TISIDB

Summary
Symbol	TYRO3
Name	TYRO3 protein tyrosine kinase
Aliases	Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location	15q15.1-q21.1
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	Cell membrane; Single-pass type I membrane protein.
Domain	PF00041 Fibronectin type III domain PF07679 Immunoglobulin I-set 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 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. ; FUNCTION: (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. ; FUNCTION: (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.

> Gene Ontology [ TOP ]
Biological Process	GO:0001779 natural killer cell differentiation GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002224 toll-like receptor signaling pathway 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:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0006909 phagocytosis GO:0007283 spermatogenesis GO:0007548 sex differentiation GO:0007596 blood coagulation GO:0007599 hemostasis GO:0014065 phosphatidylinositol 3-kinase signaling GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0019058 viral life cycle GO:0021885 forebrain cell migration GO:0030098 lymphocyte differentiation GO:0030101 natural killer cell activation GO:0030168 platelet activation GO:0030260 entry into host cell GO:0030540 female genitalia development GO:0030900 forebrain development GO:0031348 negative regulation of defense response GO:0031349 positive regulation of defense response GO:0031589 cell-substrate adhesion GO:0032102 negative regulation of response to external stimulus GO:0034109 homotypic cell-cell adhesion GO:0034121 regulation of toll-like receptor signaling pathway GO:0034122 negative regulation of toll-like receptor signaling pathway GO:0034446 substrate adhesion-dependent cell spreading GO:0042698 ovulation cycle GO:0043277 apoptotic cell clearance GO:0043491 protein kinase B signaling GO:0043523 regulation of neuron apoptotic process GO:0043524 negative regulation of neuron apoptotic process GO:0044409 entry into host GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045824 negative regulation of innate immune response GO:0046660 female sex differentiation GO:0046718 viral entry into host cell GO:0046777 protein autophosphorylation GO:0048015 phosphatidylinositol-mediated signaling GO:0048017 inositol lipid-mediated signaling GO:0048232 male gamete generation GO:0048511 rhythmic process GO:0048608 reproductive structure development GO:0048806 genitalia development GO:0050727 regulation of inflammatory response GO:0050728 negative regulation of inflammatory response GO:0050777 negative regulation of immune response GO:0050817 coagulation GO:0050865 regulation of cell activation GO:0050866 negative regulation of cell activation GO:0050878 regulation of body fluid levels GO:0051249 regulation of lymphocyte activation GO:0051250 negative regulation of lymphocyte activation GO:0051402 neuron apoptotic process GO:0051701 interaction with host GO:0051806 entry into cell of other organism involved in symbiotic interaction GO:0051828 entry into other organism involved in symbiotic interaction GO:0060068 vagina development GO:0060249 anatomical structure homeostasis GO:0061458 reproductive system development GO:0070050 neuron cellular homeostasis GO:0070527 platelet aggregation GO:0070997 neuron death GO:1901214 regulation of neuron death GO:1901215 negative regulation of neuron death
Molecular Function	GO:0001618 virus receptor activity GO:0004713 protein tyrosine kinase activity GO:0004714 transmembrane receptor protein tyrosine kinase activity GO:0004716 receptor signaling protein tyrosine kinase activity GO:0005057 receptor signaling protein activity GO:0019199 transmembrane receptor protein kinase activity GO:0043548 phosphatidylinositol 3-kinase binding GO:0046982 protein heterodimerization activity
Cellular Component	GO:0005635 nuclear envelope

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	TYRO3
Name	TYRO3 protein tyrosine kinase
Aliases	Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location	15q15.1-q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TYRO3 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 TYRO3 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.

Summary
Symbol	TYRO3
Name	TYRO3 protein tyrosine kinase
Aliases	Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location	15q15.1-q21.1
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 TYRO3 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	TYRO3
Name	TYRO3 protein tyrosine kinase
Aliases	Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location	15q15.1-q21.1
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 TYRO3 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	0.793	0.0713
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.904	0.653
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.716	0.62
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.002	0.995
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.34	0.836
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.435	0.834
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.064	0.887
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.18	0.911
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.31	0.864
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.136	0.223
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	2.086	0.105
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.098	0.373

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TYRO3 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	1.4	6	0.177
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	1.7	5.7	0.231
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	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	3.7	1.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
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	TYRO3
Name	TYRO3 protein tyrosine kinase
Aliases	Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location	15q15.1-q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TYRO3. 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	TYRO3
Name	TYRO3 protein tyrosine kinase
Aliases	Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location	15q15.1-q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TYRO3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TYRO3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TYRO3
Name	TYRO3 protein tyrosine kinase
Aliases	Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location	15q15.1-q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TYRO3. 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	TYRO3
Name	TYRO3 protein tyrosine kinase
Aliases	Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location	15q15.1-q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TYRO3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TYRO3
Name	TYRO3 protein tyrosine kinase
Aliases	Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location	15q15.1-q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TYRO3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TYRO3
Name	TYRO3 protein tyrosine kinase
Aliases	Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location	15q15.1-q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TYRO3 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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