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Protein Page:
HIPK2 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
HIPK2 homeodomain interacting protein kinase 2 is a CMGC kinase of the DYRK family. Interacts with TRADD. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Inhibits cell growth and promotes apoptosis. Involved in transcriptional activation of TP53 and TP73. In response to TGFB, cooperates with DAXX to activate JNK. Phosphorylates the antiapoptotic factor CTBP1 and promotes its proteasomal degradation. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between TAK1 and NLK to promote the proteasomal degradation of MYB. Highly expressed in neuronal tissues, heart and kidney. Weakly expressed ubiquitously. Possible tumor suppressor. Activates p53 in response to UV light, causing growth arrest and apoptosis. Required for cisplatin-induced apoptosis. Downregulated in breast and thyroid carcinomas. Three alternatively spliced isoforms have been described. Note: This description may include information from UniProtKB.
Protein type: Protein kinase, CMGC; EC 2.7.11.1; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); CMGC group; DYRK family; HIPK subfamily
Cellular Component: nuclear body; PML body; cytoplasm; nucleus
Molecular Function: protein serine/threonine kinase activity; protein binding; virion binding; SMAD binding; transcription corepressor activity; ATP binding; protein kinase activity
Biological Process: voluntary musculoskeletal movement; positive regulation of protein binding; regulation of cell cycle; positive regulation of transcription, DNA-dependent; positive regulation of JNK cascade; PML body organization and biogenesis; negative regulation of transcription from RNA polymerase II promoter; adult walking behavior; protein amino acid phosphorylation; negative regulation of BMP signaling pathway; neuron differentiation; anterior/posterior pattern formation; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; transforming growth factor beta receptor signaling pathway; positive regulation of cell proliferation; erythrocyte differentiation; negative regulation of neuron apoptosis; DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis; positive regulation of DNA binding; smoothened signaling pathway; transcription, DNA-dependent; peptidyl-threonine phosphorylation; positive regulation of transforming growth factor beta receptor signaling pathway; positive regulation of angiogenesis; peptidyl-serine phosphorylation; eye development; embryonic retina morphogenesis in camera-type eye; virus-host interaction; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; embryonic camera-type eye morphogenesis
Reference #:  Q9H2X6 (UniProtKB)
Alt. Names/Synonyms: DKFZp686K02111; FLJ23711; hHIPk2; HIPK2; homeodomain interacting protein kinase 2; Homeodomain-interacting protein kinase 2; PRO0593
Gene Symbols: HIPK2
Molecular weight: 130,966 Da
Basal Isoelectric point: 8.69  Predict pI for various phosphorylation states
CST Pathways:  G2/M DNA Damage Checkpoint
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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HIPK2

Protein Structure Not Found.

Substrate Sequence Logo
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Sites Implicated In
transcription, inhibited: K32‑sm
enzymatic activity, induced: K32‑sm
intracellular localization: K32‑sm
phosphorylation: K32‑sm
protein degradation: K32‑ub, K552‑ub, K565‑ub, K671‑ub, K803‑ub, K805‑ub, K1191‑ub
ubiquitination: K1191‑ub

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
1 0 S16 ASHVQVFSPHTLQSS
1 0 K32-ub FCSVKKLkIEPSSNW
3 0 K32-sm FCSVKKLkIEPSSNW
1 0 Y44-p SNWDMTGyGsHSKVY
0 1 S46-p WDMTGyGsHSKVYSQ
1 0 S118 PHNLMRRStVsLLDT
1 0 T119-p HNLMRRStVsLLDTY
1 0 S121-p LMRRStVsLLDTYQK
1 0 S135 KCGLKRKSEEIENTS
1 0 T141 KSEEIENTSSVQIIE
1 0 T252 SILARLSTESADDyN
1 0 Y258-p STESADDyNFVRAyE
1 0 Y264-p DyNFVRAyECFQHKN
1 0 T273 CFQHKNHTCLVFEML
0 1 S336-p NIMLVDPsRQPyRVK
0 1 Y340-p VDPsRQPyRVKVIDF
0 16 T360-p VSKAVCStyLQsRYY
4 3329 Y361-p SKAVCStyLQsRYYR
1 326 S364-p VCStyLQsRYYRAPE
1 0 Y423-p TQGLPAEyLLSAGTk
0 3 K430-ub yLLSAGTkTTRFFNR
1 0 S441 FFNRDTDSPyPLWRL
1 0 Y443-p NRDTDSPyPLWRLKT
1 0 T482 DMAQVNMTTDLEGSD
1 0 T517 IDADKRITPIETLNH
1 0 K552-ub FQNMEICkRRVNMyD
1 0 Y558-p CkRRVNMyDTVNQSk
1 0 K565-ub yDTVNQSkTPFITHV
1 0 T566 DTVNQSkTPFITHVA
1 0 S634 MAAVAQRSMPLQTGT
2 0 S668-p GFQGLQAsPSkHAGY
1 0 K671-ub GLQAsPSkHAGYSVR
1 0 T687 ENAVPIVTQAPGAQP
0 1 T796-p HVMRQQPtSTTSSRk
1 0 K803-ub tSTTSSRkSkQHQSS
1 0 K805-ub TTSSRkSkQHQSSVR
1 0 S815 QSSVRNVSTCEVSSS
0 1 S826-p VSSSQAIssPQRSKR
3 3 S827-p SSSQAIssPQRSKRV
2 1 T838-p SKRVKENtPPRCAMV
1 0 S847 PRCAMVHSsPACSTS
1 0 S848-p RCAMVHSsPACSTSV
1 0 T880-p QTIVIPDtPsPTVSV
1 0 S882-p IVIPDtPsPTVSVIT
1 1 S924-p SCVTVHDsPYSDSSS
2 2 S934-p SDSSSNTsPYSVQQR
1 0 T991 DSLVPVNTSHHSSSY
1 0 S992 SLVPVNTSHHSSSYK
1 0 S1041 QQQPLNLSQAQQHIT
1 0 T1114-p APAALGStGTVAHLV
1 0 Y1136-p HTVQHTAyPASIVHQ
1 0 S1155 MGPRVLPSPTIHPSQ
1 0 S1188 VYTGYPLSPAkVNQY
2 0 K1191-ub GYPLSPAkVNQYPyI
1 0 K1191-sm GYPLSPAkVNQYPyI
1 0 Y1197-p AkVNQYPyI______
  mouse

 
S16-p ASHVQVFsPHTLQSS
K32 FCSVKKLKVEPSSNW
K32 FCSVKKLKVEPSSNW
Y44 SNWDMTGYGSHSKVY
S46 WDMTGYGSHSKVYSQ
S118-p PHNLMRRsTVSLLDT
T119 HNLMRRsTVSLLDTY
S121 LMRRsTVSLLDTYQK
S135-p KCGLKRKsEEIENtS
T141-p KsEEIENtSSVQIIE
T252-p SILARLStESADDYN
Y258 StESADDYNFVRAYE
Y264 DYNFVRAYECFQHKN
T273-p CFQHKNHtCLVFEML
S336 NIMLVDPSRQPYRVK
Y340 VDPSRQPYRVKVIDF
T360-p VSKAVCStyLQsRYY
Y361-p SKAVCStyLQsRYYR
S364-p VCStyLQsRYYRAPE
Y423 TQGLPAEYLLSAGTk
K430-ub YLLSAGTkTTRFFNR
S441-p FFNRDTDsPYPLWRL
Y443 NRDTDsPYPLWRLKT
T482-p DMAQVNMtTDLEGSD
T517-p IDADKRVtPIETLNH
K552 FQNMEICKRRVNMYD
Y558 CKRRVNMYDTVNQSK
K565 YDTVNQSKtPFITHV
T566-p DTVNQSKtPFITHVA
S634-p MAAVAPRsMPLQTGT
S668-p GFQGLQAsPSKHAGY
K671 GLQAsPSKHAGYSVR
T687-p ENAVPIVtQAPGAQP
T796 HVMRQQPTSTTSSRK
K803 TSTTSSRKSKQHQSS
K805 TTSSRKSKQHQSSVR
S815-p QSSVRNVsTCEVTSS
S826 VTSSQAISsPQRSKR
S827-p TSSQAISsPQRSKRV
T838 SKRVKENTPPRCAMV
S847-p PRCAMVHsSPACSTS
S848 RCAMVHsSPACSTSV
T880 QTIVIPDTPSPTVSV
S882 IVIPDTPSPTVSVIT
S924-p SCVTVHDsPYSDSSS
S934-p SDSSSNTsPYSVQQR
S991-p DSLGPAIsAsHHSSS
S993-p LGPAIsAsHHSSSFK
S1042-p QQQPLNLsQAQQHMA
T1112 APTALGSTGTVAHLV
Y1134 HTVQHTAYPASIVHQ
S1153-p MGPRVLPsPTIHPSQ
S1186-p VYTGYPLsPAKVNQY
K1189 GYPLsPAKVNQYPYI
K1189 GYPLsPAKVNQYPYI
Y1195 AKVNQYPYI______
  rat

 
S16 ASHVQVFSPHTLQSS
K32 FCSVKKLKVEPSSNW
K32 FCSVKKLKVEPSSNW
Y44 SNWDMTGYGSHSKVY
S46 WDMTGYGSHSKVYSQ
S118 PHNLMRRSTVSLLDT
T119 HNLMRRSTVSLLDTY
S121 LMRRSTVSLLDTYQK
S135 KCGLKRKSEEIENTS
T141 KSEEIENTSSVQIIE
T252 SILARLSTESADDYN
Y258 STESADDYNFVRAYE
Y264 DYNFVRAYECFQHKN
T273 CFQHKNHTCLVFEML
S336 NIMLVDPSRQPYRVK
Y340 VDPSRQPYRVKVIDF
T360 VSKAVCSTyLQSRYY
Y361-p SKAVCSTyLQSRYYR
S364 VCSTyLQSRYYRAPE
Y423 TQGLPAEYLLSAGTK
K430 YLLSAGTKTTRFFNR
S441 FFNRDTDSPYPLWRL
Y443 NRDTDSPYPLWRLKT
T482 DMAQVNMTTDLEGSD
T517 IDADKRITPIETLNH
K552 FQNMEICKRRVNMYD
Y558 CKRRVNMYDTVNQSK
K565 YDTVNQSKTPFITHV
T566 DTVNQSKTPFITHVA
S634 MAAVAQRSMPLQTGT
S668 GFQGLQASPSKHAGY
K671 GLQASPSKHAGYSVR
T687 ENAVPIVTQAPGAQP
T795 HVMRQQPTSTTSSRK
K802 TSTTSSRKSKQHQSS
K804 TTSSRKSKQHQSSAR
S814 QSSARNVSTCEVTSS
S825 VTSSQAISSPQRSKR
S826 TSSQAISSPQRSKRV
T837 SKRVKENTPPRCAMV
S846 PRCAMVHSSPACSTS
S847 RCAMVHSSPACSTSL
T879 QTIVIPDTPSPTVSV
S881 IVIPDTPSPTVSVIT
S923 SCVTVHDSPYSDSSS
S933 SDSSSNTSPYSVQQR
S990 DSLGPAISTGHHSSS
G992 LGPAISTGHHSSSFK
S1041 QQQPLNLSQAQQHMA
T1111 APTALGSTSTVAHLV
Y1133 HTVQHTAYPASIVHQ
S1152 MGPRVLPSPTIHPSQ
S1185 VYTGYPLSPAKVNQY
K1188 GYPLSPAKVNQYPYI
K1188 GYPLSPAKVNQYPYI
Y1194 AKVNQYPYI______
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