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Showing Protein Homeodomain-interacting protein kinase 2 (HMDBP09471)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 2 metabolites
Identification
HMDB Protein ID HMDBP09471
Secondary Accession Numbers
  • 15360
Name Homeodomain-interacting protein kinase 2
Synonyms
  1. hHIPk2
Gene Name HIPK2
Protein Type Enzyme
Biological Properties
General Function Involved in protein kinase activity
Specific Function Protein kinase acting 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. Phosphorylation of TP53 may be mediated by a TP53-HIPK2-AXIN1 complex. 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. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Nucleus
  2. Cytoplasm
  3. PML body
Gene Properties
Chromosome Location Chromosome:7
Locus 7q32-q34
SNPs HIPK2
Gene Sequence 
>3597 bp
ATGGCCCCCGTGTACGAAGGTATGGCCTCACATGTGCAAGTTTTCTCCCCTCACACCCTT
CAATCAAGTGCCTTCTGTAGTGTGAAGAAACTGAAAATAGAGCCGAGTTCCAACTGGGAC
ATGACTGGGTACGGCTCCCACAGCAAAGTGTATAGCCAGAGCAAGAACATCCCCCTGTCG
CAGCCAGCCACCACAACCGTCAGCACCTCCTTGCCGGTCCCAAACCCAAGCCTACCTTAC
GAGCAGACCATCGTCTTCCCAGGAAGCACCGGGCACATCGTGGTCACCTCAGCAAGCAGC
ACTTCTGTCACCGGGCAAGTCCTCGGCGGACCACACAACCTAATGCGTCGAAGCACTGTG
AGCCTCCTTGATACCTACCAAAAATGTGGACTCAAGCGTAAGAGCGAGGAGATCGAGAAC
ACAAGCAGCGTGCAGATCATCGAGGAGCATCCACCCATGATTCAGAATAATGCAAGCGGG
GCCACTGTCGCCACTGCCACCACGTCTACTGCCACCTCCAAAAACAGCGGCTCCAACAGC
GAGGGCGACTATCAGCTGGTGCAGCATGAGGTGCTGTGCTCCATGACCAACACCTACGAG
GTCTTAGAGTTCTTGGGCCGAGGGACGTTTGGGCAAGTGGTCAAGTGCTGGAAACGGGGC
ACCAATGAGATCGTAGCCATCAAGATCCTGAAGAACCACCCATCCTATGCCCGACAAGGT
CAGATTGAAGTGAGCATCCTGGCCCGGTTGAGCACGGAGAGTGCCGATGACTATAACTTC
GTCCGGGCCTACGAATGCTTCCAGCACAAGAACCACACGTGCTTGGTCTTCGAGATGTTG
GAGCAGAACCTCTATGACTTTCTGAAGCAAAACAAGTTTAGCCCCTTGCCCCTCAAATAC
ATTCGCCCAGTTCTCCAGCAGGTAGCCACAGCCCTGATGAAACTCAAAAGCCTAGGTCTT
ATCCACGCTGACCTCAAACCAGAAAACATCATGCTGGTGGATCCATCTAGACAACCATAC
AGAGTCAAGGTCATCGACTTTGGTTCAGCCAGCCACGTCTCCAAGGCTGTGTGCTCCACC
TACTTGCAGTCCAGATATTACAGGGCCCCTGAGATCATCCTTGGTTTACCATTTTGTGAG
GCAATTGACATGTGGTCCCTGGGCTGTGTTATTGCAGAATTGTTCCTGGGTTGGCCGTTA
TATCCAGGAGCTTCGGAGTATGATCAGATTCGGTATATTTCACAAACACAGGGTTTGCCT
GCTGAATATTTATTAAGCGCCGGGACAAAGACAACTAGGTTTTTCAACCGTGACACGGAC
TCACCATATCCTTTGTGGAGACTGAAGACACCAGATGACCATGAAGCAGAGACAGGGATT
AAGTCAAAAGAAGCAAGAAAGTACATTTTCAACTGTTTAGATGATATGGCCCAGGTGAAC
ATGACGACAGATTTGGAAGGGAGCGACATGTTGGTAGAAAAGGCTGACCGGCGGGAGTTC
ATTGACCTGTTGAAGAAGATGCTGACCATTGATGCTGACAAGAGAATCACTCCAATCGAA
