Browse TYROBP

Summary
SymbolTYROBP
NameTYRO protein tyrosine kinase binding protein
Aliases DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location19q13.12
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 -
Function

Non-covalently associates with activating receptors of the CD300 family. Cross-linking of CD300-TYROBP complexes results in cellular activation. Involved for instance in neutrophil activation mediated by integrin.

> Gene Ontology
 
Biological Process GO:0001501 skeletal system development
GO:0002263 cell activation involved in immune response
GO:0002274 myeloid leukocyte activation
GO:0002275 myeloid cell activation involved in immune response
GO:0002281 macrophage activation involved in immune response
GO:0002283 neutrophil activation involved in immune response
GO:0002366 leukocyte activation involved in immune response
GO:0002521 leukocyte differentiation
GO:0002573 myeloid leukocyte differentiation
GO:0002761 regulation of myeloid leukocyte differentiation
GO:0006968 cellular defense response
GO:0007229 integrin-mediated signaling pathway
GO:0030099 myeloid cell differentiation
GO:0030316 osteoclast differentiation
GO:0036035 osteoclast development
GO:0036230 granulocyte activation
GO:0042116 macrophage activation
GO:0042119 neutrophil activation
GO:0045637 regulation of myeloid cell differentiation
GO:0045670 regulation of osteoclast differentiation
GO:0060348 bone development
GO:0061515 myeloid cell development
GO:0098751 bone cell development
GO:1902105 regulation of leukocyte differentiation
GO:1903010 regulation of bone development
GO:1903706 regulation of hemopoiesis
GO:2001204 regulation of osteoclast development
Molecular Function GO:0005057 receptor signaling protein activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04380 Osteoclast differentiation
hsa04650 Natural killer cell mediated cytotoxicity
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-422475: Axon guidance
R-HSA-1500931: Cell-Cell communication
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1266738: Developmental Biology
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-168249: Innate Immune System
R-HSA-6798695: Neutrophil degranulation
R-HSA-416700: Other semaphorin interactions
R-HSA-373755: Semaphorin interactions
R-HSA-391160: Signal regulatory protein (SIRP) family interactions
Summary
SymbolTYROBP
NameTYRO protein tyrosine kinase binding protein
Aliases DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location19q13.12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TYROBP 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 TYROBP and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
24586048Lung CarcinomaPromote immunity (NK cell function)Instead, TGF-β depleted DNAX activating protein 12 kDa (DAP12), which is critical for surface NK receptor stabilization and downstream signal transduction. Mechanistic analysis revealed that TGF-β induced microRNA (miR)-183 to repress DAP12 transcription/translation. Moreover, we documented reduced DAP12 expression in tumor-associated NK cells in lung cancer patients, illustrating this pathway to be consistently perturbed in the human tumor microenvironment.
16169855T-Cell Non-Hodgkin LymphomaPromote immunity (T cell function)T cells gene-engineered with DAP12 mediate effector function in an NKG2D-dependent and major histocompatibility complex-independent manner. T-DAP12 cells were demonstrated to specifically secrete interferon-gamma following receptor ligation and to mediate potent and specific lysis of the NKG2D ligand (NKG2D-L) (Rae-1beta) expressing MHC class I-deficient and class I-sufficient tumors.
Summary
SymbolTYROBP
NameTYRO protein tyrosine kinase binding protein
Aliases DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location19q13.12
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 TYROBP 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
SymbolTYROBP
NameTYRO protein tyrosine kinase binding protein
Aliases DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location19q13.12
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 TYROBP in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.5550.196
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.8020.819
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.3760.885
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1360.803
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.5590.71
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.4050.839
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.1250.823
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0080.996
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.3610.852
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.1840.668
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.7650.866
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0580.74
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TYROBP 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) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
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
SymbolTYROBP
NameTYRO protein tyrosine kinase binding protein
Aliases DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location19q13.12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TYROBP. 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
SymbolTYROBP
NameTYRO protein tyrosine kinase binding protein
Aliases DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location19q13.12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TYROBP. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TYROBP.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTYROBP
NameTYRO protein tyrosine kinase binding protein
Aliases DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location19q13.12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TYROBP. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTYROBP
NameTYRO protein tyrosine kinase binding protein
Aliases DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location19q13.12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TYROBP expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTYROBP
NameTYRO protein tyrosine kinase binding protein
Aliases DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location19q13.12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TYROBP and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTYROBP
NameTYRO protein tyrosine kinase binding protein
Aliases DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location19q13.12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TYROBP collected from DrugBank database.
> Drugs from DrugBank database
 

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