EKS-HOS-00273

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00273

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CMGC/DYRK	457.5	1.2E-136	199	527	329

Status

Reviewed

Ensembl Protein

ENSP00000343108

UniProt Accession

Q9H2X6; Q75MR7; Q8WWI4; Q9H2Y1;

Protein Name

Homeodomain-interacting protein kinase 2

Protein Synonyms/Alias

hHIPk2;

Gene Name

HIPK2

Gene Synonyms/Alias

HIPK2;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000064393	ENSP00000413724	ENST00000428878
ENSG00000064393	ENSP00000343108	ENST00000342645
ENSG00000064393	ENSP00000385571	ENST00000406875

Organism

Homo sapiens

Functional Description

Serine/threonine-protein kinase involved intranscription 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 phoyphorylation- mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis.

Protein Length

918

Protein Sequence
(FASTA)

LQPVYESMAS HVQVFSPHTL QSSAFCSVKK LKIEPSSNWD MTGYGSHSKV YSQSKNIPLS 60

QPATTTVSTS LPVPNPSLPY EQTIVFPGST GHIVVTSASS TSVTGQVLGG PHNLMRRSTV 120

SLLDTYQKCG LKRKSEEIEN TSSVQIIEEH PPMIQNNASG ATVATATTST ATSKNSGSNS 180

EGDYQLVQHE VLCSMTNTYE VLEFLGRGTF GQVVKCWKRG TNEIVAIKIL KNHPSYARQG 240

QIEVSILARL STESADDYNF VRAYECFQHK NHTCLVFEML EQNLYDFLKQ NKFSPLPLKY 300

IRPVLQQVAT ALMKLKSLGL IHADLKPENI MLVDPSRQPY RVKVIDFGSA SHVSKAVCST 360

YLQSRYYRAP EIILGLPFCE AIDMWSLGCV IAELFLGWPL YPGASEYDQI RYISQTQGLP 420

AEYLLSAGTK TTRFFNRDTD SPYPLWRLKT PDDHEAETGI KSKEARKYIF NCLDDMAQVN 480

MTTDLEGSDM LVEKADRREF IDLLKKMLTI DADKRITPIE TLNHPFVTMT HLLDFPHSTH 540

VKSCFQNMEI CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQAPSSTS 600

ATISLANPEV SILNYPSTLY QPSAASMAAV AQRSMPLQTG TAQICARPDP FQQALIVCPP 660

GFQGLQASPS KHAGYSVRME NAVPIVTQAP GAQPLQIQPG LLAQQAWPSG TQQILLPPAW 720

QQLTGVATHT SVQHATVIPE TMAGTQQLAD WRNTHAHGSH YNPIMQQPAL LTGHVTLPAA 780

QPLNVGVAHV MRQQPTSTTS SRKSKQHQSS QRKNVISCVT VHDSPYSDSS SNTSPYSVQQ 840

RAGHNNANAF DTKGSLENHC TGNPRTIIVP PLKTQASEVL VECDSLVPGN LGPGQGRNLS 900

LESGFPAFLL LEMLLYGS 918

Nucleotide Sequence
(FASTA)

