Solution structure of the SH2 domain of human Tyrosine-protein kinase TXKSolution structure of the SH2 domain of human Tyrosine-protein kinase TXK
Structural highlights
2dm0 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
TXK_HUMAN 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.[1][2][3][4][5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
↑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. PMID:9813138 doi:http://dx.doi.org/10.1006/bbrc.1998.9559
↑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. PMID:10523612
↑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. PMID:11564877 doi:http://dx.doi.org/10.1128/MCB.21.20.6939-6950.2001
↑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. PMID:11859127
↑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. PMID:17177976 doi:10.1111/j.1365-2249.2006.03249.x
