Detail Information for IndEnz0005000518
IED ID IndEnz0005000518
Enzyme Type ID lipase000518
Protein Name Tyrosine-protein kinase ITK/TSK
EC 2.7.10.2
IL-2-inducible T-cell kinase
Kinase EMT
Kinase TLK
T-cell-specific kinase
Gene Name Itk Emt Tlk Tsk
Organism Mus musculus (Mouse)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse)
Enzyme Sequence MNNFILLEEQLIKKSQQKRRTSPSNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRIKCVEIVKSDISIPCHYKYPFQTLVYLQVVHDNYLLYVFAPDCESRQRWVLTLKEETRNNNSLVSKYHPNFWMDGRWRCCSQLEKPAVGCAPYDPSKNASKKPLPPTPEDNRRSFQEPEETLVIALYDYQTNDPQELALRCDEEYYLLDSSEIHWWRVQDKNGHEGYAPSSYLVEKSPNNLETYEWYNKSISRDKAEKLLLDTGKEGAFMVRDSRTPGTYTVSVFTKAIISENPCIKHYHIKETNDSPKRYYVAEKYVFDSIPLLIQYHQYNGGGLVTRLRYPVCSWRQKAPVTAGLRYGKWVIQPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIQEGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRSQRGLFAAETLLGMCLDVCEGMAYLEKACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASCHVYQIMNHCWKEKPEDRPPFSQLLSQLAEIAEAGL
Enzyme Length 625
Uniprot Accession Number Q03526
Absorption
Active Site ACT_SITE 487; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10028"
Activity Regulation
Binding Site BINDING 396; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
DNA Binding
EC Number 2.7.10.2
Enzyme Function FUNCTION: Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Required for TCR-mediated calcium response in gamma-delta T-cells, may also be involved in the modulation of the transcriptomic signature in the Vgamma2-positive subset of immature gamma-delta T-cells (PubMed:23562159). Phosphorylates TBX21 at 'Tyr-525' and mediates its interaction with GATA3 (PubMed:15662016). {ECO:0000269|PubMed:15662016, ECO:0000269|PubMed:21036902, ECO:0000269|PubMed:23562159}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding NP_BIND 374..382; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159
Features Active site (1); Beta strand (21); Binding site (1); Chain (1); Domain (4); Helix (3); Metal binding (4); Modified residue (3); Nucleotide binding (1); Region (1); Sequence conflict (5); Turn (1); Zinc finger (1)
Keywords 3D-structure;ATP-binding;Adaptive immunity;Cytoplasm;Immunity;Kinase;Metal-binding;Nucleotide-binding;Nucleus;Phosphoprotein;Reference proteome;SH2 domain;SH3 domain;Transferase;Tyrosine-protein kinase;Ubl conjugation;Zinc;Zinc-finger
Interact With P08487
Induction INDUCTION: Through a myriad of surface receptors including the TCR/CD3 signaling complex, coreceptors, or chemokine receptors.
Subcellular Location SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:15662016}. Note=Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation. {ECO:0000250}.
Modified Residue MOD_RES 186; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:Q08881; MOD_RES 517; /note=Phosphotyrosine; by LCK; /evidence=ECO:0000250|UniProtKB:Q08881; MOD_RES 570; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q08881
Post Translational Modification PTM: Phosphorylated at Tyr-517 in the activation loop of the kinase domain by LCK. Subsequent autophosphorylation at Tyr-186 leads to the kinase activation. The autophosphorylated Tyr-186 lies within the substrate binding sequence of the SH3 domain (By similarity). {ECO:0000250}.; PTM: Ubiquitinated. {ECO:0000250}.
Signal Peptide
Structure 3D X-ray crystallography (1); NMR spectroscopy (11)
Cross Reference PDB 1AWJ; 1LUI; 1LUK; 1LUM; 1LUN; 2ETZ; 2EU0; 2K79; 2K7A; 2RN8; 2RNA; 3S9K;
Mapped Pubmed ID 10549622; 10556826; 10562318; 11015440; 11114734; 11217851; 11702066; 11859102; 12055226; 12193707; 12402030; 12466851; 12682224; 12734350; 12798690; 12810687; 12842872; 13678593; 14993283; 15102471; 15123627; 15345221; 15661896; 15778496; 15814667; 16042784; 16141072; 16237085; 16424186; 16436281; 16547221; 16602821; 16630934; 16631752; 16860759; 16880398; 17412921; 17425330; 17579028; 17724684; 18025201; 18031697; 18292523; 18320328; 18322190; 18342008; 18424706; 18453573; 18523250; 18941202; 19009524; 19361414; 19416854; 19443662; 19449311; 19682494; 19701889; 19818650; 19917685; 19946567; 19955438; 20108770; 20126642; 20305788; 20457812; 20483745; 20596543; 20670954; 20826165; 20974963; 21138328; 21212279; 21280324; 21301103; 21497118; 21677750; 21971040; 22289921; 22297986; 22403441; 22967998; 22988097; 23011795; 23028816; 23219468; 23378428; 2357970; 23768572; 23793062; 23851691; 23982207; 24270545; 24462896; 24534190; 24610010; 24620029; 24928994; 25063868; 25097034; 25105474; 25250764; 25271622; 25492967; 25548254; 25568116; 25989458; 26466958; 26581914; 26628680; 26936133; 28213500; 28406139; 28516764; 28635957; 29129599; 30770814; 31505252; 31591574; 31663508; 31757864; 32034085; 32038633; 32493815; 33324410; 33931484; 34452995; 34566971; 7522330; 7829087; 8893810; 9070927; 9177770; 9311799; 9396778; 9584150;
Motif
Gene Encoded By
Mass 72,292
Kinetics
Metal Binding METAL 127; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00432; METAL 138; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00432; METAL 139; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00432; METAL 149; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00432
Rhea ID RHEA:10596
Cross Reference Brenda 2.7.10.1;2.7.10.2;