[1]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1002/eji.1830161229; PubMed=3493153 [NCBI, ExPASy, EBI, Israel, Japan] Koga Y., Caccia N., Toyonaga B., Spolski R., Yanagi Y., Yoshikai Y., Mak T.W.; "A human T cell-specific cDNA clone (YT16) encodes a protein with extensive homology to a family of protein-tyrosine kinases."; Eur. J. Immunol. 16:1643-1646(1986).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1002/jcb.240380206; PubMed=3265417 [NCBI, ExPASy, EBI, Israel, Japan] Perlmutter R.M., Marth J.D., Lewis D.B., Peet R., Ziegler S.F., Wilson C.B.; "Structure and expression of lck transcripts in human lymphoid cells."; J. Cell. Biochem. 38:117-126(1988).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1016/0378-1119(89)90144-3; PubMed=2558056 [NCBI, ExPASy, EBI, Israel, Japan] Rouer E., van Huynh T., de Souza S.L., Lang M.C., Fischer S., Benarous R.; "Structure of the human lck gene: differences in genomic organisation within src-related genes affect only N-terminal exons."; Gene 84:105-113(1989).
[4]	NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-28; GLN-LYS-PRO-232 INS; VAL-353 AND LEU-447, AND PHOSPHORYLATION AT TYR-394 AND TYR-505. TISSUE=Leukemia; PubMed=8139546 [NCBI, ExPASy, EBI, Israel, Japan] Wright D.D., Sefton B.M., Kamps M.P.; "Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia."; Mol. Cell. Biol. 14:2429-2437(1994).
[5]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND ALTERNATIVE SPLICING. TISSUE=Leukemic T-cell; DOI=10.1016/0167-4781(95)00162-A; PubMed=7495859 [NCBI, ExPASy, EBI, Israel, Japan] Vogel L.B., Arthur R., Fujita D.J.; "An aberrant lck mRNA in two human T-cell lines."; Biochim. Biophys. Acta 1264:168-172(1995).
[6]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. PubMed=12401726 [NCBI, ExPASy, EBI, Israel, Japan] Nervi S., Nicodeme S., Gartioux C., Atlan C., Lathrop M., Reviron D., Naquet P., Matsuda F., Imbert J., Vialettes B.; "No association between lck gene polymorphisms and protein level in type 1 diabetes."; Diabetes 51:3326-3330(2002).
[7]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. DOI=10.1038/nature04727; PubMed=16710414 [NCBI, ExPASy, EBI, Israel, Japan] Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; "The DNA sequence and biological annotation of human chromosome 1."; Nature 441:315-321(2006).
[8]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.; Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[9]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). TISSUE=Lymph; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[10]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35. PubMed=2850479 [NCBI, ExPASy, EBI, Israel, Japan] Garvin A.M., Pawar S., Marth J.D., Perlmutter R.M.; "Structure of the murine lck gene and its rearrangement in a murine lymphoma cell line."; Mol. Cell. Biol. 8:3058-3064(1988).
[11]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35. PubMed=2787474 [NCBI, ExPASy, EBI, Israel, Japan] Takadera T., Leung S., Gernone A., Koga Y., Takihara Y., Miyamoto N.G., Mak T.W.; "Structure of the two promoters of the human lck gene: differential accumulation of two classes of lck transcripts in T cells."; Mol. Cell. Biol. 9:2173-2180(1989).
[12]	NUCLEOTIDE SEQUENCE [MRNA] OF 14-509. TISSUE=Peripheral blood lymphocyte; DOI=10.1002/1521-4141(200009)30:9<2632::AID-IMMU2632>3.0.CO;2-C; PubMed=11009097 [NCBI, ExPASy, EBI, Israel, Japan] Boncristiano M., Majolini M.B., D'Elios M.M., Pacini S., Valensin S., Ulivieri C., Amedei A., Falini B., Del Prete G., Telford J.L., Baldari C.T.; "Defective recruitment and activation of ZAP-70 in common variable immunodeficiency patients with T cell defects."; Eur. J. Immunol. 30:2632-2638(2000).
