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HMDB Protein ID HMDBP01356
Secondary Accession Numbers
  • 6652
Name Tyrosine-protein kinase Lck
  1. LSK
  2. Leukocyte C-terminal Src kinase
  3. Lymphocyte cell-specific protein-tyrosine kinase
  4. Protein YT16
  5. Proto-oncogene Lck
  6. T cell-specific protein-tyrosine kinase
  7. p56-LCK
Gene Name LCK
Protein Type Enzyme
Biological Properties
General Function Involved in protein kinase activity
Specific 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
Pathways Not Available
Reactions Not Available
GO Classification
protein tyrosine kinase activity
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein binding
protein kinase activity
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
Cellular Location
  1. Cell membrane
  2. Lipid-anchor
  3. Cytoplasm
  4. Cytoplasmic side
Gene Properties
Chromosome Location Chromosome:1
Locus 1p34.3
Gene Sequence
>1524 bp
Protein Properties
Number of Residues 509
Molecular Weight 58000.1
Theoretical pI 5.03
Pfam Domain Function
  • None
Transmembrane Regions
  • None
Protein Sequence
>Tyrosine-protein kinase Lck
GenBank ID Protein 36808
UniProtKB/Swiss-Prot ID P06239
UniProtKB/Swiss-Prot Entry Name LCK_HUMAN
PDB IDs Not Available
GenBank Gene ID X05027
GeneCard ID LCK
GenAtlas ID LCK
General References
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  4. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  5. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  6. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, 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. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976 ]
  7. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  8. 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 JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203. [PubMed:18083107 ]
  9. Harris RA, Yang A, Stein RC, Lucy K, Brusten L, Herath A, Parekh R, Waterfield MD, O'Hare MJ, Neville MA, Page MJ, Zvelebil MJ: Cluster analysis of an extensive human breast cancer cell line protein expression map database. Proteomics. 2002 Feb;2(2):212-23. [PubMed:11840567 ]
  10. Wissing J, Jansch 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. 2007 Mar;6(3):537-47. Epub 2006 Dec 27. [PubMed:17192257 ]
  11. Greenway A, Azad A, Mills J, McPhee D: Human immunodeficiency virus type 1 Nef binds directly to Lck and mitogen-activated protein kinase, inhibiting kinase activity. J Virol. 1996 Oct;70(10):6701-8. [PubMed:8794306 ]
  12. 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. 2003 Nov 17;198(10):1453-62. Epub 2003 Nov 10. [PubMed:14610046 ]
  13. Yasuda K, Nagafuku M, Shima T, Okada M, Yagi T, Yamada T, Minaki Y, Kato A, Tani-Ichi S, Hamaoka T, Kosugi A: Cutting edge: 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. 2002 Sep 15;169(6):2813-7. [PubMed:12218089 ]
  14. Koga Y, Caccia N, Toyonaga B, Spolski R, Yanagi Y, Yoshikai Y, Mak TW: A human T cell-specific cDNA clone (YT16) encodes a protein with extensive homology to a family of protein-tyrosine kinases. Eur J Immunol. 1986 Dec;16(12):1643-6. [PubMed:3493153 ]
  15. Perlmutter RM, Marth JD, Lewis DB, Peet R, Ziegler SF, Wilson CB: Structure and expression of lck transcripts in human lymphoid cells. J Cell Biochem. 1988 Oct;38(2):117-26. [PubMed:3265417 ]
  16. Rouer E, Van Huynh T, Lavareda de Souza S, Lang MC, Fischer S, Benarous R: Structure of the human lck gene: differences in genomic organisation within src-related genes affect only N-terminal exons. Gene. 1989 Dec 7;84(1):105-13. [PubMed:2558056 ]
  17. Wright DD, Sefton BM, Kamps MP: Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia. Mol Cell Biol. 1994 Apr;14(4):2429-37. [PubMed:8139546 ]
  18. Vogel LB, Arthur R, Fujita DJ: An aberrant lck mRNA in two human T-cell lines. Biochim Biophys Acta. 1995 Nov 7;1264(2):168-72. [PubMed:7495859 ]
  19. 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. 2002 Nov;51(11):3326-30. [PubMed:12401726 ]
  20. Garvin AM, Pawar S, Marth JD, Perlmutter RM: Structure of the murine lck gene and its rearrangement in a murine lymphoma cell line. Mol Cell Biol. 1988 Aug;8(8):3058-64. [PubMed:2850479 ]
  21. Takadera T, Leung S, Gernone A, Koga Y, Takihara Y, Miyamoto NG, Mak TW: Structure of the two promoters of the human lck gene: differential accumulation of two classes of lck transcripts in T cells. Mol Cell Biol. 1989 May;9(5):2173-80. [PubMed:2787474 ]
  22. Boncristiano M, Majolini MB, D'Elios MM, Pacini S, Valensin S, Ulivieri C, Amedei A, Falini B, Del Prete G, Telford JL, Baldari CT: Defective recruitment and activation of ZAP-70 in common variable immunodeficiency patients with T cell defects. Eur J Immunol. 2000 Sep;30(9):2632-8. [PubMed:11009097 ]
  23. Veillette A, Foss FM, Sausville EA, Bolen JB, Rosen N: Expression of the lck tyrosine kinase gene in human colon carcinoma and other non-lymphoid human tumor cell lines. Oncogene Res. 1987 Sep-Oct;1(4):357-74. [PubMed:2835736 ]
  24. Trevillyan JM, Lin Y, Chen SJ, Phillips CA, Canna C, Linna TJ: Human T lymphocytes express a protein-tyrosine kinase homologous to p56LSTRA. Biochim Biophys Acta. 1986 Oct 10;888(3):286-95. [PubMed:3489486 ]
  25. Bergman M, Mustelin T, Oetken C, Partanen J, Flint NA, Amrein KE, Autero M, Burn P, Alitalo K: The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down regulates its catalytic activity. EMBO J. 1992 Aug;11(8):2919-24. [PubMed:1639064 ]
  26. Vogel LB, Fujita DJ: The SH3 domain of p56lck is involved in binding to phosphatidylinositol 3'-kinase from T lymphocytes. Mol Cell Biol. 1993 Dec;13(12):7408-17. [PubMed:7504174 ]
  27. Vogel LB, Fujita DJ: 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. 1995 Feb 10;270(6):2506-11. [PubMed:7852312 ]
  28. Park I, Chung J, Walsh CT, Yun Y, Strominger JL, 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. 1995 Dec 19;92(26):12338-42. [PubMed:8618896 ]
  29. 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. 2000 Jun;267(12):3413-21. [PubMed:10848956 ]
  30. Hur EM, Son M, Lee OH, Choi YB, Park C, Lee H, Yun Y: LIME, a novel transmembrane adaptor protein, associates with p56lck and mediates T cell activation. J Exp Med. 2003 Nov 17;198(10):1463-73. Epub 2003 Nov 10. [PubMed:14610044 ]
  31. 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. 2003 Sep 12;278(37):34854-63. Epub 2003 Jul 1. [PubMed:12837766 ]
  32. Eck MJ, Atwell SK, Shoelson SE, Harrison SC: Structure of the regulatory domains of the Src-family tyrosine kinase Lck. Nature. 1994 Apr 21;368(6473):764-9. [PubMed:7512222 ]
  33. Mikol V, Baumann G, Keller TH, Manning U, Zurini MG: The crystal structures of the SH2 domain of p56lck complexed with two phosphonopeptides suggest a gated peptide binding site. J Mol Biol. 1995 Feb 17;246(2):344-55. [PubMed:7532720 ]
  34. Tong L, Warren TC, 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. 1996 Mar 1;256(3):601-10. [PubMed:8604142 ]
  35. Yamaguchi H, Hendrickson WA: Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation. Nature. 1996 Dec 5;384(6608):484-9. [PubMed:8945479 ]
  36. Tong L, Warren TC, Lukas S, Schembri-King J, Betageri R, Proudfoot JR, Jakes S: Carboxymethyl-phenylalanine as a replacement for phosphotyrosine in SH2 domain binding. J Biol Chem. 1998 Aug 7;273(32):20238-42. [PubMed:9685372 ]