LCK_HUMAN
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 03-AUG-2022, entry version 269.
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; 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; Q9GZU7: CTDSP1; NbExp=3; IntAct=EBI-13287659, EBI-751587;
CC P06239-3; A8MTA8-2: FAM166B; NbExp=3; IntAct=EBI-13287659, EBI-12160437;
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="http://atlasgeneticsoncology.org/Genes/LCKID14ch1p34.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Lck entry;
CC URL="https://en.wikipedia.org/wiki/Lck";
CC ---------------------------------------------------------------------------
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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 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 AlphaFoldDB; P06239; -.
DR BMRB; P06239; -.
DR SMR; P06239; -.
DR BioGRID; 110124; 406.
DR CORUM; P06239; -.
DR DIP; DIP-553N; -.
DR ELM; P06239; -.
DR IntAct; P06239; 171.
DR MINT; P06239; -.
DR STRING; 9606.ENSP00000337825; -.
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; 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; P06239; -.
DR PeptideAtlas; P06239; -.
DR PRIDE; 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; 1730 antibodies from 45 providers.
DR DNASU; 3932; -.
DR Ensembl; ENST00000333070.4; ENSP00000328213.4; ENSG00000182866.17. [P06239-3]
DR Ensembl; ENST00000336890.10; ENSP00000337825.5; ENSG00000182866.17. [P06239-1]
DR Ensembl; ENST00000619559.4; ENSP00000477713.1; ENSG00000182866.17. [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 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; ICEHCNY; -.
DR OrthoDB; 539311at2759; -.
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; 17 hits in 1098 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 141 other tissues.
DR ExpressionAtlas; P06239; baseline and differential.
DR Genevisible; P06239; HS.
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: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: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:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0006882; P:cellular zinc ion homeostasis; IEP:UniProtKB.
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: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; cd10362; SH2_Src_Lck; 1.
DR CDD; cd12005; SH3_Lck; 1.
DR DisProt; DP01580; -.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR035850; Lck_SH2.
DR InterPro; IPR035749; Lck_SH3.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 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
