TISIDB

Summary
Symbol	HDAC5
Name	histone deacetylase 5
Aliases	KIAA0600; NY-CO-9; FLJ90614; HD5; antigen NY-CO-9
Chromosomal Location	17q21
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	Nucleus. Cytoplasm. Note=Shuttles between the nucleus and the cytoplasm. In muscle cells, it shuttles into the cytoplasm during myocyte differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-259 and Ser-498 by AMPK, CaMK1 and SIK1.
Domain	PF12203 Glutamine rich N terminal domain of histone deacetylase 4 PF00850 Histone deacetylase domain
Function	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0001667 ameboidal-type cell migration GO:0002040 sprouting angiogenesis GO:0002042 cell migration involved in sprouting angiogenesis GO:0002237 response to molecule of bacterial origin GO:0002521 leukocyte differentiation GO:0006338 chromatin remodeling GO:0006342 chromatin silencing GO:0006476 protein deacetylation GO:0010594 regulation of endothelial cell migration GO:0010596 negative regulation of endothelial cell migration GO:0010631 epithelial cell migration GO:0010632 regulation of epithelial cell migration GO:0010633 negative regulation of epithelial cell migration GO:0010830 regulation of myotube differentiation GO:0010832 negative regulation of myotube differentiation GO:0014823 response to activity GO:0014902 myotube differentiation GO:0016458 gene silencing GO:0016525 negative regulation of angiogenesis GO:0016570 histone modification GO:0016575 histone deacetylation GO:0030098 lymphocyte differentiation GO:0030183 B cell differentiation GO:0030336 negative regulation of cell migration GO:0032496 response to lipopolysaccharide GO:0032868 response to insulin GO:0032869 cellular response to insulin stimulus GO:0035601 protein deacylation GO:0040013 negative regulation of locomotion GO:0040029 regulation of gene expression, epigenetic GO:0042113 B cell activation GO:0042220 response to cocaine GO:0042493 response to drug GO:0042692 muscle cell differentiation GO:0043279 response to alkaloid GO:0043393 regulation of protein binding GO:0043434 response to peptide hormone GO:0043534 blood vessel endothelial cell migration GO:0043535 regulation of blood vessel endothelial cell migration GO:0043537 negative regulation of blood vessel endothelial cell migration GO:0043542 endothelial cell migration GO:0045765 regulation of angiogenesis GO:0045814 negative regulation of gene expression, epigenetic GO:0048514 blood vessel morphogenesis GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051098 regulation of binding GO:0051146 striated muscle cell differentiation GO:0051147 regulation of muscle cell differentiation GO:0051148 negative regulation of muscle cell differentiation GO:0051153 regulation of striated muscle cell differentiation GO:0051154 negative regulation of striated muscle cell differentiation GO:0051271 negative regulation of cellular component movement GO:0070932 histone H3 deacetylation GO:0071216 cellular response to biotic stimulus GO:0071219 cellular response to molecule of bacterial origin GO:0071222 cellular response to lipopolysaccharide GO:0071375 cellular response to peptide hormone stimulus GO:0071396 cellular response to lipid GO:0071417 cellular response to organonitrogen compound GO:0090049 regulation of cell migration involved in sprouting angiogenesis GO:0090051 negative regulation of cell migration involved in sprouting angiogenesis GO:0090130 tissue migration GO:0090132 epithelium migration GO:0098732 macromolecule deacylation GO:1901342 regulation of vasculature development GO:1901343 negative regulation of vasculature development GO:1901652 response to peptide GO:1901653 cellular response to peptide GO:1903670 regulation of sprouting angiogenesis GO:1903671 negative regulation of sprouting angiogenesis GO:2000146 negative regulation of cell motility GO:2000181 negative regulation of blood vessel morphogenesis
Molecular Function	GO:0001025 RNA polymerase III transcription factor binding GO:0001047 core promoter binding GO:0003682 chromatin binding GO:0004407 histone deacetylase activity GO:0005080 protein kinase C binding GO:0008134 transcription factor binding GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds GO:0016811 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides GO:0017136 NAD-dependent histone deacetylase activity GO:0019213 deacetylase activity GO:0031078 histone deacetylase activity (H3-K14 specific) GO:0032041 NAD-dependent histone deacetylase activity (H3-K14 specific) GO:0033558 protein deacetylase activity GO:0034979 NAD-dependent protein deacetylase activity GO:0042826 histone deacetylase binding GO:0070491 repressing transcription factor binding
Cellular Component	GO:0000118 histone deacetylase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-2122947: NOTCH1 Intracellular Domain Regulates Transcription R-HSA-162582: Signal Transduction R-HSA-157118: Signaling by NOTCH R-HSA-1980143: Signaling by NOTCH1 R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer R-HSA-2644603: Signaling by NOTCH1 in Cancer

