ID LCK_HUMAN Reviewed; 509 AA. AC P06239; D3DPP8; 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 27-MAR-2024, entry version 278. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 extensive RT 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 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., 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; VAL-353 RP AND LEU-447, AND PHOSPHORYLATION AT TYR-394 AND TYR-505. RC TISSUE=Leukemia; RX PubMed=8139546; DOI=10.1128/mcb.14.4.2429-2437.1994; RA Wright D.D., Sefton B.M., Kamps M.P.; RT "Oncogenic activation of the Lck protein accompanies translocation of the RT 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 type 1 RT 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., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., 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., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., 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., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 project: RT 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; 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 [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35. RX PubMed=2787474; DOI=10.1128/mcb.9.5.2173-2180.1989; RA Takadera T., Leung S., Gernone A., Koga Y., Takihara Y., Miyamoto N.G., RA 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 and RT 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., 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; DOI=10.1002/j.1460-2075.1992.tb05361.x; RA Bergman M., Mustelin T., Oetken C., Partanen J., Flint N.A., Amrein K.E., RA Autero M., Burn P., Alitalo K.; RT "The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down RT regulates its catalytic activity."; RL EMBO J. 11:2919-2924(1992). RN [16] RP INTERACTION WITH PI3K. RX PubMed=7504174; DOI=10.1128/mcb.13.12.7408-7417.1993; RA Vogel L.B., Fujita D.J.; RT "The SH3 domain of p56lck is involved in binding to phosphatidylinositol RT 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-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 phosphorylation of RT 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 Lck RT which involves the SH2 domain of Csk and is mediated by autophosphorylation RT of Lck on tyrosine 394."; RL J. Biol. Chem. 271:7465-7472(1996). RN [20] RP INTERACTION WITH HIV-1 NEF (MICROBIAL INFECTION). RX PubMed=8794306; DOI=10.1128/jvi.70.10.6701-6708.1996; RA Greenway A.L., Azad A., Mills J., McPhee D.A.; RT "Human immunodeficiency virus type 1 Nef binds directly to LCK and mitogen- RT 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 and a RT target for signal intervention by Herpesvirus saimiri and other viral gene RT products."; RL Eur. J. Biochem. 267:3413-3421(2000). RN [23] RP INTERACTION WITH CD48. RX PubMed=12007789; DOI=10.1016/s0167-4889(02)00165-9; RA Hawash I.Y., Hu X.E., Adal A., Cassady J.M., Geahlen R.L., Harrison M.L.; RT "The oxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, RT inhibits Lck localization to lipid rafts and T cell signaling."; RL Biochim. Biophys. Acta 1589:140-150(2002). RN [24] RP SUBUNIT, AND INTERACTION WITH CD160. RX PubMed=11978774; DOI=10.1093/intimm/14.5.445; RA Nikolova M., Marie-Cardine A., Boumsell L., Bensussan A.; RT "BY55/CD160 acts as a co-receptor in TCR signal transduction of a human RT circulating cytotoxic effector T lymphocyte subset lacking CD28 RT expression."; RL Int. Immunol. 14:445-451(2002). RN [25] 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 [26] 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 protein RT expression map database."; RL Proteomics 2:212-223(2002). RN [27] RP INTERACTION WITH LIME1. RX PubMed=14610046; DOI=10.1084/jem.20031484; RA Brdickova N., Brdicka T., Angelisova P., Horvath O., Spicka J., Hilgert I., RA Paces J., Simeoni L., Kliche S., Merten C., Schraven B., Horejsi V.; RT "LIME: a new membrane raft-associated adaptor protein involved in CD4 and RT CD8 coreceptor signaling."; RL J. Exp. Med. 198:1453-1462(2003). RN [28] 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 and RT mediates T cell activation."; RL J. Exp. Med. 198:1463-1473(2003). RN [29] 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 phosphatase, RT with the tyrosine kinase Lck. Roles in regulation of T cell function."; RL J. Biol. Chem. 278:34854-34863(2003). RN [30] 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 [31] 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 [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND IDENTIFICATION BY RP 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 cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [33] 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., Clark J.M.; RT "Identification of substrates of human protein-tyrosine phosphatase RT PTPN22."; RL J. Biol. Chem. 281:11002-11010(2006). RN [34] 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 and RT CD45."; RL J. Immunol. 176:6615-6623(2006). RN [35] 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 [36] RP INTERACTION WITH CEACAM1. RX PubMed=18424730; DOI=10.4049/jimmunol.180.9.6085; RA Chen Z., Chen L., Qiao S.W., Nagaishi T., Blumberg R.S.; RT "Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits RT proximal TCR signaling by targeting ZAP-70."; RL J. Immunol. 180:6085-6093(2008). RN [37] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND IDENTIFICATION BY RP 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 the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [38] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND IDENTIFICATION BY RP 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 [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102; THR-159; SER-162; RP SER-194 AND TYR-505, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [40] 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., Li Y.H., RA 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 the RT protein in the cytoplasm."; RL J. Biol. Chem. 285:10122-10129(2010). RN [41] 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 and 580 RT occurs via a distinct mechanism than other receptor systems."; RL J. Leukoc. Biol. 87:691-701(2010). RN [42] 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 [43] 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 [44] RP SUBCELLULAR LOCATION, TOPOLOGY, AND PALMITOYLATION. RX PubMed=22034844; DOI=10.3109/09687688.2011.630682; RA Zeidman R., Buckland G., Cebecauer M., Eissmann P., Davis D.M., Magee A.I.; RT "DHHC2 is a protein S-acyltransferase for Lck."; RL Mol. Membr. Biol. 28:473-486(2011). RN [45] 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., Price C., RA Bird I.N., Perera T., Kellie S., Williamson R., Anderton B.H., RA Reynolds C.H.; RT "Tyrosine phosphorylation of tau by the SRC family kinases lck and fyn."; RL Mol. Neurodegener. 6:12-12(2011). RN [46] RP ACTIVITY 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 cell RT receptor signaling."; RL Sci. Signal. 4:RA59-RA59(2011). RN [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [48] RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 UL46 (MICROBIAL INFECTION). 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 and RT activation of the Src family kinase Lck and recruitment of p85, Grb2, and RT Shc."; RL J. Virol. 87:11276-11286(2013). RN [49] RP INTERACTION WITH FYB2 AND FYB1. RX PubMed=27335501; DOI=10.4049/jimmunol.1501913; RA Jung S.H., Yoo E.H., Yu M.J., Song H.M., Kang H.Y., Cho J.Y., Lee J.R.; RT "ARAP, a novel adaptor protein, is required for TCR signaling and integrin- RT mediated adhesion."; RL J. Immunol. 