CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002328
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tyrosine-protein kinase Lck 
Protein Synonyms/Alias
 Leukocyte C-terminal Src kinase; LSK; Lymphocyte cell-specific protein-tyrosine kinase; Protein YT16; Proto-oncogene Lck; T cell-specific protein-tyrosine kinase; p56-LCK 
Gene Name
 LCK 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
179QNQGEVVKHYKIRNLacetylation[1]
246EVPRETLKLVERLGAubiquitination[2, 3, 4]
269GYYNGHTKVAVKSLKubiquitination[3]
379VSDTLSCKIADFGLAubiquitination[2, 3, 4]
405EGAKFPIKWTAPEAIubiquitination[3, 4]
Reference
 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 
Functional Description
 Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T- cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. 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, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the 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. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. 
Sequence Annotation
 DOMAIN 61 121 SH3.
 DOMAIN 127 224 SH2.
 DOMAIN 245 498 Protein kinase.
 NP_BIND 251 259 ATP (By similarity).
 REGION 2 72 Interactions with CD4 and CD8 (By
 REGION 154 242 Interaction with PTPRH.
 ACT_SITE 364 364 Proton acceptor (By similarity).
 BINDING 273 273 ATP (By similarity).
 MOD_RES 102 102 Phosphoserine.
 MOD_RES 159 159 Phosphothreonine.
 MOD_RES 162 162 Phosphoserine.
 MOD_RES 194 194 Phosphoserine.
 MOD_RES 394 394 Phosphotyrosine; by autocatalysis.
 MOD_RES 505 505 Phosphotyrosine; by CSK.
 LIPID 2 2 N-myristoyl glycine (By similarity).
 LIPID 3 3 S-palmitoyl cysteine (By similarity).
 LIPID 5 5 S-palmitoyl cysteine (By similarity).  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Chromosomal rearrangement; Complete proteome; Cytoplasm; Disease mutation; Host-virus interaction; Kinase; Lipoprotein; Membrane; Myristate; Nucleotide-binding; Palmitate; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 509 AA 
Protein Sequence
MGCGCSSHPE DDWMENIDVC ENCHYPIVPL DGKGTLLIRN GSEVRDPLVT YEGSNPPASP 60
LQDNLVIALH SYEPSHDGDL GFEKGEQLRI LEQSGEWWKA QSLTTGQEGF IPFNFVAKAN 120
SLEPEPWFFK NLSRKDAERQ LLAPGNTHGS FLIRESESTA GSFSLSVRDF DQNQGEVVKH 180
YKIRNLDNGG FYISPRITFP GLHELVRHYT NASDGLCTRL SRPCQTQKPQ KPWWEDEWEV 240
PRETLKLVER LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHQRL 300
VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLTINK LLDMAAQIAE GMAFIEERNY 360
IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA KFPIKWTAPE AINYGTFTIK 420
SDVWSFGILL TEIVTHGRIP YPGMTNPEVI QNLERGYRMV RPDNCPEELY QLMRLCWKER 480
PEDRPTFDYL RSVLEDFFTA TEGQYQPQP 509 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0030139; C:endocytic vesicle; IEA:Compara.
 GO:0001772; C:immunological synapse; IDA:MGI.
 GO:0045121; C:membrane raft; IDA:UniProtKB.
 GO:0000242; C:pericentriolar material; IDA:UniProtKB.
 GO:0003823; F:antigen binding; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:EC.
 GO:0004722; F:protein serine/threonine phosphatase activity; IDA:UniProtKB.
 GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0042169; F:SH2 domain binding; ISS:UniProtKB.
 GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
 GO:0007568; P:aging; IEA:Compara.
 GO:0050853; P:B cell receptor signaling pathway; IEA:Compara.
 GO:0006882; P:cellular zinc ion homeostasis; IEP:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0050900; P:leukocyte migration; TAS:Reactome.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:Compara.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IEA:Compara.
 GO:0010628; P:positive regulation of gene expression; IEA:Compara.
 GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0050862; P:positive regulation of T cell receptor signaling pathway; NAS:UniProtKB.
 GO:0042523; P:positive regulation of tyrosine phosphorylation of Stat5 protein; IEA:Compara.
 GO:0070474; P:positive regulation of uterine smooth muscle contraction; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
 GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:UniProtKB.
 GO:0042493; P:response to drug; IDA:UniProtKB.
 GO:0042542; P:response to hydrogen peroxide; IEA:Compara.
 GO:0009612; P:response to mechanical stimulus; IEA:Compara.
 GO:0010043; P:response to zinc ion; IEA:Compara.
 GO:0031295; P:T cell costimulation; TAS:Reactome.
 GO:0030217; P:T cell differentiation; IMP:UniProtKB.
 GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
 GO:0016032; P:viral reproduction; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR000980; SH2.
 IPR001452; SH3_domain.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom. 
Pfam
 PF07714; Pkinase_Tyr
 PF00017; SH2
 PF00018; SH3_1 
SMART
 SM00252; SH2
 SM00326; SH3
 SM00219; TyrKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS50001; SH2
 PS50002; SH3 
PRINTS
 PR00401; SH2DOMAIN.
 PR00452; SH3DOMAIN.
 PR00109; TYRKINASE.