ACCCTGAACCATCCCTTTGTCACCATGACACACTTACTCGATTTTCCCCACAGCACACAC
GTCAAATCATGTTTCCAGAACATGGAGATCTGCAAGCGTCGGGTGAATATGTATGACACG
GTGAACCAGAGCAAAACCCCTTTCATCACGCACGTGGCCCCCAGCACGTCCACCAACCTG
ACCATGACCTTTAACAACCAGCTGACCACTGTCCACAACCAGGCTCCCTCCTCTACCAGT
GCCACTATTTCCTTAGCCAATCCCGAAGTCTCCATACTAAACTACCCATCTACACTCTAC
CAGCCCTCAGCGGCATCCATGGCTGCAGTGGCCCAGCGGAGCATGCCCCTGCAGACAGGA
ACAGCCCAGATTTGTGCCCGGCCTGACCCGTTCCAGCAAGCTCTCATCGTGTGTCCCCCC
GGCTTCCAAGGCTTGCAGGCCTCTCCCTCTAAGCACGCTGGCTACTCGGTGCGAATGGAA
AATGCAGTTCCCATCGTCACTCAAGCCCCAGGAGCTCAGCCTCTTCAGATCCAACCAGGT
CTGCTTGCCCAGCAGGCTTGGCCAAGTGGGACCCAGCAGATCCTGCTTCCCCCAGCATGG
CAGCAACTGACTGGAGTGGCCACCCACACATCAGTGCAGCATGCCACCGTGATTCCCGAG
ACCATGGCAGGCACCCAGCAGCTGGCGGACTGGAGAAATACGCATGCTCACGGAAGCCAT
TATAATCCCATCATGCAGCAGCCTGCACTATTGACCGGTCATGTGACCCTTCCAGCAGCA
CAGCCCTTAAATGTGGGTGTGGCCCACGTGATGCGGCAGCAGCCAACCAGCACCACCTCC
TCCCGGAAGAGTAAGCAGCACCAGTCATCTGTGAGAAATGTCTCCACCTGTGAGGTGTCC
TCCTCTCAGGCCATCAGCTCCCCACAGCGATCCAAGCGTGTCAAGGAGAACACACCTCCC
CGCTGTGCCATGGTGCACAGTAGCCCGGCCTGCAGCACCTCGGTCACCTGTGGGTGGGGC
GACGTGGCCTCCAGCACCACCCGGGAACGGCAGCGGCAGACAATTGTCATTCCCGACACT
CCCAGCCCCACGGTCAGCGTCATCACCATCAGCAGTGACACGGACGAGGAGGAGGAACAG
AAACACGCCCCCACCAGCACTGTCTCCAAGCAAAGAAAAAACGTCATCAGCTGTGTCACA
GTCCACGACTCCCCCTACTCCGACTCCTCCAGCAACACCAGCCCCTACTCCGTGCAGCAG
CGTGCTGGGCACAACAATGCCAATGCCTTTGACACCAAGGGGAGCCTGGAGAATCACTGC
ACGGGGAACCCCCGAACCATCATCGTGCCACCCCTGAAAACCCAGGCCAGCGAAGTATTG
GTGGAGTGTGATAGCCTGGTGCCAGTCAACACCAGTCACCACTCGTCCTCCTACAAGTCC
AAGTCCTCCAGCAACGTGACCTCCACCAGCGGTCACTCTTCAGGGAGCTCATCTGGAGCC
ATCACCTACCGGCAGCAGCGGCCGGGCCCCCACTTCCAGCAGCAGCAGCCACTCAATCTC
AGCCAGGCTCAGCAGCACATCACCACGGACCGCACTGGGAGCCACCGAAGGCAGCAGGCC
TACATCACTCCCACCATGGCCCAGGCTCCGTACTCCTTCCCGCACAACAGCCCCAGCCAC
GGCACTGTGCACCCGCATCTGGCTGCAGCCGCTGCCGCTGCCCACCTCCCCACCCAGCCC
CACCTCTACACCTACACTGCGCCGGCGGCCCTGGGCTCCACCGGCACCGTGGCCCACCTG
GTGGCCTCGCAAGGCTCTGCGCGCCACACCGTGCAGCACACTGCCTACCCAGCCAGCATC
GTCCACCAGGTCCCCGTGAGCATGGGCCCCCGGGTCCTGCCCTCGCCCACCATCCACCCG
AGTCAGTATCCAGCCCAATTTGCCCACCAGACCTACATCAGCGCCTCGCCAGCCTCCACC
GTCTACACTGGATACCCACTGAGCCCCGCCAAGGTCAACCAGTACCCTTACATATAA
Protein Properties
Number of Residues 1198
Molecular Weight 130964.7
Theoretical pI 8.52
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence 
>Homeodomain-interacting protein kinase 2
MAPVYEGMASHVQVFSPHTLQSSAFCSVKKLKIEPSSNWDMTGYGSHSKVYSQSKNIPLS
QPATTTVSTSLPVPNPSLPYEQTIVFPGSTGHIVVTSASSTSVTGQVLGGPHNLMRRSTV
SLLDTYQKCGLKRKSEEIENTSSVQIIEEHPPMIQNNASGATVATATTSTATSKNSGSNS
EGDYQLVQHEVLCSMTNTYEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQG
QIEVSILARLSTESADDYNFVRAYECFQHKNHTCLVFEMLEQNLYDFLKQNKFSPLPLKY
IRPVLQQVATALMKLKSLGLIHADLKPENIMLVDPSRQPYRVKVIDFGSASHVSKAVCST
YLQSRYYRAPEIILGLPFCEAIDMWSLGCVIAELFLGWPLYPGASEYDQIRYISQTQGLP
AEYLLSAGTKTTRFFNRDTDSPYPLWRLKTPDDHEAETGIKSKEARKYIFNCLDDMAQVN
MTTDLEGSDMLVEKADRREFIDLLKKMLTIDADKRITPIETLNHPFVTMTHLLDFPHSTH
VKSCFQNMEICKRRVNMYDTVNQSKTPFITHVAPSTSTNLTMTFNNQLTTVHNQAPSSTS
ATISLANPEVSILNYPSTLYQPSAASMAAVAQRSMPLQTGTAQICARPDPFQQALIVCPP
GFQGLQASPSKHAGYSVRMENAVPIVTQAPGAQPLQIQPGLLAQQAWPSGTQQILLPPAW
QQLTGVATHTSVQHATVIPETMAGTQQLADWRNTHAHGSHYNPIMQQPALLTGHVTLPAA
QPLNVGVAHVMRQQPTSTTSSRKSKQHQSSVRNVSTCEVSSSQAISSPQRSKRVKENTPP
RCAMVHSSPACSTSVTCGWGDVASSTTRERQRQTIVIPDTPSPTVSVITISSDTDEEEEQ
KHAPTSTVSKQRKNVISCVTVHDSPYSDSSSNTSPYSVQQRAGHNNANAFDTKGSLENHC
TGNPRTIIVPPLKTQASEVLVECDSLVPVNTSHHSSSYKSKSSSNVTSTSGHSSGSSSGA
ITYRQQRPGPHFQQQQPLNLSQAQQHITTDRTGSHRRQQAYITPTMAQAPYSFPHNSPSH
GTVHPHLAAAAAAAHLPTQPHLYTYTAPAALGSTGTVAHLVASQGSARHTVQHTAYPASI
VHQVPVSMGPRVLPSPTIHPSQYPAQFAHQTYISASPASTVYTGYPLSPAKVNQYPYI
GenBank ID Protein 164420685
UniProtKB/Swiss-Prot ID Q9H2X6
UniProtKB/Swiss-Prot Entry Name HIPK2_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_022740.4
GeneCard ID HIPK2
GenAtlas ID HIPK2
HGNC ID HGNC:14402
References
General References
  1. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  2. Shima Y, Shima T, Chiba T, Irimura T, Pandolfi PP, Kitabayashi I: PML activates transcription by protecting HIPK2 and p300 from SCFFbx3-mediated degradation. Mol Cell Biol. 2008 Dec;28(23):7126-38. doi: 10.1128/MCB.00897-08. Epub 2008 Sep 22. [PubMed:18809579 ]
  3. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203. [PubMed:18083107 ]
  4. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed:12853948 ]
  5. Heibeck TH, Ding SJ, Opresko LK, Zhao R, Schepmoes AA, Yang F, Tolmachev AV, Monroe ME, Camp DG 2nd, Smith RD, Wiley HS, Qian WJ: An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells. J Proteome Res. 2009 Aug;8(8):3852-61. doi: 10.1021/pr900044c. [PubMed:19534553 ]
  6. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846 ]
  7. Kim EJ, Park JS, Um SJ: Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo. J Biol Chem. 2002 Aug 30;277(35):32020-8. Epub 2002 Mar 29. [PubMed:11925430 ]
  8. Hofmann TG, Moller A, Sirma H, Zentgraf H, Taya Y, Droge W, Will H, Schmitz ML: Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nat Cell Biol. 2002 Jan;4(1):1-10. [PubMed:11740489 ]
