Molecule Information

General Information of the Molecule (ID: Mol04356)

• Name: Tyrosine-protein kinase receptor UFO (AXL) ,Homo sapiens
• Synonyms: AXL oncogene
• Molecule Type: Protein
• Gene Name: AXL
• Gene ID: 558
• Sequence:
  MAWRCPRMGRVPLAWCLALCGWACMAPRGTQAEESPFVGNPGNITGARGLTGTLRCQLQV
  QGEPPEVHWLRDGQILELADSTQTQVPLGEDEQDDWIVVSQLRITSLQLSDTGQYQCLV
  F LGHQTFVSQPGYVGLEGLPYFLEEPEDRTVAANTPFNLSCQAQGPPEPVDLLWLQDAV
  PL ATAPGHGPQRSLHVPGLNKTSSFSCEAHNAKGVTTSRTATITVLPQQPRNLHLVSRQ
  PTE LEVAWTPGLSGIYPLTHCTLQAVLSDDGMGIQAGEPDPPEEPLTSQASVPPHQLRL
  GSLH PHTPYHIRVACTSSQGPSSWTHWLPVETPEGVPLGPPENISATRNGSQAFVHWQE
  PRAPL QGTLLGYRLAYQGQDTPEVLMDIGLRQEVTLELQGDGSVSNLTVCVAAYTAAGD
  GPWSLP VPLEAWRPGQAQPVHQLVKEPSTPAFSWPWWYVLLGAVVAAACVLILALFLVH
  RRKKETR YGEVFEPTVERGELVVRYRVRKSYSRRTTEATLNSLGISEELKEKLRDVMVD
  RHKVALGK TLGEGEFGAVMEGQLNQDDSILKVAVKTMKIAICTRSELEDFLSEAVCMKE
  FDHPNVMRL IGVCFQGSERESFPAPVVILPFMKHGDLHSFLLYSRLGDQPVYLPTQMLV
  KFMADIASGM EYLSTKRFIHRDLAARNCMLNENMSVCVADFGLSKKIYNGDYYRQGRIA
  KMPVKWIAIES LADRVYTSKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRL
  KQPADCLDGLYA LMSRCWELNPQDRPSFTELREDLENTLKALPPAQEPDEILYVNMDEG
  GGYPEPPGAAGGA DPPTQPDPKDSCSCLTAAEVHPAGRYVLCPSTTPSPAQPADRGSPA
  APGQEDGA
• Function: Receptor tyrosine kinase that transduces signals from theextracellular matrix into the cytoplasm by binding growth factor GAS6and which is thus regulating many physiological processes includingcell survival, cell proliferation, migration and differentiation.Ligand binding at the cell surface induces dimerization andautophosphorylation of AXL. Following activation by ligand, AXL bindsand induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1,PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Otherdownstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2.Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatorysubunits by AXL leads to the downstream activation of the AKT kinase.GAS6/AXL signaling plays a role in various processes such asendothelial cell survival during acidification by preventing apoptosis,optimal cytokine signaling during human natural killer celldevelopment, hepatic regeneration, gonadotropin-releasing hormoneneuron survival and migration, platelet activation, or regulation ofthrombotic responses. Also plays an important role in inhibition ofToll-like receptors -mediated innate immune response.{ECO:0000269|PubMed:10403904, ECO:0000269|PubMed:11484958,ECO:0000269|PubMed:12364394, ECO:0000269|PubMed:12490074,ECO:0000269|PubMed:15507525, ECO:0000269|PubMed:15733062,ECO:0000269|PubMed:1656220, ECO:0000269|PubMed:18840707}.; Acts as a receptor for lassa virus andlymphocytic choriomeningitis virus, possibly through GAS6 binding tophosphatidyl-serine at the surface of virion envelope.{ECO:0000269|PubMed:17005688, ECO:0000269|PubMed:21501828,ECO:0000269|PubMed:22156524, ECO:0000269|PubMed:25277499}.; Acts as a receptor for Ebolavirus,possibly through GAS6 binding to phosphatidyl-serine at the surface ofvirion envelope. {ECO:0000269|PubMed:22673088}.; Promotes Zika virus entry in glialcells, Sertoli cells and astrocytes . Additionally, Zika virus potentiates AXL kinaseactivity to antagonize type I interferon signaling and thereby promotesinfection . Interferon signaling inhibition occurs viaan SOCS1-dependent mechanism .{ECO:0000269|PubMed:28076778, ECO:0000269|PubMed:29379210,ECO:0000269|PubMed:31311882}.
• Uniprot ID: UFO_HUMAN
• Ensembl ID: ENSG0000016760112
• HGNC ID: HGNC:905

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Sorafenib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] [1]

• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Resistant Drug: Sorafenib
• Molecule Alteration: Phosphorylation; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Axl signalling pathway; Regulation; N.A.
• In Vitro Model: MOLM-13/sor cells; Blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Apoptosis assay
• Mechanism Description: Sorafenib-resistant MOLM-13/sor cells have increased protein levels of FLT3 and Axl signaling pathways. These results suggest that activated FLT3-ITD signaling, Axl signaling, and protein translation contribute to sorafenib resistance.

References

• Ref 1: The GSK3beta/Mcl-1 axis is regulated by both FLT3-ITD and Axl and determines the apoptosis induction abilities of FLT3-ITD inhibitors. Cell Death Discov. 2023 Feb 4;9(1):44.