ID LCK_HUMAN Reviewed; 509 AA. AC P06239; P07100; Q12850; Q13152; Q5TDH8; Q5TDH9; Q7RTZ3; Q96DW4; AC Q9NYT8; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 6. DT 19-JAN-2010, entry version 150. DE RecName: Full=Proto-oncogene tyrosine-protein kinase LCK; DE EC=2.7.10.2; DE AltName: Full=Lymphocyte cell-specific protein-tyrosine kinase; DE AltName: Full=p56-LCK; DE AltName: Full=LSK; DE AltName: Full=T cell-specific protein-tyrosine kinase; 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 MEDLINE=87133831; 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 MEDLINE=89123626; 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 MEDLINE=90108697; 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 MEDLINE=94187714; PubMed=8139546; 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 MEDLINE=96085119; 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 MEDLINE=22289034; PubMed=12401726; 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 MEDLINE=89096891; 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 MEDLINE=89313764; 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 MEDLINE=20462621; 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 MEDLINE=88217332; 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 MEDLINE=87000726; 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 MEDLINE=92347326; 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 MEDLINE=94067101; 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 MEDLINE=95155308; 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 INTERACTION WITH HIV-1 NEF. RX MEDLINE=96386556; 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 [20] 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 [21] RP SUBCELLULAR LOCATION. RX PubMed=12218089; 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 [22] RP MASS SPECTROMETRY. RC TISSUE=Mammary cancer; RX MEDLINE=21829512; 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 [23] 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 [24] 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 [25] 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 [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-394 AND TYR-505, AND RP MASS SPECTROMETRY. 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 [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-192 AND TYR-505, AND RP MASS SPECTROMETRY. RX PubMed=18083107; DOI=10.1016/j.cell.2007.11.025; RA Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., RA Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., RA Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., RA Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., RA Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; RT "Global survey of phosphotyrosine signaling identifies oncogenic RT kinases in lung cancer."; RL Cell 131:1190-1203(2007). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162; TYR-192; SER-213; RP TYR-394; THR-501 AND TYR-505, AND MASS SPECTROMETRY. RX PubMed=17192257; DOI=10.1074/mcp.T600062-MCP200; RA Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., RA Keri G., Wehland J., Daub H.; RT "Proteomics analysis of protein kinases by target class-selective RT prefractionation and tandem mass spectrometry."; RL Mol. Cell. Proteomics 6:537-547(2007). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND MASS RP SPECTROMETRY. 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 [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102; THR-159; SER-162; RP TYR-192; SER-194 AND TYR-505, AND MASS SPECTROMETRY. RC TISSUE=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 [31] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-179, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 53-226. RX MEDLINE=94203291; 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 [33] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 127-221. RX MEDLINE=95173978; 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 [34] RP X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 122-226. RX MEDLINE=96177765; 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 [35] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 231-501. RX MEDLINE=97100952; 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 [36] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 119-226. RX MEDLINE=98352059; 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). CC -!