Browse HIPK2

Summary
SymbolHIPK2
Namehomeodomain interacting protein kinase 2
Aliases homeodomain-interacting protein kinase 2; PRO0593; hHIPk2
Chromosomal Location7q34
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
 
Subcellular Location Nucleus, PML body. Cytoplasm. Note=Concentrated in PML/POD/ND10 nuclear bodies. Small amounts are cytoplasmic.
Domain PF00069 Protein kinase domain
Function

Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1 and ZBTB4. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis.

> Gene Ontology
 
Biological Process GO:0001525 angiogenesis
GO:0001654 eye development
GO:0001666 response to hypoxia
GO:0002088 lens development in camera-type eye
GO:0002089 lens morphogenesis in camera-type eye
GO:0002262 myeloid cell homeostasis
GO:0003002 regionalization
GO:0003407 neural retina development
GO:0006978 DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0006997 nucleus organization
GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007224 smoothened signaling pathway
GO:0007254 JNK cascade
GO:0007389 pattern specification process
GO:0007423 sensory organ development
GO:0007626 locomotory behavior
GO:0007628 adult walking behavior
GO:0008344 adult locomotory behavior
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009952 anterior/posterior pattern specification
GO:0010842 retina layer formation
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
GO:0018105 peptidyl-serine phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0018210 peptidyl-threonine modification
GO:0019048 modulation by virus of host morphology or physiology
GO:0030099 myeloid cell differentiation
GO:0030218 erythrocyte differentiation
GO:0030330 DNA damage response, signal transduction by p53 class mediator
GO:0030509 BMP signaling pathway
GO:0030510 regulation of BMP signaling pathway
GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway
GO:0030514 negative regulation of BMP signaling pathway
GO:0030534 adult behavior
GO:0030575 nuclear body organization
GO:0030578 PML body organization
GO:0031076 embryonic camera-type eye development
GO:0031098 stress-activated protein kinase signaling cascade
GO:0031128 developmental induction
GO:0032092 positive regulation of protein binding
GO:0032872 regulation of stress-activated MAPK cascade
GO:0032874 positive regulation of stress-activated MAPK cascade
GO:0034101 erythrocyte homeostasis
GO:0035821 modification of morphology or physiology of other organism
GO:0036293 response to decreased oxygen levels
GO:0036294 cellular response to decreased oxygen levels
GO:0042770 signal transduction in response to DNA damage
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0042772 DNA damage response, signal transduction resulting in transcription
GO:0043010 camera-type eye development
GO:0043388 positive regulation of DNA binding
GO:0043393 regulation of protein binding
GO:0043410 positive regulation of MAPK cascade
GO:0043523 regulation of neuron apoptotic process
GO:0043524 negative regulation of neuron apoptotic process
GO:0044003 modification by symbiont of host morphology or physiology
GO:0044708 single-organism behavior
GO:0045765 regulation of angiogenesis
GO:0045766 positive regulation of angiogenesis
GO:0046328 regulation of JNK cascade
GO:0046330 positive regulation of JNK cascade
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:0048872 homeostasis of number of cells
GO:0050879 multicellular organismal movement
GO:0050881 musculoskeletal movement
GO:0050882 voluntary musculoskeletal movement
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:0051099 positive regulation of binding
GO:0051101 regulation of DNA binding
GO:0051402 neuron apoptotic process
GO:0051403 stress-activated MAPK cascade
GO:0051701 interaction with host
GO:0051817 modification of morphology or physiology of other organism involved in symbiotic interaction
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:0060235 lens induction in camera-type eye
GO:0060395 SMAD protein signal transduction
GO:0061072 iris morphogenesis
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0070304 positive regulation of stress-activated protein kinase signaling cascade
GO:0070482 response to oxygen levels
GO:0070997 neuron death
GO:0071453 cellular response to oxygen levels
GO:0071456 cellular response to hypoxia
GO:0071559 response to transforming growth factor beta
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0071772 response to BMP
GO:0071773 cellular response to BMP stimulus
GO:0072331 signal transduction by p53 class mediator
GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator
GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090100 positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090101 negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090287 regulation of cellular response to growth factor stimulus
GO:0090288 negative regulation of cellular response to growth factor stimulus
GO:0090596 sensory organ morphogenesis
GO:0090659 walking behavior
GO:0097193 intrinsic apoptotic signaling pathway
GO:1901214 regulation of neuron death
GO:1901215 negative regulation of neuron death
GO:1901342 regulation of vasculature development
GO:1901796 regulation of signal transduction by p53 class mediator
GO:1903844 regulation of cellular response to transforming growth factor beta stimulus
GO:1903846 positive regulation of cellular response to transforming growth factor beta stimulus
GO:1904018 positive regulation of vasculature development
Molecular Function GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding
GO:0001085 RNA polymerase II transcription factor binding
GO:0001102 RNA polymerase II activating transcription factor binding
GO:0001104 RNA polymerase II transcription cofactor activity
GO:0001105 RNA polymerase II transcription coactivator activity
GO:0001190 transcriptional activator activity, RNA polymerase II transcription factor binding
GO:0001191 transcriptional repressor activity, RNA polymerase II transcription factor binding
GO:0003713 transcription coactivator activity
GO:0003714 transcription corepressor activity
GO:0004674 protein serine/threonine kinase activity
GO:0008134 transcription factor binding
GO:0033613 activating transcription factor binding
GO:0046332 SMAD binding
GO:0046790 virion binding
GO:0098811 transcriptional repressor activity, RNA polymerase II activating transcription factor binding
Cellular Component GO:0005667 transcription factor complex
GO:0016604 nuclear body
GO:0016605 PML body
GO:0044798 nuclear transcription factor complex
GO:0090575 RNA polymerase II transcription factor complex
> KEGG and Reactome Pathway
 
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
SymbolHIPK2
Namehomeodomain interacting protein kinase 2
Aliases homeodomain-interacting protein kinase 2; PRO0593; hHIPk2
Chromosomal Location7q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between HIPK2 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
 

There is no record.
Summary
SymbolHIPK2
Namehomeodomain interacting protein kinase 2
Aliases homeodomain-interacting protein kinase 2; PRO0593; hHIPk2
Chromosomal Location7q34
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
  Statistical results of HIPK2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: -2.80; FDR: 0.01020 Resistant to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolHIPK2
Namehomeodomain interacting protein kinase 2
Aliases homeodomain-interacting protein kinase 2; PRO0593; hHIPk2
Chromosomal Location7q34
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
 
Points in the above scatter plot represent the expression difference of HIPK2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0350.926
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.4560.729
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.4070.734
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.360.211
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0440.987
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.8680.788
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.3340.499
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.6150.749
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0410.985
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.8420.559
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.4260.505
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2290.0101
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of HIPK2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.45.51.90.66
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.46.80.61
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.63.7-1.11
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.27.1-0.91
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolHIPK2
Namehomeodomain interacting protein kinase 2
Aliases homeodomain-interacting protein kinase 2; PRO0593; hHIPk2
Chromosomal Location7q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HIPK2. 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
 
Summary
SymbolHIPK2
Namehomeodomain interacting protein kinase 2
Aliases homeodomain-interacting protein kinase 2; PRO0593; hHIPk2
Chromosomal Location7q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HIPK2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HIPK2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolHIPK2
Namehomeodomain interacting protein kinase 2
Aliases homeodomain-interacting protein kinase 2; PRO0593; hHIPk2
Chromosomal Location7q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HIPK2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolHIPK2
Namehomeodomain interacting protein kinase 2
Aliases homeodomain-interacting protein kinase 2; PRO0593; hHIPk2
Chromosomal Location7q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of HIPK2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolHIPK2
Namehomeodomain interacting protein kinase 2
Aliases homeodomain-interacting protein kinase 2; PRO0593; hHIPk2
Chromosomal Location7q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between HIPK2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolHIPK2
Namehomeodomain interacting protein kinase 2
Aliases homeodomain-interacting protein kinase 2; PRO0593; hHIPk2
Chromosomal Location7q34
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting HIPK2 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.