunodysregulation caused by RT autosomal recessive LCK deficiency."; RL J. Allergy Clin. Immunol. 130:1144-1152(2012). CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that plays an CC essential role in the selection and maturation of developing T- CC cells in the thymus and in the function of mature T-cells. Plays a CC key role in T-cell antigen receptor (TCR)-linked signal CC transduction pathways. Constitutively associated with the CC cytoplasmic portions of the CD4 and CD8 surface receptors. CC Association of the TCR with a peptide antigen-bound MHC complex CC facilitates the interaction of CD4 and CD8 with MHC class II and CC class I molecules, respectively, thereby recruiting the associated CC LCK protein to the vicinity of the TCR/CD3 complex. LCK then CC phosphorylates tyrosines residues within the immunoreceptor CC tyrosine-based activation motifs (ITAM) of the cytoplasmic tails CC of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 CC signaling pathway. Once stimulated, the TCR recruits the tyrosine CC kinase ZAP70, that becomes phosphorylated and activated by LCK. CC Following this, a large number of signaling molecules are CC recruited, ultimately leading to lymphokine production. LCK also CC contributes to signaling by other receptor molecules. Associates CC directly with the cytoplasmic tail of CD2, which leads to CC hyperphosphorylation and activation of LCK. Also plays a role in CC the IL2 receptor-linked signaling pathway that controls the T-cell CC proliferative response. Binding of IL2 to its receptor results in CC increased activity of LCK. Is expressed at all stages of thymocyte CC development and is required for the regulation of maturation CC events that are governed by both pre-TCR and mature alpha beta CC TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, CC the microtubule-associated protein MAPT, RHOH or TYROBP. CC {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, CC ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, CC ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, CC ECO:0000269|PubMed:22080863}. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- CC ProRule:PRU10028}. CC -!- ENZYME 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 CC response to TCR stimulation. {ECO:0000269|PubMed:21917715}. CC -!- SUBUNIT: Binds to the cytoplasmic domain of cell surface CC receptors, such as AXL, CD2, CD4, CD5, CD8, CD44, CD45 and CD122. CC Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB CC and to other protein kinases including CDK1, RAF1, ZAP70 and SYK. CC Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes CC through its SH3 domain and to the tyrosine phosphorylated form of CC KHDRBS1/p70 through its SH2 domain. Binds to HIV-1 Nef through its CC SH3 domain. This interaction inhibits its tyrosine-kinase CC activity. Interacts with herpes simplex virus 1 UL46; this CC interaction acitivates LCK. Interacts with SQSTM1. Interacts with CC phosphorylated LIME1. Interacts with CBLB and