- FUNCTION: Tyrosine kinase that plays an essential role for the CC selection and maturation of developing T-cell in the thymus and in CC mature T-cell function. Is constitutively associated with the CC cytoplasmic portions of the CD4 and CD8 surface receptors and CC plays a key role in T-cell antigen receptor(TCR)-linked signal CC transduction pathways. Association of the TCR with a peptide CC antigen-bound MHC complex facilitates the interaction of CD4 and CC CD8 with MHC class II and class I molecules, respectively, and CC thereby recruits the associated LCK to the vicinity of the TCR/CD3 CC complex. LCK then phosphorylates tyrosines residues within the CC immunoreceptor tyrosines-based activation motifs (ITAMs) in the CC cytoplasmic tails of the TCRgamma chains and CD3 subunits, CC initiating the TCR/CD3 signaling pathway. In addition, contributes CC to signaling by other receptor molecules. Associates directly with CC the cytoplasmic tail of CD2, and upon engagement of the CD2 CC molecule, LCK undergoes hyperphosphorylation and activation. Also CC plays a role in the IL2 receptor-linked signaling pathway that CC controls T-cell proliferative response. Binding of IL2 to its CC receptor results in increased activity of LCK. Is expressed at all CC stages of thymocyte development and is required for the regulation CC of maturation events that are governed by both pre-TCR and mature CC alpha beta TCR. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- ENZYME REGULATION: Inhibited by tyrosine phosphorylation. CC -!- SUBUNIT: Binds to the cytoplasmic domain of cell surface CC receptors, such as CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also CC binds to effector molecules, such as PI4K, VAV1, RASA1, FYB and to CC other protein kinases including CDC2, RAF1, ZAP70 and SYK. Binds CC 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 SQSTM1. Interacts with phosphorylated CC LIME1. Interacts with CBLB and PTPRH. CC -!- INTERACTION: CC P27958:- (xeno); NbExp=1; IntAct=EBI-1348, EBI-706378; CC Q9WMX2:- (xeno); NbExp=1; IntAct=EBI-1348, EBI-710918; CC P20963:CD247; NbExp=1; IntAct=EBI-1348, EBI-1165705; CC Q07666:KHDRBS1; NbExp=3; IntAct=EBI-1348, EBI-1364; CC O43561:LAT; NbExp=1; IntAct=EBI-1348, EBI-1222766; CC Q9H204:MED28; NbExp=2; IntAct=EBI-1348, EBI-514199; CC Q05209:PTPN12; NbExp=1; IntAct=EBI-1348, EBI-2266035; CC Q9Y2R2:PTPN22; NbExp=3; IntAct=EBI-1348, EBI-1211241; CC P29350:PTPN6; NbExp=1; IntAct=EBI-1348, EBI-78260; CC P23467:PTPRB; NbExp=1; IntAct=EBI-1348, EBI-1265766; CC P08575:PTPRC; NbExp=1; IntAct=EBI-1348, EBI-1341; CC P23470:PTPRG; NbExp=1; IntAct=EBI-1348, EBI-2258115; CC Q12913:PTPRJ; NbExp=1; IntAct=EBI-1348, EBI-2264500; CC Q15262:PTPRK; NbExp=1; IntAct=EBI-1348, EBI-474052; CC P28827:PTPRM; NbExp=1; IntAct=EBI-1348, EBI-2257317; CC Q16827:PTPRO; NbExp=1; IntAct=EBI-1348, EBI-723739; CC P23471:PTPRZ1; NbExp=1; IntAct=EBI-1348, EBI-2263175; CC Q9NP31:SH2D2A; NbExp=1; IntAct=EBI-1348, EBI-490630; CC O00401:WASL; NbExp=1; IntAct=EBI-1348, EBI-957615; CC P43403:ZAP70; NbExp=1; IntAct=EBI-1348, EBI-1211276; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Lipid-anchor; CC Cytoplasmic side. Note=Present in lipid rafts in an unactive 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: Phosphorylated on Tyr-394, which increases enzymatic activity CC (By similarity). Phosphorylated on Tyr-505, which decreases CC activity. CC -!- MASS SPECTROMETRY: Mass=57869.42; Method=MALDI; Range=2-509; CC Source=PubMed:11840567; CC -!- DISEASE: A chromosomal aberration involving LCK is found in CC leukemias. Translocation t(1;7)(p34;q34) with TCRB. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. SRC subfamily. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 SH2 domain. CC -!- SIMILARITY: Contains 1 SH3 domain. 