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FLASH GENE

Symbol

AXL

contributors: mct/npt/pgu - updated : 25-01-2016

HGNC name	AXL receptor tyrosine kinase
HGNC id	905

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	19q13.2      Physical location : 41.725.107 - 41.767.670
Synonym name	AXL oncogene
	AXL transforming sequence/gene
Synonym symbol(s)	TYRO7, UFO, JTK11, ARK
EC.number	2.7.10.1

DNA

TYPE	functioning gene
STRUCTURE	42.57 kb     20 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001699 20 - 4716 NP_001690 - 885 - 2009 18840707 full length isoform NM_021913 19 initiation site 4743 NP_068713 - 894 - 2009 18840707 lacking exon 10 otherwise similar to variant 1 NM_001278599 4128 - 17 NP_001265528 - 626 - -

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Homo sapiens Reproductive female system uterus cervix   highly reproductive reproductive tract

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two Ig-like domains linked to two fibronectin,type III repeats
	a cytoplamic region that contains an intrinsic protein tyrosine kinase domain

HOMOLOGY

Homologene

FAMILY	protein kinase superfamily
	Tyr protein kinase family
	AXL/UFO subfamily

CATEGORY

enzyme , protooncogene , receptor membrane tyrosine

SUBCELLULAR LOCALIZATION	plasma membrane
text	integral to plasma membrane

basic FUNCTION	receptor tyrosine kinase
	involved in the protection of neurons from apoptosis across neuronal migration
	involved in the regulation of spermatogenesis, immunity, platelet function, cancer
	enhances the expression of matrix metalloproteinase 9 MMP9, required for AXL-mediated invasion
	promotes cell invasion by inducing MMP9 activity through activation of NF-kappaB and SMARCA4
	with its ligand, GAS6, are involved in IL-15-mediated human NK differentiation from CD34(+) hematopoietic progenitor cells (HPCs)
	regulates endothelial cell functions by modulation of signaling through angiopoietin/TIE2 and Dickkopf-homologue 3 (DKK3) pathways
	its expression is required for metastasis of breast cancer cells to the lung
	enhances endothelial tube formation by acting through the angiopoietin and DKK3 signaling system
	GAS6/AXL-mediated signaling regulates dendritic cell activities, and identifies GAS6/AXL as a new dendritic cell chemotaxis pathway
	unique epithelial-to-mesenchymal transition effector that is essential for breast cancer progression
	is a key downstream target that drives YAP1-dependent oncogenic functions
	regulates mesothelioma proliferation and invasiveness
	contributes to carotid remodeling not only by inhibition of apoptosis but also via regulation of immune heterogeneity of vascular cells, cytokine/chemokine expression, and extracellular matrix remodeling
	is a key TGFB1 effector
	AXL in both hematopoietic and nonhematopoietic lineages contributes to the late phase of hypertension.
	potential contribution of AXL-mediated phosphorylation dynamics to pluripotency-related signaling networks
	contributes to cell migration and invasion, and promotes cell proliferation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

	AXL/GAS6 pathway contributes to normal NK-cell development, at least in part via its regulatory effects on both the IL15 and c-Kit signaling
	GAS6/AXL signaling plays an important role in vascular biology by modulating survival and migration of vascular smooth muscle cells and endothelial cells

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with RANBP9
	ligand GAS6
	ability of TNK2 to modulate AXL and perhaps anaplastic lymphoma kinase (altered in anaplastic large cell lymphomas) might explain why TNK2 can promote metastatic and transformed behavior in a number of cancers
	GAS6 in circulation is bound to AXL suggesting circulating GAS6 to be inhibited and incapable of stimulating the TAM receptors
	interacting with MZF1 (binds to the AXL promoter, transactivates promoter activity, and enhances AXL-mRNA and protein expression in a dose-dependent manner
	TULP1 interacts with TYRO3, AXL and MERTK of the TAM receptor tyrosine kinase subfamily, whereas tubby binds only to MERTK
	AXL expression is induced by TGFB1 during Langerhans cells (LCs) differentiation and LC precursors acquire AXL early during differentiation
	GAS6 interact with AXL in endothelial cells, inducing several signaling pathways involved in cell survival and proliferation
	binding of AXL to YWHAZ, which is essentially required for AXL-mediated cell invasion, transendothelial migration, and resistance against TGFB1
	ELMO2 scaffolds to be direct substrates and binding partners of AXL
	GAS6-induced AXL signaling is a critical driver of pancreatic cancer progression
	ARL2 inhibits the proliferation, migration and tumorigenicity of glioma cells by regulating the expression of AXL

cell & other

REGULATION

induced by

IFN-alpha during human dendritic cell (DC) differentiation from monocytes

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   myelogenous leukemia tumoral     --over   lung carcinoma, invasion and progression tumoral     --over   colon carcinoma tumoral     --over   melanoma tumoral     --over   in both glioma and vascular cells and predict poor prognosis in glioblastoma multiformis patients tumoral     --over   in breast cancer independently predicts poor overall patient survival tumoral   amplification     in mesotheliomas tumoral     --over   in triple-negative/basal B cell lines of breast cancer compared with luminal or basal A cell lines constitutional     --over   myocardial expression and serum concentration of AXL is elevated in heart failure patients compared to controls constitutional     --over   plasma soluble AXL concentrations were higher in the preeclampsia patients, and plasma soluble AXL levels were correlated with the clinical parameters of severe preeclampsia

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	role of soluble AXL as a marker for NF1 related tumor burden
Therapy target
	System Type Disorder Pubmed cancer brain glioma/neuroblstoma specific targeting of the Axl/Gas6 signaling pathway may represent a potential new approach for glioma treatment cancer angiogenesis   additive effect of AXL inhibition with anti-VEGF suggests that blocking AXL function might be a useful approach for enhancing antiangiogenic therapy and warrant further investigation cancer reproductive breast detection and targeted treatment of AXL-expressing tumors represents an important new therapeutic strategy for breast cancer cancer hemopathy   unique target for chronic lymphocytic leukemia treatment cancer digestive liver potential therapeutic target for hepatocellular carcinoma cancer endocrine thyroid TYRO3/AXL-GAS6 autocrine circuit sustains the malignant features of thyroid cancer cells and targeting the circuit could offer a novel therapeutic approach in this cancer cancer lung   AXL inhibition suppressed mesothelioma anchorage-independent growth cancer endocrine pancreas GAS6 inhibition with low-dose warfarin or other AXL-targeting agents may improve outcome in patients with AXL-expressing tumors cancer reproductive prostate role for AXL in prostate cancer tumorigenesis with implications for prostate cancer treatment

ANIMAL & CELL MODELS

Axl /Tyro3 null mice have delayed first estrus and abnormal cyclicity due to developmental defects in GnRH neuron migration and survival