Q9QZR5
Gene name |
Hipk2 (Nbak1, Stank) |
Protein name |
Homeodomain-interacting protein kinase 2 |
Names |
Nuclear body-associated kinase 1, Sialophorin tail-associated nuclear serine/threonine-protein kinase |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:15258 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
|

Descriptions
Homeodomain interacting protein kinase 2 (HIPK2) is an evolutionary conserved serine/threonine kinase that regulates gene expression by phosphorylation of transcription factors and accessory components of the transcription machinery. HIPK2 is activated in response to DNA-damaging agents or morphogenic signals and accordingly HIPK2-guided gene expression programs trigger differentiation and development or alternatively apoptosis. In a study with human HIPK2 (Q9H2X6), the truncated form lacking the autoinhibitory C-terminal region resulted in a hyperactive kinase, which potentiates p53/TP53 Ser-46 phosphorylation and subsequent activation of the cell death machinery.
Autoinhibitory domains (AIDs)
Target domain |
199-527 (Protein kinase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
345-366 (Activation loop from InterPro)
Target domain |
199-527 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
Autoinhibited structure

Activated structure

1 structures for Q9QZR5
Entry ID | Method | Resolution | Chain | Position | Source |
---|---|---|---|---|---|
AF-Q9QZR5-F1 | Predicted | AlphaFoldDB |
7 variants for Q9QZR5
Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
---|---|---|---|---|---|
rs238002402 | 76 | P>S | No | Ensembl | |
rs1132217988 | 477 | A>S | No | Ensembl | |
rs265337776 | 516 | V>I | No | Ensembl | |
rs243151223 | 539 | A>T | No | Ensembl | |
rs256461805 | 952 | T>A | No | Ensembl | |
rs216485394 | 1065 | P>S | No | Ensembl | |
rs214378777 | 1112 | T>S | No | Ensembl |
No associated diseases with Q9QZR5
Functions
Description | ||
---|---|---|
EC Number | 2.7.11.1 | Protein-serine/threonine kinases |
Subcellular Localization |
|
|
PANTHER Family | ||
PANTHER Subfamily | ||
PANTHER Protein Class | ||
PANTHER Pathway Category | No pathway information available |
6 GO annotations of cellular component
Name | Definition |
---|---|
cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
nuclear body | Extra-nucleolar nuclear domains usually visualized by confocal microscopy and fluorescent antibodies to specific proteins. |
nucleoplasm | That part of the nuclear content other than the chromosomes or the nucleolus. |
nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
PML body | A class of nuclear body; they react against SP100 auto-antibodies (PML, promyelocytic leukemia); cells typically contain 10-30 PML bodies per nucleus; alterations in the localization of PML bodies occurs after viral infection. |
RNA polymerase II transcription regulator complex | A transcription factor complex that acts at a regulatory region of a gene transcribed by RNA polymerase II. |
10 GO annotations of molecular function
Name | Definition |
---|---|
ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
protein kinase activity | Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP. |
protein serine kinase activity | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate. |
protein serine/threonine kinase activity | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. |
protein serine/threonine/tyrosine kinase activity | Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate. |
protein tyrosine kinase activity | Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate. |
RNA polymerase II-specific DNA-binding transcription factor binding | Binding to a sequence-specific DNA binding RNA polymerase II transcription factor, any of the factors that interact selectively and non-covalently with a specific DNA sequence in order to modulate transcription. |
SMAD binding | Binding to a SMAD signaling protein. |
transcription corepressor activity | A transcription coregulator activity that represses or decreases the transcription of specific gene sets via binding to a DNA-bound DNA-binding transcription factor, either on its own or as part of a complex. Corepressors often act by altering chromatin structure and modifications. For example, one class of transcription corepressors modifies chromatin structure through covalent modification of histones. A second class remodels the conformation of chromatin in an ATP-dependent fashion. A third class modulates interactions of DNA-bound DNA-binding transcription factors with other transcription coregulators. |
virion binding | Binding to a virion, either by binding to components of the capsid or the viral envelope. |