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="http://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; 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 IPI; IPI00411413; -. DR IPI; IPI00515097; -. DR IPI; IPI00940423; -. DR PIR; JQ0152; OKHULK. DR RefSeq; NP_001036236.1; -. DR RefSeq; NP_005347.3; -. 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=226-502. DR PDB; 2OG8; X-ray; 2.30 A; A/B=236-500. 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; 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; 3LCK; X-ray; 1.70 A; A=231-501. 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; 3B2W; -. DR PDBsum; 3BRH; -. DR PDBsum; 3BYM; -. DR PDBsum; 3BYO; -. DR PDBsum; 3BYS; -. DR PDBsum; 3BYU; -. DR PDBsum; 3LCK; -. DR SMR; P06239; 65-509. DR DIP; DIP-553N; -. DR IntAct; P06239; 23. DR STRING; P06239; -. DR PhosphoSite; P06239; -. DR PRIDE; P06239; -. DR Ensembl; ENST00000336890; ENSP00000337825; ENSG00000182866; Homo sapiens. DR Ensembl; ENST00000398345; ENSP00000381387; ENSG00000182866; Homo sapiens. DR GeneID; 3932; -. DR KEGG; hsa:3932; -. DR UCSC; uc001bux.1; human. DR UCSC; uc001buz.1; human. DR CTD; 3932; -. DR GeneCards; GC01P032489; -. DR H-InvDB; HIX0019954; -. DR HGNC; HGNC:6524; LCK. DR HPA; CAB003816; -. DR HPA; HPA003494; -. DR MIM; 153390; gene. DR PharmGKB; PA30307; -. DR eggNOG; prNOG11382; -. DR HOVERGEN; P06239; -. DR OMA; ATLPMRN; -. DR OrthoDB; EOG9BZQMQ; -. DR BRENDA; 2.7.10.2; 247. DR Pathway_Interaction_DB; alphasynuclein_pathway; Alpha-synuclein signaling. DR Pathway_Interaction_DB; amb2_neutrophils_pathway; amb2 Integrin signaling. DR Pathway_Interaction_DB; nfkappabatypicalpathway; Atypical NF-kappaB pathway. DR Pathway_Interaction_DB; pi3kcipathway; Class I PI3K signaling events. DR Pathway_Interaction_DB; epha_fwdpathway; EPHA forward signaling. DR Pathway_Interaction_DB; ephrinbrevpathway; Ephrin B reverse signaling. DR Pathway_Interaction_DB; glypican_1pathway; Glypican 1 network. DR Pathway_Interaction_DB; il12_2pathway; IL12-mediated signaling events. DR Pathway_Interaction_DB; il2_pi3kpathway; IL2 signaling events mediated by PI3K. DR Pathway_Interaction_DB; il2_stat5pathway; IL2 signaling events mediated by STAT5. DR Pathway_Interaction_DB; il2_1pathway; IL2-mediated signaling events. DR Pathway_Interaction_DB; pdgfrbpathway; PDGFR-beta signaling pathway. DR Pathway_Interaction_DB; p38alphabetapathway; Regulation of p38-alpha and p38-beta. DR Pathway_Interaction_DB; ptp1bpathway; Signaling events mediated by PTP1B. DR Pathway_Interaction_DB; tcrpathway; TCR signaling in naive CD4+ T cells. DR Pathway_Interaction_DB; cd8tcrpathway; TCR signaling in naive CD8+ T cells. DR Pathway_Interaction_DB; txa2pathway; Thromboxane A2 receptor signaling. DR Reactome; REACT_604; Hemostasis. DR Reactome; REACT_6185; HIV Infection. DR Reactome; REACT_6900; Signaling in Immune system. DR BindingDB; P06239; -. DR DrugBank; DB01254; Dasatinib. DR NextBio; 15441; -. DR ArrayExpress; P06239; -. DR Bgee; P06239; -. DR CleanEx; HS_LCK; -. DR Genevestigator; P06239; -. DR GermOnline; ENSG00000182866; Homo sapiens. DR GO; GO:0005829; C:cytosol; EXP:Reactome. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. 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; IEA:UniProtKB-KW. 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:0004715; F:non-membrane spanning protein tyrosine kina...; IEA:EC. DR GO; GO:0043548; F:phosphoinositide 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:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB. DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB. DR GO; GO:0006919; P:activation of caspase activity; IDA:UniProtKB. DR GO; GO:0006882; P:cellular zinc ion homeostasis; IEP:UniProtKB. DR GO; GO:0006917; P:induction of apoptosis; IMP:UniProtKB. DR GO; GO:0044419; P:interspecies interaction between organisms; IEA:UniProtKB-KW. DR GO; GO:0050870; P:positive regulation of T cell activation; IDA:UniProtKB. DR GO; GO:0050862; P:positive regulation of T cell receptor sign...; NAS:UniProtKB. DR GO; GO:0006468; P:protein amino acid phosphorylation; IDA:UniProtKB. DR GO; GO:0051209; P:release of sequestered calcium ion into cyt...; ISS:UniProtKB. DR GO; GO:0042493; P:response to drug; IDA:UniProtKB. DR GO; GO:0030217; P:T cell differentiation; IMP:UniProtKB. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR000980; SH2. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR020473; SH3_region. DR InterPro; IPR020749; Tyr_kinase_non-rcpt_Lck. DR InterPro; IPR020685; Tyr_prot_kinase. DR InterPro; IPR008266; Tyr_prot_kinase_AS. DR InterPro; IPR001245; Tyr_prot_kinase_cat_dom. DR InterPro; IPR020635; Tyr_prot_kinase_subgr_cat_dom. DR Gene3D; G3DSA:3.30.505.10; SH2; 1. DR PANTHER; PTHR23256:SF260; Tyr_kinase_non-rcpt_Lck; 1. DR PANTHER; PTHR23256; Tyr_prot_kinase; 1. 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 SMART; SM00252; SH2; 1. DR SMART; SM00326; SH3; 1. DR SMART; SM00219; TyrKc; 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; Acetylation; Alternative splicing; ATP-binding; KW Cell membrane; Chromosomal rearrangement; Complete proteome; KW Cytoplasm; Disease mutation; Host-virus interaction; Kinase; KW Lipoprotein; Membrane; Myristate; Nucleotide-binding; Palmitate; KW Phosphoprotein; Polymorphism; Proto-oncogene; SH2 domain; SH3 domain; KW Transferase; Tyrosine-protein kinase. FT INIT_MET 1 1 Removed (Probable). FT CHAIN 2 509 Proto-oncogene tyrosine-protein kinase FT LCK. FT /FTId=PRO_0000088124. FT DOMAIN 61 121 SH3. FT DOMAIN 127 224 SH2. FT DOMAIN 245 498 Protein kinase. FT NP_BIND 251 259 ATP (By similarity). FT REGION 2 72 Interactions with CD4 and CD8 (By FT similarity). FT REGION 154 242 Interaction with PTPRH. FT ACT_SITE 364 364 Proton acceptor (By similarity). FT BINDING 273 273 ATP (By similarity). FT MOD_RES 102 102 Phosphoserine. FT MOD_RES 159 159 Phosphothreonine. FT MOD_RES 162 162 Phosphoserine. FT MOD_RES 179 179 N6-acetyllysine. FT MOD_RES 192 192 Phosphotyrosine. FT MOD_RES 194 194 Phosphoserine. FT MOD_RES 213 213 Phosphoserine. FT MOD_RES 394 394 Phosphotyrosine; by autocatalysis. FT MOD_RES 501 501 Phosphothreonine. FT MOD_RES 505 505 Phosphotyrosine. FT LIPID 2 2 N-myristoyl glycine (By similarity). FT LIPID 3 3 S-palmitoyl cysteine (By similarity). FT LIPID 5 5 S-palmitoyl cysteine (By similarity). FT VAR_SEQ 321 321 N -> NDTLLDSQLEEKGLGASPWGNLGQQLLLLPT (in FT isoform 3). FT /FTId=VSP_016049. FT VAR_SEQ 348 363 IAEGMAFIEERNYIHR -> VRRLGRGAGQGNRPVT (in FT isoform Short). FT /FTId=VSP_005000. FT VAR_SEQ 364 509 Missing (in isoform Short). FT /FTId=VSP_005001. FT VARIANT 28 28 V -> L (in leukemia). 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 353 353 A -> V (in leukemia). FT /FTId=VAR_013465. FT VARIANT 447 447 P -> L (in leukemia). FT /FTId=VAR_013466. FT MUTAGEN 59 59 S->E: Allows interaction with SQSTM1. FT MUTAGEN 154 154 R->K: No effect on interaction with FT SQSTM1. FT CONFLICT 29 29 P -> R (in Ref. 2; AAA59502). FT CONFLICT 35 35 T -> R (in Ref. 2; AAA59502). FT CONFLICT 87 87 Q -> P (in Ref. 2; CAA31884/AAA59502). FT CONFLICT 206 211 VRHYTN -> ASAITPI (in Ref. 1; CAA28691). FT CONFLICT 254 254 G -> A (in Ref. 2; AAA59502). FT CONFLICT 258 267 EVWMGYYNGH -> RCGWGTTTGT (in Ref. 1; FT CAA28691). FT CONFLICT 282 286 PDAFL -> AGRLP (in Ref. 1; CAA28691). FT CONFLICT 375 375 T -> A (in Ref. 14). FT CONFLICT 472 472 L -> H (in Ref. 13). FT CONFLICT 504 509 QYQPQP -> STA (in Ref. 1; CAA28691). FT HELIX 12 15 FT STRAND 21 23 FT TURN 60 63 FT STRAND 65 70 FT STRAND 87 92 FT STRAND 95 102 FT TURN 103 105 FT STRAND 108 112 FT HELIX 113 115 FT STRAND 116 118 FT HELIX 134 141 FT STRAND 151 155 FT STRAND 157 159 FT STRAND 163 171 FT TURN 172 174 FT STRAND 175 185 FT STRAND 191 194 FT STRAND 199 201 FT HELIX 202 211 FT STRAND 216 218 FT TURN 233 235 FT HELIX 242 244 FT STRAND 245 254 FT STRAND 257 264 FT TURN 265 267 FT STRAND 268 275 FT HELIX 282 294 FT STRAND 303 307 FT STRAND 309 311 FT STRAND 313 317 FT HELIX 324 327 FT HELIX 331 334 FT HELIX 338 357 FT HELIX 367 369 FT STRAND 370 372 FT STRAND 378 380 FT STRAND 390 392 FT TURN 404 406 FT HELIX 409 414 FT HELIX 419 434 FT TURN 435 437 FT HELIX 446 454 FT HELIX 467 476 FT HELIX 481 483 FT HELIX 487 500 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 //