PTPRH. Interacts CC with RUNX3. Forms a signaling complex with EPHA1, PTK2B AND PI3- CC KINASE; upon activation by EFNA1 which may regulate T-lymphocyte CC migration. Associates with ZAP70 and RHOH; these interactions CC allow LCK-mediated RHOH and CD3 subunit phosphorylation in the CC presence of functional ZAP70. Interacts with UNC119; this CC interaction plays a crucial role in activation of LCK. CC {ECO:0000269|PubMed:12837766, ECO:0000269|PubMed:14610044, CC ECO:0000269|PubMed:14610046, ECO:0000269|PubMed:14757743, CC ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:23946459, CC ECO:0000269|PubMed:7504174, ECO:0000269|PubMed:7852312, CC ECO:0000269|PubMed:8618896, ECO:0000269|PubMed:8794306, CC ECO:0000269|PubMed:9178760}. CC -!- INTERACTION: CC Self; NbExp=3; IntAct=EBI-1348, EBI-1348; CC P22575:- (xeno); NbExp=7; IntAct=EBI-1348, EBI-866709; CC Q9YJQ8:- (xeno); NbExp=2; IntAct=EBI-1348, EBI-7709835; CC Q13444:ADAM15; NbExp=3; IntAct=EBI-1348, EBI-77818; CC P10275:AR; NbExp=7; IntAct=EBI-1348, EBI-608057; CC P20749:BCL3; NbExp=3; IntAct=EBI-1348, EBI-958997; CC P01730:CD4; NbExp=2; IntAct=EBI-1348, EBI-353826; CC Q5VV42:CDKAL1; NbExp=3; IntAct=EBI-1348, EBI-10194801; CC Q13480:GAB1; NbExp=10; IntAct=EBI-1348, EBI-517684; CC P08238:HSP90AB1; NbExp=2; IntAct=EBI-1348, EBI-352572; CC Q07666:KHDRBS1; NbExp=5; IntAct=EBI-1348, EBI-1364; CC P10721:KIT; NbExp=8; IntAct=EBI-1348, EBI-1379503; CC O43561:LAT; NbExp=2; IntAct=EBI-1348, EBI-1222766; CC Q9BRK4:LZTS2; NbExp=3; IntAct=EBI-1348, EBI-741037; CC Q9H204:MED28; NbExp=4; IntAct=EBI-1348, EBI-514199; CC P08581:MET; NbExp=3; IntAct=EBI-1348, EBI-1039152; CC P04150:NR3C1; NbExp=3; IntAct=EBI-1348, EBI-493507; CC Q04759:PRKCQ; NbExp=2; IntAct=EBI-1348, EBI-374762; CC Q9Y2R2:PTPN22; NbExp=6; IntAct=EBI-1348, EBI-1211241; CC P29350:PTPN6; NbExp=5; IntAct=EBI-1348, EBI-78260; CC P08575:PTPRC; NbExp=7; IntAct=EBI-1348, EBI-1341; CC Q9NP31:SH2D2A; NbExp=12; IntAct=EBI-1348, EBI-490630; CC P43405:SYK; NbExp=7; IntAct=EBI-1348, EBI-78302; CC P0CG48:UBC; NbExp=2; IntAct=EBI-1348, EBI-3390054; CC P43403:ZAP70; NbExp=2; IntAct=EBI-1348, EBI-1211276; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12218089}. CC Cell membrane {ECO:0000269|PubMed:12218089}; Lipid-anchor CC {ECO:0000269|PubMed:12218089}; Cytoplasmic side CC {ECO:0000269|PubMed:12218089}. Note=Present in lipid rafts in an CC inactive form. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=Long; CC IsoId=P06239-1; Sequence=Displayed; CC Name=Short; CC IsoId=P06239-2; Sequence=VSP_005000, VSP_005001; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=P06239-3; Sequence=VSP_016049; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed specifically in lymphoid cells. CC -!- DOMAIN: The SH2 domain mediates interaction with SQSTM1. CC Interaction is regulated by Ser-59 phosphorylation. CC -!