Molecule Information

General Information of the Molecule (ID: Mol00409)
Name
Homeodomain-interacting protein kinase 3 (HIPK3) ,Homo sapiens
Synonyms
Androgen receptor-interacting nuclear protein kinase; ANPK; Fas-interacting serine/threonine-protein kinase; FIST; Homolog of protein kinase YAK1; DYRK6; FIST3; PKY
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Molecule Type
Protein
Gene Name
HIPK3
Gene ID
10114
Location
chr11:33256672-33357023[+]
Sequence
MASQVLVYPPYVYQTQSSAFCSVKKLKVEPSSCVFQERNYPRTYVNGRNFGNSHPPTKGS
AFQTKIPFNRPRGHNFSLQTSAVVLKNTAGATKVIAAQAQQAHVQAPQIGAWRNRLHFLE
GPQRCGLKRKSEELDNHSSAMQIVDELSILPAMLQTNMGNPVTVVTATTGSKQNCTTGEG
DYQLVQHEVLCSMKNTYEVLDFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQI
EVSILARLSTENADEYNFVRAYECFQHRNHTCLVFEMLEQNLYDFLKQNKFSPLPLKVIR
PILQQVATALKKLKSLGLIHADLKPENIMLVDPVRQPYRVKVIDFGSASHVSKTVCSTYL
QSRYYRAPEIILGLPFCEAIDMWSLGCVIAELFLGWPLYPGALEYDQIRYISQTQGLPGE
QLLNVGTKSTRFFCKETDMSHSGWRLKTLEEHEAETGMKSKEARKYIFNSLDDVAHVNTV
MDLEGSDLLAEKADRREFVSLLKKMLLIDADLRITPAETLNHPFVNMKHLLDFPHSNHVK
SCFHIMDICKSHLNSCDTNNHNKTSLLRPVASSSTATLTANFTKIGTLRSQALTTSAHSV
VHHGIPLQAGTAQFGCGDAFQQTLIICPPAIQGIPATHGKPTSYSIRVDNTVPLVTQAPA
VQPLQIRPGVLSQTWSGRTQQMLVPAWQQVTPLAPATTTLTSESVAGSHRLGDWGKMISC
SNHYNSVMPQPLLTNQITLSAPQPVSVGIAHVVWPQPATTKKNKQCQNRGILVKLMEWEP
GREEINAFSWSNSLQNTNIPHSAFISPKIINGKDVEEVSCIETQDNQNSEGEARNCCETS
IRQDSDSSVSDKQRQTIIIADSPSPAVSVITISSDTDEEETSQRHSLRECKGSLDCEACQ
STLNIDRMCSLSSPDSTLSTSSSGQSSPSPCKRPNSMSDEEQESSCDTVDGSPTSDSSGH
DSPFAESTFVEDTHENTELVSSADTETKPAVCSVVVPPVELENGLNADEHMANTDSICQP
LIKGRSAPGRLNQPSAVGTRQQKLTSAFQQQHLNFSQVQHFGSGHQEWNGNFGHRRQQAY
IPTSVTSNPFTLSHGSPNHTAVHAHLAGNTHLGGQPTLLPYPSSATLSSAAPVAHLLASP
CTSRPMLQHPTYNISHPSGIVHQVPVGLNPRLLPSPTIHQTQYKPIFPPHSYIAASPAYT
GFPLSPTKLSQYPYM
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Function
Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE).
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Uniprot ID
HIPK3_HUMAN
Ensembl ID
ENSG00000110422
HGNC ID
HGNC:4915
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
3 drug(s) in total
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Cisplatin
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Osteosarcoma [1]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
Sensitive Drug Cisplatin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
Doxorubicin
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Osteosarcoma [1]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
Sensitive Drug Doxorubicin
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
Methotrexate
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Osteosarcoma [1]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
Sensitive Drug Methotrexate
 Drug Info 
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
References
Ref 1 miR-382 inhibits tumor growth and enhance chemosensitivity in osteosarcoma. Oncotarget. 2014 Oct 15;5(19):9472-83. doi: 10.18632/oncotarget.2418.

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