Browse TYRO3

Summary
SymbolTYRO3
NameTYRO3 protein tyrosine kinase
Aliases Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location15q15.1-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
 
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
 
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
 
KEGG -
Reactome -
Summary
SymbolTYRO3
NameTYRO3 protein tyrosine kinase
Aliases Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location15q15.1-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
 
  Literatures describing the relation between TYRO3 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.
Summary
SymbolTYRO3
NameTYRO3 protein tyrosine kinase
Aliases Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location15q15.1-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
  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
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
SymbolTYRO3
NameTYRO3 protein tyrosine kinase
Aliases Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location15q15.1-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
 
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 Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.7930.0713
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.9040.653
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.7160.62
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0020.995
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.340.836
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.4350.834
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0640.887
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.180.911
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.310.864
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.1360.223
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 282.0860.105
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0980.373
> Mutation difference between responders and non-responders
 
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 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) 27737.41.460.177
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.41.75.70.231
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) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.33.71.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.57.7-3.21
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
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
SymbolTYRO3
NameTYRO3 protein tyrosine kinase
Aliases Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location15q15.1-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
 
Summary
SymbolTYRO3
NameTYRO3 protein tyrosine kinase
Aliases Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location15q15.1-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
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTYRO3
NameTYRO3 protein tyrosine kinase
Aliases Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location15q15.1-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
 
> Receptor
 
Summary
SymbolTYRO3
NameTYRO3 protein tyrosine kinase
Aliases Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location15q15.1-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
 
> Molecular subtype
 
Summary
SymbolTYRO3
NameTYRO3 protein tyrosine kinase
Aliases Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location15q15.1-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
 
> Stage
 
> Grade
 
Summary
SymbolTYRO3
NameTYRO3 protein tyrosine kinase
Aliases Dtk; Brt; Tif; Sky; Etk-2; Rek; RSE; BYK; tyrosine-protein kinase DTK; tyrosine-protein kinase RSE; tyrosine ......
Chromosomal Location15q15.1-q21.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TYRO3 collected from DrugBank database.
> Drugs from DrugBank database
 

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