Tyrosine-protein kinase TXK

Details

Name
Tyrosine-protein kinase TXK
Synonyms
  • 2.7.10.2
  • Protein-tyrosine kinase 4
  • PTK4
  • Resting lymphocyte kinase
  • RLK
Gene Name
TXK
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051684|Tyrosine-protein kinase TXK
MILSSYNTIQSVFCCCCCCSVQKRQMRTQISLSTDEELPEKYTQRRRPWLSQLSNKKQSN
TGRVQPSKRKPLPPLPPSEVAEEKIQVKALYDFLPREPCNLALRRAEEYLILEKYNPHWW
KARDRLGNEGLIPSNYVTENKITNLEIYEWYHRNITRNQAEHLLRQESKEGAFIVRDSRH
LGSYTISVFMGARRSTEAAIKHYQIKKNDSGQWYVAERHAFQSIPELIWYHQHNAAGLMT
RLRYPVGLMGSCLPATAGFSYEKWEIDPSELAFIKEIGSGQFGVVHLGEWRSHIQVAIKA
INEGSMSEEDFIEEAKVMMKLSHSKLVQLYGVCIQRKPLYIVTEFMENGCLLNYLRENKG
KLRKEMLLSVCQDICEGMEYLERNGYIHRDLAARNCLVSSTCIVKISDFGMTRYVLDDEY
VSSFGAKFPIKWSPPEVFLFNKYSSKSDVWSFGVLMWEVFTEGKMPFENKSNLQVVEAIS
EGFRLYRPHLAPMSIYEVMYSCWHEKPEGRPTFAELLRAVTEIAETW
Number of residues
527
Molecular Weight
61257.9
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / non-membrane spanning protein tyrosine kinase activity / RNA polymerase II proximal promoter sequence-specific DNA binding / RNA polymerase II regulatory region DNA binding / transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding
Processes
activation of phospholipase C activity / adaptive immune response / cell differentiation / cytokine production / integrin-mediated signaling pathway / peptidyl-tyrosine autophosphorylation / positive regulation of interferon-gamma production / positive regulation of interferon-gamma-mediated signaling pathway / positive regulation of transcription by RNA polymerase II / protein autophosphorylation / protein phosphorylation / regulation of cell proliferation / regulation of platelet activation / regulation of transcription by RNA polymerase II / T cell receptor signaling pathway / tissue regeneration / transmembrane receptor protein tyrosine kinase signaling pathway
Components
cytoplasm / extrinsic component of cytoplasmic side of plasma membrane / nucleus
General Function
Non-receptor tyrosine kinase that plays a redundant role with ITK 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 TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Contributes also to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskeleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by 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. With PARP1 and EEF1A1, TXK forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFNG to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Phosphorylates both PARP1 and EEF1A1. Phosphorylates also key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr-201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051685|Tyrosine-protein kinase TXK (TXK)
ATGATCCTTTCCTCCTATAACACCATCCAGTCGGTTTTCTGTTGCTGCTGTTGCTGTTCA
GTGCAGAAGCGACAAATGAGAACACAGATAAGCCTGAGCACAGATGAAGAGCTTCCAGAA
AAATACACCCAGCGTCGCAGGCCGTGGCTCAGCCAATTGTCAAATAAGAAGCAATCCAAC
ACGGGCCGTGTGCAGCCGTCAAAACGAAAGCCACTGCCTCCCCTCCCACCCTCTGAGGTT
GCTGAAGAGAAGATCCAAGTCAAGGCACTTTATGATTTTCTGCCCAGAGAACCCTGTAAT
TTAGCCTTAAGGAGAGCAGAAGAATACCTGATACTGGAGAAATACAATCCTCACTGGTGG
AAGGCAAGAGACCGTTTGGGGAATGAAGGCTTAATCCCAAGCAACTATGTGACTGAAAAC
AAAATAACTAATTTAGAAATATATGAGTGGTACCATAGAAACATTACCAGAAATCAGGCA
GAACATCTATTGAGACAAGAGTCTAAAGAAGGTGCATTTATTGTCAGAGATTCAAGACAT
TTAGGATCCTACACAATTTCCGTATTTATGGGAGCTAGAAGAAGTACGGAGGCTGCCATA
AAACATTATCAGATAAAAAAGAATGACTCAGGACAGTGGTATGTGGCTGAAAGACACGCC
TTTCAATCAATCCCTGAGTTAATCTGGTATCACCAGCACAATGCAGCCGGTCTCATGACT