[13]	NUCLEOTIDE SEQUENCE [MRNA] OF 368-509. PubMed=2835736 [NCBI, ExPASy, EBI, Israel, Japan] Veillette A., Foss F.M., Sausville E.A., Bolen J.B., Rosen N.; "Expression of the lck tyrosine kinase gene in human colon carcinoma and other non-lymphoid human tumor cell lines."; Oncogene Res. 1:357-374(1987).
[14]	NUCLEOTIDE SEQUENCE [MRNA] OF 375-509. DOI=10.1016/0167-4889(86)90228-4; PubMed=3489486 [NCBI, ExPASy, EBI, Israel, Japan] Trevillyan J.M., Lin Y., Chen S.J., Phillips C.A., Canna C., Linna T.J.; "Human T lymphocytes express a protein-tyrosine kinase homologous to p56LSTRA."; Biochim. Biophys. Acta 888:286-295(1986).
[15]	PHOSPHORYLATION AT TYR-505. PubMed=1639064 [NCBI, ExPASy, EBI, Israel, Japan] Bergman M., Mustelin T., Oetken C., Partanen J., Flint N.A., Amrein K.E., Autero M., Burn P., Alitalo K.; "The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down regulates its catalytic activity."; EMBO J. 11:2919-2924(1992).
[16]	INTERACTION WITH PI3K. PubMed=7504174 [NCBI, ExPASy, EBI, Israel, Japan] Vogel L.B., Fujita D.J.; "The SH3 domain of p56lck is involved in binding to phosphatidylinositol 3'-kinase from T lymphocytes."; Mol. Cell. Biol. 13:7408-7417(1993).
[17]	INTERACTION WITH KHDRBS1. DOI=10.1074/jbc.270.6.2506; PubMed=7852312 [NCBI, ExPASy, EBI, Israel, Japan] Vogel L.B., Fujita D.J.; "p70 phosphorylation and binding to p56lck is an early event in interleukin-2-induced onset of cell cycle progression in T-lymphocytes."; J. Biol. Chem. 270:2506-2511(1995).
[18]	INTERACTION WITH SQSTM1, AND MUTAGENESIS OF SER-59 AND ARG-154. DOI=10.1073/pnas.92.26.12338; PubMed=8618896 [NCBI, ExPASy, EBI, Israel, Japan] Park I., Chung J., Walsh C.T., Yun Y., Strominger J.L., Shin J.; "Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region."; Proc. Natl. Acad. Sci. U.S.A. 92:12338-12342(1995).
[19]	INTERACTION WITH HIV-1 NEF. PubMed=8794306 [NCBI, ExPASy, EBI, Israel, Japan] Greenway A.L., Azad A., Mills J., McPhee D.A.; "Human immunodeficiency virus type 1 Nef binds directly to LCK and mitogen-activated protein kinase, inhibiting kinase activity."; J. Virol. 70:6701-6708(1996).
[20]	REVIEW. DOI=10.1046/j.1432-1327.2000.01412.x; PubMed=10848956 [NCBI, ExPASy, EBI, Israel, Japan] Isakov N., Biesinger B.; "Lck protein tyrosine kinase is a key regulator of T-cell activation and a target for signal intervention by Herpesvirus saimiri and other viral gene products."; Eur. J. Biochem. 267:3413-3421(2000).
[21]	SUBCELLULAR LOCATION. PubMed=12218089 [NCBI, ExPASy, EBI, Israel, Japan] Yasuda K., Nagafuku M., Shima T., Okada M., Yagi T., Yamada T., Minaki Y., Kato A., Tani-Ichi S., Hamaoka T., Kosugi A.; "Fyn is essential for tyrosine phosphorylation of Csk-binding protein/phosphoprotein associated with glycolipid-enriched microdomains in lipid rafts in resting T cells."; J. Immunol. 169:2813-2817(2002).
[22]	MASS SPECTROMETRY. TISSUE=Mammary cancer; DOI=10.1002/1615-9861(200202)2:2<212::AID-PROT212>3.0.CO;2-H; PubMed=11840567 [NCBI, ExPASy, EBI, Israel, Japan] Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., Zvelebil M.J.; "Cluster analysis of an extensive human breast cancer cell line protein expression map database."; Proteomics 2:212-223(2002).
[23]	INTERACTION WITH LIME1. DOI=10.1084/jem.20031484; PubMed=14610046 [NCBI, ExPASy, EBI, Israel, Japan] Brdickova N., Brdicka T., Angelisova P., Horvath O., Spicka J., Hilgert I., Paces J., Simeoni L., Kliche S., Merten C., Schraven B., Horejsi V.; "LIME: a new membrane raft-associated adaptor protein involved in CD4 and CD8 coreceptor signaling."; J. Exp. Med. 198:1453-1462(2003).
[24]	INTERACTION WITH LIME1. DOI=10.1084/jem.20030232; PubMed=14610044 [NCBI, ExPASy, EBI, Israel, Japan] Hur E.M., Son M., Lee O.-H., Choi Y.B., Park C., Lee H., Yun Y.; "LIME, a novel transmembrane adaptor protein, associates with p56lck and mediates T cell activation."; J. Exp. Med. 198:1463-1473(2003).
[25]	INTERACTION WITH PTPRH. DOI=10.1074/jbc.M300648200; PubMed=12837766 [NCBI, ExPASy, EBI, Israel, Japan] Ito T., Okazawa H., Maruyama K., Tomizawa K., Motegi S., Ohnishi H., Kuwano H., Kosugi A., Matozaki T.; "Interaction of SAP-1, a transmembrane-type protein-tyrosine phosphatase, with the tyrosine kinase Lck. Roles in regulation of T cell function."; J. Biol. Chem. 278:34854-34863(2003).
[26]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-394 AND TYR-505, AND MASS SPECTROMETRY. DOI=10.1038/nbt1046; PubMed=15592455 [NCBI, ExPASy, EBI, Israel, Japan] Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.; "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; Nat. Biotechnol. 23:94-101(2005).
[27]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-192 AND TYR-505, AND MASS SPECTROMETRY. DOI=10.1016/j.cell.2007.11.025; PubMed=18083107 [NCBI, ExPASy, EBI, Israel, Japan] Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; "Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."; Cell 131:1190-1203(2007).
[28]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162; TYR-192; SER-213; TYR-394; THR-501 AND TYR-505, AND MASS SPECTROMETRY. DOI=10.1074/mcp.T600062-MCP200; PubMed=17192257 [NCBI, ExPASy, EBI, Israel, Japan] Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H.; "Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry."; Mol. Cell. Proteomics 6:537-547(2007).
[29]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-505, AND MASS SPECTROMETRY. DOI=10.1016/j.molcel.2008.07.007; PubMed=18691976 [NCBI, ExPASy, EBI, Israel, Japan] Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.; "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."; Mol. Cell 31:438-448(2008).
[30]	X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 53-226. DOI=10.1038/368764a0; PubMed=7512222 [NCBI, ExPASy, EBI, Israel, Japan] Eck M.J., Atweell S.K., Shoelson S.E., Harrison S.C.; "Structure of the regulatory domains of the Src-family tyrosine kinase Lck."; Nature 368:764-769(1994).
[31]	X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 127-221. DOI=10.1006/jmbi.1994.0089; PubMed=7532720 [NCBI, ExPASy, EBI, Israel, Japan] Mikol V., Baumann G., Keller T.H., Manning U.M., Zurini M.G.M.; "The crystal structures of the SH2 domain of p56lck complexed with two phosphonopeptides suggest a gated peptide binding site."; J. Mol. Biol. 246:344-355(1995).
[32]	X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 122-226. DOI=10.1006/jmbi.1996.0112; PubMed=8604142 [NCBI, ExPASy, EBI, Israel, Japan] Tong L., Warren T.C., King J., Betageri R., Rose J., Jakes S.; "Crystal structures of the human p56lck SH2 domain in complex with two short phosphotyrosyl peptides at 1.0-A and 1.8-A resolution."; J. Mol. Biol. 256:601-610(1996).
[33]	X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 231-501. DOI=10.1038/384484a0; PubMed=8945479 [NCBI, ExPASy, EBI, Israel, Japan] Yamaguchi H., Hendrickson W.A.; "Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation."; Nature 384:484-489(1996).
[34]	X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 119-226. DOI=10.1074/jbc.273.32.20238; PubMed=9685372 [NCBI, ExPASy, EBI, Israel, Japan] Tong L., Warren T.C., Lukas S., Schembri-King J., Betageri R., Proudfoot J.R., Jakes S.; "Carboxymethyl-phenylalanine as a replacement for phosphotyrosine in SH2 domain binding."; J. Biol. Chem. 273:20238-20242(1998).