- PTM: Autophosphorylated on Tyr-394, increasing enzymatic activity, CC this site is dephosphorylated by PTN22. Phosphorylated on Tyr-505 CC by CSK, decreasing activity. Dephosphorylated by PTPRC/CD45. CC Dephosphorylation at Tyr-394 by PTPN2 negatively regulates T-cell CC receptor signaling. {ECO:0000269|PubMed:1639064, CC ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:8139546, CC ECO:0000269|PubMed:8631775}. CC -!- PTM: Myristoylation is required prior to palmitoylation. CC {ECO:0000250}. CC -!- PTM: Palmitoylation regulates subcellular location. {ECO:0000250}. CC -!- MASS SPECTROMETRY: Mass=57869.42; Method=MALDI; Range=2-509; CC Evidence={ECO:0000269|PubMed:11840567}; CC -!- DISEASE: Note=A chromosomal aberration involving LCK is found in CC leukemias. Translocation t(1;7)(p34;q34) with TCRB. CC -!- DISEASE: Immunodeficiency 22 (IMD22) [MIM:615758]: A primary CC immunodeficiency characterized by T-cell dysfunction. Affected CC individuals present with lymphopenia, recurrent infections, severe CC diarrhea, and failure to thrive. {ECO:0000269|PubMed:22985903}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. SRC subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SIMILARITY: Contains 1 SH2 domain. {ECO:0000255|PROSITE- CC ProRule:PRU00191}. CC -!- SIMILARITY: Contains 1 SH3 domain. {ECO:0000255|PROSITE- CC ProRule:PRU00192}. CC -!- SEQUENCE CAUTION: CC Sequence=CAI22320.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=CAI22321.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/LCKID14ch1p34.html"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Lck entry; CC URL="https://en.wikipedia.org/wiki/Lck"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X05027; CAA28691.1; -; mRNA. DR EMBL; X13529; CAA31884.1; -; mRNA. DR EMBL; M36881; AAA59502.1; -; mRNA. DR EMBL; X14055; CAA32211.1; -; Genomic_DNA. DR EMBL; X14053; CAA32211.1; JOINED; Genomic_DNA. DR EMBL; X14054; CAA32211.1; JOINED; Genomic_DNA. DR EMBL; U07236; AAA18225.1; -; mRNA. DR EMBL; U23852; AAC50287.1; -; mRNA. DR EMBL; BN000073; CAD55807.1; -; Genomic_DNA. DR EMBL; AL121991; CAI22320.1; ALT_INIT; Genomic_DNA. DR EMBL; AL121991; CAI22321.1; ALT_INIT; Genomic_DNA. DR EMBL; CH471059; EAX07543.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07546.1; -; Genomic_DNA. DR EMBL; BC013200; AAH13200.1; -; mRNA. DR EMBL; M21510; AAA59501.1; ALT_TERM; Genomic_DNA. DR EMBL; M26692; AAA59503.1; -; Genomic_DNA. DR EMBL; AF228313; AAF34794.1; -; mRNA. DR EMBL; X06369; CAA29667.1; -; mRNA. DR EMBL; X04476; CAA28165.1; -; mRNA. DR CCDS; CCDS359.1; -. [P06239-1] DR PIR; JQ0152; OKHULK. DR RefSeq; NP_001036236.1; NM_001042771.2. [P06239-1] DR RefSeq; NP_005347.3; NM_005356.4. [P06239-1] DR UniGene; Hs.470627; -. DR PDB; 1BHF; X-ray; 1.80 A; A=119-226. DR PDB; 1BHH; X-ray; 1.90 A; A=119-226, B=124-226. DR PDB; 1CWD; X-ray; 2.25 A; L=127-222. DR PDB; 1CWE; X-ray; 2.30 A; A/C=127-222. DR PDB; 1FBZ; X-ray; 2.40 A; A/B=123-226. DR PDB; 1H92; NMR; -; A=59-120. DR PDB; 1IJR; X-ray; 2.20 A; A=124-226. DR PDB; 1KIK; NMR; -; A=64-120. DR PDB; 1LCJ; X-ray; 1.80 A; A=119-226. DR PDB; 1LCK; X-ray; 2.50 A; A=53-226, B=502-509. DR