Tyrosine-protein kinase Mer

Function

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. Also plays 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.

Classification

Family (Pfam)

PF00041 fn3, PF00047 ig, PF13927 Ig_3, PF07714 PK_Tyr_Ser-Thr

InterPro

FN3_dom, FN3_sf, Ig-like_dom, Ig-like_dom_sf, Ig-like_fold, Ig_sub, Immunoglobulin_dom, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom

Functional cluster

Eukaryotic Transcription Factors & related

Experimental structures · PDB · 42

• 2DBJ NMR
• 2P0C X-ray 2.40A
• 3BPR X-ray 2.80A
• 3BRB X-ray 1.90A
• 3TCP X-ray 2.69A
• 4M3Q X-ray 2.72A
• 4MH7 X-ray 2.51A
• 4MHA X-ray 2.59A
• 5K0K X-ray 2.54A
• 5K0X X-ray 2.23A
• 5TC0 X-ray 2.24A
• 5TD2 X-ray 2.68A
• … and 30 more

A predicted model is available from AlphaFold.

Gene Ontology · 16

• GO:0005737 cytoplasm
• GO:0005615 extracellular space
• GO:0001750 photoreceptor outer segment
• GO:0005886 plasma membrane
• GO:0043235 receptor complex
• GO:0005524 ATP binding
• GO:0004714 transmembrane receptor protein tyrosine kinase activity
• GO:0016477 cell migration
• GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
• GO:0007166 cell surface receptor signaling pathway
• GO:0007267 cell-cell signaling
• GO:2000107 negative regulation of leukocyte apoptotic process
• GO:0007399 nervous system development
• GO:0006909 phagocytosis
• GO:0050766 positive regulation of phagocytosis
• GO:0006468 protein phosphorylation

Disease associations

• retinitis pigmentosa 38 MONDO:0013469

Drugs targeting this protein · 1

• NINGETINIB inhibitor

Related proteins · sequence + function similarity

• Tyrosine-protein kinase Mer 0.98
• Tyrosine-protein kinase Mer 0.98
• Tyrosine-protein kinase receptor TYRO3 0.87
• Tyrosine-protein kinase receptor TYRO3 0.84
• Tyrosine-protein kinase receptor TYRO3 0.84
• Tyrosine-protein kinase receptor TYRO3 0.80
• Tyrosine-protein kinase receptor TYRO3 0.79
• Tyrosine-protein kinase receptor TYRO3 0.79
• Mast/stem cell growth factor receptor Kit 0.74
• Tyrosine-protein kinase receptor TYRO3 0.73
• Fibroblast growth factor receptor 1 0.72
• Fibroblast growth factor receptor 1 0.71

Co-cited proteins · studied together in the literature

• Tyrosine-protein kinase receptor TYRO3 3 shared papers
• T-cell immunoglobulin and mucin domain-containing protein 4 1 shared papers
• Tyrosine-protein kinase Mer 1 shared papers
• WW domain-containing oxidoreductase 1 shared papers
• Activated CDC42 kinase 1 1 shared papers
• Envelope glycoprotein 1 shared papers
• Envelope glycoprotein 1 shared papers
• Envelope glycoprotein 1 shared papers
• Aryl-hydrocarbon-interacting protein-like 1 1 shared papers
• Growth arrest-specific protein 6 1 shared papers
• Spermatogenesis-associated protein 7 1 shared papers
• Retinal guanylyl cyclase 1 1 shared papers

Literature · 16 cited papers

• Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis. Cells · 2020
• Galectin-3 is a new MerTK-specific eat-me signal. J. Cell. Physiol. · 2012
• Detection of variants in 15 genes in 87 unrelated Chinese patients with Leber congenital amaurosis. PLoS ONE · 2011
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Immunobiology of the TAM receptors. Nat. Rev. Immunol. · 2008
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• Tyro3 family-mediated cell entry of Ebola and Marburg viruses. J. Virol. · 2006
• Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev. · 2006
• Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J. Proteome Res. · 2005
• Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Cancer Res. · 2005
• Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
• An SH2 domain-dependent, phosphotyrosine-independent interaction between Vav1 and the Mer receptor tyrosine kinase: a mechanism for localizing guanine nucleotide-exchange factor action. J. Biol. Chem. · 2003
• … and 4 more in the literature graph