Homeodomain-interacting protein kinase 2

Details

Name

Homeodomain-interacting protein kinase 2

Synonyms

• 2.7.11.1
• hHIPk2

Gene Name

HIPK2

Organism

Humans

Amino acid sequence

>lcl|BSEQ0051772|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

Number of residues

1198

Molecular Weight

130964.705

Theoretical pI

Not Available

GO Classification

Functions

ATP binding / protein kinase activity / protein serine/threonine kinase activity / RNA polymerase II activating transcription factor binding / RNA polymerase II transcription coactivator activity / SMAD binding / transcription corepressor activity / virion binding

Processes

adult walking behavior / anterior/posterior pattern specification / cellular response to hypoxia / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / embryonic camera-type eye morphogenesis / embryonic retina morphogenesis in camera-type eye / erythrocyte differentiation / eye development / intrinsic apoptotic signaling pathway / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / iris morphogenesis / lens induction in camera-type eye / modulation by virus of host morphology or physiology / negative regulation of BMP signaling pathway / negative regulation of neuron apoptotic process / negative regulation of transcription by RNA polymerase II / negative regulation of ubiquitin-dependent protein catabolic process / neuron differentiation / peptidyl-serine phosphorylation / peptidyl-threonine phosphorylation / PML body organization / positive regulation of angiogenesis / positive regulation of cell proliferation / positive regulation of DNA binding / positive regulation of DNA binding transcription factor activity / positive regulation of JNK cascade / positive regulation of protein binding / positive regulation of transcription by RNA polymerase II / positive regulation of transcription, DNA-templated / positive regulation of transforming growth factor beta receptor signaling pathway / protein phosphorylation / regulation of cell cycle / regulation of signal transduction by p53 class mediator / retina layer formation / SMAD protein signal transduction / smoothened signaling pathway / transforming growth factor beta receptor signaling pathway / voluntary musculoskeletal movement

Components

cytoplasm / nuclear body / nucleoplasm / nucleus / PML body / RNA polymerase II transcription factor complex

General Function

Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1 and ZBTB4. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis.

Specific Function

Atp binding

Pfam Domain Function

• Pkinase (PF00069)

Transmembrane Regions

Not Available

Cellular Location

Nucleus

Gene sequence

>lcl|BSEQ0051773|Homeodomain-interacting protein kinase 2 (HIPK2)
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

Chromosome Location

7

Locus

7q34

External Identifiers

Resource	Link
UniProtKB ID	Q9H2X6
UniProtKB Entry Name	HIPK2_HUMAN
HGNC ID	HGNC:14402

General References

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2. 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. [Article]
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Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB12010	Fostamatinib	approved, investigational	unknown	inhibitor	Details