Cytoplasmic tyrosine-protein kinase BMX

Function

Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G protein-coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Also plays a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells.

Classification

Family (Pfam)

PF00779 BTK, PF00169 PH, PF07714 PK_Tyr_Ser-Thr, PF00017 SH2

InterPro

BMX_SH2, Kinase-like_dom_sf, Non-receptor_tyrosine_kinases, PH-like_dom_sf, PH_domain, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser-Thr/Tyr_kinase_cat_dom, SH2, SH2_dom_sf, Tyr_kinase_AS, Tyr_kinase_cat_dom, Znf_Btk_motif

Functional cluster

Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 6

• 2EKX NMR
• 2YS2 NMR
• 3SXR X-ray 2.40A
• 3SXS X-ray 1.89A
• 6I99 X-ray 2.00A
• 8X2A X-ray 1.30A

A predicted model is available from AlphaFold.

Gene Ontology · 16

• GO:0005829 cytosol
• GO:0005886 plasma membrane
• GO:0032587 ruffle membrane
• GO:0005524 ATP binding
• GO:0004715 non-membrane spanning protein tyrosine kinase activity
• GO:0004713 protein tyrosine kinase activity
• GO:0008270 zinc ion binding
• GO:0002250 adaptive immune response
• GO:0006915 apoptotic process
• GO:0050853 B cell receptor signaling pathway
• GO:0007155 cell adhesion
• GO:0035556 intracellular signal transduction
• GO:0007498 mesoderm development
• GO:0006661 phosphatidylinositol biosynthetic process
• GO:0006468 protein phosphorylation
• GO:0007165 signal transduction

Drugs targeting this protein · 2

• RITLECITINIB inhibitor
• RITLECITINIB TOSYLATE inhibitor

Related proteins · sequence + function similarity

• Cytoplasmic tyrosine-protein kinase BMX 0.97
• Tyrosine-protein kinase BTK 0.94
• Tyrosine-protein kinase BTK 0.93
• Tyrosine-protein kinase BTK 0.93
• Tyrosine-protein kinase Tec 0.89
• Tyrosine-protein kinase ITK/TSK 0.89
• Tyrosine-protein kinase TXK 0.88
• Tyrosine-protein kinase ITK/TSK 0.88
• Tyrosine-protein kinase Tec 0.88
• Tyrosine-protein kinase FRK 0.86
• Tyrosine-protein kinase TXK 0.86
• Tyrosine-protein kinase SYK 0.86

Co-cited proteins · studied together in the literature

• Cytoplasmic tyrosine-protein kinase BMX 3 shared papers
• Tumor necrosis factor receptor superfamily member 1B 1 shared papers
• RUN and FYVE domain-containing protein 2 1 shared papers
• RUN and FYVE domain-containing protein 2 1 shared papers
• Breast cancer anti-estrogen resistance protein 1 1 shared papers
• Focal adhesion kinase 1 2 shared papers
• Tyrosine-protein kinase BTK 2 shared papers
• RUN and FYVE domain-containing protein 1 1 shared papers
• Tyrosine-protein kinase ITK/TSK 1 shared papers
• Signal transducer and activator of transcription 3 1 shared papers
• Tyrosine-protein kinase Tec 1 shared papers
• Caveolin-1 1 shared papers

Literature · 17 cited papers

• Etk/BMX, a Btk family tyrosine kinase, and Mal contribute to the cross-talk between MyD88 and FAK pathways. J. Immunol. · 2008
• Tec kinases, actin, and cell adhesion. Immunol. Rev. · 2007
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• Etk/Bmx mediates expression of stress-induced adaptive genes VEGF, PAI-1, and iNOS via multiple signaling cascades in different cell systems. Am. J. Physiol. · 2005
• The DNA sequence of the human X chromosome. Nature · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• p130Cas Couples the tyrosine kinase Bmx/Etk with regulation of the actin cytoskeleton and cell migration. J. Biol. Chem. · 2003
• Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases. Biochim. Biophys. Acta · 2003
• Etk/Bmx as a tumor necrosis factor receptor type 2-specific kinase: role in endothelial cell migration and angiogenesis. Mol. Cell. Biol. · 2002
• Interaction between tyrosine kinase Etk and a RUN-domain and FYVE-domain containing protein RUFY1. A possible role of Etk in regulation of vesicle trafficking. J. Biol. Chem. · 2002
• Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx. J. Biol. Chem. · 2002
• The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species. Bioessays · 2001
• … and 5 more in the literature graph