TISIDB

Summary
Symbol	HIPK1
Name	homeodomain interacting protein kinase 1
Aliases	KIAA0630; Myak; MGC26642; Nbak2; MGC33446; MGC33548; homeodomain interacting protein kinase 1-like protein; ......
Chromosomal Location	1p13.1
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	Nucleus. Cytoplasm. Note=Predominantly nuclear. Translocates from nucleus to cytoplasm in response to stress stimuli via SENP1-mediated desumoylation.
Domain	PF00069 Protein kinase domain
Function	Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti-oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0001654 eye development GO:0001959 regulation of cytokine-mediated signaling pathway GO:0002088 lens development in camera-type eye GO:0002089 lens morphogenesis in camera-type eye GO:0003002 regionalization GO:0003407 neural retina development GO:0007224 smoothened signaling pathway GO:0007389 pattern specification process GO:0007423 sensory organ development GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0009952 anterior/posterior pattern specification GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway GO:0010842 retina layer formation GO:0031076 embryonic camera-type eye development GO:0031128 developmental induction GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0034329 cell junction assembly GO:0034330 cell junction organization GO:0034332 adherens junction organization GO:0034333 adherens junction assembly GO:0034612 response to tumor necrosis factor GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator GO:0043010 camera-type eye development GO:0045216 cell-cell junction organization GO:0045765 regulation of angiogenesis GO:0045766 positive regulation of angiogenesis GO:0048048 embryonic eye morphogenesis GO:0048514 blood vessel morphogenesis GO:0048562 embryonic organ morphogenesis GO:0048568 embryonic organ development GO:0048592 eye morphogenesis GO:0048593 camera-type eye morphogenesis GO:0048596 embryonic camera-type eye morphogenesis GO:0060041 retina development in camera-type eye GO:0060042 retina morphogenesis in camera-type eye GO:0060059 embryonic retina morphogenesis in camera-type eye GO:0060216 definitive hemopoiesis GO:0060235 lens induction in camera-type eye GO:0060759 regulation of response to cytokine stimulus GO:0061072 iris morphogenesis GO:0071356 cellular response to tumor necrosis factor GO:0072331 signal transduction by p53 class mediator GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator GO:0072577 endothelial cell apoptotic process GO:0090596 sensory organ morphogenesis GO:0097191 extrinsic apoptotic signaling pathway GO:0097193 intrinsic apoptotic signaling pathway GO:1901342 regulation of vasculature development GO:1901796 regulation of signal transduction by p53 class mediator GO:1904018 positive regulation of vasculature development GO:1904019 epithelial cell apoptotic process
Molecular Function	GO:0004674 protein serine/threonine kinase activity
Cellular Component	GO:0016604 nuclear body GO:0016605 PML body GO:0016607 nuclear speck

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-5576891: Cardiac conduction R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-397014: Muscle contraction R-HSA-5578768: Physiological factors R-HSA-5633007: Regulation of TP53 Activity R-HSA-6804756: Regulation of TP53 Activity through Phosphorylation R-HSA-3700989: Transcriptional Regulation by TP53 R-HSA-2032785: YAP1- and WWTR1 (TAZ)-stimulated gene expression

> KEGG and Reactome Pathway

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KEGG

Reactome

R-HSA-5576891: Cardiac conduction
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-397014: Muscle contraction
R-HSA-5578768: Physiological factors
R-HSA-5633007: Regulation of TP53 Activity
R-HSA-6804756: Regulation of TP53 Activity through Phosphorylation
R-HSA-3700989: Transcriptional Regulation by TP53
R-HSA-2032785: YAP1- and WWTR1 (TAZ)-stimulated gene expression

Summary
Symbol	HIPK1
Name	homeodomain interacting protein kinase 1
Aliases	KIAA0630; Myak; MGC26642; Nbak2; MGC33446; MGC33548; homeodomain interacting protein kinase 1-like protein; ......
Chromosomal Location	1p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between HIPK1 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	HIPK1
Name	homeodomain interacting protein kinase 1
Aliases	KIAA0630; Myak; MGC26642; Nbak2; MGC33446; MGC33548; homeodomain interacting protein kinase 1-like protein; ......
Chromosomal Location	1p13.1
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

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Statistical results of HIPK1 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	Total # shRNA with >= 4-fold: 4	Resistant to T-cell proliferation

Summary
Symbol	HIPK1
Name	homeodomain interacting protein kinase 1
Aliases	KIAA0630; Myak; MGC26642; Nbak2; MGC33446; MGC33548; homeodomain interacting protein kinase 1-like protein; ......
Chromosomal Location	1p13.1
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 HIPK1 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	-0.012	0.961
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.127	0.938
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.105	0.922
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.236	0.54
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.283	0.9
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.895	0.764
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.245	0.53
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.291	0.87
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.209	0.915
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.571	0.642
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	1.159	0.513
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.021	0.654

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of HIPK1 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	4.1	-0.4	1
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	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	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	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	7.4	-2.1	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	6.2	7.1	-0.9	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	0	9.1	0.458
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	16.7	0	16.7	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	HIPK1
Name	homeodomain interacting protein kinase 1
Aliases	KIAA0630; Myak; MGC26642; Nbak2; MGC33446; MGC33548; homeodomain interacting protein kinase 1-like protein; ......
Chromosomal Location	1p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HIPK1. 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	HIPK1
Name	homeodomain interacting protein kinase 1
Aliases	KIAA0630; Myak; MGC26642; Nbak2; MGC33446; MGC33548; homeodomain interacting protein kinase 1-like protein; ......
Chromosomal Location	1p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HIPK1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HIPK1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	HIPK1
Name	homeodomain interacting protein kinase 1
Aliases	KIAA0630; Myak; MGC26642; Nbak2; MGC33446; MGC33548; homeodomain interacting protein kinase 1-like protein; ......
Chromosomal Location	1p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HIPK1. 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	HIPK1
Name	homeodomain interacting protein kinase 1
Aliases	KIAA0630; Myak; MGC26642; Nbak2; MGC33446; MGC33548; homeodomain interacting protein kinase 1-like protein; ......
Chromosomal Location	1p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of HIPK1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	HIPK1
Name	homeodomain interacting protein kinase 1
Aliases	KIAA0630; Myak; MGC26642; Nbak2; MGC33446; MGC33548; homeodomain interacting protein kinase 1-like protein; ......
Chromosomal Location	1p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between HIPK1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	HIPK1
Name	homeodomain interacting protein kinase 1
Aliases	KIAA0630; Myak; MGC26642; Nbak2; MGC33446; MGC33548; homeodomain interacting protein kinase 1-like protein; ......
Chromosomal Location	1p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting HIPK1 collected from DrugBank database.

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

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