> KEGG and Reactome Pathway

[ TOP ]

KEGG

Reactome

R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-2122947: NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-162582: Signal Transduction
R-HSA-157118: Signaling by NOTCH
R-HSA-1980143: Signaling by NOTCH1
R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603: Signaling by NOTCH1 in Cancer

Summary
Symbol	HDAC5
Name	histone deacetylase 5
Aliases	KIAA0600; NY-CO-9; FLJ90614; HD5; antigen NY-CO-9
Chromosomal Location	17q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HDAC5 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

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Literatures describing the relation between HDAC5 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26704363	Lung Adenocarcinoma	Promote immunity (T cell function)	Taken together, targeting HDAC5 weakens suppressive function and de-novo induction of Tregs, but also reduces the ability of CD8(+) T cells to produce IFN-γ.

Summary
Symbol	HDAC5
Name	histone deacetylase 5
Aliases	KIAA0600; NY-CO-9; FLJ90614; HD5; antigen NY-CO-9
Chromosomal Location	17q21
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 HDAC5 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	logFC: -3.00; FDR: 0.00979	Resistant to T cell-mediated killing
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	HDAC5
Name	histone deacetylase 5
Aliases	KIAA0600; NY-CO-9; FLJ90614; HD5; antigen NY-CO-9
Chromosomal Location	17q21
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

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Points in the above scatter plot represent the expression difference of HDAC5 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	0.252	0.297
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.1	0.954
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.509	0.691
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.319	0.3
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.209	0.928
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.461	0.879
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.084	0.795
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.168	0.911
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.063	0.971
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.667	0.661
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	1.208	0.576
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.014	0.851

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of HDAC5 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	3.7	1.4	2.3	0.469
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	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	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	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	12.5	9.7	0.602
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	11.1	8.9	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	14.3	10.7	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	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	HDAC5
Name	histone deacetylase 5
Aliases	KIAA0600; NY-CO-9; FLJ90614; HD5; antigen NY-CO-9
Chromosomal Location	17q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HDAC5. 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	HDAC5
Name	histone deacetylase 5
Aliases	KIAA0600; NY-CO-9; FLJ90614; HD5; antigen NY-CO-9
Chromosomal Location	17q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HDAC5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HDAC5. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HDAC5
Name	histone deacetylase 5
Aliases	KIAA0600; NY-CO-9; FLJ90614; HD5; antigen NY-CO-9
Chromosomal Location	17q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HDAC5. 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	HDAC5
Name	histone deacetylase 5
Aliases	KIAA0600; NY-CO-9; FLJ90614; HD5; antigen NY-CO-9
Chromosomal Location	17q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HDAC5 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HDAC5
Name	histone deacetylase 5
Aliases	KIAA0600; NY-CO-9; FLJ90614; HD5; antigen NY-CO-9
Chromosomal Location	17q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HDAC5 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HDAC5
Name	histone deacetylase 5
Aliases	KIAA0600; NY-CO-9; FLJ90614; HD5; antigen NY-CO-9
Chromosomal Location	17q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HDAC5 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting HDAC5.

ID	Name	Drug Type	Targets	#Targets
DB05015	Belinostat	Small Molecule	HDAC1, HDAC10, HDAC11, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, H ......	11
DB06603	Panobinostat	Small Molecule	HDAC1, HDAC10, HDAC11, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, H ......	11

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