| + |
HIPK2 | up-regulates 
phosphorylation
|
CDKN1B |
0.257 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-174617 |
Ser10 |
NVRVSNGsPSLERMD |
Homo sapiens |
|
| pmid |
sentence |
| 21715331 |
Homeodomain-interacting protein kinase-2 stabilizes p27(kip1) by its phosphorylation at serine 10 and contributes to cell motility |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G2/M phase transition |
| + |
PRKAA1 | up-regulates activity
phosphorylation
|
HIPK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276467 |
Ser121 |
LMRRSTVsLLDTYQK |
in vitro |
|
| pmid |
sentence |
| 23871434 |
These results indicate that HIPK2 is a substrate of AMPKα2 in vitro and in vivo. Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKα2 in vitro (Figure S5J). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276469 |
Thr1114 |
APAALGStGTVAHLV |
in vitro |
|
| pmid |
sentence |
| 23871434 |
These results indicate that HIPK2 is a substrate of AMPKα2 in vitro and in vivo. Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKα2 in vitro (Figure S5J). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276468 |
Thr119 |
HNLMRRStVSLLDTY |
in vitro |
|
| pmid |
sentence |
| 23871434 |
These results indicate that HIPK2 is a substrate of AMPKα2 in vitro and in vivo. Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKα2 in vitro (Figure S5J). |
|
| Publications: |
3 |
Organism: |
In Vitro |
| + |
PRKAA2 | down-regulates activity 
phosphorylation
|
HIPK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275486 |
Ser121 |
LMRRSTVsLLDTYQK |
|
|
| pmid |
sentence |
| 23871434 |
AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275487 |
Thr1116 |
AALGSTGtVAHLVAS |
|
|
| pmid |
sentence |
| 23871434 |
AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275485 |
Thr119 |
HNLMRRStVSLLDTY |
|
|
| pmid |
sentence |
| 23871434 |
AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro |
|
| Publications: |
3 |
| + |
AMPK | down-regulates activity
phosphorylation
|
HIPK2 |
0.25 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275483 |
Ser121 |
LMRRSTVsLLDTYQK |
|
|
| pmid |
sentence |
| 23871434 |
AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275484 |
Thr1116 |
AALGSTGtVAHLVAS |
|
|
| pmid |
sentence |
| 23871434 |
AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275482 |
Thr119 |
HNLMRRStVSLLDTY |
|
|
| pmid |
sentence |
| 23871434 |
AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro |
|
| Publications: |
3 |
| + |
HIPK2 | up-regulates
phosphorylation
|
CREB1 |
0.398 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-166338 |
Ser257 |
PGVVMASsPALPTQP |
Homo sapiens |
|
| pmid |
sentence |
| 20573984 |
Ere we found that homeodomain-interacting protein kinase 2 (hipk2), a dna-damage responsive nuclear kinase, is a new creb kinase for phosphorylation at ser-271 but not ser-133, and activates creb transactivation function |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Rett syndrome |
| + |
HIPK2 |
phosphorylation
|
PDX1 |
0.36 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255539 |
Ser268 |
LPPGLSAsPQPSSVA |
Mus musculus |
Pancreatic Beta Cell, MIN-6 Cell |
| pmid |
sentence |
| 20637728 |
Our results suggest that HIPK2-mediated phosphorylation of PDX1 at Ser-269 might be a regulatory mechanism connecting signals generated by changes in extracellular glucose concentration to downstream effectors via changes in subnuclear localization of PDX1, thereby influencing islet cell differentiation and function |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
HIPK2 | down-regulates
phosphorylation
|
HMGA1 |
0.506 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-158616 |
Ser36 |
PRKQPPVsPGTALVG |
Homo sapiens |
|
| pmid |
sentence |
| 17960875 |
Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-158620 |
Thr53 |
KEPSEVPtPKRPRGR |
Homo sapiens |
|
| pmid |
sentence |
| 17960875 |
Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
HIPK2 | down-regulates activity
phosphorylation
|
HDAC3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277568 |
Ser374 |
KMLNHAPsVQIHDVP |
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 34244427 |
Mechanistically, HIPK2 bound and phosphorylated histone deacetylase 3 (HDAC3) at serine 374 to inhibit its enzymatic activity, thus reducing the deacetylation of p65 at lysine 218 to suppress NF-κB activation. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
HIPK2 | up-regulates
phosphorylation
|
PML |
0.448 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182428 |
Ser38 |
EGRQPSPsPSPTERA |
Homo sapiens |
|
| pmid |
sentence |
| 19015637 |
In response to dna damage, hipk2 phosphorylates pml at serines 8 and 38. he n-terminal phosphorylation sites contribute to the dna damage-induced pml sumoylation and are required for the ability of pml to cooperate with hipk2 for the induction of cell death. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-182432 |
Ser8 |
MEPAPARsPRPQQDP |
Homo sapiens |
|
| pmid |
sentence |
| 19015637 |
In response to dna damage, hipk2 phosphorylates pml at serines 8 and 38. he n-terminal phosphorylation sites contribute to the dna damage-induced pml sumoylation and are required for the ability of pml to cooperate with hipk2 for the induction of cell death. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
HIPK2 | down-regulates
phosphorylation
|
CTBP1 |
0.482 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-134040 |
Ser422 |
AHPPHAPsPGQTVKP |
Homo sapiens |
NCI-H1299 Cell |
| pmid |
sentence |
| 15708980 |
Homeodomain-interacting protein kinase-2 mediates ctbp phosphorylation and degradation in uv-triggered apoptosishipk2 phosphorylates ctbp at ser-422 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HIPK2 | up-regulates
phosphorylation
|
TP53 |
0.792 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-151930 |
Ser46 |
AMDDLMLsPDDIEQW |
Homo sapiens |
|
| pmid |
sentence |
| 17210684 |
Based on all these observations, it is legitimate to suggest that axin and daxx seem to adopt both parallel routes and a convergent means to activate p53. In either case, hipk2 seems to be the protein kinase that catalyzes the ser46 phosphorylation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G2/M phase transition |
| + |
HIPK2 | down-regulates quantity by destabilization
phosphorylation
|
PPM1D |
0.43 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275480 |
Ser54 |
QPLPPRPsPAALPGG |
|
|
| pmid |
sentence |
| 23871434 |
WIP1, a homeostatic regulator of the DNA damage response, is targeted by HIPK2 for phosphorylation and degradation|Analysis of the phosphoamino acids of WIP1 revealed that both Ser85 and Ser54 are phosphorylation sites, confirming that HIPK2 is a protein kinase for WIP1 phosphorylation at Ser54 as well as Ser85 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278229 |
Ser54 |
QPLPPRPsPAALPGG |
Homo sapiens |
|
| pmid |
sentence |
| 27308327 |
HIPK2 phosphorylates WIP1 at Ser54 and Ser85, and phosphorylated WIP1 is subject to proteasomal degradation so that WIP1 is maintained at low levels. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278230 |
Ser85 |
PLPDAGAsPAPSRCC |
Homo sapiens |
|
| pmid |
sentence |
| 27308327 |
HIPK2 phosphorylates WIP1 at Ser54 and Ser85, and phosphorylated WIP1 is subject to proteasomal degradation so that WIP1 is maintained at low levels. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275481 |
Ser85 |
PLPDAGAsPAPSRCC |
|
|
| pmid |
sentence |
| 23871434 |
WIP1, a homeostatic regulator of the DNA damage response, is targeted by HIPK2 for phosphorylation and degradation|Analysis of the phosphoamino acids of WIP1 revealed that both Ser85 and Ser54 are phosphorylation sites, confirming that HIPK2 is a protein kinase for WIP1 phosphorylation at Ser54 as well as Ser85 |
|
| Publications: |
4 |
Organism: |
, Homo Sapiens |
| + |
HIPK2 | up-regulates activity
phosphorylation
|
MECP2 |
0.489 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-264549 |
Ser80 |
AVPEASAsPKQRRSI |
Homo sapiens |
|
| pmid |
sentence |
| 19820693 |
Here, we identify the homeodomain-interacting protein kinase 2 (HIPK2) as a kinase that binds MeCP2 and phosphorylates it at Ser 80 in vitro and in vivo. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Rett syndrome |
| + |
HIPK2 | up-regulates activity
phosphorylation
|
HIPK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276600 |
Ser882 |
IVIPDTPsPTVSVIT |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 24145406 |
Here, we deciphered the molecular mechanism of HIPK2 activation and show its relevance for DNA damage-induced apoptosis in cellulo and in vivo. HIPK2 autointeracts and site-specifically autophosphorylates upon DNA damage at Thr880/Ser882. Autophosphorylation regulates HIPK2 activity and mutation of the phosphorylation-acceptor sites deregulates p53 Ser46 phosphorylation and apoptosis in cellulo. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276601 |
Thr880 |
QTIVIPDtPSPTVSV |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 24145406 |
Here, we deciphered the molecular mechanism of HIPK2 activation and show its relevance for DNA damage-induced apoptosis in cellulo and in vivo. HIPK2 autointeracts and site-specifically autophosphorylates upon DNA damage at Thr880/Ser882. Autophosphorylation regulates HIPK2 activity and mutation of the phosphorylation-acceptor sites deregulates p53 Ser46 phosphorylation and apoptosis in cellulo. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G2/M phase transition, Rett syndrome |
| + |
HIPK2 | up-regulates activity
phosphorylation
|
PAX6 |
0.474 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251269 |
Thr281 |
QRRQASNtPSHIPIS |
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 16407227 |
HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300. Mass spectrometric analysis identified three Pax6 phosphorylation sites as threonines 281, 304, and 373. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251270 |
Thr304 |
QPIPQPTtPVSSFTS |
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 16407227 |
HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300. Mass spectrometric analysis identified three Pax6 phosphorylation sites as threonines 281, 304, and 373. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251271 |
Thr373 |
GRSYDTYtPPHMQTH |
Homo sapiens |
U2-OS Cell |
| pmid |
sentence |
| 16407227 |
HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300. Mass spectrometric analysis identified three Pax6 phosphorylation sites as threonines 281, 304, and 373. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
HIPK2 | down-regulates activity
phosphorylation
|
ZBTB4 |
0.385 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262880 |
Thr795 |
AAERPGGtPTPVIAY |
in vitro |
|
| pmid |
sentence |
| 19448668 |
The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262881 |
Thr797 |
ERPGGTPtPVIAYSK |
in vitro |
|
| pmid |
sentence |
| 19448668 |
The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262882 |
Thr983 |
AAPPAPPtPPPPTLP |
in vitro |
|
| pmid |
sentence |
| 19448668 |
The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4. |
|
| Publications: |
3 |
Organism: |
In Vitro |
| + |
ABL1 | up-regulates activity
phosphorylation
|
HIPK2 |
0.41 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260936 |
Tyr367 |
TYLQSRYyRAPEIIL |
Homo sapiens |
|
| pmid |
sentence |
| 25944899 |
The Tyrosine Kinase c-Abl Promotes Homeodomain-interacting Protein Kinase 2 (HIPK2) Accumulation and Activation in Response to DNA Damage |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Cell cycle: G2/M phase transition |
| + |
SIAH1 | down-regulates quantity
ubiquitination
|
HIPK2 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278715 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18536714 |
Downregulation of Siah-1 inhibits HIPK2 degradation and recovery from damage, driving the cells into apoptosis|Siah-1 knockdown increases HIPK2 stability and steady-state levels, whereas Siah-1 expression facilitates HIPK2 polyubiquitination, degradation and thereby inactivation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 1-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination
|
HIPK2 |
0.313 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271745 |
|
|
Homo sapiens |
BOSC-23 Cell |
| pmid |
sentence |
| 18809579 |
O clarify the role of PML in transcription regulation, we purified the PML complex and identified Fbxo3 (Fbx3), Skp1, and Cullin1 as novel components of this complex. Fbx3 formed SCF(Fbx3) ubiquitin ligase and promoted the degradation of HIPK2 and p300 by the ubiquitin-proteasome pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SIAH1 | down-regulates quantity by destabilization
polyubiquitination
|
HIPK2 |
0.527 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276166 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 18536714 |
Here we demonstrate that HIPK2 is an unstable protein that colocalizes and interacts with the E3 ubiquitin ligase Siah-1 in unstressed cells. Siah-1 knockdown increases HIPK2 stability and steady-state levels, whereas Siah-1 expression facilitates HIPK2 polyubiquitination, degradation and thereby inactivation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WSB1 | down-regulates
ubiquitination
|
HIPK2 |
0.583 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-160032 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18093972 |
Ubiquitination and degradation of homeodomain-interacting protein kinase 2 by wd40 repeat/socs box protein wsb-1 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HIPK2 | up-regulates 
|
Apoptosis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-264551 |
|
|
Homo sapiens |
Fibroblast |
| pmid |
sentence |
| 19820693 |
We show that MeCP2 cooperates with HIPK2 in induction of apoptosis and that Ser 80 phosphorylation is required together with the DNA binding of MeCP2. | We found increased cell death in each of the tested cell lines not only, as expected, when HIPK2 was overexpressed but also with MeCP2 alone. When both proteins were expressed together, the number of dead cells increased in an additive manner. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Rett syndrome |
| + |
HIPK2 | up-regulates activity
phosphorylation
|
CBX4 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278484 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17018294 |
In addition, HIPK2 phosphorylates Pc2 at several sites, including threonine 495. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FBXO3 | down-regulates quantity by destabilization
binding
|
HIPK2 |
0.412 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271741 |
|
|
Homo sapiens |
BOSC-23 Cell |
| pmid |
sentence |
| 18809579 |
O clarify the role of PML in transcription regulation, we purified the PML complex and identified Fbxo3 (Fbx3), Skp1, and Cullin1 as novel components of this complex. Fbx3 formed SCF(Fbx3) ubiquitin ligase and promoted the degradation of HIPK2 and p300 by the ubiquitin-proteasome pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
HIPK2
- 
- 