197:942-952(2016). RN [50] 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 [51] 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 [52] 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 [53] 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 [54] 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 SH2 RT domain binding."; RL J. Biol. Chem. 273:20238-20242(1998). RN [55] 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 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. Interacts with CC FYB2 (PubMed:27335501). {ECO:0000269|PubMed:16339550, CC ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, CC ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, CC ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863, CC ECO:0000269|PubMed:27335501}. 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. {ECO:0000269|PubMed:21917715}. 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. This interaction inhibits its tyrosine-kinase CC activity. Interacts with SQSTM1. Interacts with phosphorylated LIME1. CC Interacts with CBLB and PTPRH. Interacts with RUNX3. Forms a signaling CC complex with EPHA1, PTK2B and PI3-KINASE; upon activation by EFNA1 CC which may regulate T-lymphocyte migration. Associates with ZAP70 and CC RHOH; these interactions allow LCK-mediated RHOH and CD3 subunit CC phosphorylation in the presence of functional ZAP70. Interacts with CC UNC119; this interaction plays a crucial role in activation of LCK. CC Interacts with CEACAM1 (via cytoplasmic domain); mediates CEACAM1 CC phosphorylation resulting in PTPN6 recruitment that dephosphorylates CC TCR stimulation-induced CD247 and ZAP70 (PubMed:18424730). Interacts CC with CD160. Interacts with CD48 (PubMed:12007789). CC {ECO:0000269|PubMed:11978774, ECO:0000269|PubMed:12007789, 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:18424730, CC ECO:0000269|PubMed:7504174, ECO:0000269|PubMed:7852312, CC ECO:0000269|PubMed:8618896, ECO:0000269|PubMed:9178760}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1 CC UL46; this interaction activates LCK. {ECO:0000269|PubMed:23946459}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Nef through its SH3 CC domain. {ECO:0000269|PubMed:8794306}. CC -!- INTERACTION: CC P06239; O14672: ADAM10; NbExp=3; IntAct=EBI-1348, EBI-1536151; CC P06239; Q13444: ADAM15; NbExp=4; IntAct=EBI-1348, EBI-77818; CC P06239; P10275: AR; NbExp=7; IntAct=EBI-1348, EBI-608057; CC P06239; P20749: BCL3; NbExp=3; IntAct=EBI-1348, EBI-958997; CC P06239; P01730: CD4; NbExp=2; IntAct=EBI-1348, EBI-353826; CC P06239; Q5VV42: CDKAL1; NbExp=3; IntAct=EBI-1348, EBI-10194801; CC P06239; P36888: FLT3; NbExp=2; IntAct=EBI-1348, EBI-3946257; CC P06239; Q13480: GAB1; NbExp=10; IntAct=EBI-1348, EBI-517684; CC P06239; P23771: GATA3; NbExp=3; IntAct=EBI-1348, EBI-6664760; CC P06239; P07900: HSP90AA1; NbExp=3; IntAct=EBI-1348, EBI-296047; CC P06239; P08238: HSP90AB1; NbExp=4; IntAct=EBI-1348, EBI-352572; CC P06239; Q07666: KHDRBS1; NbExp=5; IntAct=EBI-1348, EBI-1364; CC P06239; P10721: KIT; NbExp=8; IntAct=EBI-1348, EBI-1379503; CC P06239; O43561: LAT; NbExp=2; IntAct=EBI-1348, EBI-1222766; CC P06239; P06239: LCK; NbExp=5; IntAct=EBI-1348, EBI-1348; CC P06239; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-1348, EBI-741037; CC P06239; Q9H204: MED28; NbExp=4; IntAct=EBI-1348, EBI-514199; CC P06239; P08581: MET; NbExp=3; IntAct=EBI-1348, EBI-1039152; CC P06239; P04150: NR3C1; NbExp=3; IntAct=EBI-1348, EBI-493507; CC P06239; Q04759: PRKCQ; NbExp=2; IntAct=EBI-1348, EBI-374762; CC P06239; Q9Y2R2: PTPN22; NbExp=6; IntAct=EBI-1348, EBI-1211241; CC P06239; P29350: PTPN6; NbExp=5; IntAct=EBI-1348, EBI-78260; CC P06239; P08575: PTPRC; NbExp=7; IntAct=EBI-1348, EBI-1341; CC P06239; Q9NP31: SH2D2A; NbExp=12; IntAct=EBI-1348, EBI-490630; CC P06239; P43405: SYK; NbExp=7; IntAct=EBI-1348, EBI-78302; CC P06239; Q8N1K5-1: THEMIS; NbExp=3; IntAct=EBI-1348, EBI-15102259; CC P06239; P0CG48: UBC; NbExp=2; IntAct=EBI-1348, EBI-3390054; CC P06239; P62258: YWHAE; NbExp=2; IntAct=EBI-1348, EBI-356498; CC P06239; P43403: ZAP70; NbExp=2; IntAct=EBI-1348, EBI-1211276; CC P06239; P22575; Xeno; NbExp=7; IntAct=EBI-1348, EBI-866709; CC P06239; Q9YJQ8; Xeno; NbExp=2; IntAct=EBI-1348, EBI-7709835; CC P06239-3; Q96DX5: ASB9; NbExp=3; IntAct=EBI-13287659, EBI-745641; CC P06239-3; Q9BXJ5: C1QTNF2; NbExp=3; IntAct=EBI-13287659, EBI-2817707; CC P06239-3; A8MTA8-2: CIMIP2B; NbExp=3; IntAct=EBI-13287659, EBI-12160437; CC P06239-3; Q9GZU7: CTDSP1; NbExp=3; IntAct=EBI-13287659, EBI-751587; CC P06239-3; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-13287659, EBI-10271199; CC P06239-3; I6L996: PTK2; NbExp=3; IntAct=EBI-13287659, EBI-10181089; CC P06239-3; Q92753-1: RORB; NbExp=3; IntAct=EBI-13287659, EBI-18560266; CC P06239-3; Q9UPQ4-2: TRIM35; NbExp=3; IntAct=EBI-13287659, EBI-17716262; CC P06239-3; Q5T6F2: UBAP2; NbExp=3; IntAct=EBI-13287659, EBI-2514383; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12218089, CC ECO:0000269|PubMed:22034844}; Lipid-anchor CC {ECO:0000269|PubMed:12218089, ECO:0000269|PubMed:22034844}; Cytoplasmic CC side {ECO:0000269|PubMed:12218089, ECO:0000269|PubMed:22034844}. CC Cytoplasm, cytosol {ECO:0000269|PubMed:12218089, CC ECO:0000269|PubMed:22034844}. Note=Present in lipid rafts in an CC inactive form. {ECO:0000269|PubMed:12218089}. 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 Name=3; CC IsoId=P06239-3; Sequence=VSP_016049; CC -!- TISSUE SPECIFICITY: Expressed specifically in lymphoid cells. CC -!- DOMAIN: The SH2 domain mediates interaction with SQSTM1. Interaction is CC regulated by Ser-59 phosphorylation. 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-cell receptor signaling. CC {ECO:0000269|PubMed:1639064, ECO:0000269|PubMed:22080863, CC ECO:0000269|PubMed:8139546, ECO:0000269|PubMed:8631775}. CC -!- PTM: Myristoylation is required prior to palmitoylation. {ECO:0000250}. CC -!- PTM: Palmitoylation regulates association with the plasma membrane and CC could be mediated by ZDHHC2. {ECO:0000269|PubMed:22034844}. CC -!- MASS SPECTROMETRY: Mass=57869.42; Method=MALDI; 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 variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/14/LCK"; 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; -; NOT_ANNOTATED_CDS; 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 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 PDB; 5MTM; X-ray; 2.40 A; A=118-231. DR PDB; 5MTN; X-ray; 2.85 A; A=118-231. DR PDB; 6H6A; X-ray; 2.00 A; E/H/K=2-11. DR PDB; 6PDJ; X-ray; 1.81 A; A=225-509. DR PDB; 8X2P; X-ray; 1.40 A; A/B=119-226. 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 PDBsum; 5MTM; -. DR PDBsum; 5MTN; -. DR PDBsum; 6H6A; -. DR PDBsum; 6PDJ; -. DR PDBsum; 8X2P; -. DR AlphaFoldDB; P06239; -. DR BMRB; P06239; -. DR SMR; P06239; -. DR BioGRID; 110124; 417. DR CORUM; P06239; -. DR DIP; DIP-553N; -. DR ELM; P06239; -. DR IntAct; P06239; 173. DR MINT; P06239; -. DR STRING; 9606.ENSP00000477713; -. DR BindingDB; P06239; -. DR ChEMBL; CHEMBL258; -. DR DrugBank; DB03023; 1-Tert-Butyl-3-(4-Chloro-Phenyl)-1h-Pyrazolo[3,4-D]Pyrimidin-4-Ylamine. DR DrugBank; DB07146; 2,3-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-B]PYRIDIN-4-AMINE. DR DrugBank; DB06925; 3-(2-AMINOQUINAZOLIN-6-YL)-4-METHYL-N-[3-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE. DR DrugBank; DB07297; 5,6-DIPHENYL-N-(2-PIPERAZIN-1-YLETHYL)FURO[2,3-D]PYRIMIDIN-4-AMINE. DR DrugBank; DB01830; AP-22408. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB08056; N-(2,6-dimethylphenyl)-5-phenylimidazo[1,5-a]pyrazin-8-amine. DR DrugBank; DB08057; N-(2-chloro-6-methylphenyl)-8-[(3S)-3-methylpiperazin-1-yl]imidazo[1,5-a]quinoxalin-4-amine. DR DrugBank; DB08055; N-(2-chlorophenyl)-5-phenylimidazo[1,5-a]pyrazin-8-amine. DR DrugBank; DB09079; Nintedanib. DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester. DR DrugBank; DB08901; Ponatinib. DR DrugBank; DB02010; Staurosporine. DR DrugBank; DB15035; Zanubrutinib. DR DrugBank; DB16656; Zotiraciclib. DR DrugBank; DB04003; {4-[(2S)-2-Acetamido-3-({(1S)-1-[3-carbamoyl-4-(cyclohexylmethoxy)phenyl]ethyl}amino)-3-oxopropyl]-2-phosphonophenoxy}acetic acid. DR DrugCentral; P06239; -. DR GuidetoPHARMACOLOGY; 2053; -. DR iPTMnet; P06239; -. DR PhosphoSitePlus; P06239; -. DR SwissPalm; P06239; -. DR BioMuta; LCK; -. DR DMDM; 125474; -. DR CPTAC; CPTAC-1775; -. DR CPTAC; CPTAC-929; -. DR EPD; P06239; -. DR jPOST; P06239; -. DR MassIVE; P06239; -. DR MaxQB; P06239; -. DR PaxDb; 9606-ENSP00000337825; -. DR PeptideAtlas; P06239; -. DR ProteomicsDB; 51874; -. [P06239-1] DR ProteomicsDB; 51875; -. [P06239-2] DR ProteomicsDB; 51876; -. [P06239-3] DR ABCD; P06239; 2 sequenced antibodies. DR Antibodypedia; 735; 1855 antibodies from 45 providers. DR DNASU; 3932; -. DR Ensembl; ENST00000333070.4; ENSP00000328213.4; ENSG00000182866.18. [P06239-3] DR Ensembl; ENST00000336890.10; ENSP00000337825.5; ENSG00000182866.18. [P06239-1] DR GeneID; 3932; -. DR KEGG; hsa:3932; -. DR MANE-Select; ENST00000336890.10; ENSP00000337825.5; NM_005356.5; NP_005347.3. DR UCSC; uc001bux.3; human. [P06239-1] DR AGR; HGNC:6524; -. DR CTD; 3932; -. DR DisGeNET; 3932; -. DR GeneCards; LCK; -. DR HGNC; HGNC:6524; LCK. DR HPA; ENSG00000182866; Tissue enriched (lymphoid). DR MalaCards; LCK; -. DR MIM; 153390; gene. DR MIM; 615758; phenotype. DR neXtProt; NX_P06239; -. DR OpenTargets; ENSG00000182866; -. DR Orphanet; 280142; Severe combined immunodeficiency due to LCK deficiency. DR PharmGKB; PA30307; -. DR VEuPathDB; HostDB:ENSG00000182866; -. DR eggNOG; KOG0197; Eukaryota. DR GeneTree; ENSGT00940000161163; -. DR HOGENOM; CLU_000288_7_2_1; -. DR InParanoid; P06239; -. DR OMA; CSPMQDK; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P06239; -. DR TreeFam; TF351634; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; P06239; -. 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-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-9013407; RHOH GTPase cycle. DR Reactome; R-HSA-9020558; Interleukin-2 signaling. DR Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants. DR Reactome; R-HSA-9706374; FLT3 signaling through SRC family kinases. DR SignaLink; P06239; -. DR SIGNOR; P06239; -. DR BioGRID-ORCS; 3932; 24 hits in 1189 CRISPR screens. DR ChiTaRS; LCK; human. DR EvolutionaryTrace; P06239; -. DR GeneWiki; Lck; -. DR GenomeRNAi; 3932; -. DR Pharos; P06239; Tclin. DR PRO; PR:P06239; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P06239; Protein. DR Bgee; ENSG00000182866; Expressed in thymus and 143 other cell types or tissues. DR ExpressionAtlas; P06239; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA: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: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:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:ARUK-UCL. DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:UniProtKB. DR GO; GO:0016004; F:phospholipase activator activity; IDA:ARUK-UCL. DR GO; GO:0043274; F:phospholipase binding; IPI:ARUK-UCL. DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA. 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:0005102; F:signaling receptor binding; IBA:GO_Central. DR GO; GO:0042608; F:T cell receptor binding; IPI:CAFA. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0050853; P:B cell receptor signaling pathway; IBA:GO_Central. DR GO; GO:0038094; P:Fc-gamma receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0030097; P:hemopoiesis; NAS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IBA:GO_Central. DR GO; GO:0035556; P:intracellular signal transduction; IDA:ARUK-UCL. DR GO; GO:0006882; P:intracellular zinc ion homeostasis; IEP:UniProtKB. DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IMP:ARUK-UCL. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IMP:BHF-UCL. DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:1903039; P:positive regulation of leukocyte cell-cell adhesion; IMP:BHF-UCL. 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:0006468; P:protein phosphorylation; IDA:UniProtKB. 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:0009410; P:response to xenobiotic stimulus; IDA:UniProtKB. 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 CDD; cd05067; PTKc_Lck_Blk; 1. DR CDD; cd10362; SH2_Src_Lck; 1. DR CDD; cd12005; SH3_Lck; 1. DR DisProt; DP01580; -. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24418:SF39; TYROSINE-PROTEIN KINASE LCK; 1. 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; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF50044; SH3-domain; 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. DR Genevisible; P06239; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Chromosomal rearrangement; Cytoplasm; Disease variant; KW Host-virus interaction; Kinase; Lipoprotein; Membrane; Myristate; KW 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 CHAIN 2..509 FT /note="Tyrosine-protein kinase Lck" FT /id="PRO_0000088124" 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 /evidence="ECO:0000250" FT REGION 154..242 FT /note="Interaction with PTPRH" FT /evidence="ECO:0000269|PubMed:12837766" 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:0007744|PubMed:19690332" FT MOD_RES 159 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 162 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 192 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P06240" FT MOD_RES 194 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 394 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:8139546" FT MOD_RES 505 FT /note="Phosphotyrosine; by CSK" FT /evidence="ECO:0000269|PubMed:1639064, FT ECO:0000269|PubMed:8139546, ECO:0000269|PubMed:8631775, FT ECO:0007744|PubMed:15592455, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:21406692" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000250" FT LIPID 3 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT LIPID 5 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT VAR_SEQ 321 FT /note="N -> NDTLLDSQLEEKGLGASPWGNLGQQLLLLPT (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_016049" FT VAR_SEQ 348..363 FT /note="IAEGMAFIEERNYIHR -> VRRLGRGAGQGNRPVT (in isoform FT Short)" FT /evidence="ECO:0000303|PubMed:7495859" FT /id="VSP_005000" FT VAR_SEQ 364..509 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000303|PubMed:7495859" FT /id="VSP_005001" FT VARIANT 28 FT /note="V -> L (found in leukemia)" FT /evidence="ECO:0000269|PubMed:8139546" FT /id="VAR_013463" FT VARIANT 201 FT /note="G -> S (in dbSNP:rs11567841)" FT /id="VAR_051697" FT VARIANT 232 FT /note="P -> PQKP (in leukemia)" FT /id="VAR_013464" FT VARIANT 341 FT /note="L -> P (in IMD22; dbSNP:rs587777335)" FT /evidence="ECO:0000269|PubMed:22985903" FT /id="VAR_071291" FT VARIANT 353 FT /note="A -> V (found in leukemia)" FT /evidence="ECO:0000269|PubMed:8139546" FT /id="VAR_013465" FT VARIANT 447 FT /note="P -> L (found in leukemia)" FT /evidence="ECO:0000269|PubMed:8139546" FT /id="VAR_013466" FT MUTAGEN 59 FT /note="S->E: Allows interaction with SQSTM1." FT /evidence="ECO:0000269|PubMed:8618896" FT MUTAGEN 154 FT /note="R->K: No effect on interaction with SQSTM1." FT /evidence="ECO:0000269|PubMed:8618896" FT CONFLICT 29 FT /note="P -> R (in Ref. 2; AAA59502)" FT /evidence="ECO:0000305" FT CONFLICT 35 FT /note="T -> R (in Ref. 2; AAA59502)" FT /evidence="ECO:0000305" FT CONFLICT 87 FT /note="Q -> P (in Ref. 2; CAA31884/AAA59502)" FT /evidence="ECO:0000305" FT CONFLICT 206..211 FT /note="VRHYTN -> ASAITPI (in Ref. 1; CAA28691)" FT /evidence="ECO:0000305" FT CONFLICT 254 FT /note="G -> A (in Ref. 2; AAA59502)" FT /evidence="ECO:0000305" FT CONFLICT 258..267 FT /note="EVWMGYYNGH -> RCGWGTTTGT (in Ref. 1; CAA28691)" FT /evidence="ECO:0000305" FT CONFLICT 282..286 FT /note="PDAFL -> AGRLP (in Ref. 1; CAA28691)" FT /evidence="ECO:0000305" FT CONFLICT 375 FT /note="T -> A (in Ref. 14; CAA28165)" FT /evidence="ECO:0000305" FT CONFLICT 472 FT /note="L -> H (in Ref. 13; CAA29667)" FT /evidence="ECO:0000305" FT CONFLICT 504..509 FT /note="QYQPQP -> STA (in Ref. 1; CAA28691)" FT /evidence="ECO:0000305" FT HELIX 12..15 FT /evidence="ECO:0007829|PDB:1Q68" FT STRAND 21..23 FT /evidence="ECO:0007829|PDB:1Q68" FT STRAND 24..27 FT /evidence="ECO:0007829|PDB:1Q69" FT TURN 60..63 FT /evidence="ECO:0007829|PDB:2IIM" FT STRAND 65..70 FT /evidence="ECO:0007829|PDB:2IIM" FT STRAND 76..79 FT /evidence="ECO:0007829|PDB:4D8K" FT STRAND 87..92 FT /evidence="ECO:0007829|PDB:2IIM" FT STRAND 95..102 FT /evidence="ECO:0007829|PDB:2IIM" FT TURN 103..105 FT /evidence="ECO:0007829|PDB:2IIM" FT STRAND 108..112 FT /evidence="ECO:0007829|PDB:2IIM" FT HELIX 113..115 FT /evidence="ECO:0007829|PDB:2IIM" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:2IIM" FT STRAND 128..131 FT /evidence="ECO:0007829|PDB:1CWD" FT HELIX 134..141 FT /evidence="ECO:0007829|PDB:1LKK" FT STRAND 151..155 FT /evidence="ECO:0007829|PDB:1LKK" FT STRAND 157..159 FT /evidence="ECO:0007829|PDB:1LKK" FT STRAND 163..171 FT /evidence="ECO:0007829|PDB:1LKK" FT TURN 172..174 FT /evidence="ECO:0007829|PDB:1LKK" FT STRAND 175..185 FT /evidence="ECO:0007829|PDB:1LKK" FT TURN 187..189 FT /evidence="ECO:0007829|PDB:1LCJ" FT STRAND 191..194 FT /evidence="ECO:0007829|PDB:1LKK" FT STRAND 199..201 FT /evidence="ECO:0007829|PDB:1LKK" FT HELIX 202..211 FT /evidence="ECO:0007829|PDB:1LKK" FT STRAND 216..218 FT /evidence="ECO:0007829|PDB:1LKK" FT TURN 233..235 FT /evidence="ECO:0007829|PDB:1QPC" FT STRAND 237..239 FT /evidence="ECO:0007829|PDB:1QPE" FT HELIX 242..244 FT /evidence="ECO:0007829|PDB:1QPC" FT STRAND 245..254 FT /evidence="ECO:0007829|PDB:1QPC" FT STRAND 257..264 FT /evidence="ECO:0007829|PDB:1QPC" FT TURN 265..267 FT /evidence="ECO:0007829|PDB:1QPC" FT STRAND 268..275 FT /evidence="ECO:0007829|PDB:1QPC" FT TURN 277..279 FT /evidence="ECO:0007829|PDB:1QPD" FT HELIX 282..294 FT /evidence="ECO:0007829|PDB:1QPC" FT STRAND 303..307 FT /evidence="ECO:0007829|PDB:1QPC" FT STRAND 309..311 FT /evidence="ECO:0007829|PDB:1QPC" FT STRAND 313..317 FT /evidence="ECO:0007829|PDB:1QPC" FT HELIX 324..327 FT /evidence="ECO:0007829|PDB:1QPC" FT HELIX 331..334 FT /evidence="ECO:0007829|PDB:1QPC" FT HELIX 338..357 FT /evidence="ECO:0007829|PDB:1QPC" FT HELIX 367..369 FT /evidence="ECO:0007829|PDB:1QPC" FT STRAND 370..372 FT /evidence="ECO:0007829|PDB:1QPC" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:1QPC" FT HELIX 383..385 FT /evidence="ECO:0007829|PDB:1QPE" FT HELIX 386..389 FT /evidence="ECO:0007829|PDB:3B2W" FT STRAND 390..392 FT /evidence="ECO:0007829|PDB:1QPC" FT STRAND 393..395 FT /evidence="ECO:0007829|PDB:4C3F" FT TURN 404..406 FT /evidence="ECO:0007829|PDB:1QPC" FT HELIX 409..414 FT /evidence="ECO:0007829|PDB:1QPC" FT HELIX 419..434 FT /evidence="ECO:0007829|PDB:1QPC" FT TURN 435..437 FT /evidence="ECO:0007829|PDB:1QPC" FT HELIX 446..454 FT /evidence="ECO:0007829|PDB:1QPC" FT HELIX 467..476 FT /evidence="ECO:0007829|PDB:1QPC" FT HELIX 481..483 FT /evidence="ECO:0007829|PDB:1QPC" FT HELIX 487..500 FT /evidence="ECO:0007829|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 //