Comments

FUNCTION: Tyrosine kinase that plays an essential role for the selection and maturation of developing T-cell in the thymus and in mature T-cell function. Is constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors and plays a key role in T-cell antigen receptor(TCR)-linked signal transduction pathways. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, and thereby recruits the associated LCK to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosines-based activation motifs (ITAMs) in the cytoplasmic tails of the TCRgamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. In addition, contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, and upon engagement of the CD2 molecule, LCK undergoes hyperphosphorylation and activation. Also plays a role in the IL2 receptor-linked signaling pathway that controls T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR.
CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
ENZYME REGULATION: Inhibited by tyrosine phosphorylation.
SUBUNIT: Binds to the cytoplasmic domain of cell surface receptors, such as CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB and to other protein kinases including CDC2, RAF1, ZAP70 and SYK. Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of KHDRBS1/p70 through its SH2 domain. Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with SQSTM1. Interacts with phosphorylated LIME1. Interacts with CBLB and PTPRH.
INTERACTION:
P27958:- (xeno); NbExp=1; IntAct=EBI-1348, EBI-706378;
Q9WMX2:- (xeno); NbExp=1; IntAct=EBI-1348, EBI-710918;
P20963:CD247; NbExp=1; IntAct=EBI-1348, EBI-1165705;
Q07666:KHDRBS1; NbExp=3; IntAct=EBI-1348, EBI-1364;
O43561:LAT; NbExp=1; IntAct=EBI-1348, EBI-1222766;
Q9H204:MED28; NbExp=2; IntAct=EBI-1348, EBI-514199;
Q05209:PTPN12; NbExp=1; IntAct=EBI-1348, EBI-2266035;
Q9Y2R2:PTPN22; NbExp=3; IntAct=EBI-1348, EBI-1211241;
P29350:PTPN6; NbExp=1; IntAct=EBI-1348, EBI-78260;
P23467:PTPRB; NbExp=1; IntAct=EBI-1348, EBI-1265766;
P08575:PTPRC; NbExp=1; IntAct=EBI-1348, EBI-1341;
P23470:PTPRG; NbExp=1; IntAct=EBI-1348, EBI-2258115;
Q12913:PTPRJ; NbExp=1; IntAct=EBI-1348, EBI-2264500;
Q15262:PTPRK; NbExp=1; IntAct=EBI-1348, EBI-474052;
P28827:PTPRM; NbExp=1; IntAct=EBI-1348, EBI-2257317;
Q16827:PTPRO; NbExp=1; IntAct=EBI-1348, EBI-723739;
P23471:PTPRZ1; NbExp=1; IntAct=EBI-1348, EBI-2263175;
Q9NP31:SH2D2A; NbExp=1; IntAct=EBI-1348, EBI-490630;
O00401:WASL; NbExp=1; IntAct=EBI-1348, EBI-957615;
P43403:ZAP70; NbExp=1; IntAct=EBI-1348, EBI-1211276;
SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Lipid-anchor; Cytoplasmic side. Note=Present in lipid rafts in an unactive form.

ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing.

Name	Long
Isoform ID	P06239-1
This is the isoform sequence displayed in this entry.

Name	Short
Isoform ID	P06239-2
Note: No experimental confirmation available.
Features which should be applied to build the isoform sequence: VSP_005000, VSP_005001.

Name	3
Isoform ID	P06239-3
Note: No experimental confirmation available.
Features which should be applied to build the isoform sequence: VSP_016049.

TISSUE SPECIFICITY: Expressed specifically in lymphoid cells.
DOMAIN: The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation.
PTM: Phosphorylated on Tyr-394, which increases enzymatic activity (By similarity). Phosphorylated on Tyr-505, which decreases activity.
MASS SPECTROMETRY: Mass=57869.42; Method=MALDI; Range=2-509; Source=PubMed:11840567;.
DISEASE: A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.
SIMILARITY: Contains 1 protein kinase domain.
SIMILARITY: Contains 1 SH2 domain.
SIMILARITY: Contains 1 SH3 domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/LCKID14ch1p34.html";.
WEB RESOURCE: Name=Wikipedia; Note=Lck entry; URL="http://en.wikipedia.org/wiki/Lck";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

X05027; CAA28691.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X13529; CAA31884.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M36881; AAA59502.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X14055; CAA32211.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X14053; CAA32211.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X14054; CAA32211.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U07236; AAA18225.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U23852; AAC50287.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BN000073; CAD55807.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL121991; CAI22320.1; ALT_INIT; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AL121991; CAI22321.1; ALT_INIT; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
CH471059; EAX07543.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC013200; AAH13200.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M21510; AAA59501.1; ALT_TERM; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M26692; AAA59503.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF228313; AAF34794.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X06369; CAA29667.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X04476; CAA28165.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00394952; -.
IPI00411413; -.
IPI00515097; -.

PIR

JQ0152; OKHULK.

RefSeq

NP_001036236.1; -.
NP_005347.3; -.

