InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: AXL

Summary

InnateDB Protein

IDBP-52653.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

AXL

Protein Name

AXL receptor tyrosine kinase

Synonyms

JTK11; UFO;

Species

Homo sapiens

Ensembl Protein

ENSP00000301178

InnateDB Gene

IDBG-52651 (AXL)

Protein Structure

UniProt Annotation

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, 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 TENC1. 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. In case of filovirus infection, seems to function as a cell entry factor. {ECO:0000269PubMed:10403904, ECO:0000269PubMed:11484958, ECO:0000269PubMed:12364394, ECO:0000269PubMed:12490074, ECO:0000269PubMed:15507525, ECO:0000269PubMed:15733062, ECO:0000269PubMed:1656220, ECO:0000269PubMed:17005688, ECO:0000269PubMed:18840707}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:7896447}; Single-pass type I membrane protein {ECO:0000269PubMed:7896447}.

Disease Associations

Note=AXL and its ligand GAS6 are highly expressed in thyroid carcinoma tissues, and might thus be involved in thyroid tumorigenesis. Overexpression of AXL and its ligand was also detected in many other cancers such as myeloproliferative disorders, prostatic carcinoma cells, or breast cancer.

Tissue Specificity

Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue. {ECO:0000269PubMed:7896447}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 41 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	41 [view]
Protein-Protein	39 [view]
Protein-DNA	0
Protein-RNA	1 [view]
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001786	phosphatidylserine binding
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004714	transmembrane receptor protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0032036	myosin heavy chain binding
GO:0043548	phosphatidylinositol 3-kinase binding
GO:0046982	protein heterodimerization activity

Biological Process

GO:0001764	neuron migration
GO:0001779	natural killer cell differentiation
GO:0001961	positive regulation of cytokine-mediated signaling pathway
GO:0001974	blood vessel remodeling
GO:0006468	protein phosphorylation
GO:0006909	phagocytosis
GO:0006954	inflammatory response
GO:0007165	signal transduction
GO:0007167	enzyme linked receptor protein signaling pathway
GO:0007283	spermatogenesis
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0021885	forebrain cell migration
GO:0030154	cell differentiation
GO:0030168	platelet activation
GO:0031100	organ regeneration
GO:0031668	cellular response to extracellular stimulus
GO:0032689	negative regulation of interferon-gamma production
GO:0032720	negative regulation of tumor necrosis factor production
GO:0032825	positive regulation of natural killer cell differentiation
GO:0032940	secretion by cell
GO:0034101	erythrocyte homeostasis
GO:0034446	substrate adhesion-dependent cell spreading
GO:0035457	cellular response to interferon-alpha
GO:0042698	ovulation cycle
GO:0043066	negative regulation of apoptotic process
GO:0043277	apoptotic cell clearance
GO:0043491	protein kinase B signaling
GO:0043524	negative regulation of neuron apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0048469	cell maturation
GO:0051250	negative regulation of lymphocyte activation
GO:0051897	positive regulation of protein kinase B signaling
GO:0060068	vagina development
GO:0070301	cellular response to hydrogen peroxide
GO:0071222	cellular response to lipopolysaccharide
GO:0097028	dendritic cell differentiation
GO:2000669	negative regulation of dendritic cell apoptotic process

Cellular Component

GO:0005615	extracellular space
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
GO:0016021	integral component of membrane
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR003599 Immunoglobulin subtype
IPR003961 Fibronectin, type III
IPR007110 Immunoglobulin-like domain
IPR011009 Protein kinase-like domain
IPR013098 Immunoglobulin I-set
IPR013106 Immunoglobulin V-set domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF00041
PF01108
PF07679
PF07686

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00409
SM00060
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt