TISIDB

Summary
Symbol	HCK
Name	HCK proto-oncogene, Src family tyrosine kinase
Aliases	JTK9; hemopoietic cell kinase; p59Hck; p61Hck; hematopoietic cell kinase; p59-HCK/p60-HCK; Tyrosine-protein ......
Chromosomal Location	20q11-q12
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	Isoform 1: Lysosome. Membrane; Lipid-anchor. Cell projection, podosome membrane; Lipid-anchor. Cytoplasm, cytosol. Note=Associated with specialized secretory lysosomes called azurophil granules. At least half of this isoform is found in the cytoplasm, some of this fraction is myristoylated.; SUBCELLULAR LOCATION: Isoform 2: Cell membrane Lipid-anchor Membrane, caveola Lipid-anchor Cell junction, focal adhesion Cytoplasm, cytoskeleton Golgi apparatus Cytoplasmic vesicle Lysosome Nucleus Note=20% of this isoform is associated with caveolae. Localization at the cell membrane and at caveolae requires palmitoylation at Cys-3. Colocalizes with the actin cytoskeleton at focal adhesions.; SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle. Cytoplasm, cytosol.
Domain	PF07714 Protein tyrosine kinase PF00017 SH2 domain PF00018 SH3 domain
Function	Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.

> Gene Ontology [ TOP ]
Biological Process	GO:0002218 activation of innate immune response GO:0002237 response to molecule of bacterial origin GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002431 Fc receptor mediated stimulatory signaling pathway GO:0002433 immune response-regulating cell surface receptor signaling pathway involved in phagocytosis GO:0002522 leukocyte migration involved in immune response GO:0002679 respiratory burst involved in defense response GO:0002697 regulation of immune effector process GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0002831 regulation of response to biotic stimulus GO:0006887 exocytosis GO:0006909 phagocytosis GO:0007015 actin filament organization GO:0007229 integrin-mediated signaling pathway GO:0007498 mesoderm development GO:0008064 regulation of actin polymerization or depolymerization GO:0008154 actin polymerization or depolymerization GO:0008360 regulation of cell shape GO:0009615 response to virus GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0022604 regulation of cell morphogenesis GO:0030041 actin filament polymerization GO:0030100 regulation of endocytosis GO:0030832 regulation of actin filament length GO:0030833 regulation of actin filament polymerization GO:0030838 positive regulation of actin filament polymerization GO:0031334 positive regulation of protein complex assembly GO:0031349 positive regulation of defense response GO:0031532 actin cytoskeleton reorganization GO:0031663 lipopolysaccharide-mediated signaling pathway GO:0032271 regulation of protein polymerization GO:0032273 positive regulation of protein polymerization GO:0032496 response to lipopolysaccharide GO:0032535 regulation of cellular component size GO:0032956 regulation of actin cytoskeleton organization GO:0032970 regulation of actin filament-based process GO:0034341 response to interferon-gamma GO:0038083 peptidyl-tyrosine autophosphorylation GO:0038093 Fc receptor signaling pathway GO:0038094 Fc-gamma receptor signaling pathway GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis GO:0043254 regulation of protein complex assembly GO:0043299 leukocyte degranulation GO:0043900 regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0044089 positive regulation of cellular component biogenesis GO:0045055 regulated exocytosis GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045728 respiratory burst after phagocytosis GO:0045730 respiratory burst GO:0046777 protein autophosphorylation GO:0050688 regulation of defense response to virus GO:0050690 regulation of defense response to virus by virus GO:0050727 regulation of inflammatory response GO:0050764 regulation of phagocytosis GO:0050792 regulation of viral process GO:0050900 leukocyte migration GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051258 protein polymerization GO:0051493 regulation of cytoskeleton organization GO:0051495 positive regulation of cytoskeleton organization GO:0051607 defense response to virus GO:0060333 interferon-gamma-mediated signaling pathway GO:0060627 regulation of vesicle-mediated transport GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071222 cellular response to lipopolysaccharide GO:0071346 cellular response to interferon-gamma GO:0071396 cellular response to lipid GO:0071800 podosome assembly GO:0071801 regulation of podosome assembly GO:0090066 regulation of anatomical structure size GO:0098542 defense response to other organism GO:1902115 regulation of organelle assembly GO:2000249 regulation of actin cytoskeleton reorganization GO:2000251 positive regulation of actin cytoskeleton reorganization
Molecular Function	GO:0004713 protein tyrosine kinase activity GO:0004715 non-membrane spanning protein tyrosine kinase activity
Cellular Component	GO:0005884 actin filament GO:0005901 caveola GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0009898 cytoplasmic side of plasma membrane GO:0015629 actin cytoskeleton GO:0019897 extrinsic component of plasma membrane GO:0019898 extrinsic component of membrane GO:0030055 cell-substrate junction GO:0030133 transport vesicle GO:0031234 extrinsic component of cytoplasmic side of plasma membrane GO:0044853 plasma membrane raft GO:0045121 membrane raft GO:0098552 side of membrane GO:0098562 cytoplasmic side of membrane GO:0098589 membrane region GO:0098857 membrane microdomain

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04062 Chemokine signaling pathway hsa04666 Fc gamma R-mediated phagocytosis
Reactome	R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-1643685: Disease R-HSA-2029481: FCGR activation R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis R-HSA-162906: HIV Infection R-HSA-162909: Host Interactions of HIV factors R-HSA-168256: Immune System R-HSA-5663205: Infectious disease R-HSA-168249: Innate Immune System R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-164944: Nef and signal transduction R-HSA-912631: Regulation of signaling by CBL R-HSA-449147: Signaling by Interleukins R-HSA-164952: The role of Nef in HIV-1 replication and disease pathogenesis

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04062 Chemokine signaling pathway
hsa04666 Fc gamma R-mediated phagocytosis

Reactome

R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-1643685: Disease
R-HSA-2029481: FCGR activation
R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-162906: HIV Infection
R-HSA-162909: Host Interactions of HIV factors
R-HSA-168256: Immune System
R-HSA-5663205: Infectious disease
R-HSA-168249: Innate Immune System
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-164944: Nef and signal transduction
R-HSA-912631: Regulation of signaling by CBL
R-HSA-449147: Signaling by Interleukins
R-HSA-164952: The role of Nef in HIV-1 replication and disease pathogenesis

Summary
Symbol	HCK
Name	HCK proto-oncogene, Src family tyrosine kinase
Aliases	JTK9; hemopoietic cell kinase; p59Hck; p61Hck; hematopoietic cell kinase; p59-HCK/p60-HCK; Tyrosine-protein ......
Chromosomal Location	20q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HCK 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 ]
There is no record.

Summary
Symbol	HCK
Name	HCK proto-oncogene, Src family tyrosine kinase
Aliases	JTK9; hemopoietic cell kinase; p59Hck; p61Hck; hematopoietic cell kinase; p59-HCK/p60-HCK; Tyrosine-protein ......
Chromosomal Location	20q11-q12
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 HCK 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	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	HCK
Name	HCK proto-oncogene, Src family tyrosine kinase
Aliases	JTK9; hemopoietic cell kinase; p59Hck; p61Hck; hematopoietic cell kinase; p59-HCK/p60-HCK; Tyrosine-protein ......
Chromosomal Location	20q11-q12
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 HCK 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	-0.202	0.592
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.256	0.875
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.163	0.895
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.12	0.837
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.871	0.566
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.384	0.524
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.186	0.708
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.482	0.727
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.153	0.921
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.926	0.541
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	0.931	0.699
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.04	0.821

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of HCK 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	4.1	3.3	0.61
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	5.1	2.3	0.647
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	5.9	3.6	1
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	15.4	9.1	6.3	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	12.5	-12.5	0.52
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	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	0	0	0	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	HCK
Name	HCK proto-oncogene, Src family tyrosine kinase
Aliases	JTK9; hemopoietic cell kinase; p59Hck; p61Hck; hematopoietic cell kinase; p59-HCK/p60-HCK; Tyrosine-protein ......
Chromosomal Location	20q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HCK. 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	HCK
Name	HCK proto-oncogene, Src family tyrosine kinase
Aliases	JTK9; hemopoietic cell kinase; p59Hck; p61Hck; hematopoietic cell kinase; p59-HCK/p60-HCK; Tyrosine-protein ......
Chromosomal Location	20q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HCK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HCK. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HCK
Name	HCK proto-oncogene, Src family tyrosine kinase
Aliases	JTK9; hemopoietic cell kinase; p59Hck; p61Hck; hematopoietic cell kinase; p59-HCK/p60-HCK; Tyrosine-protein ......
Chromosomal Location	20q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HCK. 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	HCK
Name	HCK proto-oncogene, Src family tyrosine kinase
Aliases	JTK9; hemopoietic cell kinase; p59Hck; p61Hck; hematopoietic cell kinase; p59-HCK/p60-HCK; Tyrosine-protein ......
Chromosomal Location	20q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HCK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HCK
Name	HCK proto-oncogene, Src family tyrosine kinase
Aliases	JTK9; hemopoietic cell kinase; p59Hck; p61Hck; hematopoietic cell kinase; p59-HCK/p60-HCK; Tyrosine-protein ......
Chromosomal Location	20q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HCK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HCK
Name	HCK proto-oncogene, Src family tyrosine kinase
Aliases	JTK9; hemopoietic cell kinase; p59Hck; p61Hck; hematopoietic cell kinase; p59-HCK/p60-HCK; Tyrosine-protein ......
Chromosomal Location	20q11-q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HCK collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting HCK.

ID	Name	Drug Type	Targets	#Targets
DB01809	1-Ter-Butyl-3-P-Tolyl-1h-Pyrazolo[3,4-D]Pyrimidin-4-Ylamine	Small Molecule	HCK, RET	2
DB01962	Phosphonotyrosine	Small Molecule	HCK, KIT, SRC	3
DB04216	Quercetin	Small Molecule	ACTB, AHR, ATP5A1, ATP5B, ATP5C1, CBR1, CEBPB, CSNK2A1, CSNK2B, CY ......	27
DB06616	Bosutinib	Small Molecule	ABL1, BCR, CAMK2G, CDK2, HCK, LYN, MAP2K1, MAP2K2, MAP3K2, SRC	10

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