UniProt Accession

 LCK_HUMAN; P06239; D3DPP8; P07100; Q12850; Q13152; Q5TDH8; Q5TDH9; Q7RTZ3; Q96DW4; Q9NYT8 

Genbank Protein ID

 X05027; X13529; M36881; X14055; X14053; X14054; U07236; U23852; BN000073; AL121991; AL121991; CH471059; CH471059; BC013200; M21510; M26692; AF228313; X06369; X04476 

Genbank Nucleotide ID

 CAA28691.1; CAA31884.1; AAA59502.1; CAA32211.1; CAA32211.1; CAA32211.1; AAA18225.1; AAC50287.1; CAD55807.1; CAI22320.1; CAI22321.1; EAX07543.1; EAX07546.1; AAH13200.1; AAA59501.1; AAA59503.1; AAF34794.1; CAA29667.1; CAA28165.1 

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
99	EQSGEWWKAQSLTTG	ubiquitination	[1]
130	EPEPWFFKNLSRKDA	ubiquitination	[1, 2]
179	QNQGEVVKHYKIRNL	ubiquitination	[1, 2]
182	GEVVKHYKIRNLDNG	ubiquitination	[1, 2]
246	EVPRETLKLVERLGA	ubiquitination	[1, 2]
269	GYYNGHTKVAVKSLK	ubiquitination	[2]
273	GHTKVAVKSLKQGSM	ubiquitination	[2]
276	KVAVKSLKQGSMSPD	ubiquitination	[1, 2]
293	LAEANLMKQLQHQRL	ubiquitination	[1, 2]
365	LKTPSGIKLTINKLL	ubiquitination	[2]
409	VSDTLSCKIADFGLA	ubiquitination	[1, 2]
431	YTAREGAKFPIKWTA	ubiquitination	[2]
435	EGAKFPIKWTAPEAI	ubiquitination	[2]

Reference

 [1] 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]
 [2] 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] 

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

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.