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Identification
HMDB Protein ID HMDBP01356
Secondary Accession Numbers
  • 6652
Name Tyrosine-protein kinase Lck
Synonyms
  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
Function
protein tyrosine kinase activity
binding
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
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Cell membrane
  2. Lipid-anchor
  3. Cytoplasm
  4. Cytoplasmic side
Gene Properties
Chromosome Location Chromosome:1
Locus 1p34.3
SNPs LCK
Gene Sequence
>1524 bp
ATGGGCTGTGGCTGCAGCTCACACCCGGAAGATGACTGGATGGAAAACATCGATGTGTGT
GAGAACTGCCATTATCCCATAGTCCCACTGGATGGCAAGGGCACGCTGCTCATCCGAAAT
GGCTCTGAGGTGCGGGACCCACTGGTTACCTACGAAGGCTCCAATCCGCCGGCTTCCCCA
CTGCAAGACAACCTGGTTATCGCTCTGCACAGCTATGAGCCCTCTCACGACGGAGATCTG
GGCTTTGAGAAGGGGGAACAGCTCCGCATCCTGGAGCAGAGCGGCGAGTGGTGGAAGGCG
CAGTCCCTGACCACGGGCCAGGAAGGCTTCATCCCCTTCAATTTTGTGGCCAAAGCGAAC
AGCCTGGAGCCCGAACCCTGGTTCTTCAAGAACCTGAGCCGCAAGGACGCGGAGCGGCAG
CTCCTGGCGCCCGGGAACACTCACGGCTCCTTCCTCATCCGGGAGAGCGAGAGCACCGCG
GGATCGTTTTCACTGTCGGTCCGGGACTTCGACCAGAACCAGGGAGAGGTGGTGAAACAT
TACAAGATCCGTAATCTGGACAACGGTGGCTTCTACATCTCCCCTCGAATCACTTTTCCC
GGCCTGCATGAACTGGCCTCCGCCATTACACCAATCGCTTCAGATGGGCTGTGCACACGG
TTGAGCCGCCCCTGCCAGACCCAGAAGCCCCAGAAGCCGTGGTGGGAGGACGAGTGGGAG
GTTCCCAGGGAGACGCTGAAGCTGGTGGAGCGGCTGGGGGCTGGACAGTTCGGGAGGTGT
GGATGGGGTACTACAACGGGCACAACGAAGGTGGCGGTGAAGAGCCTGAAGCAGGGCAGC
ATGTCCGCCGGACGCCTTCCTGCCGAGGCCAACCTCATGAAGCAGCTGCAACACCAGCGG
CTGGTTCGGCTCTACGCTGTGGTCACCCAGGAGCCCATCTACATCATCACTGAATACATG
GAGAATGGGAGTCTAGTGGATTTTCTCAAGACCCCTTCAGGCATCAAGTTGACCATCAAC
AAACTCCTGGACATGGCAGCCCAAATTGCAGAAGGCATGGCATTCATTGAAGAGCGGAAT
TATATTCATCGTGACCTTCGGGCTGCCAACATTCTGGTGTCTGACACCCTGAGCTGCAAG
ATTGCAGACTTTGGCCTAGCACGCCTCATTGAGGACAACGAGTACACAGCCAGGGAGGGG
GCCAAGTTTCCCATTAAGTGGACAGCGCCAGAAGCCATTAACTACGGGACATTCACCATC
AAGTCAGATGTGTGGTCTTTTGGGATCCTGCTGACGGAAATTGTCACCCACGGCCGCATC
CCTTACCCAGGGATGACCAACCCGGAGGTGATTCAGAACCTGGAGCGAGGCTACCGCATG
GTGCGCCCTGACAACTGTCCAGAGGAGCTGTACCAACTCATGAGGCTGTGCTGGAAGGAG
CGCCCAGAGGACCGGCCCACCTTTGACTACCTGCGCAGTGTGCTGGAGGACTTCTTCACG
GCCACAGAGGGCAGTACAGCCTAG
Protein Properties
Number of Residues 509
Molecular Weight 58000.1
Theoretical pI 5.03
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Tyrosine-protein kinase Lck
MGCGCSSHPEDDWMENIDVCENCHYPIVPLDGKGTLLIRNGSEVRDPLVTYEGSNPPASP
LQDNLVIALHSYEPSHDGDLGFEKGEQLRILEQSGEWWKAQSLTTGQEGFIPFNFVAKAN
SLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKH
YKIRNLDNGGFYISPRITFPGLHELVRHYTNASDGLCTRLSRPCQTQKPQKPWWEDEWEV
PRETLKLVERLGAGQFGEVWMGYYNGHTKVAVKSLKQGSMSPDAFLAEANLMKQLQHQRL
VRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNY
IHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIK
SDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMVRPDNCPEELYQLMRLCWKER
PEDRPTFDYLRSVLEDFFTATEGQYQPQP
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
HGNC ID HGNC:6524
References
General References
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  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 ]
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  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 ]
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  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 ]
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  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 ]
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  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 ]
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  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 ]