Tyrosine-protein kinase ITK/TSK

Details

Name
Tyrosine-protein kinase ITK/TSK
Synonyms
  • 2.7.10.2
  • EMT
  • IL-2-inducible T-cell kinase
  • Interleukin-2-inducible T-cell kinase
  • Kinase EMT
  • LYK
  • T-cell-specific kinase
  • Tyrosine-protein kinase Lyk
Gene Name
ITK
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010935|Tyrosine-protein kinase ITK/TSK
MNNFILLEEQLIKKSQQKRRTSPSNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRI
KCVEIVKSDISIPCHYKYPFQVVHDNYLLYVFAPDRESRQRWVLALKEETRNNNSLVPKY
HPNFWMDGKWRCCSQLEKLATGCAQYDPTKNASKKPLPPTPEDNRRPLWEPEETVVIALY
DYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVEKSPNNLETYEWY
NKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVVSENNPCIKHYHIKETND
NPKRYYVAEKYVFDSIPLLINYHQHNGGGLVTRLRYPVCFGRQKAPVTAGLRYGKWVIDP
SELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQ
LYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIH
RDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSD
VWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPE
DRPAFSRLLRQLAEIAESGL
Number of residues
620
Molecular Weight
71830.405
Theoretical pI
7.63
GO Classification
Functions
ATP binding / metal ion binding / non-membrane spanning protein tyrosine kinase activity
Processes
activation of phospholipase C activity / adaptive immune response / cellular defense response / cytokine production / Fc-epsilon receptor signaling pathway / innate immune response / interferon-gamma production / interleukin-4 production / intracellular signal transduction / NK T cell differentiation / peptidyl-tyrosine autophosphorylation / regulation of cell proliferation / signal transduction / T cell activation / T cell receptor signaling pathway / transmembrane receptor protein tyrosine kinase signaling pathway
Components
cell-cell junction / cytosol / extrinsic component of cytoplasmic side of plasma membrane
General Function
Non-membrane spanning protein tyrosine kinase activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010936|Tyrosine-protein kinase ITK/TSK (ITK)
ATGAACAACTTTATCCTCCTGGAAGAACAGCTCATCAAGAAATCCCAACAAAAGAGAAGA
ACTTCTCCCTCGAACTTTAAAGTCCGCTTCTTTGTGTTAACCAAAGCCAGCCTGGCATAC
TTTGAAGATCGTCATGGGAAGAAGCGCACGCTGAAGGGGTCCATTGAGCTCTCCCGAATC
AAATGTGTTGAGATTGTGAAAAGTGACATCAGCATCCCATGCCACTATAAATACCCGTTT
CAGGTGGTGCATGACAACTACCTCCTATATGTGTTTGCTCCAGATCGTGAGAGCCGGCAG
CGCTGGGTGCTGGCCCTTAAAGAAGAAACGAGGAATAATAACAGTTTGGTGCCTAAATAT
CATCCTAATTTCTGGATGGATGGGAAGTGGAGGTGCTGTTCTCAGCTGGAGAAGCTTGCA
ACAGGCTGTGCCCAATATGATCCAACCAAGAATGCTTCAAAGAAGCCTCTTCCTCCTACT
CCTGAAGACAACAGGCGACCACTTTGGGAACCTGAAGAAACTGTGGTCATTGCCTTATAT
GACTACCAAACCAATGATCCTCAGGAACTCGCACTGCGGCGCAACGAAGAGTACTGCCTG
CTGGACAGTTCTGAGATTCACTGGTGGAGAGTCCAGGACAGGAATGGGCATGAAGGATAT
GTACCAAGCAGTTATCTGGTGGAAAAATCTCCAAATAATCTGGAAACCTATGAGTGGTAC
AATAAGAGTATCAGCCGAGACAAAGCTGAAAAACTTCTTTTGGACACAGGCAAAGAAGGA
GCCTTCATGGTAAGGGATTCCAGGACTGCAGGAACATACACCGTGTCTGTTTTCACCAAG
GCTGTTGTAAGTGAGAACAATCCCTGTATAAAGCATTATCACATCAAGGAAACAAATGAC
AATCCTAAGCGATACTATGTGGCTGAAAAGTATGTGTTCGATTCCATCCCTCTTCTCATC
AACTATCACCAACATAATGGAGGAGGCCTGGTGACTCGACTCCGGTATCCAGTTTGTTTT
GGGAGGCAGAAAGCCCCAGTTACAGCAGGGCTGAGATACGGGAAATGGGTGATCGACCCC
TCAGAGCTCACTTTTGTGCAAGAGATTGGCAGTGGGCAATTTGGGTTGGTGCATCTGGGC
TACTGGCTCAACAAGGACAAGGTGGCTATCAAAACCATTCGGGAAGGGGCTATGTCAGAA
GAGGACTTCATAGAGGAGGCTGAAGTAATGATGAAACTCTCTCATCCCAAACTGGTGCAG
CTGTATGGGGTGTGCCTGGAGCAGGCCCCCATCTGCCTGGTGTTTGAGTTCATGGAGCAC
GGCTGCCTGTCAGATTATCTACGCACCCAGCGGGGACTTTTTGCTGCAGAGACCCTGCTG
GGCATGTGTCTGGATGTGTGTGAGGGCATGGCCTACCTGGAAGAGGCATGTGTCATCCAC
AGAGACTTGGCTGCCAGAAATTGTTTGGTGGGAGAAAACCAAGTCATCAAGGTGTCTGAC
TTTGGGATGACAAGGTTCGTTCTGGATGATCAGTACACCAGTTCCACAGGCACCAAATTC
CCGGTGAAGTGGGCATCCCCAGAGGTTTTCTCTTTCAGTCGCTATAGCAGCAAGTCCGAT
GTGTGGTCATTTGGTGTGCTGATGTGGGAAGTTTTCAGTGAAGGCAAAATCCCGTATGAA
AACCGAAGCAACTCAGAGGTGGTGGAAGACATCAGTACCGGATTTCGGTTGTACAAGCCC
CGGCTGGCCTCCACACACGTCTACCAGATTATGAATCACTGCTGGAAAGAGAGACCAGAA
GATCGGCCAGCCTTCTCCAGACTGCTGCGTCAACTGGCTGAAATTGCAGAATCAGGACTT
TAG
Chromosome Location
5
Locus
5q31-q32
External Identifiers
ResourceLink
UniProtKB IDQ08881
UniProtKB Entry NameITK_HUMAN
GenBank Protein ID399658
GenBank Gene IDD13720
GenAtlas IDITK
HGNC IDHGNC:6171
General References
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  7. King PD, Sadra A, Teng JM, Bell GM, Dupont B: CD2-mediated activation of the Tec-family tyrosine kinase ITK is controlled by proline-rich stretch-4 of the CD2 cytoplasmic tail. Int Immunol. 1998 Jul;10(7):1009-16. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02010StaurosporineexperimentalunknownDetails
DB06589PazopanibapprovedunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB15035Zanubrutinibapproved, investigationalunknowninhibitorDetails