Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TYRO3 (Q06418) - Overview - Molecular Target Synopsis

Protein


TYRO3, Tyrosine-protein kinase receptor TYRO3
Enzyme Classification 2.7.10.1
UniProt Q06418

Also Known as TYRO3_HUMAN, TYRO3, BYK, DTK, RSE, SKY, TIF

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., (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., (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. Monomer and homodimer. Interacts (via N-terminus) with extracellular ligands TULP1 and GAS6 (By similarity). Interacts with PIK3R1; this interaction increases PI3-kinase activity.

1RHF
CRYSTAL STRUCTURE OF HUMAN TYRO3-D1D2
RCSB/PDB
Inspect Structure
See all 3D Structures for TYRO3

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: TYRO3 is active in the following subcellular-locations: cell membrane.
GO terms: TYRO3 is active in the following subcellular-locations: cell surface, endoplasmic reticulum membrane, integral component of plasma membrane, nuclear envelope, nucleus, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TYRO3 has gain in 0 cell-lines, loss in 2 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MALME_3M, UACC_62, SK_MEL_5

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: A3/KAW, COLO-818, CPC-N

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HeLa-S3, K562, SK-N-SH

(see details)

RNA Interference


TYRO3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: ASPC1, PL5. (see details)

3D Structures


For TYRO3 there are:
1 structures (2 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TYRO3 has been screened with 1001 compounds (1671 bioactivities), 129 compounds have bioactivities that show binding affinity of <= 500nM (140 bioactivities). (see details)