AXL

The protein encoded by this gene is a member of the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase subfamily. The encoded protein possesses an extracellular domain which is composed of two immunoglobulin-like motifs at the N-terminal, followed by two fibronectin type-III motifs. It transduces signals from the extracellular matrix into the cytoplasm by binding to the vitamin K-dependent protein growth arrest-specific 6 (Gas6). This gene may be involved in several cellular functions including growth, migration, aggregation and anti-inflammation in multiple cell types. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

AXL Receptor Tyrosine Kinase

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. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response.
(Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.
(Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.

Animal organ regeneration Source: Ensembl
Blood vessel remodeling Source: Ensembl
Cell maturation Source: UniProtKB
Cell migration Source: GO_Central
Cellular response to extracellular stimulus Source: Ensembl
Cellular response to hydrogen peroxide Source: Ensembl
Cellular response to interferon-alpha Source: UniProtKB
Cellular response to lipopolysaccharide Source: UniProtKB
Dendritic cell differentiation Source: UniProtKB
Erythrocyte homeostasis Source: Ensembl
Forebrain cell migration Source: Ensembl
Inflammatory response Source: Ensembl
Innate immune response Source: UniProtKB-KW
Multicellular organism development Source: GO_Central
Natural killer cell differentiation Source: GO_Central
Negative regulation of apoptotic process Source: GO_Central
Negative regulation of dendritic cell apoptotic process Source: UniProtKB
Negative regulation of interferon-gamma production Source: UniProtKB
Negative regulation of lymphocyte activation Source: Ensembl
Negative regulation of neuron apoptotic process Source: Ensembl
Negative regulation of tumor necrosis factor production Source: Ensembl
Nervous system development Source: GO_Central
Neuron migration Source: Ensembl
Neutrophil clearance Source: Ensembl
Ovulation cycle Source: Ensembl
Phagocytosis Source: UniProtKB
Platelet activation Source: GO_Central
Positive regulation of cytokine-mediated signaling pathway Source: UniProtKB
Positive regulation of kinase activity Source: GO_Central
Positive regulation of natural killer cell differentiation Source: UniProtKB
Positive regulation of pinocytosis Source: CACAO
Positive regulation of protein kinase B signaling Source: GO_Central
Positive regulation of viral life cycle Source: FlyBase
Protein kinase B signaling Source: Ensembl
Secretion by cell Source: Ensembl
Signal transduction Source: ProtInc
Spermatogenesis Source: Ensembl
Substrate adhesion-dependent cell spreading Source: Ensembl
Transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Vagina development Source: Ensembl
Vascular endothelial growth factor receptor signaling pathway Source: Reactome
Viral entry into host cell Source: CACAO

Cell membrane

Extracellular: 26-451 aa
Helical: 452-472 aa
Cytoplasmic: 473-894 aa

Monoubiquitinated upon GAS6-binding. A very small proportion of the receptor could be subjected to polyubiquitination in a very transient fashion.
Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity.