HIPK2 homeodomain interacting protein kinase 2 [Homo sapiens] - Gene

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Summary

Official Symbol: HIPK2provided by HGNC
Official Full Name: homeodomain interacting protein kinase 2provided by HGNC
Primary source: HGNC:14402
See related: Ensembl:ENSG00000064393; HPRD:06039; MIM:606868; Vega:OTTHUMG00000157704
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PRO0593; FLJ23711; DKFZp686K02111
Summary: This gene encodes a conserved serine/threonine kinase that is a member of the homeodomain-interacting protein kinase family. The encoded protein interacts with homeodomain transcription factors and many other transcription factors such as p53, and can function as both a corepressor and a coactivator depending on the transcription factor and its subcellular localization. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
Annotation information: Annotation category: suggests misassembly; Annotation category: partial on reference assembly

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Genomic context

Location :: 7q32-q34

Sequence :: Chromosome: 7; NC_000007.13 (139246316..139342363, complement); Chromosome: 7; NC_000007.13 (139415730..139477693, complement)

See HIPK2 in Epigenomics, MapViewer

Chromosome 7 - NC_000007.13 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

cutaneous HPV23 E6 prevents HIPK2-mediated p53 Ser 46 phosphorylation
Title: Cutaneous HPV23 E6 prevents p53 phosphorylation through interaction with HIPK2.
show that HIPK2 depletion interferes with DeltaNp63alpha degradation, and expression of a HIPK2-resistant DeltaNp63alpha-Delta390 mutant induces chemoresistance
Title: HIPK2 phosphorylates ΔNp63α and promotes its degradation in response to DNA damage.
HIPK2-mediated regulation of p27(kip1) revealed a contribution to cell motility, rather than to cell proliferation, but only in cells that do not express wild-type p53.
Title: Homeodomain-interacting protein kinase-2 stabilizes p27(kip1) by its phosphorylation at serine 10 and contributes to cell motility.
our results point to a prominent and p53-independent role of HIPK2 in colon cancer survival.
Title: Tissue microarray cytometry reveals positive impact of homeodomain interacting protein kinase 2 in colon cancer survival irrespective of p53 function.
Thus, these results suggest that the mutations of the HIPK2 gene maybe a rare event in the development of KA and SCC of the skin in Korean population.
Title: Mutational analysis of the HIPK2 gene in keratoacanthoma and squamous cell carcinoma of the skin.
Findings suggest an unforeseen role for Zyxin in DNA damage-induced cell fate control through modulating the HIPK2-p53 signaling axis.
Title: Zyxin is a critical regulator of the apoptotic HIPK2-p53 signaling axis.
HIPK2 up-regulates transcription by phosphorylating TCF3, a transcriptional repressor, but inhibits transcription by phosphorylating LEF1, a transcriptional activator.
Title: Phosphorylation of TCF proteins by homeodomain-interacting protein kinase 2.
These findings identify a novel circuitry between HIF-1alpha and p53, and provide a paradigm for HIPK2 dictating cell response to antitumor therapies.
Title: HIF-1α antagonizes p53-mediated apoptosis by triggering HIPK2 degradation.
beta-amyloid 1-40 induces HIPK2 degradation and alters HIPK2 binding activity to DNA, in turn regulating the p53 conformational state and vulnerability to a noxious stimulus.
Title: Homeodomain interacting protein kinase 2: a target for Alzheimer's beta amyloid leading to misfolded p53 and inappropriate cell survival.
These results suggest that SUMO interaction motif-mediated HIPK2 targeting to PML-NBs is crucial for HIPK2-mediated p53 activation and induction of apoptosis.
Title: Role of the SUMO-interacting motif in HIPK2 targeting to the PML nuclear bodies and regulation of p53.

Submit: New GeneRIF Correction See all (69)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_073577.1	NP_941977.1	HTNVsSgp1	BIND	PubMed	Hantaan virus nucleocapsid protein interacts with HIPK2.
NP_073577.1	P17881		BIND	PubMed	Seoul virus nucleocapsid protein interacts with HIPK2.
NP_073577.2	NP_005484.2	RANBP9	BIND	PubMed	The nuclear protein kinase HIPK2 interacts with the Ran binding protein RanBPM
NP_073577.2	NP_003343.1	SUMO1	BIND	PubMed	SUMO-1 interacts with HIPK2.
NP_073577.2	NP_000537.2	TP53	BIND	PubMed	HIPK2 does not interact directly with tumour suppressor protein p53 but enhances p53 activity and p53 expression or stability
NP_073577.2	NP_003336.1	UBE2I	BIND	PubMed	Ubc9 with HIPK2.
Q9H2X6	Q9H444	CHMP4B	HPRD	PubMed
Q9H2X6	Q92793	CREBBP	HPRD	PubMed
Q9H2X6	Q9UER7	DAXX	HPRD	PubMed
Q9H2X6	O00148	DDX39A	HPRD	PubMed
Q9H2X6	Q13838	DDX39B	HPRD	PubMed
Q9H2X6	Q9H2X6	HIPK2	HPRD	PubMed
Q9H2X6	P17096	HMGA1	HPRD	PubMed
Q9H2X6	Q92831	KAT2B	HPRD	PubMed
Q9H2X6	O43318	MAP3K7	HPRD	PubMed
Q9H2X6	Q00987	MDM2	HPRD	PubMed
Q9H2X6	P10242	MYB	HPRD	PubMed
Q9H2X6	P43699	NKX2-1	HPRD	PubMed
Q9H2X6	P52952	NKX2-5	HPRD	PubMed
Q9H2X6	Q99801	NKX3-1	HPRD	PubMed
Q9H2X6	Q9UBE8	NLK	HPRD	PubMed
Q9H2X6	P26367	PAX6	HPRD	PubMed
Q9H2X6	Q13635	PTCH1	HPRD	PubMed
Q9H2X6	Q96S59	RANBP9	HPRD	PubMed
Q9H2X6	Q01196	RUNX1	HPRD	PubMed
Q9H2X6	P12755	SKI	HPRD	PubMed
Q9H2X6	Q15797	SMAD1	HPRD	PubMed
Q9H2X6	Q15796	SMAD2	HPRD	PubMed
Q9H2X6	P23497	SP100	HPRD	PubMed
Q9H2X6	P63165	SUMO1	HPRD	PubMed
Q9H2X6	P04637	TP53	HPRD	PubMed
Q9H2X6	Q96A56	TP53INP1	HPRD	PubMed
Q9H2X6	Q9H3D4	TP63	HPRD	PubMed
Q9H2X6	O15350	TP73	HPRD	PubMed
Q9H2X6	Q15628	TRADD	HPRD	PubMed
Q9H2X6	P63279	UBE2I	HPRD	PubMed
BioGRID:118815	BioGRID:113909	AXIN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118815	BioGRID:114457	BTRC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118815	BioGRID:107777	CREBBP	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118815	BioGRID:114032	CUL1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118815	BioGRID:109176	CXCL1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:118815	BioGRID:107985	DAXX	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:118815	BioGRID:108347	EP300	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:118815	BioGRID:120581	FBXW7	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118815	BioGRID:118815	HIPK2	BioGRID	PubMed	Reconstituted Complex
BioGRID:118815	BioGRID:112748	MAP3K7	BioGRID	PubMed	Biochemical Activity
BioGRID:118815	BioGRID:110687	MYB	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:118815	BioGRID:110688	MYBL1	BioGRID	PubMed	Reconstituted Complex
BioGRID:118815	BioGRID:110690	MYBL2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118815	BioGRID:112936	NKX2-1	BioGRID	PubMed	Two-hybrid
BioGRID:118815	BioGRID:119685	NLK	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:118815	BioGRID:202265	Pml	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118815	BioGRID:115359	RANBP9	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:118815	BioGRID:107309	RUNX1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:118815	BioGRID:112372	SIAH1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:118815	BioGRID:131078	SIAH1P1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118815	BioGRID:112373	SIAH2	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:118815	BioGRID:112388	SKI	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:118815	BioGRID:110261	SMAD1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:118815	BioGRID:110262	SMAD2	BioGRID	PubMed	Reconstituted Complex
BioGRID:118815	BioGRID:110263	SMAD3	BioGRID	PubMed	Reconstituted Complex
BioGRID:118815	BioGRID:112555	SP100	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118815	BioGRID:113188	SUMO1	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:118815	BioGRID:113010	TP53	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex; Two-hybrid
BioGRID:118815	BioGRID:125152	TP53INP1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:118815	BioGRID:114181	TP63	BioGRID	PubMed	Two-hybrid
BioGRID:118815	BioGRID:113014	TP73	BioGRID	PubMed	Two-hybrid
BioGRID:118815	BioGRID:114257	TRADD	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118815	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:118815	BioGRID:113177	UBE2I	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:118815	BioGRID:204408	Ube2i	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:118815	BioGRID:117560	WSB1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex; Two-hybrid

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
RNA polymerase II activating transcription factor binding	ISS Inferred from Sequence or Structural Similarity more info
contributes_to RNA polymerase II transcription coactivator activity	ISS Inferred from Sequence or Structural Similarity more info
SMAD binding	IPI Inferred from Physical Interaction more info	PubMed
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase activity	TAS Traceable Author Statement more info	PubMed
protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
transcription corepressor activity	IDA Inferred from Direct Assay more info	PubMed
virion binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis	TAS Traceable Author Statement more info	PubMed
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator	IDA Inferred from Direct Assay more info	PubMed
PML body organization	TAS Traceable Author Statement more info	PubMed
SMAD protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
adult walking behavior	IEA Inferred from Electronic Annotation more info
anterior/posterior pattern specification	IEA Inferred from Electronic Annotation more info
apoptotic process	IEA Inferred from Electronic Annotation more info
cellular response to hypoxia	TAS Traceable Author Statement more info	PubMed
embryonic camera-type eye morphogenesis	IEA Inferred from Electronic Annotation more info
embryonic retina morphogenesis in camera-type eye	IEA Inferred from Electronic Annotation more info
erythrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
eye development	ISS Inferred from Sequence or Structural Similarity more info
induction of apoptosis by intracellular signals	NAS Non-traceable Author Statement more info	PubMed
iris morphogenesis	IEA Inferred from Electronic Annotation more info
lens induction in camera-type eye	IEA Inferred from Electronic Annotation more info
negative regulation of BMP signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of neuron apoptosis	IEA Inferred from Electronic Annotation more info
negative regulation of transcription from RNA polymerase II promoter	IEA Inferred from Electronic Annotation more info
neuron differentiation	IEA Inferred from Electronic Annotation more info
peptidyl-serine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
peptidyl-threonine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of DNA binding	IEA Inferred from Electronic Annotation more info
positive regulation of JNK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of angiogenesis	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of protein binding	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of sequence-specific DNA binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription from RNA polymerase II promoter	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription, DNA-dependent	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transforming growth factor beta receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
protein phosphorylation	TAS Traceable Author Statement more info	PubMed
regulation of cell cycle	TAS Traceable Author Statement more info	PubMed
response to DNA damage stimulus	IEA Inferred from Electronic Annotation more info
retina layer formation	IEA Inferred from Electronic Annotation more info
smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
virus-host interaction	NAS Non-traceable Author Statement more info	PubMed
voluntary musculoskeletal movement	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
colocalizes_with PML body	IDA Inferred from Direct Assay more info	PubMed
centrosome	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
nuclear body	IDA Inferred from Direct Assay more info	PubMed
nuclear body	TAS Traceable Author Statement more info	PubMed
nuclear membrane	IDA Inferred from Direct Assay more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: homeodomain-interacting protein kinase 2

Names: homeodomain-interacting protein kinase 2; hHIPk2

NP_001106710.1

EC 2.7.11.1

NP_073577.3

EC 2.7.11.1

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001113239.2 → NP_001106710.1 homeodomain-interacting protein kinase 2 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an internal segment in the CDS, as compared to variant 1. The resulting isoform (2) is shorter, as compared to isoform 1.

Source sequence(s)

AC005531, AF208291, AF326592, AI580907, CK818532

UniProtKB/Swiss-Prot

Q9H2X6

Related

ENSP00000413724, OTTHUMP00000212369, ENST00000428878, OTTHUMT00000349431

Conserved Domains (2) summary

smart00220
Location:199 – 527
Blast Score: 568

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl09925
Location:199 – 526
Blast Score: 507

PKc_like; Protein Kinases, catalytic domain
NM_022740.4 → NP_073577.3 homeodomain-interacting protein kinase 2 isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the full-length isoform (1).

Source sequence(s)

AC005531, AF208291, AF326592, AI580907, CK818532

UniProtKB/Swiss-Prot

Q9H2X6

Related

ENSP00000385571, OTTHUMP00000212368, ENST00000406875, OTTHUMT00000349430

Conserved Domains (2) summary

smart00220
Location:199 – 527
Blast Score: 569

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl09925
Location:199 – 526
Blast Score: 508

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000007.13 Reference GRCh37.p5 Primary Assembly

Range

139246316..139342363, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000139.1 Alternate HuRef

Range

133556840..133652889, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CRA_TCAGchr7v2

Genomic

AC_000068.1 Alternate CRA_TCAGchr7v2

Range

138590861..138806654, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC005531.2	AAS00368.1
genomic	AC006021.2 (62240..94288)	None
genomic	AC073184.5	None
genomic	AC141932.2	None
genomic	AC232988.1 (11352..41266)	None
genomic	CH236950.1	EAL24035.1
genomic	CH471070.1	EAW83925.1
		EAW83926.1
		EAW83927.1
		EAW83928.1
		EAW83929.1
genomic	CQ967477.1	CAI38625.1
mRNA	AF055019.1	None
mRNA	AF207702.1	AAG35710.1
mRNA	AF208291.1	AAG41236.1
mRNA	AF326592.1	AAL37371.1
mRNA	AI580907.1	None
mRNA	AK074291.1	None
mRNA	BC041926.1	None
mRNA	BC043184.2	None
mRNA	BC043652.1	None
mRNA	BC045719.1	None
mRNA	BX647377.1	None
mRNA	CK818532.1	None
mRNA	CN413736.1	None
mRNA	AL833223.1	None
other-genetic	BC168360.1	AAI68360.1