PDB; 1LKK; X-ray; 1.00 A; A=122-226. DR PDB; 1LKL; X-ray; 1.80 A; A=123-226. DR PDB; 1Q68; NMR; -; B=7-35. DR PDB; 1Q69; NMR; -; B=7-35. DR PDB; 1QPC; X-ray; 1.60 A; A=231-509. DR PDB; 1QPD; X-ray; 2.00 A; A=231-509. DR PDB; 1QPE; X-ray; 2.00 A; A=231-509. DR PDB; 1QPJ; X-ray; 2.20 A; A=231-509. DR PDB; 1X27; X-ray; 2.70 A; A/B/C/D/E/F=64-226. DR PDB; 2IIM; X-ray; 1.00 A; A=59-119. DR PDB; 2OF2; X-ray; 2.00 A; A=231-501. DR PDB; 2OF4; X-ray; 2.70 A; A=231-501. DR PDB; 2OFU; X-ray; 2.00 A; A=229-501. DR PDB; 2OFV; X-ray; 2.00 A; A/B=232-498. DR PDB; 2OG8; X-ray; 2.30 A; A/B=237-499. DR PDB; 2PL0; X-ray; 2.80 A; A=225-509. DR PDB; 2ZM1; X-ray; 2.10 A; A=225-509. DR PDB; 2ZM4; X-ray; 2.70 A; A=225-509. DR PDB; 2ZYB; X-ray; 2.55 A; A=225-509. DR PDB; 3AC1; X-ray; 1.99 A; A=225-509. DR PDB; 3AC2; X-ray; 2.10 A; A=225-509. DR PDB; 3AC3; X-ray; 2.55 A; A=225-509. DR PDB; 3AC4; X-ray; 2.70 A; A=225-509. DR PDB; 3AC5; X-ray; 2.50 A; A=225-509. DR PDB; 3AC8; X-ray; 2.30 A; A=225-509. DR PDB; 3ACJ; X-ray; 2.20 A; A=225-509. DR PDB; 3ACK; X-ray; 2.60 A; A=225-509. DR PDB; 3AD4; X-ray; 2.20 A; A=225-509. DR PDB; 3AD5; X-ray; 2.00 A; A=225-509. DR PDB; 3AD6; X-ray; 2.15 A; A=225-509. DR PDB; 3B2W; X-ray; 2.30 A; A=226-502. DR PDB; 3BRH; X-ray; 2.20 A; C/D=391-397. DR PDB; 3BYM; X-ray; 2.00 A; A=230-501. DR PDB; 3BYO; X-ray; 2.00 A; A=231-501. DR PDB; 3BYS; X-ray; 2.20 A; A=225-501. DR PDB; 3BYU; X-ray; 2.30 A; A=225-501. DR PDB; 3KMM; X-ray; 2.80 A; A=229-509. DR PDB; 3KXZ; X-ray; 2.37 A; A=225-509. DR PDB; 3LCK; X-ray; 1.70 A; A=231-501. DR PDB; 3MPM; X-ray; 1.95 A; A=237-501. DR PDB; 4C3F; X-ray; 1.72 A; A=237-501. DR PDB; 4D8K; X-ray; 2.36 A; A=53-226. DR PDBsum; 1BHF; -. DR PDBsum; 1BHH; -. DR PDBsum; 1CWD; -. DR PDBsum; 1CWE; -. DR PDBsum; 1FBZ; -. DR PDBsum; 1H92; -. DR PDBsum; 1IJR; -. DR PDBsum; 1KIK; -. DR PDBsum; 1LCJ; -. DR PDBsum; 1LCK; -. DR PDBsum; 1LKK; -. DR PDBsum; 1LKL; -. DR PDBsum; 1Q68; -. DR PDBsum; 1Q69; -. DR PDBsum; 1QPC; -. DR PDBsum; 1QPD; -. DR PDBsum; 1QPE; -. DR PDBsum; 1QPJ; -. DR PDBsum; 1X27; -. DR PDBsum; 2IIM; -. DR PDBsum; 2OF2; -. DR PDBsum; 2OF4; -. DR PDBsum; 2OFU; -. DR PDBsum; 2OFV; -. DR PDBsum; 2OG8; -. DR PDBsum; 2PL0; -. DR PDBsum; 2ZM1; -. DR PDBsum; 2ZM4; -. DR PDBsum; 2ZYB; -. DR PDBsum; 3AC1; -. DR PDBsum; 3AC2; -. DR PDBsum; 3AC3; -. DR PDBsum; 3AC4; -. DR PDBsum; 3AC5; -. DR PDBsum; 3AC8; -. DR PDBsum; 3ACJ; -. DR PDBsum; 3ACK; -. DR PDBsum; 3AD4; -. DR PDBsum; 3AD5; -. DR PDBsum; 3AD6; -. DR PDBsum; 3B2W; -. DR PDBsum; 3BRH; -. DR PDBsum; 3BYM; -. DR PDBsum; 3BYO; -. DR PDBsum; 3BYS; -. DR PDBsum; 3BYU; -. DR PDBsum; 3KMM; -. DR PDBsum; 3KXZ; -. DR PDBsum; 3LCK; -. DR PDBsum; 3MPM; -. DR PDBsum; 4C3F; -. DR PDBsum; 4D8K; -. DR ProteinModelPortal; P06239; -. DR SMR; P06239; 7-35, 64-509. DR BioGrid; 110124; 85. DR DIP; DIP-553N; -. DR IntAct; P06239; 69. DR MINT; MINT-110378; -. DR STRING; 9606.ENSP00000337825; -. DR BindingDB; P06239; -. DR ChEMBL; CHEMBL258; -. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB09079; Nintedanib. DR DrugBank; DB08901; Ponatinib. DR GuidetoPHARMACOLOGY; 2053; -. DR PhosphoSite; P06239; -. DR BioMuta; LCK; -. DR DMDM; 125474; -. DR MaxQB; P06239; -. DR PaxDb; P06239; -. DR PRIDE; P06239; -. DR DNASU; 3932; -. DR Ensembl; ENST00000333070; ENSP00000328213; ENSG00000182866. [P06239-3] DR Ensembl; ENST00000336890; ENSP00000337825; ENSG00000182866. [P06239-1] DR Ensembl; ENST00000619559; ENSP00000477713; ENSG00000182866. [P06239-1] DR GeneID; 3932; -. DR KEGG; hsa:3932; -. DR UCSC; uc001bux.3; human. [P06239-1] DR UCSC; uc001buz.3; human. [P06239-3] DR CTD; 3932; -. DR GeneCards; LCK; -. DR H-InvDB; HIX0019954; -. DR HGNC; HGNC:6524; LCK. DR HPA; CAB003816; -. DR HPA; HPA003494; -. DR MIM; 153390; gene. DR MIM; 615758; phenotype. DR neXtProt; NX_P06239; -. DR Orphanet; 280142; Severe combined immunodeficiency due to LCK deficiency. DR PharmGKB; PA30307; -. DR eggNOG; KOG0197; Eukaryota. DR eggNOG; COG0515; LUCA. DR GeneTree; ENSGT00760000118938; -. DR HOVERGEN; HBG008761; -. DR InParanoid; P06239; -. DR KO; K05856; -. DR OMA; HTKVAIK; -. DR OrthoDB; EOG7GTT2V; -. DR PhylomeDB; P06239; -. DR TreeFam; TF351634; -. DR BRENDA; 2.7.10.2; 2681. DR Reactome; R-HSA-114604; GPVI-mediated activation cascade. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-1433559; Regulation of KIT signaling. DR Reactome; R-HSA-164944; Nef and signal transduction. DR Reactome; R-HSA-167590; Nef Mediated CD4 Down-regulation. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-202427; Phosphorylation of CD3 and TCR zeta chains. DR Reactome; R-HSA-202430; Translocation of ZAP-70 to Immunological synapse. DR Reactome; R-HSA-202433; Generation of second messenger molecules. DR Reactome; R-HSA-210990; PECAM1 interactions. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-2424491; DAP12 signaling. DR Reactome; R-HSA-389356; CD28 co-stimulation. DR Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling. DR Reactome; R-HSA-389359; CD28 dependent Vav1 pathway. DR Reactome; R-HSA-389513; CTLA4 inhibitory signaling. DR Reactome; R-HSA-389948; PD-1 signaling. DR Reactome; R-HSA-451927; Interleukin-2 signaling. DR SignaLink; P06239; -. DR ChiTaRS; LCK; human. DR EvolutionaryTrace; P06239; -. DR GeneWiki; Lck; -. DR GenomeRNAi; 3932; -. DR NextBio; 15441; -. DR PRO; PR:P06239; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; P06239; -. DR CleanEx; HS_LCK; -. DR ExpressionAtlas; P06239; baseline and differential. DR Genevisible; P06239; HS. DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030139; C:endocytic vesicle; IEA:Ensembl. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central. DR GO; GO:0001772; C:immunological synapse; IDA:MGI. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0000242; C:pericentriolar material; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0003823; F:antigen binding; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0051117; F:ATPase binding; IPI:UniProtKB. DR GO; GO:0042609; F:CD4 receptor binding; IPI:UniProtKB. DR GO; GO:0042610; F:CD8 receptor binding; IPI:UniProtKB. DR GO; GO:0001948; F:glycoprotein binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central. DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:UniProtKB. DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0007568; P:aging; IEA:Ensembl. DR GO; GO:0050853; P:B cell receptor signaling pathway; IBA:GO_Central. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IBA:GO_Central. DR GO; GO:0006882; P:cellular zinc ion homeostasis; IEP:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0030097; P:hemopoiesis; NAS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IBA:GO_Central. DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IBA:GO_Central. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0050870; P:positive regulation of T cell activation; IDA:UniProtKB. DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; NAS:UniProtKB. DR GO; GO:0042523; P:positive regulation of tyrosine phosphorylation of Stat5 protein; IEA:Ensembl. DR GO; GO:0070474; P:positive regulation of uterine smooth muscle contraction; IEA:Ensembl. DR GO; GO:0006470; P:protein dephosphorylation; IDA:GOC. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0042127; P:regulation of cell proliferation; IBA:GO_Central. DR GO; GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome. DR GO; GO:0051249; P:regulation of lymphocyte activation; NAS:UniProtKB. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:UniProtKB. DR GO; GO:0042493; P:response to drug; IDA:UniProtKB. DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl. DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome. DR GO; GO:0030217; P:T cell differentiation; IMP:UniProtKB. DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR GO; GO:0016032; P:viral process; TAS:Reactome. DR Gene3D; 3.30.505.10; -; 1. DR InterPro; IPR011009; Kinase-like_dom. 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; IPR001452; SH3_domain. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR Pfam; PF07714; Pkinase_Tyr; 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 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Chromosomal rearrangement; Complete proteome; Cytoplasm; KW Disease mutation; Host-virus interaction; Kinase; Lipoprotein; KW Membrane; Myristate; Nucleotide-binding; Palmitate; Phosphoprotein; KW Polymorphism; Proto-oncogene; Reference proteome; SH2 domain; KW SH3 domain; Transferase; Tyrosine-protein kinase. FT INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:P51451}. FT CHAIN 2 509 Tyrosine-protein kinase Lck. FT /FTId=PRO_0000088124. FT DOMAIN 61 121 SH3. {ECO:0000255|PROSITE- FT ProRule:PRU00192}. FT DOMAIN 127 224 SH2. {ECO:0000255|PROSITE- FT ProRule:PRU00191}. FT DOMAIN 245 498 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 251 259 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 2 72 Interactions with CD4 and CD8. FT {ECO:0000250}. FT REGION 154 242 Interaction with PTPRH. FT ACT_SITE 364 364 