CGTCTCCGATATCCAGTTGGGCTGATGGGCAGTTGTTTACCAGCCACAGCTGGGTTTAGC
TACGAAAAGTGGGAGATAGATCCATCTGAGTTGGCTTTTATAAAGGAGATTGGAAGCGGT
CAGTTTGGAGTGGTCCATTTAGGTGAATGGCGGTCACATATCCAGGTAGCTATCAAGGCC
ATCAATGAAGGCTCCATGTCTGAAGAGGATTTCATTGAAGAGGCCAAAGTGATGATGAAA
TTATCTCATTCAAAGCTAGTGCAACTTTATGGAGTCTGTATACAGCGGAAGCCCCTTTAC
ATTGTGACAGAGTTCATGGAAAATGGCTGCCTGCTTAACTATCTCAGGGAGAATAAAGGA
AAGCTTAGGAAGGAAATGCTACTGAGTGTATGCCAGGATATATGTGAAGGAATGGAATAT
CTGGAGAGGAATGGCTATATTCATAGGGATTTGGCGGCAAGGAATTGTTTGGTCAGTTCA
ACATGCATAGTAAAAATTTCAGACTTTGGAATGACAAGGTACGTTTTGGATGATGAGTAT
GTCAGTTCTTTTGGAGCCAAGTTCCCAATCAAGTGGTCCCCTCCTGAAGTTTTTCTTTTC
AATAAGTACAGCAGTAAATCTGATGTCTGGTCATTTGGAGTTTTAATGTGGGAAGTTTTT
ACAGAAGGAAAAATGCCTTTTGAAAATAAGTCAAATTTGCAAGTCGTGGAAGCTATTTCT
GAAGGCTTCAGGCTATATCGCCCTCACCTGGCACCAATGTCCATATATGAAGTCATGTAC
AGCTGCTGGCATGAGAAACCTGAAGGCCGCCCTACATTTGCCGAGCTGCTGCGGGCTGTC
ACAGAGATTGCGGAAACCTGGTGA
Chromosome Location
4
Locus
4p12
External Identifiers
ResourceLink
UniProtKB IDP42681
UniProtKB Entry NameTXK_HUMAN
HGNC IDHGNC:12434
General References
  1. Haire RN, Ohta Y, Lewis JE, Fu SM, Kroisel P, Litman GW: TXK, a novel human tyrosine kinase expressed in T cells shares sequence identity with Tec family kinases and maps to 4p12. Hum Mol Genet. 1994 Jun;3(6):897-901. [Article]
  2. Ohta Y, Haire RN, Amemiya CT, Litman RT, Trager T, Riess O, Litman GW: Human Txk: genomic organization, structure and contiguous physical linkage with the Tec gene. Oncogene. 1996 Feb 15;12(4):937-42. [Article]
  3. Schneider H, Schwartzberg PL, Rudd CE: Resting lymphocyte kinase (Rlk/Txk) phosphorylates the YVKM motif and regulates PI 3-kinase binding to T-cell antigen CTLA-4. Biochem Biophys Res Commun. 1998 Nov 9;252(1):14-9. [Article]
  4. Kashiwakura J, Suzuki N, Nagafuchi H, Takeno M, Takeba Y, Shimoyama Y, Sakane T: Txk, a nonreceptor tyrosine kinase of the Tec family, is expressed in T helper type 1 cells and regulates interferon gamma production in human T lymphocytes. J Exp Med. 1999 Oct 18;190(8):1147-54. [Article]
  5. Veri MC, DeBell KE, Seminario MC, DiBaldassarre A, Reischl I, Rawat R, Graham L, Noviello C, Rellahan BL, Miscia S, Wange RL, Bonvini E: Membrane raft-dependent regulation of phospholipase Cgamma-1 activation in T lymphocytes. Mol Cell Biol. 2001 Oct;21(20):6939-50. [Article]
  6. Kashiwakura J, Suzuki N, Takeno M, Itoh S, Oku T, Sakane T, Nakajin S, Toyoshima S: Evidence of autophosphorylation in Txk: Y91 is an autophosphorylation site. Biol Pharm Bull. 2002 Jun;25(6):718-21. [Article]
  7. Takeba Y, Nagafuchi H, Takeno M, Kashiwakura J, Suzuki N: Txk, a member of nonreceptor tyrosine kinase of Tec family, acts as a Th1 cell-specific transcription factor and regulates IFN-gamma gene transcription. J Immunol. 2002 Mar 1;168(5):2365-70. [Article]
  8. Maruyama T, Nara K, Yoshikawa H, Suzuki N: Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha and regulates interferon-gamma gene transcription in Th1 cells. Clin Exp Immunol. 2007 Jan;147(1):164-75. [Article]
  9. Readinger JA, Mueller KL, Venegas AM, Horai R, Schwartzberg PL: Tec kinases regulate T-lymphocyte development and function: new insights into the roles of Itk and Rlk/Txk. Immunol Rev. 2009 Mar;228(1):93-114. doi: 10.1111/j.1600-065X.2008.00757.x. [Article]
  10. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

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