32 GO annotations of biological process
Name | Definition |
---|---|
adult locomotory behavior | Locomotory behavior in a fully developed and mature organism. |
adult walking behavior | The behavior of an adult relating to the progression of that organism along the ground by the process of lifting and setting down each leg. |
anterior/posterior pattern specification | The regionalization process in which specific areas of cell differentiation are determined along the anterior-posterior axis. The anterior-posterior axis is defined by a line that runs from the head or mouth of an organism to the tail or opposite end of the organism. |
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator | A cascade of processes induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, resulting in the induction of the transcription of p21 (also known as WAF1, CIP1 and SDI1) or any equivalent protein, in response to the detection of DNA damage. |
embryonic camera-type eye morphogenesis | The process in which the anatomical structures of the eye are generated and organized during embryonic development. |
embryonic retina morphogenesis in camera-type eye | The process in which the anatomical structure of the retina is generated and organized in a camera-type eye during the embryonic life stage. |
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | The series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage, and ends when the execution phase of apoptosis is triggered. |
iris morphogenesis | The process in which the iris is generated and organized. The iris is an anatomical structure in the eye whose opening forms the pupil. The iris is responsible for controlling the diameter and size of the pupil and the amount of light reaching the retina. |
lens induction in camera-type eye | Signaling at short range between the head ectoderm and the optic vesicle that results in the head ectoderm forming a lens. |
negative regulation of BMP signaling pathway | Any process that stops, prevents, or reduces the frequency, rate or extent of the BMP signaling pathway. |
negative regulation of neuron apoptotic process | Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons. |
negative regulation of transcription by RNA polymerase II | Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. |
negative regulation of ubiquitin-dependent protein catabolic process | Any process that stops, prevents, or reduces the frequency, rate or extent of ubiquitin-dependent protein catabolic process. |
neuron differentiation | The process in which a relatively unspecialized cell acquires specialized features of a neuron. |
peptidyl-serine phosphorylation | The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine. |
peptidyl-threonine phosphorylation | The phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine. |
positive regulation of angiogenesis | Any process that activates or increases angiogenesis. |
positive regulation of cell population proliferation | Any process that activates or increases the rate or extent of cell proliferation. |
positive regulation of DNA binding | Any process that increases the frequency, rate or extent of DNA binding. DNA binding is any process in which a gene product interacts selectively with DNA (deoxyribonucleic acid). |
positive regulation of DNA-binding transcription factor activity | Any process that activates or increases the frequency, rate or extent of activity of a transcription factor, any factor involved in the initiation or regulation of transcription. |
positive regulation of JNK cascade | Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade. |
positive regulation of protein binding | Any process that activates or increases the frequency, rate or extent of protein binding. |
positive regulation of protein phosphorylation | Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein. |
positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
positive regulation of transcription, DNA-templated | Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription. |
positive regulation of transforming growth factor beta receptor signaling pathway | Any process that activates or increases the frequency, rate or extent of TGF-beta receptor signaling pathway activity. |
protein phosphorylation | The process of introducing a phosphate group on to a protein. |
retina layer formation | The process in which the vertebrate retina is organized into three laminae: the outer nuclear layer (ONL), which contains photoreceptor nuclei; the inner nuclear layer (INL), which contains amacrine, bipolar and horizontal cells; and the retinal ganglion cell (RGC) layer. Between the inner and outer nuclear layers, the outer plexiform layer (OPL) contains connections between the photoreceptors and bipolar and horizontal cells. The inner plexiform layer (IPL) is positioned between the INL and the ganglion cell layer and contains the dendrites of RGCs and processes of bipolar and amacrine cells. Spanning all layers of the retina are the radially oriented Mueller glia. |
SMAD protein signal transduction | The cascade of processes by which a signal interacts with a receptor, causing a change in the activity of a SMAD protein, and ultimately effecting a change in the functioning of the cell. |
smoothened signaling pathway | The series of molecular signals generated as a consequence of activation of the transmembrane protein Smoothened. |
transforming growth factor beta receptor signaling pathway | The series of molecular signals initiated by an extracellular ligand binding to a transforming growth factor beta receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
voluntary musculoskeletal movement | The movement of an organism or part of an organism using mechanoreceptors, the nervous system, striated muscle and/or the skeletal system that can be controlled at will. |
10 homologous proteins in AiPD
UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
---|---|---|---|---|
Q92630 | DYRK2 | Dual specificity tyrosine-phosphorylation-regulated kinase 2 | Homo sapiens (Human) | PR |
Q13627 | DYRK1A | Dual specificity tyrosine-phosphorylation-regulated kinase 1A | Homo sapiens (Human) | PR |
Q9NR20 | DYRK4 | Dual specificity tyrosine-phosphorylation-regulated kinase 4 | Homo sapiens (Human) | PR |
Q8NE63 | HIPK4 | Homeodomain-interacting protein kinase 4 | Homo sapiens (Human) | PR |
Q9H422 | HIPK3 | Homeodomain-interacting protein kinase 3 | Homo sapiens (Human) | SS |
Q9H2X6 | HIPK2 | Homeodomain-interacting protein kinase 2 | Homo sapiens (Human) | EV |
Q61214 | Dyrk1a | Dual specificity tyrosine-phosphorylation-regulated kinase 1A | Mus musculus (Mouse) | PR |
Q3V016 | Hipk4 | Homeodomain-interacting protein kinase 4 | Mus musculus (Mouse) | PR |
Q8BI55 | Dyrk4 | Dual specificity tyrosine-phosphorylation-regulated kinase 4 | Mus musculus (Mouse) | PR |
Q4V793 | Hipk4 | Homeodomain-interacting protein kinase 4 | Rattus norvegicus (Rat) | PR |
10 | 20 | 30 | 40 | 50 | 60 |
MAPVYEGMAS | HVQVFSPHTL | QSSAFCSVKK | LKVEPSSNWD | MTGYGSHSKV | YSQSKNIPPS |
70 | 80 | 90 | 100 | 110 | 120 |
QPASTTVSTS | LPIPNPSLPY | EQTIIFPGST | GHIVVTSASS | TSVTGQVLGG | PHNLMRRSTV |
130 | 140 | 150 | 160 | 170 | 180 |
SLLDTYQKCG | LKRKSEEIEN | TSSVQIIEEH | PPMIQNNASG | ATVATATTST | ATSKNSGSNS |
190 | 200 | 210 | 220 | 230 | 240 |
EGDYQLVQHE | VLCSMTNTYE | VLEFLGRGTF | GQVVKCWKRG | TNEIVAIKIL | KNHPSYARQG |
250 | 260 | 270 | 280 | 290 | 300 |
QIEVSILARL | STESADDYNF | VRAYECFQHK | NHTCLVFEML | EQNLYDFLKQ | NKFSPLPLKY |
310 | 320 | 330 | 340 | 350 | 360 |
IRPVLQQVAT | ALMKLKSLGL | IHADLKPENI | MLVDPSRQPY | RVKVIDFGSA | SHVSKAVCST |
370 | 380 | 390 | 400 | 410 | 420 |
YLQSRYYRAP | EIILGLPFCE | AIDMWSLGCV | IAELFLGWPL | YPGASEYDQI | RYISQTQGLP |
430 | 440 | 450 | 460 | 470 | 480 |
AEYLLSAGTK | TTRFFNRDTD | SPYPLWRLKT | PDDHEAETGI | KSKEARKYIF | NCLDDMAQVN |
490 | 500 | 510 | 520 | 530 | 540 |
MTTDLEGSDM | LVEKADRREF | IDLLKKMLTI | DADKRVTPIE | TLNHPFVTMT | HLLDFPHSAH |
550 | 560 | 570 | 580 | 590 | 600 |
VKSCFQNMEI | CKRRVNMYDT | VNQSKTPFIT | HVAPSTSTNL | TMTFNNQLTT | VHNQAPTTSS |
610 | 620 | 630 | 640 | 650 | 660 |
ATLSLANPEV | SILNYQSALY | QPSAASMAAV | APRSMPLQTG | TAQICARPDP | FQQALIVCPP |
670 | 680 | 690 | 700 | 710 | 720 |
GFQGLQASPS | KHAGYSVRME | NAVPIVTQAP | GAQPLQIQPG | LLAQQAWPGG | AQQILLPPAW |
730 | 740 | 750 | 760 | 770 | 780 |
QQLTGVATHT | SVQHAAVIPE | TMAGTQQLAD | WRNTHAHGSH | YNPIMQQPAL | LTGHVTLPAA |
790 | 800 | 810 | 820 | 830 | 840 |
QPLNVGVAHV | MRQQPTSTTS | SRKSKQHQSS | VRNVSTCEVT | SSQAISSPQR | SKRVKENTPP |
850 | 860 | 870 | 880 | 890 | 900 |
RCAMVHSSPA | CSTSVTCGWG | DVASSTTRER | QRQTIVIPDT | PSPTVSVITI | SSDTDEEEEQ |
910 | 920 | 930 | 940 | 950 | 960 |
KHAPTSTVSK | QRKNVISCVT | VHDSPYSDSS | SNTSPYSVQQ | RTGHNGTNTL | DTKGGLENHC |
970 | 980 | 990 | 1000 | 1010 | 1020 |
TGNPRTIIVP | PLKTQASEVL | VECDSLGPAI | SASHHSSSFK | SKSSSTVTST | SGHSSGSSSG |
1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
AIAYRQQRPG | PHFQQQQPLN | LSQAQQHMAA | DRTGSHRRQQ | AYITPTMAQA | PYTFPHNSPS |
1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
HGTVHPHLAA | AAHLPTQPHL | YTYTAPTALG | STGTVAHLVA | SQGSARHTVQ | HTAYPASIVH |
1150 | 1160 | 1170 | 1180 | 1190 | |
QVPVSMGPRV | LPSPTIHPSQ | YPAQFAHQTY | ISASPASTVY | TGYPLSPAKV | NQYPYI |