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10028}. FT BINDING 273 273 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 42 42 Phosphoserine. FT {ECO:0000250|UniProtKB:Q6P6U0}. FT MOD_RES 102 102 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 159 159 Phosphothreonine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 162 162 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 192 192 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P06240}. FT MOD_RES 194 194 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 304 304 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P07948}. FT MOD_RES 313 313 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P07948}. FT MOD_RES 394 394 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:8139546}. FT MOD_RES 457 457 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P07948}. FT MOD_RES 470 470 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P07948}. FT MOD_RES 505 505 Phosphotyrosine; by CSK. FT {ECO:0000244|PubMed:15592455, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:21406692, FT ECO:0000269|PubMed:1639064, FT ECO:0000269|PubMed:8139546, FT ECO:0000269|PubMed:8631775}. FT LIPID 2 2 N-myristoyl glycine. {ECO:0000250}. FT LIPID 3 3 S-palmitoyl cysteine. {ECO:0000250}. FT LIPID 5 5 S-palmitoyl cysteine. {ECO:0000250}. FT VAR_SEQ 321 321 N -> NDTLLDSQLEEKGLGASPWGNLGQQLLLLPT (in FT isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_016049. FT VAR_SEQ 348 363 IAEGMAFIEERNYIHR -> VRRLGRGAGQGNRPVT (in FT isoform Short). FT {ECO:0000303|PubMed:7495859}. FT /FTId=VSP_005000. FT VAR_SEQ 364 509 Missing (in isoform Short). FT {ECO:0000303|PubMed:7495859}. FT /FTId=VSP_005001. FT VARIANT 28 28 V -> L (found in leukemia). FT {ECO:0000269|PubMed:8139546}. FT /FTId=VAR_013463. FT VARIANT 201 201 G -> S (in dbSNP:rs11567841). FT /FTId=VAR_051697. FT VARIANT 232 232 P -> PQKP (in leukemia). FT /FTId=VAR_013464. FT VARIANT 341 341 L -> P (in IMD22). FT {ECO:0000269|PubMed:22985903}. FT /FTId=VAR_071291. FT VARIANT 353 353 A -> V (found in leukemia). FT {ECO:0000269|PubMed:8139546}. FT /FTId=VAR_013465. FT VARIANT 447 447 P -> L (found in leukemia). FT {ECO:0000269|PubMed:8139546}. FT /FTId=VAR_013466. FT MUTAGEN 59 59 S->E: Allows interaction with SQSTM1. FT {ECO:0000269|PubMed:8618896}. FT MUTAGEN 154 154 R->K: No effect on interaction with FT SQSTM1. {ECO:0000269|PubMed:8618896}. FT CONFLICT 29 29 P -> R (in Ref. 2; AAA59502). FT {ECO:0000305}. FT CONFLICT 35 35 T -> R (in Ref. 2; AAA59502). FT {ECO:0000305}. FT CONFLICT 87 87 Q -> P (in Ref. 2; CAA31884/AAA59502). FT {ECO:0000305}. FT CONFLICT 206 211 VRHYTN -> ASAITPI (in Ref. 1; CAA28691). FT {ECO:0000305}. FT CONFLICT 254 254 G -> A (in Ref. 2; AAA59502). FT {ECO:0000305}. FT CONFLICT 258 267 EVWMGYYNGH -> RCGWGTTTGT (in Ref. 1; FT CAA28691). {ECO:0000305}. FT CONFLICT 282 286 PDAFL -> AGRLP (in Ref. 1; CAA28691). FT {ECO:0000305}. FT CONFLICT 375 375 T -> A (in Ref. 14; CAA28165). FT {ECO:0000305}. FT CONFLICT 472 472 L -> H (in Ref. 13; CAA29667). FT {ECO:0000305}. FT CONFLICT 504 509 QYQPQP -> STA (in Ref. 1; CAA28691). FT {ECO:0000305}. FT HELIX 12 15 {ECO:0000244|PDB:1Q68}. FT STRAND 21 23 {ECO:0000244|PDB:1Q68}. FT STRAND 24 27 {ECO:0000244|PDB:1Q69}. FT TURN 60 63 {ECO:0000244|PDB:2IIM}. FT STRAND 65 70 {ECO:0000244|PDB:2IIM}. FT STRAND 76 79 {ECO:0000244|PDB:4D8K}. FT STRAND 87 92 {ECO:0000244|PDB:2IIM}. FT STRAND 95 102 {ECO:0000244|PDB:2IIM}. FT TURN 103 105 {ECO:0000244|PDB:2IIM}. FT STRAND 108 112 {ECO:0000244|PDB:2IIM}. FT HELIX 113 115 {ECO:0000244|PDB:2IIM}. FT STRAND 116 118 {ECO:0000244|PDB:2IIM}. FT STRAND 128 131 {ECO:0000244|PDB:1CWD}. FT HELIX 134 141 {ECO:0000244|PDB:1LKK}. FT STRAND 151 155 {ECO:0000244|PDB:1LKK}. FT STRAND 157 159 {ECO:0000244|PDB:1LKK}. FT STRAND 163 171 {ECO:0000244|PDB:1LKK}. FT TURN 172 174 {ECO:0000244|PDB:1LKK}. FT STRAND 175 185 {ECO:0000244|PDB:1LKK}. FT TURN 187 189 {ECO:0000244|PDB:1LCJ}. FT STRAND 191 194 {ECO:0000244|PDB:1LKK}. FT STRAND 199 201 {ECO:0000244|PDB:1LKK}. FT HELIX 202 211 {ECO:0000244|PDB:1LKK}. FT STRAND 216 218 {ECO:0000244|PDB:1LKK}. FT TURN 233 235 {ECO:0000244|PDB:1QPC}. FT STRAND 237 239 {ECO:0000244|PDB:1QPE}. FT HELIX 242 244 {ECO:0000244|PDB:1QPC}. FT STRAND 245 254 {ECO:0000244|PDB:1QPC}. FT STRAND 257 264 {ECO:0000244|PDB:1QPC}. FT TURN 265 267 {ECO:0000244|PDB:1QPC}. FT STRAND 268 275 {ECO:0000244|PDB:1QPC}. FT TURN 277 279 {ECO:0000244|PDB:1QPD}. FT HELIX 282 294 {ECO:0000244|PDB:1QPC}. FT STRAND 303 307 {ECO:0000244|PDB:1QPC}. FT STRAND 309 311 {ECO:0000244|PDB:1QPC}. FT STRAND 313 317 {ECO:0000244|PDB:1QPC}. FT HELIX 324 327 {ECO:0000244|PDB:1QPC}. FT HELIX 331 334 {ECO:0000244|PDB:1QPC}. FT HELIX 338 357 {ECO:0000244|PDB:1QPC}. FT HELIX 367 369 {ECO:0000244|PDB:1QPC}. FT STRAND 370 372 {ECO:0000244|PDB:1QPC}. FT STRAND 378 380 {ECO:0000244|PDB:1QPC}. FT HELIX 383 385 {ECO:0000244|PDB:1QPE}. FT HELIX 386 389 {ECO:0000244|PDB:3B2W}. FT STRAND 390 392 {ECO:0000244|PDB:1QPC}. FT STRAND 393 395 {ECO:0000244|PDB:4C3F}. FT TURN 404 406 {ECO:0000244|PDB:1QPC}. FT HELIX 409 414 {ECO:0000244|PDB:1QPC}. FT HELIX 419 434 {ECO:0000244|PDB:1QPC}. FT TURN 435 437 {ECO:0000244|PDB:1QPC}. FT HELIX 446 454 {ECO:0000244|PDB:1QPC}. FT HELIX 467 476 {ECO:0000244|PDB:1QPC}. FT HELIX 481 483 {ECO:0000244|PDB:1QPC}. FT HELIX 487 500 {ECO:0000244|PDB:1QPC}. SQ SEQUENCE 509 AA; 58001 MW; 44BFF0D43FFB420D CRC64; MGCGCSSHPE DDWMENIDVC ENCHYPIVPL DGKGTLLIRN GSEVRDPLVT YEGSNPPASP LQDNLVIALH SYEPSHDGDL GFEKGEQLRI LEQSGEWWKA QSLTTGQEGF IPFNFVAKAN SLEPEPWFFK NLSRKDAERQ LLAPGNTHGS FLIRESESTA GSFSLSVRDF DQNQGEVVKH YKIRNLDNGG FYISPRITFP GLHELVRHYT NASDGLCTRL SRPCQTQKPQ KPWWEDEWEV PRETLKLVER LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHQRL VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLTINK LLDMAAQIAE GMAFIEERNY IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA KFPIKWTAPE AINYGTFTIK SDVWSFGILL TEIVTHGRIP YPGMTNPEVI QNLERGYRMV RPDNCPEELY QLMRLCWKER PEDRPTFDYL RSVLEDFFTA TEGQYQPQP //