Tyrosine-Protein Kinase RSE, BYK, Tyrosine-Protein Kinase Receptor TYRO3, Tyrosine-Protein Kinase BYK, Etk-2, Rek, DTK, SKY, TIF, Brt, RSE, Tyrosine-protein kinase DTK, Tyrosine-protein kinase SKY, TYRO3, Tyrosine-protein kinase TIF, TYRO3 Protein Tyrosine Kinase


TYRO3 is a receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.

KO Status

RenMab: F1 (+/-)

Drug Information

Launched drug: 1
Drugs in clinical trials: 3
Latest Research Phase: Approved

Drug Name





Clinical Trials

Cabozantinib S-malate

BMS-907351, XL-184


Exelixis Inc

Solid tumours, Pain, Stomach Neoplasms, Carcinoma, Renal Cell, Esophageal Neoplasms, Glioblastoma, Kidney Diseases, Prostatic Neoplasms, Colorectal Neoplasms, Astrocytoma, Hepatic Insufficiency, Thyroid Neoplasms, Carcinoma, Neuroendocrine, Lymphoma, Carcinoma, Non-Small-Cell Lung, Carcinoma, Hepatocellular

Insulin icodec

148-0287-A, Insulin-287, LAI-287, Long-acting basal insulin analogue, Long-acting-insulin-287, NN-1436, NN-1956, NNC-0148-0000-0287, NNC0148-0287 C, OI-287GT

Phase 3 Clinical

Novo Nordisk A/S

Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetes Mellitus

Insulin tregopil (Biocon)

HIM-2, IN-105, NIN-058, GW-843362

Phase 2 Clinical


Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2



Phase 1 Clinical

Teva, Daiichi Sankyo Co Ltd

Solid tumours, Neoplasms




Max Planck Innovation, Lead Discovery Center


Insulin biosimilar (SemBioSys/Tasly)



Tasly Pharmaceuticals, Sembiosys

Diabetes Mellitus, Type 1

Insulin transdermal (Phosphagenics)




Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2

Insulin transdermal patch (Zosano Pharma)



Diabetes Mellitus





Immunobiology of the TAM receptors

Lemke G., Rothlin C.V.,

Nat. Rev. Immunol. 8:327-336(2008)

Potentiating role of Gas6 and Tyro3, Axl and Mer (TAM) receptors in human and murine platelet activation and thrombus stabilization

Cosemans J.M., Van Kruchten R., Olieslagers S., Schurgers L.J., Verheyen F.K., Munnix I.C., Waltenberger J., Angelillo-Scherrer A., Hoylaerts M.F., Carmeliet P., Heemskerk J.W.,

J. Thromb. Haemost. 8:1797-1808(2010)

Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry

Shimojima M., Stroher U., Ebihara H., Feldmann H., Kawaoka Y.,

J. Virol. 86:2067-2078(2012)

Cell surface molecules involved in infection mediated by lymphocytic choriomeningitis virus glycoprotein

Shimojima M., Kawaoka Y.,

J. Vet. Med. Sci. 74:1363-1366(2012)

Toward a comprehensive characterization of a human cancer cell phosphoproteome

Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., Mohammed S.,

J. Proteome Res. 12:260-271(2013)

Phosphatidylserine receptors: enhancers of enveloped virus entry and infection

Moller-Tank S., Maury W.,

Virology 468:565-580(2014)

Ligand recognition and homophilic interactions in Tyro3: structural insights into the Axl/Tyro3 receptor tyrosine kinase family

Heiring C., Dahlbaeck B., Muller Y.A.,

J. Biol. Chem. 279:6952-6958(2004)

Patterns of somatic mutation in human cancer genomes

Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., Stratton M.R.,

Nature 446:153-158(2007)

RSE, a novel receptor-type tyrosine kinase with homology to Axl/Ufo, is expressed at high levels in the brain

Mark M.R., Scadden D.T., Wang Z., Gu Q., Goddard A., Godowski P.J.,

J. Biol. Chem. 269:10720-10728(1994)

Cloning of the cDNA for a novel receptor tyrosine kinase, Sky, predominantly expressed in brain

Ohashi K., Mizuno K., Kuma K., Miyata T., Nakamura T.,

Oncogene 9:699-705(1994)