TISIDB

Summary
Symbol	TYROBP
Name	TYRO protein tyrosine kinase binding protein
Aliases	DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location	19q13.12
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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

> KEGG and Reactome Pathway

[ TOP ]

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
Symbol	TYROBP
Name	TYRO protein tyrosine kinase binding protein
Aliases	DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location	19q13.12
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

[ TOP ]

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

PMID	Cancer type	Relation to immunity	Evidence sentences
24586048	Lung Carcinoma	Promote 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.
16169855	T-Cell Non-Hodgkin Lymphoma	Promote 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
Symbol	TYROBP
Name	TYRO protein tyrosine kinase binding protein
Aliases	DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location	19q13.12
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

[ TOP ]

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
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	TYROBP
Name	TYRO protein tyrosine kinase binding protein
Aliases	DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location	19q13.12
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

[ TOP ]

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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.555	0.196
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.802	0.819
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.376	0.885
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.136	0.803
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.559	0.71
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.405	0.839
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.125	0.823
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.008	0.996
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.361	0.852
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.184	0.668
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	0.765	0.866
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.058	0.74

> Mutation difference between responders and non-responders

[ TOP ]

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/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	TYROBP
Name	TYRO protein tyrosine kinase binding protein
Aliases	DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location	19q13.12
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 [ TOP ]

Summary
Symbol	TYROBP
Name	TYRO protein tyrosine kinase binding protein
Aliases	DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location	19q13.12
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TYROBP
Name	TYRO protein tyrosine kinase binding protein
Aliases	DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location	19q13.12
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	TYROBP
Name	TYRO protein tyrosine kinase binding protein
Aliases	DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location	19q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TYROBP expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TYROBP
Name	TYRO protein tyrosine kinase binding protein
Aliases	DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location	19q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TYROBP and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TYROBP
Name	TYRO protein tyrosine kinase binding protein
Aliases	DAP12; PLO-SL; KARAP; killer activating receptor associated protein; DNAX-activation protein 12; PLOSL; KAR- ......
Chromosomal Location	19q13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TYROBP collected from DrugBank database.

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

Browse TYROBP