UniGene

Hs.470627

3D structure databases

PDB

1BHF; X-ray; 1.80 A; A=119-226.	[ExPASy / RCSB / EBI]
1BHH; X-ray; 1.90 A; A=119-226, B=124-226.	[ExPASy / RCSB / EBI]
1CWD; X-ray; 2.25 A; L=127-222.	[ExPASy / RCSB / EBI]
1CWE; X-ray; 2.30 A; A/C=127-222.	[ExPASy / RCSB / EBI]
1FBZ; X-ray; 2.40 A; A/B=123-226.	[ExPASy / RCSB / EBI]
1H92; NMR; -; A=59-120.	[ExPASy / RCSB / EBI]
1IJR; X-ray; 2.20 A; A=124-226.	[ExPASy / RCSB / EBI]
1KIK; NMR; -; A=64-120.	[ExPASy / RCSB / EBI]
1LCJ; X-ray; 1.80 A; A=119-226.	[ExPASy / RCSB / EBI]
1LCK; X-ray; 2.50 A; A=53-226, B=502-509.	[ExPASy / RCSB / EBI]
1LKK; X-ray; 1.00 A; A=122-226.	[ExPASy / RCSB / EBI]
1LKL; X-ray; 1.80 A; A=123-226.	[ExPASy / RCSB / EBI]
1Q68; NMR; -; B=7-35.	[ExPASy / RCSB / EBI]
1Q69; NMR; -; B=7-35.	[ExPASy / RCSB / EBI]
1QPC; X-ray; 1.60 A; A=231-509.	[ExPASy / RCSB / EBI]
1QPD; X-ray; 2.00 A; A=231-509.	[ExPASy / RCSB / EBI]
1QPE; X-ray; 2.00 A; A=231-509.	[ExPASy / RCSB / EBI]
1QPJ; X-ray; 2.20 A; A=231-509.	[ExPASy / RCSB / EBI]
1X27; X-ray; 2.70 A; A/B/C/D/E/F=64-226.	[ExPASy / RCSB / EBI]
2IIM; X-ray; 1.00 A; A=59-119.	[ExPASy / RCSB / EBI]
2OF2; X-ray; 2.00 A; A=231-501.	[ExPASy / RCSB / EBI]
2OF4; X-ray; 2.70 A; A=231-501.	[ExPASy / RCSB / EBI]
2OFU; X-ray; 2.00 A; A=229-501.	[ExPASy / RCSB / EBI]
2OFV; X-ray; 2.00 A; A/B=226-502.	[ExPASy / RCSB / EBI]
2OG8; X-ray; 2.30 A; A/B=236-500.	[ExPASy / RCSB / EBI]
2PL0; X-ray; 2.80 A; A=225-509.	[ExPASy / RCSB / EBI]
2ZM1; X-ray; 2.10 A; A=225-509.	[ExPASy / RCSB / EBI]
2ZM4; X-ray; 2.70 A; A=225-509.	[ExPASy / RCSB / EBI]
2ZYB; X-ray; 2.55 A; A=225-509.	[ExPASy / RCSB / EBI]
3B2W; X-ray; 2.30 A; A=226-502.	[ExPASy / RCSB / EBI]
3BRH; X-ray; 2.20 A; C/D=391-397.	[ExPASy / RCSB / EBI]
3BYM; X-ray; 2.00 A; A=230-501.	[ExPASy / RCSB / EBI]
3BYO; X-ray; 2.00 A; A=231-501.	[ExPASy / RCSB / EBI]
3BYS; X-ray; 2.20 A; A=225-501.	[ExPASy / RCSB / EBI]
3BYU; X-ray; 2.30 A; A=225-501.	[ExPASy / RCSB / EBI]
3LCK; X-ray; 1.70 A; A=231-501.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1BHF; -.
1BHH; -.
1CWD; -.
1CWE; -.
1FBZ; -.
1H92; -.
1IJR; -.
1KIK; -.
1LCJ; -.
1LCK; -.
1LKK; -.
1LKL; -.
1Q68; -.
1Q69; -.
1QPC; -.
1QPD; -.
1QPE; -.
1QPJ; -.
1X27; -.
2IIM; -.
2OF2; -.
2OF4; -.
2OFU; -.
2OFV; -.
2OG8; -.
2PL0; -.
2ZM1; -.
2ZM4; -.
2ZYB; -.
3B2W; -.
3BRH; -.
3BYM; -.
3BYO; -.
3BYS; -.
3BYU; -.
3LCK; -.

