CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-010867
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Proto-oncogene tyrosine-protein kinase LCK 
Protein Synonyms/Alias
 Lymphocyte cell-specific protein-tyrosine kinase; p56-LCK 
Gene Name
 Lck 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Rattus norvegicus (Rat) 
NCBI Taxa ID
 10116 
Lysine Modification
Position
Peptide
Type
References
179QNQGEVVKHYKIRNLacetylation[1]
Reference
 [1] Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
 Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV.
 Cell Rep. 2012 Aug 30;2(2):419-31. [PMID: 22902405] 
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 (By similarity). 
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 (By similarity).
 ACT_SITE 364 364 Proton acceptor (By similarity).
 BINDING 273 273 ATP (By similarity).
 MOD_RES 102 102 Phosphoserine (By similarity).
 MOD_RES 159 159 Phosphothreonine (By similarity).
 MOD_RES 162 162 Phosphoserine (By similarity).
 MOD_RES 194 194 Phosphoserine (By similarity).
 MOD_RES 394 394 Phosphotyrosine; by autocatalysis (By
 MOD_RES 505 505 Phosphotyrosine; by CSK (By similarity).
 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
 ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Kinase; Lipoprotein; Membrane; Myristate; Nucleotide-binding; Palmitate; Phosphoprotein; Proto-oncogene; Reference proteome; SH3 domain; Transferase; Tyrosine-protein kinase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 509 AA 
Protein Sequence
MGCVCSSNPE DDWMENIDVC ENCHYPIVPL DSKSTLPIRT GSEVRDPLVT YEGSLPPASP 60
LQDNLVIALH SYEPSHDGDL GFEKGEQLRI LEQSGEWWKA QSLTTGQEGF IPFNFVAKAN 120
SLEPEPWFFK NLSRKDAERQ LLAPGNTHGS FLIRESESTA GSFSLSVRDF DQNQGEVVKH 180
YKIRNLDNGG FYISPRITFP GLHDLVRHYT NASDGLCTKL SRPCQTQKPQ KPWWEDEWEV 240
PRETLKLVER LGAGQFGEVW MGYYNGHTKV AVKSLKQGSM SPDAFLAEAN LMKQLQHPRL 300
VRLYAVVTQE PIYIITEYME NGSLVDFLKT PSGIKLNVNK LLDMAAQIAE GMAFIEEQNY 360
IHRDLRAANI LVSDTLSCKI ADFGLARLIE DNEYTAREGA KFPIKWTAPE AINYGTFTIK 420
SDVWSFGILL TEIVTHGRIP YPGMTNPEVI QNLEKGYRMV RPDNCPEELY HLMMLCWKER 480
PEDRPTFDYL RSVLDDFFTA TEGQYQPQP 509 
Gene Ontology
 GO:0030139; C:endocytic vesicle; IDA:RGD.
 GO:0001772; C:immunological synapse; IEA:Compara.
 GO:0045121; C:membrane raft; IDA:RGD.
 GO:0005886; C:plasma membrane; IDA:RGD.
 GO:0003823; F:antigen binding; IPI:RGD.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:EC.
 GO:0032403; F:protein complex binding; IDA:RGD.
 GO:0004713; F:protein tyrosine kinase activity; IDA:RGD.
 GO:0007568; P:aging; IEP:RGD.
 GO:0006915; P:apoptotic process; IEP:RGD.
 GO:0050853; P:B cell receptor signaling pathway; IEA:Compara.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:RGD.
 GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IEA:Compara.
 GO:0010628; P:positive regulation of gene expression; IEA:Compara.
 GO:0042523; P:positive regulation of tyrosine phosphorylation of Stat5 protein; IEA:Compara.
 GO:0070474; P:positive regulation of uterine smooth muscle contraction; IMP:RGD.
 GO:0046777; P:protein autophosphorylation; IDA:RGD.
 GO:0050856; P:regulation of T cell receptor signaling pathway; IEA:Compara.
 GO:0051209; P:release of sequestered calcium ion into cytosol; IEA:Compara.
 GO:0042542; P:response to hydrogen peroxide; IDA:RGD.
 GO:0009612; P:response to mechanical stimulus; IMP:RGD.
 GO:0010043; P:response to zinc ion; IEP:RGD. 
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.