CTTCAGCCTG TTTATGAGAG TATGGCCTCA CATGTGCAAG TTTTCTCCCC TCACACCCTT 60

CAATCAAGTG CCTTCTGTAG TGTGAAGAAA CTGAAAATAG AGCCGAGTTC CAACTGGGAC 120

ATGACTGGGT ACGGCTCCCA CAGCAAAGTG TATAGCCAGA GCAAGAACAT CCCCCTGTCG 180

CAGCCAGCCA CCACAACCGT CAGCACCTCC TTGCCGGTCC CAAACCCAAG CCTACCTTAC 240

GAGCAGACCA TCGTCTTCCC AGGAAGCACC GGGCACATCG TGGTCACCTC AGCAAGCAGC 300

ACTTCTGTCA CCGGGCAAGT CCTCGGCGGA CCACACAACC TAATGCGTCG AAGCACTGTG 360

AGCCTCCTTG ATACCTACCA AAAATGTGGA CTCAAGCGTA AGAGCGAGGA GATCGAGAAC 420

ACAAGCAGCG TGCAGATCAT CGAGGAGCAT CCACCCATGA TTCAGAATAA TGCAAGCGGG 480

GCCACTGTCG CCACTGCCAC CACGTCTACT GCCACCTCCA AAAACAGCGG CTCCAACAGC 540

GAGGGCGACT ATCAGCTGGT GCAGCATGAG GTGCTGTGCT CCATGACCAA CACCTACGAG 600

GTCTTAGAGT TCTTGGGCCG AGGGACGTTT GGGCAAGTGG TCAAGTGCTG GAAACGGGGC 660

ACCAATGAGA TCGTAGCCAT CAAGATCCTG AAGAACCACC CATCCTATGC CCGACAAGGT 720

CAGATTGAAG TGAGCATCCT GGCCCGGTTG AGCACGGAGA GTGCCGATGA CTATAACTTC 780

GTCCGGGCCT ACGAATGCTT CCAGCACAAG AACCACACGT GCTTGGTCTT CGAGATGTTG 840

GAGCAGAACC TCTATGACTT TCTGAAGCAA AACAAGTTTA GCCCCTTGCC CCTCAAATAC 900

ATTCGCCCAG TTCTCCAGCA GGTAGCCACA GCCCTGATGA AACTCAAAAG CCTAGGTCTT 960

ATCCACGCTG ACCTCAAACC AGAAAACATC ATGCTGGTGG ATCCATCTAG ACAACCATAC 1020

AGAGTCAAGG TCATCGACTT TGGTTCAGCC AGCCACGTCT CCAAGGCTGT GTGCTCCACC 1080

TACTTGCAGT CCAGATATTA CAGGGCCCCT GAGATCATCC TTGGTTTACC ATTTTGTGAG 1140

GCAATTGACA TGTGGTCCCT GGGCTGTGTT ATTGCAGAAT TGTTCCTGGG TTGGCCGTTA 1200

TATCCAGGAG CTTCGGAGTA TGATCAGATT CGGTATATTT CACAAACACA GGGTTTGCCT 1260

GCTGAATATT TATTAAGCGC CGGGACAAAG ACAACTAGGT TTTTCAACCG TGACACGGAC 1320

TCACCATATC CTTTGTGGAG ACTGAAGACA CCAGATGACC ATGAAGCAGA GACAGGGATT 1380

AAGTCAAAAG AAGCAAGAAA GTACATTTTC AACTGTTTAG ATGATATGGC CCAGGTGAAC 1440

ATGACGACAG ATTTGGAAGG GAGCGACATG TTGGTAGAAA AGGCTGACCG GCGGGAGTTC 1500

ATTGACCTGT TGAAGAAGAT GCTGACCATT GATGCTGACA AGAGAATCAC TCCAATCGAA 1560

ACCCTGAACC ATCCCTTTGT CACCATGACA CACTTACTCG ATTTTCCCCA CAGCACACAC 1620

GTCAAATCAT GTTTCCAGAA CATGGAGATC TGCAAGCGTC GGGTGAATAT GTATGACACG 1680

GTGAACCAGA GCAAAACCCC TTTCATCACG CACGTGGCCC CCAGCACGTC CACCAACCTG 1740

ACCATGACCT TTAACAACCA GCTGACCACT GTCCACAACC AGGCTCCCTC CTCTACCAGT 1800

GCCACTATTT CCTTAGCCAA TCCCGAAGTC TCCATACTAA ACTACCCATC TACACTCTAC 1860

CAGCCCTCAG CGGCATCCAT GGCTGCAGTG GCCCAGCGGA GCATGCCCCT GCAGACAGGA 1920

ACAGCCCAGA TTTGTGCCCG GCCTGACCCG TTCCAGCAAG CTCTCATCGT GTGTCCCCCC 1980

GGCTTCCAAG GCTTGCAGGC CTCTCCCTCT AAGCACGCTG GCTACTCGGT GCGAATGGAA 2040

AATGCAGTTC CCATCGTCAC TCAAGCCCCA GGAGCTCAGC CTCTTCAGAT CCAACCAGGT 2100

CTGCTTGCCC AGCAGGCTTG GCCAAGTGGG ACCCAGCAGA TCCTGCTTCC CCCAGCATGG 2160

CAGCAACTGA CTGGAGTGGC CACCCACACA TCAGTGCAGC ATGCCACCGT GATTCCCGAG 2220

ACCATGGCAG GCACCCAGCA GCTGGCGGAC TGGAGAAATA CGCATGCTCA CGGAAGCCAT 2280

TATAATCCCA TCATGCAGCA GCCTGCACTA TTGACCGGTC ATGTGACCCT TCCAGCAGCA 2340

CAGCCCTTAA ATGTGGGTGT GGCCCACGTG ATGCGGCAGC AGCCAACCAG CACCACCTCC 2400

TCCCGGAAGA GTAAGCAGCA CCAGTCATCT CAAAGAAAAA ACGTCATCAG CTGTGTCACA 2460

GTCCACGACT CCCCCTACTC CGACTCCTCC AGCAACACCA GCCCCTACTC CGTGCAGCAG 2520

CGTGCTGGGC ACAACAATGC CAATGCCTTT GACACCAAGG GGAGCCTGGA GAATCACTGC 2580

ACGGGGAACC CCCGAACCAT CATCGTGCCA CCCCTGAAAA CCCAGGCCAG CGAAGTATTG 2640

GTGGAGTGTG ATAGCCTGGT GCCAGGTAAT TTGGGGCCAG GACAGGGCAG GAACCTCTCC 2700

CTGGAGAGTG GTTTTCCTGC TTTTCTGCTG CTAGAAATGT TGCTGTATGG GAGCTAG 2757

Domain Profile

S: 1     yevlevigkGsfgqVvkaldkktkeivaikiiknkkrfarqaqeEveiLeklnkkdkeek  60

         yevle++g+G+fgqVvk++++ t+eivaiki+kn++++arq+q+Ev+iL++l++ +++++

Q: 199   YEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILARLST-ESADD  257

         9****************************************************9.999**

S: 61    ynvvrllelfvfrnhlclvfellsqnLyellkknkfsglslklvrklaqqilkaLklLke  120

         yn+vr++e+f+++nh+clvfe+l+qnLy++lk+nkfs+l+lk++r+++qq+++aL++Lk+

Q: 258   YNFVRAYECFQHKNHTCLVFEMLEQNLYDFLKQNKFSPLPLKYIRPVLQQVATALMKLKS  317

         ************************************************************

S: 121   lkiiHaDlKPeNillvekkrse..vkviDFGsssavsqkeiytyiqsrfYraPEiilglk  178

         l++iHaDlKPeNi+lv+++r++  vkviDFGs+s+vs+++++ty+qsr+YraPEiilgl+

Q: 318   LGLIHADLKPENIMLVDPSRQPyrVKVIDFGSASHVSKAVCSTYLQSRYYRAPEIILGLP  377

         *********************999************************************

S: 179   ydeaiDmWSlGcvlaElftGkpLfpGenevdqlalivevlglppekllekakkakkff..  236

         ++eaiDmWSlGcv+aElf+G+pL+pG++e+dq+++i++++glp+e+ll++++k+++ff

Q: 378   FCEAIDMWSLGCVIAELFLGWPLYPGASEYDQIRYISQTQGLPAEYLLSAGTKTTRFFnr  437

         **********************************************************88

S: 237   .tkkeapkyilktk.........ksdrkkklvlnvkkaakkrkaplskelgealkekedk  286

          t++ +p ++lkt          ks++++k+++n+ +++++++++++ e +++l ek+d+

Q: 438   dTDSPYPLWRLKTPddheaetgiKSKEARKYIFNCLDDMAQVNMTTDLEGSDMLVEKADR  497

         87889999999999********************************************99

S: 287   l.fkdllkrmleldpakRitpkealkhpfv  315

         + f+dllk+ml++d++kRitp e+l+hpfv

Q: 498   ReFIDLLKKMLTIDADKRITPIETLNHPFV  527

         99***************************7

Domain Sequence
(FASTA)

YEVLEFLGRG TFGQVVKCWK RGTNEIVAIK ILKNHPSYAR QGQIEVSILA RLSTESADDY 60

NFVRAYECFQ HKNHTCLVFE MLEQNLYDFL KQNKFSPLPL KYIRPVLQQV ATALMKLKSL 120

GLIHADLKPE NIMLVDPSRQ PYRVKVIDFG SASHVSKAVC STYLQSRYYR APEIILGLPF 180

CEAIDMWSLG CVIAELFLGW PLYPGASEYD QIRYISQTQG LPAEYLLSAG TKTTRFFNRD 240

TDSPYPLWRL KTPDDHEAET GIKSKEARKY IFNCLDDMAQ VNMTTDLEGS DMLVEKADRR 300

EFIDLLKKML TIDADKRITP IETLNHPFV 329

Keyword

Alternative splicing; Apoptosis; ATP-binding; Complete proteome; Cytoplasm; DNA damage; Isopeptide bond; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Oreochromis niloticus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>

Gene Ontology

GO:0005813	; C:centrosome
GO:0016604	; C:nuclear body
GO:0031965	; C:nuclear membrane
GO:0016605	; C:PML body
GO:0005524	; F:ATP binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0001102	; F:RNA polymerase II activating transcription factor binding
GO:0001105	; F:RNA polymerase II transcription coactivator activity
GO:0003714	; F:transcription corepressor activity
GO:0046790	; F:virion binding
GO:0007628	; P:adult walking behavior
GO:0009952	; P:anterior/posterior pattern specification
GO:0071456	; P:cellular response to hypoxia
GO:0006978	; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0048596	; P:embryonic camera-type eye morphogenesis
GO:0060059	; P:embryonic retina morphogenesis in camera-type eye
GO:0030218	; P:erythrocyte differentiation
GO:0001654	; P:eye development
GO:0042771	; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0061072	; P:iris morphogenesis
GO:0060235	; P:lens induction in camera-type eye
GO:0030514	; P:negative regulation of BMP signaling pathway
GO:0043524	; P:negative regulation of neuron apoptotic process
GO:0000122	; P:negative regulation of transcription from RNA polymerase II promoter
GO:0030182	; P:neuron differentiation
GO:0018105	; P:peptidyl-serine phosphorylation
GO:0018107	; P:peptidyl-threonine phosphorylation
GO:0030578	; P:PML body organization
GO:0045766	; P:positive regulation of angiogenesis
GO:0008284	; P:positive regulation of cell proliferation
GO:0043388	; P:positive regulation of DNA binding
GO:0046330	; P:positive regulation of JNK cascade
GO:0032092	; P:positive regulation of protein binding
GO:0051091	; P:positive regulation of sequence-specific DNA binding transcription factor activity
GO:0045944	; P:positive regulation of transcription from RNA polymerase II promoter
GO:0030511	; P:positive regulation of transforming growth factor beta receptor signaling pathway
GO:0051726	; P:regulation of cell cycle
GO:0010842	; P:retina layer formation
GO:0060395	; P:SMAD protein signal transduction
GO:0007224	; P:smoothened signaling pathway
GO:0007179	; P:transforming growth factor beta receptor signaling pathway
GO:0019048	; P:virus-host interaction
GO:0050882	; P:voluntary musculoskeletal movement

KEGG

hsa:28996

;

InterPros

IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR002290	; Ser/Thr_dual-sp_kinase_dom.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF00069

; Pkinase; 1.

SMARTs

SM00220

; S_TKc; 1.

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.

Prints

Created Date

20-Feb-2013