LipidDB ID

LipidDB-10090-00586

Entry Name

UniProt Accession

P06240; Q61794; Q61795; Q62320; Q91X65;

Theoretical PI

5.13

Molecular Weight

57942.62

Genbank Protein ID

AAB59674.1; CAA27234.1; CAA27235.1; CAA27236.1; BAC40086.1; AAH11474.1; AAA39422.1; AAA39421.1;

Genbank Nucleotide ID

M12056; X03533; X03533; X03533; AK088001; BC011474; M21511; M18098;

Protein Name

Proto-oncogene tyrosine-protein kinase LCK

Protein Synonyms/Alias

2.7.10.2; Leukocyte C-terminal Src kinase; LSK; Lymphocyte cell-specific protein-tyrosine kinase; p56-LCK;

Gene Name

Lck

Gene Synonyms/Alias

Lsk-t;

Created Date

01-JAN-1988

Organism

Mus musculus (Mouse)

NCBI Taxa ID

10090

Reference

[1] Hawash IY, Hu XE, Adal A, Cassady JM, Geahlen RL, Harrison ML. Theoxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, inhibits Lcklocalization to lipid rafts and T cell signaling. Biochim Biophys Acta. 2002 Apr 3;1589(2):140-50.[PMID:12007789]
[2] Yasuda K, Kosugi A, Hayashi F, Saitoh S, Nagafuku M, Mori Y, Ogata M, Hamaoka T. Serine 6 of Lck tyrosine kinase: a critical site for Lck myristoylation,membrane localization, and function in T lymphocytes. J Immunol. 2000 Sep15;165(6):3226-31.[PMID:10975838]

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). Interacts with UNC119; this interaction plays a crucial role in activation of LCK (By similarity).

Sequence Annotation

Domain: 61 121 SH3.
Domain: 127 224 SH2.
Domain: 245 498 Protein kinase.
Nucleotide-binding: 251 259 ATP.
Region: 2 72 Interactions with CD4 and CD8.
Region: 154 242 Interaction with PTPRH.
Active site: 364 364 Proton acceptor.
Binding site: 273 273 ATP.
Modified residue: 102 102 Phosphoserine.
Modified residue: 159 159 Phosphothreonine.
Modified residue: 162 162 Phosphoserine.
Modified residue: 194 194 Phosphoserine.
Modified residue: 394 394 Phosphotyrosine; by autocatalysis.
Modified residue: 505 505 Phosphotyrosine; by CSK.

Protein Length

509 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0005911; C:cell-cell junction; IDA:MGI
GO:0005829; C:cytosol; TAS:Reactome
GO:0030139; C:endocytic vesicle; IEA:Ensembl
GO:0070062; C:extracellular vesicular exosome; IEA:Ensembl
GO:0001772; C:immunological synapse; IEA:Ensembl
GO:0045121; C:membrane raft; ISS:UniProtKB
GO:0000242; C:pericentriolar material; ISS:UniProtKB
GO:0003823; F:antigen binding; IEA:Ensembl
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC
GO:0004722; F:protein serine/threonine phosphatase activity; ISS:UniProtKB
GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB
GO:0042169; F:SH2 domain binding; ISS:UniProtKB
GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB
GO:0007568; P:aging; IEA:Ensembl
GO:0050853; P:B cell receptor signaling pathway; IDA:MGI
GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI
GO:0006882; P:cellular zinc ion homeostasis; ISS:UniProtKB
GO:0016311; P:dephosphorylation; ISS:GOC
GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI
GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IMP:MGI
GO:0010628; P:positive regulation of gene expression; IDA:MGI
GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB
GO:0050870; P:positive regulation of T cell activation; ISS:UniProtKB
GO:0042523; P:positive regulation of tyrosine phosphorylation of Stat5 protein; IDA:MGI
GO:0070474; P:positive regulation of uterine smooth muscle contraction; IEA:Ensembl
GO:0046777; P:protein autophosphorylation; IDA:MGI
GO:0006468; P:protein phosphorylation; IDA:MGI
GO:0050856; P:regulation of T cell receptor signaling pathway; IDA:MGI
GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:UniProtKB
GO:0042493; P:response to drug; ISS:UniProtKB
GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl
GO:0009612; P:response to mechanical stimulus; IEA:Ensembl
GO:0010043; P:response to zinc ion; IEA:Ensembl
GO:0030217; P:T cell differentiation; ISS:UniProtKB

Interpro

InterPro; IPR011009; Kinase-like_dom
InterPro; IPR000719; Prot_kinase_dom
InterPro; IPR017441; Protein_kinase_ATP_BS
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom
InterPro; IPR000980; SH2
InterPro; IPR001452; SH3_domain
InterPro; IPR008266; Tyr_kinase_AS
InterPro; IPR020635; Tyr_kinase_cat_dom

Pfam

Pfam; PF07714; Pkinase_Tyr;
Pfam; PF00017; SH2;
Pfam; PF00018; SH3_1;

SMART

SMART; SM00252; SH2;
SMART; SM00326; SH3;
SMART; SM00219; TyrKc;

PROSITE

PROSITE; PS00107; PROTEIN_KINASE_ATP;
PROSITE; PS50011; PROTEIN_KINASE_DOM;
PROSITE; PS00109; PROTEIN_KINASE_TYR;
PROSITE; PS50001; SH2;
PROSITE; PS50002; SH3;

PRINTS

PRINTS; PR00401; SH2DOMAIN;
PRINTS; PR00452; SH3DOMAIN;
PRINTS; PR00109; TYRKINASE;