UniProt functional annotation for P30530



	UniProt functional annotation for P30530

UniProt code: P30530.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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, 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. {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}.

Function: (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. {ECO:0000269|PubMed:17005688, ECO:0000269|PubMed:21501828, ECO:0000269|PubMed:22156524, ECO:0000269|PubMed:25277499}.

Function: (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:22673088}.

Catalytic activity: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};

Activity regulation: Activated by GAS6-binding and subsequent autophosphorylation. {ECO:0000269|PubMed:15507525, ECO:0000269|PubMed:8621659}.

Subunit: 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. {ECO:0000269|PubMed:12470648, ECO:0000269|PubMed:15958209, ECO:0000269|PubMed:16362042, ECO:0000269|PubMed:18346204, ECO:0000269|PubMed:19815557, ECO:0000269|PubMed:7854420, ECO:0000269|PubMed:8621659, ECO:0000269|PubMed:9178760}.

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

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

Ptm: Monoubiquitinated upon GAS6-binding. A very small proportion of the receptor could be subjected to polyubiquitination in a very transient fashion. {ECO:0000269|PubMed:15958209}.

Ptm: Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity. {ECO:0000269|PubMed:18346204, ECO:0000269|PubMed:9178760}.

Disease: 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.

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily. {ECO:0000255|PROSITE- ProRule:PRU00159}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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, 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. {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}.



Function:		(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. {ECO:0000269\|PubMed:17005688, ECO:0000269\|PubMed:21501828, ECO:0000269\|PubMed:22156524, ECO:0000269\|PubMed:25277499}.



Function:		(Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269\|PubMed:22673088}.


Catalytic activity:		Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255\|PROSITE-ProRule:PRU10028};
Activity regulation:		Activated by GAS6-binding and subsequent autophosphorylation. {ECO:0000269\|PubMed:15507525, ECO:0000269\|PubMed:8621659}.
Subunit:		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. {ECO:0000269\|PubMed:12470648, ECO:0000269\|PubMed:15958209, ECO:0000269\|PubMed:16362042, ECO:0000269\|PubMed:18346204, ECO:0000269\|PubMed:19815557, ECO:0000269\|PubMed:7854420, ECO:0000269\|PubMed:8621659, ECO:0000269\|PubMed:9178760}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:7896447}; Single-pass type I membrane protein {ECO:0000269\|PubMed:7896447}.
Tissue specificity:		Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue. {ECO:0000269\|PubMed:7896447}.
Ptm:		Monoubiquitinated upon GAS6-binding. A very small proportion of the receptor could be subjected to polyubiquitination in a very transient fashion. {ECO:0000269\|PubMed:15958209}.
Ptm:		Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity. {ECO:0000269\|PubMed:18346204, ECO:0000269\|PubMed:9178760}.
Disease:		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.
Similarity:		Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily. {ECO:0000255\|PROSITE- ProRule:PRU00159}.