SMR

P06239; 65-509.

ModBase

P06239.

Protein-protein interaction databases

DIP

DIP:553N; -.

IntAct

P06239; 23.

PTM databases

PhosphoSite

P06239; -.

Enzyme and pathway databases

BRENDA

2.7.10.2; 247.

Pathway_Interaction_DB

alphasynuclein_pathway; Alpha-synuclein signaling.
amb2_neutrophils_pathway; amb2 Integrin signaling.
nfkappabatypicalpathway; Atypical NF-kappaB pathway.
pi3kcipathway; Class I PI3K signaling events.
epha_fwdpathway; EPHA forward signaling.
ephrinbrevpathway; Ephrin B reverse signaling.
glypican_1pathway; Glypican 1 network.
il12_2pathway; IL12-mediated signaling events.
il2_pi3kpathway; IL2 signaling events mediated by PI3K.
il2_stat5pathway; IL2 signaling events mediated by STAT5.
il2_1pathway; IL2-mediated signaling events.
pdgfrbpathway; PDGFR-beta signaling pathway.
p38alphabetapathway; Regulation of p38-alpha and p38-beta.
ptp1bpathway; Signaling events mediated by PTP1B.
tcrpathway; TCR signaling in naive CD4+ T cells.
cd8tcrpathway; TCR signaling in naive CD8+ T cells.
txa2pathway; Thromboxane A2 receptor signaling.

Reactome

REACT_6185; HIV Infection.
REACT_6900; Signaling in Immune system.

Organism-specific databases

GC01P032489; -.

HIX0019954; -.

HGNC:6524; LCK.

LCK.

CAB003816; -.
HPA003494; -.

MIM

153390; gene. [NCBI / EBI]

PharmGKB

PA30307; -.

Gene expression databases

P06239; -.

P06239; -.

HS_LCK; -.

ENSG00000182866; Homo sapiens.

Ontologies

GO:0005829;	Cellular component: cytosol (inferred from experiment from Reactome).
GO:0005794;	Cellular component: Golgi apparatus (inferred from direct assay from HPA).
GO:0045121;	Cellular component: membrane raft (inferred from direct assay from UniProtKB).
GO:0000242;	Cellular component: pericentriolar material (inferred from direct assay from UniProtKB).
GO:0005886;	Cellular component: plasma membrane (inferred from experiment from Reactome).
GO:0005524;	Molecular function: ATP binding (inferred from electronic annotation from UniProtKB-KW).
GO:0051117;	Molecular function: ATPase binding (inferred from physical interaction from UniProtKB).
GO:0042609;	Molecular function: CD4 receptor binding (inferred from physical interaction from UniProtKB).
GO:0042610;	Molecular function: CD8 receptor binding (inferred from physical interaction from UniProtKB).
GO:0001948;	Molecular function: glycoprotein binding (inferred from physical interaction from UniProtKB).
GO:0004715;	Molecular function: non-membrane spanning protein tyrosine kinase activity (inferred from electronic annotation from EC).
GO:0043548;	Molecular function: phosphoinositide 3-kinase binding (inferred from physical interaction from UniProtKB).
GO:0008022;	Molecular function: protein C-terminus binding (inferred from physical interaction from UniProtKB).
GO:0019901;	Molecular function: protein kinase binding (inferred from physical interaction from UniProtKB).
GO:0004722;	Molecular function: protein serine/threonine phosphatase activity (inferred from direct assay from UniProtKB).
GO:0042169;	Molecular function: SH2 domain binding (inferred from physical interaction from UniProtKB).
GO:0006919;	Biological process: activation of caspase activity (inferred from direct assay from UniProtKB).
GO:0006882;	Biological process: cellular zinc ion homeostasis (inferred from expression pattern from UniProtKB).
GO:0006917;	Biological process: induction of apoptosis (inferred from mutant phenotype from UniProtKB).
GO:0044419;	Biological process: interspecies interaction between organisms (inferred from electronic annotation from UniProtKB-KW).
GO:0050862;	Biological process: positive regulation of T cell receptor signaling pathway (non-traceable author statement from UniProtKB).
GO:0051209;	Biological process: release of sequestered calcium ion into cytosol (inferred from sequence or structural similarity from UniProtKB).
GO:0042493;	Biological process: response to drug (inferred from direct assay from UniProtKB).
GO:0030217;	Biological process: T cell differentiation (inferred from mutant phenotype from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_BS.
IPR000980; SH2.
IPR001452; SH3_domain.
IPR001245; Tyr_pkinase.
IPR008266; Tyr_pkinase_AS.
Graphical view of domain structure.

Gene3D

G3DSA:3.30.505.10; SH2; 1.

Pfam

PF07714; Pkinase_Tyr; 1.
PF00017; SH2; 1.
PF00018; SH3_1; 1.
Pfam graphical view of domain structure.

PRINTS

PR00401; SH2DOMAIN.
PR00109; TYRKINASE.

ProDom

PD000001; Prot_kinase; 1.
PD000093; SH2; 1.
PD000066; SH3; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00252; SH2; 1.
SM00326; SH3; 1.
SM00219; TyrKc; 1.
SMART graphical view of domain structure.

PROSITE

PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00109; PROTEIN_KINASE_TYR; 1.
PS50001; SH2; 1.
PS50002; SH3; 1.
PROSITE graphical view of domain structure (profiles).

Other

SWISS-3DIMAGE

P06239.

Proteomic databases

PRIDE

P06239; -.

Genome annotation databases

Ensembl

ENSG00000182866; Homo sapiens. [Contig view]

GeneID

3932; -.

KEGG

hsa:3932; -.

Phylogenomic databases

HOVERGEN

P06239; -.

OMA

P06239; MAFIEEQ.

Other

P06239; -.

DB01254; Dasatinib.

15441; -.

LCK; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Alternative splicing; ATP-binding; Cell membrane; Chromosomal rearrangement; Cytoplasm; Disease mutation; Host-virus interaction; Kinase; Lipoprotein; Membrane; Myristate; Nucleotide-binding; Palmitate; Phosphoprotein; Polymorphism; Proto-oncogene; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`INIT_MET`	`1 1`		`Removed (Probable).`
`CHAIN`	`2 509`	`508`	`Proto-oncogene tyrosine-protein kinase LCK.`	`PRO_0000088124`
`DOMAIN`	`61 121`	`61`	`SH3.`
`DOMAIN`	`127 224`	`98`	`SH2.`
`DOMAIN`	`245 498`	`254`	`Protein kinase.`
`NP_BIND`	`251 259`	`9`	`ATP (By similarity).`
`REGION`	`2 72`	`71`	`Interactions with CD4 and CD8 (By similarity).`
`REGION`	`154 242`	`89`	`Interaction with PTPRH.`
`ACT_SITE`	`364 364`		`Proton acceptor (By similarity).`
`BINDING`	`273 273`		`ATP (By similarity).`
`MOD_RES`	`162 162`		`Phosphoserine.`
`MOD_RES`	`192 192`		`Phosphotyrosine.`
`MOD_RES`	`213 213`		`Phosphoserine.`
`MOD_RES`	`394 394`		`Phosphotyrosine; by autocatalysis.`
`MOD_RES`	`501 501`		`Phosphothreonine.`
`MOD_RES`	`505 505`		`Phosphotyrosine.`
`LIPID`	`2 2`		`N-myristoyl glycine (By similarity).`
`LIPID`	`3 3`		`S-palmitoyl cysteine (By similarity).`
`LIPID`	`5 5`		`S-palmitoyl cysteine (By similarity).`
`VAR_SEQ`	`321 321`		`N -> NDTLLDSQLEEKGLGASPWGNLGQQLLLLPT (in isoform 3).`	`VSP_016049`
`VAR_SEQ`	`348 363`		`IAEGMAFIEERNYIHR -> VRRLGRGAGQGNRPVT (in isoform Short).`	`VSP_005000`
`VAR_SEQ`	`364 509`		`Missing (in isoform Short).`	`VSP_005001`
`VARIANT`	`28 28`	`1`	`V -> L (in leukemia).`	`VAR_013463`
`VARIANT`	`201 201`	`1`	`G -> S (in dbSNP:rs11567841 [NCBI]).`	`VAR_051697`
`VARIANT`	`232 232`	`1`	`P -> PQKP (in leukemia).`	`VAR_013464`
`VARIANT`	`353 353`	`1`	`A -> V (in leukemia).`	`VAR_013465 [3D]`
`VARIANT`	`447 447`	`1`	`P -> L (in leukemia).`	`VAR_013466 [3D]`
`MUTAGEN`	`59 59`		`S->E: Allows interaction with SQSTM1.`
`MUTAGEN`	`154 154`		`R->K: No effect on interaction with SQSTM1.`
`CONFLICT`	`29 29`		`P -> R (in Ref. 2; AAA59502).`
`CONFLICT`	`35 35`		`T -> R (in Ref. 2; AAA59502).`
`CONFLICT`	`87 87`		`Q -> P (in Ref. 2; CAA31884/AAA59502).`
`CONFLICT`	`206 211`		`VRHYTN -> ASAITPI (in Ref. 1; CAA28691).`
`CONFLICT`	`254 254`		`G -> A (in Ref. 2; AAA59502).`
`CONFLICT`	`258 267`		`EVWMGYYNGH -> RCGWGTTTGT (in Ref. 1; CAA28691).`
`CONFLICT`	`282 286`		`PDAFL -> AGRLP (in Ref. 1; CAA28691).`
`CONFLICT`	`375 375`		`T -> A (in Ref. 14).`
`CONFLICT`	`472 472`		`L -> H (in Ref. 13).`
`CONFLICT`	`504 509`		`QYQPQP -> STA (in Ref. 1; CAA28691).`
`HELIX`	`12 15`	`4`
`STRAND`	`21 23`	`3`
`TURN`	`60 63`	`4`
`STRAND`	`65 70`	`6`
`STRAND`	`87 92`	`6`
`STRAND`	`95 102`	`8`
`TURN`	`103 105`	`3`
`STRAND`	`108 112`	`5`
`HELIX`	`113 115`	`3`
`STRAND`	`116 118`	`3`
`HELIX`	`134 141`	`8`
`STRAND`	`151 155`	`5`
`STRAND`	`157 159`	`3`
`STRAND`	`163 171`	`9`
`TURN`	`172 174`	`3`
`STRAND`	`175 185`	`11`
`STRAND`	`191 194`	`4`
`STRAND`	`199 201`	`3`
`HELIX`	`202 211`	`10`
`STRAND`	`216 218`	`3`
`TURN`	`233 235`	`3`
`HELIX`	`242 244`	`3`
`STRAND`	`245 254`	`10`
`STRAND`	`257 264`	`8`
`TURN`	`265 267`	`3`
`STRAND`	`268 275`	`8`
`HELIX`	`282 294`	`13`
`STRAND`	`303 307`	`5`
`STRAND`	`309 311`	`3`
`STRAND`	`313 317`	`5`
`HELIX`	`324 327`	`4`
`HELIX`	`331 334`	`4`
`HELIX`	`338 357`	`20`
`HELIX`	`367 369`	`3`
`STRAND`	`370 372`	`3`
`STRAND`	`378 380`	`3`
`STRAND`	`390 392`	`3`
`TURN`	`404 406`	`3`
`HELIX`	`409 414`	`6`
`HELIX`	`419 434`	`16`
`TURN`	`435 437`	`3`
`HELIX`	`446 454`	`9`
`HELIX`	`467 476`	`10`
`HELIX`	`481 483`	`3`
`HELIX`	`487 500`	`14`

Sequence information

Length: 509 AA [This is the length of the unprocessed precursor]

Molecular weight: 58001 Da [This is the MW of the unprocessed precursor]

CRC64: 44BFF0D43FFB420D [This is a checksum on the sequence]

        10         20         30         40         50         60 
MGCGCSSHPE DDWMENIDVC ENCHYPIVPL DGKGTLLIRN GSEVRDPLVT YEGSNPPASP 

        70         80         90        100        110        120 
LQDNLVIALH SYEPSHDGDL GFEKGEQLRI LEQSGEWWKA QSLTTGQEGF IPFNFVAKAN 

       130        140        150        160        170        180 
SLEPEPWFFK NLSRKDAERQ LLAPGNTHGS FLIRESESTA GSFSLSVRDF DQNQGEVVKH 

       190        200        210        220        230        240 
YKIRNLDNGG FYISPRITFP GLHELVRHYT NASDGLCTRL SRPCQTQKPQ KPWWEDEWEV 

       250        260        270        280        290        300 
PRETLKLVER LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHQRL 

       310        320        330        340        350        360 
VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLTINK LLDMAAQIAE GMAFIEERNY 

       370        380        390        400        410        420 
IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA KFPIKWTAPE AINYGTFTIK 

       430        440        450        460        470        480 
SDVWSFGILL TEIVTHGRIP YPGMTNPEVI QNLERGYRMV RPDNCPEELY QLMRLCWKER 

       490        500 
PEDRPTFDYL RSVLEDFFTA TEGQYQPQP

P06239 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools