TISIDB

Summary
Symbol	MERTK
Name	MER proto-oncogene, tyrosine kinase
Aliases	RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location	2q14.1
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
KEGG	-
Reactome	R-HSA-202733: Cell surface interactions at the vascular wall R-HSA-109582: Hemostasis

Summary
Symbol	MERTK
Name	MER proto-oncogene, tyrosine kinase
Aliases	RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location	2q14.1
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

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Literatures describing the relation between MERTK and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29708510	Melanoma	Inhibit immunity	Tyro3, 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.
25074939	Breast Carcinoma	Inhibit immunity	Finally, 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
Symbol	MERTK
Name	MER proto-oncogene, tyrosine kinase
Aliases	RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location	2q14.1
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	MERTK
Name	MER proto-oncogene, tyrosine kinase
Aliases	RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location	2q14.1
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.502	0.28
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.622	0.611
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.434	0.718
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.154	0.61
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.398	0.845
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.153	0.952
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.141	0.739
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.432	0.738
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.267	0.862
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.731	0.529
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.592	0.326
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.231	0.0229

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	6.8	0.6	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	8.5	-1.1	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	0	22.2	0.12
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	7.4	-7.4	0.169
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	7.7	-7.7	0.371
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	MERTK
Name	MER proto-oncogene, tyrosine kinase
Aliases	RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location	2q14.1
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 [ TOP ]

Summary
Symbol	MERTK
Name	MER proto-oncogene, tyrosine kinase
Aliases	RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location	2q14.1
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MERTK
Name	MER proto-oncogene, tyrosine kinase
Aliases	RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location	2q14.1
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	MERTK
Name	MER proto-oncogene, tyrosine kinase
Aliases	RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location	2q14.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MERTK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MERTK
Name	MER proto-oncogene, tyrosine kinase
Aliases	RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location	2q14.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MERTK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MERTK
Name	MER proto-oncogene, tyrosine kinase
Aliases	RP38; c-Eyk; Tyro12; c-mer proto-oncogene tyrosine kinase; c-mer; MER receptor tyrosine kinase; STK kinase; ......
Chromosomal Location	2q14.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MERTK collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting MERTK.

ID	Name	Drug Type	Targets	#Targets
DB08325	2-(2-HYDROXYETHYLAMINO)-6-(3-CHLOROANILINO)-9-ISOPROPYLPURINE	Small Molecule	CSNK1G1, MERTK	2

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