TISIDB

Summary
Symbol	HCST
Name	hematopoietic cell signal transducer
Aliases	DAP10; DKFZP586C1522; KAP10; DNAX-activation protein 10; kinase assoc pro of ~10kDa; PIK3AP; phosphoinositid ......
Chromosomal Location	19q13.1
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	PF07213 DAP10 membrane protein
Function	Transmembrane adapter protein which associates with KLRK1 to form an activation receptor KLRK1-HCST in lymphoid and myeloid cells; this receptor plays a major role in triggering cytotoxicity against target cells expressing cell surface ligands such as MHC class I chain-related MICA and MICB, and UL16-binding proteins (ULBPs); these ligands are up-regulated by stress conditions and pathological state such as viral infection and tumor transformation. Functions as docking site for PI3-kinase PIK3R1 and GRB2. Interaction of ULBPs with KLRK1-HCST triggers calcium mobilization and activation of the PIK3R1, MAP2K/ERK, and JAK2/STAT5 signaling pathways. Both PIK3R1 and GRB2 are required for full KLRK1-HCST-mediated activation and ultimate killing of target cells. In NK cells, KLRK1-HCST signaling directly induces cytotoxicity and enhances cytokine production initiated via DAP12/TYROBP-associated receptors. In T-cells, it provides primarily costimulation for TCR-induced signals. KLRK1-HCST receptor plays a role in immune surveillance against tumors and is required for cytolysis of tumors cells; indeed, melanoma cells that do not express KLRK1 ligands escape from immune surveillance mediated by NK cells.

> Gene Ontology [ TOP ]
Biological Process	GO:0014065 phosphatidylinositol 3-kinase signaling GO:0014066 regulation of phosphatidylinositol 3-kinase signaling GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling GO:0048015 phosphatidylinositol-mediated signaling GO:0048017 inositol lipid-mediated signaling
Molecular Function	GO:0043548 phosphatidylinositol 3-kinase binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04650 Natural killer cell mediated cytotoxicity
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-168256: Immune System R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Summary
Symbol	HCST
Name	hematopoietic cell signal transducer
Aliases	DAP10; DKFZP586C1522; KAP10; DNAX-activation protein 10; kinase assoc pro of ~10kDa; PIK3AP; phosphoinositid ......
Chromosomal Location	19q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HCST 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 HCST and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
17785813	Melanoma	Inhibit immunity (NK cell function)	Mice lacking DAP10 (DAP10KO), showed enhanced immunity against melanoma malignancies due to hyperactive functioning of NK1.1+CD3+ NKT cells. DAP10 deficiency resulted in substantially increased NKT cell functions, including cytokine production and cytotoxicity, leading to efficient killing of melanoma tumors. Moreover, the antitumor phenotype of DAP10KO mice correlated with impaired activation status of CD4+CD25+ T regulatory cells (Tregs).

Summary
Symbol	HCST
Name	hematopoietic cell signal transducer
Aliases	DAP10; DKFZP586C1522; KAP10; DNAX-activation protein 10; kinase assoc pro of ~10kDa; PIK3AP; phosphoinositid ......
Chromosomal Location	19q13.1
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

[ TOP ]

Statistical results of HCST 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	HCST
Name	hematopoietic cell signal transducer
Aliases	DAP10; DKFZP586C1522; KAP10; DNAX-activation protein 10; kinase assoc pro of ~10kDa; PIK3AP; phosphoinositid ......
Chromosomal Location	19q13.1
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

[ TOP ]

Points in the above scatter plot represent the expression difference of HCST 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	-0.577	0.242
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.561	0.83
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.586	0.757
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.443	0.582
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.175	0.883
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.801	0.621
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.092	0.852
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.397	0.683
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.333	0.771
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.943	0.644
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	0.068	0.983
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.153	0.428

> Mutation difference between responders and non-responders [ TOP ]
There is no record.

Summary
Symbol	HCST
Name	hematopoietic cell signal transducer
Aliases	DAP10; DKFZP586C1522; KAP10; DNAX-activation protein 10; kinase assoc pro of ~10kDa; PIK3AP; phosphoinositid ......
Chromosomal Location	19q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HCST. 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	HCST
Name	hematopoietic cell signal transducer
Aliases	DAP10; DKFZP586C1522; KAP10; DNAX-activation protein 10; kinase assoc pro of ~10kDa; PIK3AP; phosphoinositid ......
Chromosomal Location	19q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HCST. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HCST. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HCST
Name	hematopoietic cell signal transducer
Aliases	DAP10; DKFZP586C1522; KAP10; DNAX-activation protein 10; kinase assoc pro of ~10kDa; PIK3AP; phosphoinositid ......
Chromosomal Location	19q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HCST. 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	HCST
Name	hematopoietic cell signal transducer
Aliases	DAP10; DKFZP586C1522; KAP10; DNAX-activation protein 10; kinase assoc pro of ~10kDa; PIK3AP; phosphoinositid ......
Chromosomal Location	19q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HCST expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HCST
Name	hematopoietic cell signal transducer
Aliases	DAP10; DKFZP586C1522; KAP10; DNAX-activation protein 10; kinase assoc pro of ~10kDa; PIK3AP; phosphoinositid ......
Chromosomal Location	19q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HCST and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HCST
Name	hematopoietic cell signal transducer
Aliases	DAP10; DKFZP586C1522; KAP10; DNAX-activation protein 10; kinase assoc pro of ~10kDa; PIK3AP; phosphoinositid ......
Chromosomal Location	19q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HCST collected from DrugBank database.

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

Browse HCST