HIPK2

Homeodomain interacting protein kinase 2
Identifiers
Symbols	HIPK2 ; PRO0593
External IDs	OMIM: 606868 HomoloGene: 68766 ChEMBL: 4576 GeneCards: HIPK2 Gene
EC number	2.7.11.1
Gene ontology Molecular function • RNA polymerase II activating transcription factor binding • RNA polymerase II transcription coactivator activity • transcription corepressor activity • protein kinase activity • protein serine/threonine kinase activity • protein binding • ATP binding • SMAD binding • virion binding Cellular component • nucleus • cytoplasm • nuclear body • PML body • RNA polymerase II transcription factor complex Biological process • negative regulation of transcription from RNA polymerase II promoter • eye development • transcription, DNA-templated • protein phosphorylation • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator • transforming growth factor beta receptor signaling pathway • smoothened signaling pathway • adult walking behavior • positive regulation of cell proliferation • anterior/posterior pattern specification • retina layer formation • peptidyl-serine phosphorylation • peptidyl-threonine phosphorylation • modulation by virus of host morphology or physiology • neuron differentiation • erythrocyte differentiation • positive regulation of transforming growth factor beta receptor signaling pathway • negative regulation of BMP signaling pathway • PML body organization • positive regulation of protein binding • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • positive regulation of DNA binding • negative regulation of neuron apoptotic process • positive regulation of angiogenesis • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • positive regulation of JNK cascade • embryonic camera-type eye morphogenesis • voluntary musculoskeletal movement • positive regulation of sequence-specific DNA binding transcription factor activity • regulation of cell cycle • embryonic retina morphogenesis in camera-type eye • lens induction in camera-type eye • SMAD protein signal transduction • iris morphogenesis • cellular response to hypoxia • intrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	28996	15258
Ensembl	ENSG00000064393	ENSMUSG00000061436
UniProt	Q9H2X6	Q9QZR5
RefSeq (mRNA)	NM_001113239	NM_001136065
RefSeq (protein)	NP_001106710	NP_001129537
Location (UCSC)	Chr 7: 139.56 – 139.78 Mb	Chr 6: 38.69 – 38.88 Mb
PubMed search

Homeodomain-interacting protein kinase 2 is an enzyme that in humans is encoded by the HIPK2 gene.^[1]

Function

HIPK2 is a conserved serine/threonine nuclear kinase that interacts with homeodomain transcription factors.[supplied by OMIM]^[2]

Interactions

HIPK2 has been shown to interact with:

• CREB binding protein,^[3]
• Death associated protein 6,^[4]
• Mothers against decapentaplegic homolog 1,^[5]
• P53,^[3][6][7]
• RANBP9,^[8]
• SKI protein,^[5] and
• TP53INP1^[9]

References

1. 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.
2. "Entrez Gene: HIPK2 homeodomain interacting protein kinase 2".
3. 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.
4. 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.
5. 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.
6. 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. PMC 48146. PMID 11532197.
7. 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.
8. 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. PMID 12220523.
9. 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.