Browse MERTK

Summary
SymbolMERTK
NameMER proto-oncogene, tyrosine kinase
Aliases RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location2q14.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Membrane Single-pass type I membrane protein
Domain PF00041 Fibronectin type III domain
PF00047 Immunoglobulin domain
PF07714 Protein tyrosine kinase
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. 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.

> Gene Ontology
 
Biological Process GO:0001654 eye development
GO:0001779 natural killer cell differentiation
GO:0002521 leukocyte differentiation
GO:0002683 negative regulation of immune system process
GO:0002694 regulation of leukocyte activation
GO:0002695 negative regulation of leukocyte activation
GO:0006909 phagocytosis
GO:0007283 spermatogenesis
GO:0007423 sensory organ development
GO:0007548 sex differentiation
GO:0007596 blood coagulation
GO:0007599 hemostasis
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0030098 lymphocyte differentiation
GO:0030100 regulation of endocytosis
GO:0030101 natural killer cell activation
GO:0030168 platelet activation
GO:0030540 female genitalia development
GO:0031589 cell-substrate adhesion
GO:0034446 substrate adhesion-dependent cell spreading
GO:0043010 camera-type eye development
GO:0043277 apoptotic cell clearance
GO:0043491 protein kinase B signaling
GO:0045807 positive regulation of endocytosis
GO:0046660 female sex differentiation
GO:0048232 male gamete generation
GO:0048608 reproductive structure development
GO:0048806 genitalia development
GO:0050764 regulation of phagocytosis
GO:0050766 positive regulation of phagocytosis
GO:0050817 coagulation
GO:0050865 regulation of cell activation
GO:0050866 negative regulation of cell activation
GO:0050878 regulation of body fluid levels
GO:0050900 leukocyte migration
GO:0051249 regulation of lymphocyte activation
GO:0051250 negative regulation of lymphocyte activation
GO:0060041 retina development in camera-type eye
GO:0060068 vagina development
GO:0060627 regulation of vesicle-mediated transport
GO:0061458 reproductive system development
GO:0071887 leukocyte apoptotic process
GO:2000106 regulation of leukocyte apoptotic process
GO:2000107 negative regulation of leukocyte apoptotic process
Molecular Function GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0019199 transmembrane receptor protein kinase activity
Cellular Component GO:0001750 photoreceptor outer segment
GO:0005929 cilium
GO:0016028 rhabdomere
GO:0031513 nonmotile primary cilium
GO:0072372 primary cilium
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-202733: Cell surface interactions at the vascular wall
R-HSA-109582: Hemostasis
Summary
SymbolMERTK
NameMER proto-oncogene, tyrosine kinase
Aliases RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location2q14.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between MERTK and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between MERTK and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
29708510MelanomaInhibit immunityTyro3, Axl, Mer (TAM) receptor tyrosine kinases reduce inflammatory, innate immune responses. We demonstrate that tumor-secreted protein S (Pros1), a Mer/Tyro3 ligand, decreased macrophage M1 cytokine expression in vitro and in vivo. Tumor cell-associated Pros1 action was abrogated in macrophages from Mer- and Tyro3- but not Axl-KO mice.
25074939Breast CarcinomaInhibit immunityFinally, through MERTK, apoptotic cells induced PD-L1 expression, an immune checkpoint blockade, suggesting that cancer cells may adopt MERTK-driven efferocytosis as an immune suppression mechanism for their advantage.
Summary
SymbolMERTK
NameMER proto-oncogene, tyrosine kinase
Aliases RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location2q14.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of MERTK in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolMERTK
NameMER proto-oncogene, tyrosine kinase
Aliases RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location2q14.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of MERTK in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.5020.28
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.6220.611
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.4340.718
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1540.61
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.3980.845
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.1530.952
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1410.739
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.4320.738
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2670.862
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.7310.529
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.5920.326
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2310.0229
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of MERTK in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.46.80.61
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.48.5-1.11
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91622.2022.20.12
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 382707.4-7.40.169
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221307.7-7.70.371
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolMERTK
NameMER proto-oncogene, tyrosine kinase
Aliases RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location2q14.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MERTK. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolMERTK
NameMER proto-oncogene, tyrosine kinase
Aliases RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location2q14.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MERTK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MERTK.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolMERTK
NameMER proto-oncogene, tyrosine kinase
Aliases RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location2q14.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MERTK. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolMERTK
NameMER proto-oncogene, tyrosine kinase
Aliases RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location2q14.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of MERTK expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolMERTK
NameMER proto-oncogene, tyrosine kinase
Aliases RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location2q14.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between MERTK and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolMERTK
NameMER proto-oncogene, tyrosine kinase
Aliases RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location2q14.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting MERTK collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting MERTK.
ID Name Drug Type Targets #Targets
DB083252-(2-HYDROXYETHYLAMINO)-6-(3-CHLOROANILINO)-9-ISOPROPYLPURINESmall MoleculeCSNK1G1, MERTK2