| IED ID | IndEnz0005000679 |
| Enzyme Type ID | lipase000679 |
| Protein Name |
Tyrosine-protein kinase ITK/TSK EC 2.7.10.2 Interleukin-2-inducible T-cell kinase IL-2-inducible T-cell kinase Kinase EMT T-cell-specific kinase Tyrosine-protein kinase Lyk |
| Gene Name | ITK EMT LYK |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MNNFILLEEQLIKKSQQKRRTSPSNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRIKCVEIVKSDISIPCHYKYPFQVVHDNYLLYVFAPDRESRQRWVLALKEETRNNNSLVPKYHPNFWMDGKWRCCSQLEKLATGCAQYDPTKNASKKPLPPTPEDNRRPLWEPEETVVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVEKSPNNLETYEWYNKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVVSENNPCIKHYHIKETNDNPKRYYVAEKYVFDSIPLLINYHQHNGGGLVTRLRYPVCFGRQKAPVTAGLRYGKWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIAESGL |
| Enzyme Length | 620 |
| Uniprot Accession Number | Q08881 |
| Absorption | |
| Active Site | ACT_SITE 482; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10028" |
| Activity Regulation | |
| Binding Site | BINDING 391; /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 (PubMed:12186560, PubMed:12682224, PubMed:21725281). 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 (By similarity). Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3 (By similarity). {ECO:0000250|UniProtKB:Q03526, ECO:0000269|PubMed:12186560, ECO:0000269|PubMed:12682224, ECO:0000269|PubMed:21725281}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 369..377; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Features | Active site (1); Beta strand (19); Binding site (1); Chain (1); Domain (4); Helix (16); Metal binding (4); Modified residue (3); Mutagenesis (1); Natural variant (7); Nucleotide binding (1); Sequence conflict (2); Turn (5); Zinc finger (1) |
| Keywords | 3D-structure;ATP-binding;Adaptive immunity;Cytoplasm;Direct protein sequencing;Disease variant;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 | P04626; P48023; P08238; Q13094; P10686 |
| Induction | INDUCTION: Through a myriad of surface receptors including the TCR/CD3 signaling complex, coreceptors, or chemokine receptors. {ECO:0000269|PubMed:8504851, ECO:0000269|PubMed:9701039}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17060314}. Nucleus {ECO:0000250|UniProtKB:Q03526}. Note=Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation. |
| Modified Residue | MOD_RES 180; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000269|PubMed:12573241; MOD_RES 512; /note=Phosphotyrosine; by LCK; /evidence=ECO:0007744|PubMed:19690332; MOD_RES 565; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:19690332 |
| Post Translational Modification | PTM: Phosphorylated at Tyr-512 in the activation loop of the kinase domain by LCK. Subsequent autophosphorylation at Tyr-180 leads to the kinase activation. The autophosphorylated Tyr-180 lies within the substrate binding sequence of the SH3 domain. {ECO:0000269|PubMed:12573241, ECO:0000269|PubMed:9312162}.; PTM: Ubiquitinated. {ECO:0000269|PubMed:20596523}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (33); NMR spectroscopy (3) |
| Cross Reference PDB | 1SM2; 1SNU; 1SNX; 2E6I; 2LMJ; 2YUQ; 3MIY; 3MJ1; 3MJ2; 3QGW; 3QGY; 3T9T; 3V5J; 3V5L; 3V8T; 3V8W; 4HCT; 4HCU; 4HCV; 4KIO; 4L7S; 4M0Y; 4M0Z; 4M12; 4M13; 4M14; 4M15; 4MF0; 4MF1; 4PP9; 4PPA; 4PPB; 4PPC; 4PQN; 4QD6; 4RFM; |
| Mapped Pubmed ID | 10556826; 11048639; 11279148; 11395409; 11437596; 11507089; 11830645; 12842872; 14766749; 14968112; 15184383; 15743820; 16159638; 16176929; 16273093; 16931156; 17237383; 17652306; 17724684; 17897671; 18155796; 18322190; 18443296; 19222422; 19240061; 19535334; 19701889; 19714314; 19717557; 20098747; 20305788; 20439541; 20457812; 20545945; 20598684; 20807769; 21280324; 21323647; 21391610; 21674762; 21958547; 22302878; 22449075; 22464456; 22829599; 22939624; 23071622; 23098091; 23260110; 23293025; 23454662; 23935099; 24076779; 24138940; 24376268; 24462896; 24593284; 24658140; 24728074; 24767842; 24900590; 24918870; 25061172; 25337257; 25455497; 25492967; 25512530; 25593320; 25844760; 25934889; 27729219; 27780854; 28213500; 28635957; 29453458; 30242208; 30778533; 31022269; 31196981; 31507602; 32628964; 32640487; 33017570; 33931484; 34282055; 34702300; 7518558; 8629002; 8630736; 8892607; 9547335; |
| Motif | |
| Gene Encoded By | |
| Mass | 71,831 |
| Kinetics | |
| Metal Binding | METAL 121; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00432; METAL 132; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00432; METAL 133; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00432; METAL 143; /note=Zinc; /evidence=ECO:0000255|PROSITE-ProRule:PRU00432 |
| Rhea ID | RHEA:10596 |
| Cross Reference Brenda | 2.7.10.2; |