HIPK2

HIPK2
Identifiers
Aliases	HIPK2, PRO0593, homeodomain interacting protein kinase 2
External IDs	MGI: 1314872 HomoloGene: 68766 GeneCards: HIPK2
Gene ontology Molecular function • nucleotide binding • RNA polymerase II transcription coactivator activity • RNA polymerase II activating transcription factor binding • SMAD binding • transferase activity • kinase activity • virion binding • ATP binding • protein binding • protein kinase activity • transcription corepressor activity • protein serine/threonine kinase activity Cellular component • cytoplasm • PML body • RNA polymerase II transcription factor complex • nuclear body • nucleus • nucleoplasm Biological process • anterior/posterior pattern specification • smoothened signaling pathway • regulation of cell cycle • transforming growth factor beta receptor signaling pathway • positive regulation of DNA binding • intrinsic apoptotic signaling pathway • transcription, DNA-templated • lens induction in camera-type eye • peptidyl-serine phosphorylation • embryonic camera-type eye morphogenesis • peptidyl-threonine phosphorylation • eye development • positive regulation of transforming growth factor beta receptor signaling pathway • positive regulation of sequence-specific DNA binding transcription factor activity • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator • voluntary musculoskeletal movement • SMAD protein signal transduction • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • adult walking behavior • apoptotic process • adult locomotory behavior • protein phosphorylation • negative regulation of transcription from RNA polymerase II promoter • iris morphogenesis • positive regulation of cell proliferation • positive regulation of transcription, DNA-templated • cellular response to DNA damage stimulus • positive regulation of JNK cascade • PML body organization • negative regulation of neuron apoptotic process • positive regulation of angiogenesis • regulation of transcription, DNA-templated • embryonic retina morphogenesis in camera-type eye • modulation by virus of host morphology or physiology • retina layer formation • positive regulation of transcription from RNA polymerase II promoter • neuron differentiation • positive regulation of protein binding • cellular response to hypoxia • positive regulation of protein phosphorylation • erythrocyte differentiation • negative regulation of BMP signaling pathway • phosphorylation • regulation of signal transduction by p53 class mediator Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	28996	15258
Ensembl	ENSG00000064393	ENSMUSG00000061436
UniProt	Q9H2X6	Q9QZR5
RefSeq (mRNA)	NM_001113239 NM_022740	NM_001136065 NM_001294143 NM_001294144 NM_010433
RefSeq (protein)	NP_001106710.1 NP_073577.3	NP_001129537.1 NP_001281072.1 NP_001281073.1 NP_034563.2
Location (UCSC)	Chr 7: 139.56 – 139.78 Mb	Chr 6: 38.69 – 38.88 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

View/Edit Mouse

Homeodomain-interacting protein kinase 2 is an enzyme that in humans is encoded by the HIPK2 gene.^[3]

Function

HIPK2 is a conserved serine/threonine nuclear kinase that interacts with homeodomain transcription factors.[supplied by OMIM]^[4] Its identified substrates include the coactivator CBP ((CREB-binding_protein) that is phosphorylated at several sites by HIPK2. ^[5]

Interactions

HIPK2 has been shown to interact with:

• CREB binding protein,^[6]
• Death associated protein 6,^[7]
• Mothers against decapentaplegic homolog 1,^[8]
• P53,^[6][9][10]
• RANBP9,^[11]
• SKI protein,^[8] and
• TP53INP1^[12]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Wang Y, Hofmann TG, Runkel L, Haaf T, Schaller H, Debatin K, Hug H (Mar 2001). "Isolation and characterization of cDNAs for the protein kinase HIPK2". Biochimica et Biophysica Acta. 1518 (1-2): 168–72. doi:10.1016/S0167-4781(00)00308-0. PMID 11267674.
4. "Entrez Gene: HIPK2 homeodomain interacting protein kinase 2".
5. Kovacs KA, Steinmann M, Halfon O, Magistretti PJ, Cardinaux JR (Nov 2015). "Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2". Cell Signaling. 27 (11): 2252–60. doi:10.1016/j.cellsig.2015.08.001. PMID 26247811.
6. Hofmann TG, Möller A, Sirma H, Zentgraf H, Taya Y, Dröge W, Will H, Schmitz ML (Jan 2002). "Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2". Nature Cell Biology. 4 (1): 1–10. doi:10.1038/ncb715. PMID 11740489.
7. Hofmann TG, Stollberg N, Schmitz ML, Will H (Dec 2003). "HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal kinase activation and apoptosis in human hepatoma cells". Cancer Research. 63 (23): 8271–7. PMID 14678985.
8. Harada J, Kokura K, Kanei-Ishii C, Nomura T, Khan MM, Kim Y, Ishii S (Oct 2003). "Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation". The Journal of Biological Chemistry. 278 (40): 38998–9005. doi:10.1074/jbc.M307112200. PMID 12874272.
9. Wang Y, Debatin KM, Hug H (Aug 2001). "HIPK2 overexpression leads to stabilization of p53 protein and increased p53 transcriptional activity by decreasing Mdm2 protein levels". BMC Molecular Biology. 2: 8. doi:10.1186/1471-2199-2-8. PMC 48146. PMID 11532197.
10. Kim EJ, Park JS, Um SJ (Aug 2002). "Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo". The Journal of Biological Chemistry. 277 (35): 32020–8. doi:10.1074/jbc.M200153200. PMID 11925430.
11. Wang Y, Marion Schneider E, Li X, Duttenhöfer I, Debatin K, Hug H (Sep 2002). "HIPK2 associates with RanBPM". Biochemical and Biophysical Research Communications. 297 (1): 148–53. doi:10.1016/s0006-291x(02)02020-x. PMID 12220523.
12. Tomasini R, Samir AA, Carrier A, Isnardon D, Cecchinelli B, Soddu S, Malissen B, Dagorn JC, Iovanna JL, Dusetti NJ (Sep 2003). "TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity". The Journal of Biological Chemistry. 278 (39): 37722–9. doi:10.1074/jbc.M301979200. PMID 12851404.

Further reading

• Möller A, Schmitz ML (2004). "Viruses as hijackers of PML nuclear bodies". Archivum Immunologiae et Therapiae Experimentalis. 51 (5): 295–300. PMID 14626429.
• Calzado MA, Renner F, Roscic A, Schmitz ML (Jan 2007). "HIPK2: a versatile switchboard regulating the transcription machinery and cell death". Cell Cycle. 6 (2): 139–43. doi:10.4161/cc.6.2.3788. PMID 17245128.
• Kim YH, Choi CY, Lee SJ, Conti MA, Kim Y (Oct 1998). "Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors". The Journal of Biological Chemistry. 273 (40): 25875–9. doi:10.1074/jbc.273.40.25875. PMID 9748262.
• Kim YH, Choi CY, Kim Y (Oct 1999). "Covalent modification of the homeodomain-interacting protein kinase 2 (HIPK2) by the ubiquitin-like protein SUMO-1". Proceedings of the National Academy of Sciences of the United States of America. 96 (22): 12350–5. doi:10.1073/pnas.96.22.12350. PMC 22920. PMID 10535925.
• Choi CY, Kim YH, Kwon HJ, Kim Y (Nov 1999). "The homeodomain protein NK-3 recruits Groucho and a histone deacetylase complex to repress transcription". The Journal of Biological Chemistry. 274 (47): 33194–7. doi:10.1074/jbc.274.47.33194. PMID 10559189.
• Li X, Wang Y, Debatin KM, Hug H (Oct 2000). "The serine/threonine kinase HIPK2 interacts with TRADD, but not with CD95 or TNF-R1 in 293T cells". Biochemical and Biophysical Research Communications. 277 (2): 513–7. doi:10.1006/bbrc.2000.3700. PMID 11032752.
• Wang Y, Hofmann TG, Runkel L, Haaf T, Schaller H, Debatin K, Hug H (Mar 2001). "Isolation and characterization of cDNAs for the protein kinase HIPK2". Biochimica et Biophysica Acta. 1518 (1-2): 168–72. doi:10.1016/S0167-4781(00)00308-0. PMID 11267674.
• Missero C, Pirro MT, Simeone S, Pischetola M, Di Lauro R (Sep 2001). "The DNA glycosylase T:G mismatch-specific thymine DNA glycosylase represses thyroid transcription factor-1-activated transcription". The Journal of Biological Chemistry. 276 (36): 33569–75. doi:10.1074/jbc.M104963200. PMID 11438542.
• Wang Y, Debatin KM, Hug H (2003). "HIPK2 overexpression leads to stabilization of p53 protein and increased p53 transcriptional activity by decreasing Mdm2 protein levels". BMC Molecular Biology. 2: 8. doi:10.1186/1471-2199-2-8. PMC 48146. PMID 11532197.
• Pierantoni GM, Fedele M, Pentimalli F, Benvenuto G, Pero R, Viglietto G, Santoro M, Chiariotti L, Fusco A (Sep 2001). "High mobility group I (Y) proteins bind HIPK2, a serine-threonine kinase protein which inhibits cell growth". Oncogene. 20 (43): 6132–41. doi:10.1038/sj.onc.1204635. PMID 11593421.
• Hofmann TG, Möller A, Sirma H, Zentgraf H, Taya Y, Dröge W, Will H, Schmitz ML (Jan 2002). "Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2". Nature Cell Biology. 4 (1): 1–10. doi:10.1038/ncb715. PMID 11740489.
• D'Orazi G, Cecchinelli B, Bruno T, Manni I, Higashimoto Y, Saito S, Gostissa M, Coen S, Marchetti A, Del Sal G, Piaggio G, Fanciulli M, Appella E, Soddu S (Jan 2002). "Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis". Nature Cell Biology. 4 (1): 11–9. doi:10.1038/ncb714. PMID 11780126.
• Pierantoni GM, Bulfone A, Pentimalli F, Fedele M, Iuliano R, Santoro M, Chiariotti L, Ballabio A, Fusco A (Jan 2002). "The homeodomain-interacting protein kinase 2 gene is expressed late in embryogenesis and preferentially in retina, muscle, and neural tissues". Biochemical and Biophysical Research Communications. 290 (3): 942–7. doi:10.1006/bbrc.2001.6310. PMID 11798164.
• Kim EJ, Park JS, Um SJ (Aug 2002). "Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo". The Journal of Biological Chemistry. 277 (35): 32020–8. doi:10.1074/jbc.M200153200. PMID 11925430.
• Wang Y, Marion Schneider E, Li X, Duttenhöfer I, Debatin K, Hug H (Sep 2002). "HIPK2 associates with RanBPM". Biochemical and Biophysical Research Communications. 297 (1): 148–53. doi:10.1016/S0006-291X(02)02020-X. PMID 12220523.
• Tomasini R, Samir AA, Carrier A, Isnardon D, Cecchinelli B, Soddu S, Malissen B, Dagorn JC, Iovanna JL, Dusetti NJ (Sep 2003). "TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity". The Journal of Biological Chemistry. 278 (39): 37722–9. doi:10.1074/jbc.M301979200. PMID 12851404.
• Harada J, Kokura K, Kanei-Ishii C, Nomura T, Khan MM, Kim Y, Ishii S (Oct 2003). "Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation". The Journal of Biological Chemistry. 278 (40): 38998–9005. doi:10.1074/jbc.M307112200. PMID 12874272.