Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

AXL (P30530) - Overview - Molecular Target Synopsis

Protein


AXL, Tyrosine-protein kinase receptor UFO
Enzyme Classification 2.7.10.1
UniProt P30530

Also Known as UFO_HUMAN, AXL, UFO

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, ALX 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. Heterodimer and heterotetramer with ligand GAS6. Interacts with CBL, GRB2, LCK, NCK2, PIK3R1, PIK3R2, PIK3R3, PLCG1, SOCS1 and TNS2. Part of a complex including AXL, TNK2 and GRB2, in which GRB2 promotes AXL recruitment by TNK2.

5U6B
STRUCTURE OF THE AXL KINASE DOMAIN IN COMPLEX WITH A MACROCYCLIC INHIBITOR
RCSB/PDB
Inspect Structure
See all 3D Structures for AXL

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: AXL is active in the following subcellular-locations: cell membrane.
GO terms: AXL is active in the following subcellular-locations: cell surface, extracellular exosome, extracellular space, host cell surface, integral component of plasma membrane, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project AXL has gain in 4 cell-lines, loss in 0 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SN12C, HS578T, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HCC1576, NCI-H2373, MKN-7

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, IMR-90, SK-N-SH

(see details)

RNA Interference


AXL was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: BT20, SMOV2. (see details)

3D Structures


For AXL there are:
4 structures (10 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


AXL has been screened with 1315 compounds (2097 bioactivities), 240 compounds have bioactivities that show binding affinity of <= 500nM (303 bioactivities). (see details)