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

MERTK (Q12866) - Overview - Molecular Target Synopsis

Protein


MERTK, Tyrosine-protein kinase Mer
Enzyme Classification 2.7.10.1
UniProt Q12866

Also Known as MERTK_HUMAN, MERTK, MER

Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. 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. Interacts (upon activation) with TNK2; stimulates TNK2 autophosphorylation. Interacts (via N-terminus) with extracellular ligands LGALS3, TUB, TULP1 and GAS6 (By similarity). Interacts with VAV1 in a phosphotyrosine-independent manner.

5U6C
CRYSTAL STRUCTURE OF THE MER KINASE DOMAIN IN COMPLEX WITH A MACROCYCLIC INHIBITOR
RCSB/PDB
Inspect Structure
See all 3D Structures for MERTK

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MERTK is active in the following subcellular-locations: membrane.
GO terms: MERTK is active in the following subcellular-locations: cytoplasm, extracellular space, integral component of plasma membrane, photoreceptor outer segment, plasma membrane, receptor complex, rhabdomere.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MERTK has gain in 0 cell-lines, loss in 1 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SK_MEL_5, UACC_257, MALME_3M

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: TYK-nu, SK-MEL-5, Hep G2

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: SK-N-SH, HUVEC, GM12878

(see details)

RNA Interference


MERTK was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: ZR7530, CAL51. (see details)

3D Structures


For MERTK there are:
13 structures (27 chains) solved
12 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MERTK has been screened with 918 compounds (1971 bioactivities), 126 compounds have bioactivities that show binding affinity of <= 500nM (148 bioactivities). (see details)