  9. Tomasini R, Samir AA, Carrier A, Isnardon D, Cecchinelli B, Soddu S, Malissen B, Dagorn JC, Iovanna JL, Dusetti NJ: TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity. J Biol Chem. 2003 Sep 26;278(39):37722-9. Epub 2003 Jul 7. [PubMed:12851404 ]
  10. Wang Y, Marion Schneider E, Li X, Duttenhofer I, Debatin K, Hug H: HIPK2 associates with RanBPM. Biochem Biophys Res Commun. 2002 Sep 13;297(1):148-53. [PubMed:12220523 ]
  11. Wang Y, Hofmann TG, Runkel L, Haaf T, Schaller H, Debatin K, Hug H: Isolation and characterization of cDNAs for the protein kinase HIPK2. Biochim Biophys Acta. 2001 Mar 19;1518(1-2):168-72. [PubMed:11267674 ]
  12. Li X, Wang Y, Debatin KM, Hug H: The serine/threonine kinase HIPK2 interacts with TRADD, but not with CD95 or TNF-R1 in 293T cells. Biochem Biophys Res Commun. 2000 Oct 22;277(2):513-7. [PubMed:11032752 ]
  13. Pierantoni GM, Bulfone A, Pentimalli F, Fedele M, Iuliano R, Santoro M, Chiariotti L, Ballabio A, Fusco A: The homeodomain-interacting protein kinase 2 gene is expressed late in embryogenesis and preferentially in retina, muscle, and neural tissues. Biochem Biophys Res Commun. 2002 Jan 25;290(3):942-7. [PubMed:11798164 ]
  14. Moller A, Sirma H, Hofmann TG, Rueffer S, Klimczak E, Droge W, Will H, Schmitz ML: PML is required for homeodomain-interacting protein kinase 2 (HIPK2)-mediated p53 phosphorylation and cell cycle arrest but is dispensable for the formation of HIPK domains. Cancer Res. 2003 Aug 1;63(15):4310-4. [PubMed:12907596 ]
  15. Hofmann TG, Stollberg N, Schmitz ML, Will H: HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal kinase activation and apoptosis in human hepatoma cells. Cancer Res. 2003 Dec 1;63(23):8271-7. [PubMed:14678985 ]
  16. Harada J, Kokura K, Kanei-Ishii C, Nomura T, Khan MM, Kim Y, Ishii S: Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation. J Biol Chem. 2003 Oct 3;278(40):38998-9005. Epub 2003 Jul 21. [PubMed:12874272 ]
  17. Kim YH, Sung KS, Lee SJ, Kim YO, Choi CY, Kim Y: Desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) through the cytoplasmic-nuclear shuttling of the SUMO-specific protease SENP1. FEBS Lett. 2005 Nov 7;579(27):6272-8. Epub 2005 Oct 19. [PubMed:16253240 ]
  18. Roscic A, Moller A, Calzado MA, Renner F, Wimmer VC, Gresko E, Ludi KS, Schmitz ML: Phosphorylation-dependent control of Pc2 SUMO E3 ligase activity by its substrate protein HIPK2. Mol Cell. 2006 Oct 6;24(1):77-89. [PubMed:17018294 ]