Tyrosine-protein kinase receptor UFO

Function

Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, AXL binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response.

Classification

Family (Pfam)

PF00041 fn3, PF13927 Ig_3, PF07714 PK_Tyr_Ser-Thr

InterPro

FN3_dom, FN3_sf, Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_sub, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom

Functional cluster

Secreted Growth Factors & Cytokines

Experimental structures · PDB · 4

• 2C5D X-ray 3.30A
• 4RA0 X-ray 3.07A
• 5U6B X-ray 2.84A
• 5VXZ X-ray 2.30A

A predicted model is available from AlphaFold.

Gene Ontology · 32

• GO:0009986 cell surface
• GO:0070062 extracellular exosome
• GO:0005615 extracellular space
• GO:0005886 plasma membrane
• GO:0043235 receptor complex
• GO:0005524 ATP binding
• GO:0001786 phosphatidylserine binding
• GO:0004713 protein tyrosine kinase activity
• GO:0004714 transmembrane receptor protein tyrosine kinase activity
• GO:0001618 virus receptor activity
• GO:0048469 cell maturation
• GO:0016477 cell migration
• GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
• GO:0035457 cellular response to interferon-alpha
• GO:0071222 cellular response to lipopolysaccharide
• GO:0097028 dendritic cell differentiation
• GO:0045087 innate immune response
• GO:0001779 natural killer cell differentiation
• GO:0043066 negative regulation of apoptotic process
• GO:2000669 negative regulation of dendritic cell apoptotic process
• GO:0032689 negative regulation of type II interferon production
• GO:0007399 nervous system development
• GO:0006909 phagocytosis
• GO:0030168 platelet activation
• GO:0001961 positive regulation of cytokine-mediated signaling pathway
• GO:0032825 positive regulation of natural killer cell differentiation
• GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:0048549 positive regulation of pinocytosis
• GO:1903902 positive regulation of viral life cycle
• GO:0007165 signal transduction
• GO:0046718 symbiont entry into host cell
• GO:0048010 vascular endothelial growth factor receptor signaling pathway

Drugs targeting this protein · 4

• GILTERITINIB FUMARATE inhibitor
• GILTERITINIB inhibitor
• BEMCENTINIB inhibitor
• NINGETINIB inhibitor

Related proteins · sequence + function similarity

• Tyrosine-protein kinase receptor UFO 0.99
• Tyrosine-protein kinase receptor TYRO3 0.91
• Tyrosine-protein kinase receptor TYRO3 0.90
• Tyrosine-protein kinase receptor TYRO3 0.90
• Ephrin type-A receptor 1 0.83
• Ephrin type-A receptor 1 0.81
• Fibroblast growth factor receptor 4 0.81
• Roundabout homolog 4 0.80
• Tyrosine-protein kinase receptor TYRO3 0.80
• High affinity nerve growth factor receptor 0.80
• Tyrosine-protein kinase receptor TYRO3 0.79
• High affinity nerve growth factor receptor 0.79

Co-cited proteins · studied together in the literature

• Growth arrest-specific protein 6 7 shared papers
• Tyrosine-protein kinase receptor TYRO3 4 shared papers
• C-type lectin domain family 4 member G 2 shared papers
• Platelet-derived growth factor receptor-like protein 1 shared papers
• Phosphatidylinositol 3-kinase regulatory subunit gamma 1 shared papers
• Tumor necrosis factor receptor superfamily member 3 1 shared papers
• Lymphotoxin beta receptor inhibitor 1 shared papers
• Tyrosine-protein kinase JAK1 2 shared papers
• E3 ubiquitin-protein ligase CBL 1 shared papers
• Envelope glycoprotein 1 shared papers
• Tumor necrosis factor receptor superfamily member 3 1 shared papers
• Leukocyte tyrosine kinase receptor 1 shared papers

Literature · 33 cited papers

• Axl Promotes Zika Virus Entry and Modulates the Antiviral State of Human Sertoli Cells. MBio · 2019
• Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-beta receptor. Nat. Immunol. · 2018
• AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling. Nat. Microbiol. · 2018
• Axl Mediates ZIKA Virus Entry in Human Glial Cells and Modulates Innate Immune Responses. Cell Rep. · 2017
• Phosphatidylserine receptors: enhancers of enveloped virus entry and infection. Virology · 2014
• Cell surface molecules involved in infection mediated by lymphocytic choriomeningitis virus glycoprotein. J. Vet. Med. Sci. · 2012
• Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry. J. Virol. · 2012
• The soluble serum protein Gas6 bridges virion envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry. Cell Host Microbe · 2011
• Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling. J. Biol. Chem. · 2009
• The Axl/Gas6 pathway is required for optimal cytokine signaling during human natural killer cell development. Blood · 2009
• Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
• In brain, Axl recruits Grb2 and the p85 regulatory subunit of PI3 kinase; in vitro mutagenesis defines the requisite binding sites for downstream Akt activation. J. Neurochem. · 2008
• … and 21 more in the literature graph