CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-022713
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Homeodomain-interacting protein kinase 2 
Protein Synonyms/Alias
 Nuclear body-associated kinase 1; Sialophorin tail-associated nuclear serine/threonine-protein kinase 
Gene Name
 Hipk2 
Gene Synonyms/Alias
 Nbak1; Stank 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
32FCSVKKLKVEPSSNWsumoylation[1, 2, 3]
1189GYPLSPAKVNQYPYIsumoylation[4]
Reference
 [1] Covalent modification of human homeodomain interacting protein kinase 2 by SUMO-1 at lysine 25 affects its stability.
 Gresko E, Möller A, Roscic A, Schmitz ML.
 Biochem Biophys Res Commun. 2005 Apr 22;329(4):1293-9. [PMID: 15766567]
 [2] Differential interactions of the homeodomain-interacting protein kinase 2 (HIPK2) by phosphorylation-dependent sumoylation.
 Sung KS, Go YY, Ahn JH, Kim YH, Kim Y, Choi CY.
 FEBS Lett. 2005 Jun 6;579(14):3001-8. [PMID: 15896780]
 [3] Regulation of homeodomain-interacting protein kinase 2 (HIPK2) effector function through dynamic small ubiquitin-related modifier-1 (SUMO-1) modification.
 Hofmann TG, Jaffray E, Stollberg N, Hay RT, Will H.
 J Biol Chem. 2005 Aug 12;280(32):29224-32. [PMID: 15958389]
 [4] Covalent modification of the homeodomain-interacting protein kinase 2 (HIPK2) by the ubiquitin-like protein SUMO-1.
 Kim YH, Choi CY, Kim Y.
 Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12350-5. [PMID: 10535925] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 199 527 Protein kinase.
 NP_BIND 205 213 ATP (Probable).
 REGION 97 230 Transcriptional corepression.
 REGION 189 520 Interaction with DAXX (By similarity).
 REGION 539 844 Interaction with SKI and SMAD1 (By
 REGION 752 897 Interaction with POU4F1.
 REGION 774 876 Interaction with CTBP1.
 REGION 787 897 Interaction with HMGA1.
 REGION 802 805 Nuclear localization signal 1 (NLS1) (By
 REGION 832 835 Nuclear localization signal 2 (NLS2) (By
 REGION 839 934 Interaction with TP53 and TP73.
 REGION 873 980 Localization to nuclear speckles.
 REGION 873 980 Required for localization to nuclear
 REGION 873 907 Interaction with UBE2I.
 REGION 884 908 SUMO interaction motifs (SIM); required
 REGION 935 1050 Interaction with AXIN1.
 REGION 984 1196 Autoinhibitory domain (AID) (By
 ACT_SITE 324 324 Proton acceptor (Probable).
 BINDING 228 228 ATP (Probable).
 MOD_RES 16 16 Phosphoserine (By similarity).
 MOD_RES 118 118 Phosphoserine (By similarity).
 MOD_RES 135 135 Phosphoserine (By similarity).
 MOD_RES 141 141 Phosphothreonine (By similarity).
 MOD_RES 252 252 Phosphothreonine (By similarity).
 MOD_RES 273 273 Phosphothreonine (By similarity).
 MOD_RES 361 361 Phosphotyrosine.
 MOD_RES 441 441 Phosphoserine (By similarity).
 MOD_RES 482 482 Phosphothreonine (By similarity).
 MOD_RES 517 517 Phosphothreonine (By similarity).
 MOD_RES 566 566 Phosphothreonine (By similarity).
 MOD_RES 634 634 Phosphoserine (By similarity).
 MOD_RES 668 668 Phosphoserine (By similarity).
 MOD_RES 687 687 Phosphothreonine (By similarity).
 MOD_RES 815 815 Phosphoserine (By similarity).
 MOD_RES 827 827 Phosphoserine (By similarity).
 MOD_RES 934 934 Phosphoserine (By similarity).
 MOD_RES 993 993 Phosphoserine (By similarity).
 MOD_RES 1042 1042 Phosphoserine (By similarity).
 MOD_RES 1153 1153 Phosphoserine (By similarity).
 MOD_RES 1186 1186 Phosphoserine (By similarity).
 CROSSLNK 32 32 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 1189 1189 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 Alternative splicing; Apoptosis; ATP-binding; Complete proteome; Cytoplasm; DNA damage; Isopeptide bond; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase; Tumor suppressor; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1196 AA 
Protein Sequence
MAPVYEGMAS HVQVFSPHTL QSSAFCSVKK LKVEPSSNWD MTGYGSHSKV YSQSKNIPPS 60
QPASTTVSTS LPIPNPSLPY EQTIIFPGST 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 DADKRVTPIE TLNHPFVTMT HLLDFPHSAH 540
VKSCFQNMEI CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQAPTTSS 600
ATLSLANPEV SILNYQSALY QPSAASMAAV APRSMPLQTG TAQICARPDP FQQALIVCPP 660
GFQGLQASPS KHAGYSVRME NAVPIVTQAP GAQPLQIQPG LLAQQAWPGG AQQILLPPAW 720
QQLTGVATHT SVQHAAVIPE TMAGTQQLAD WRNTHAHGSH YNPIMQQPAL LTGHVTLPAA 780
QPLNVGVAHV MRQQPTSTTS SRKSKQHQSS VRNVSTCEVT SSQAISSPQR SKRVKENTPP 840
RCAMVHSSPA CSTSVTCGWG DVASSTTRER QRQTIVIPDT PSPTVSVITI SSDTDEEEEQ 900
KHAPTSTVSK QRKNVISCVT VHDSPYSDSS SNTSPYSVQQ RTGHNGTNTL DTKGGLENHC 960
TGNPRTIIVP PLKTQASEVL VECDSLGPAI SASHHSSSFK SKSSSTVTST SGHSSGSSSG 1020
AIAYRQQRPG PHFQQQQPLN LSQAQQHMAA DRTGSHRRQQ AYITPTMAQA PYTFPHNSPS 1080
HGTVHPHLAA AAHLPTQPHL YTYTAPTALG STGTVAHLVA SQGSARHTVQ HTAYPASIVH 1140
QVPVSMGPRV LPSPTIHPSQ YPAQFAHQTY ISASPASTVY TGYPLSPAKV NQYPYI 1196 
Gene Ontology
 GO:0005813; C:centrosome; IEA:Compara.
 GO:0005737; C:cytoplasm; IDA:MGI.
 GO:0031965; C:nuclear membrane; IEA:Compara.
 GO:0016605; C:PML body; TAS:MGI.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
 GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
 GO:0046790; F:virion binding; ISS:UniProtKB.
 GO:0007628; P:adult walking behavior; IMP:MGI.
 GO:0009952; P:anterior/posterior pattern specification; IGI:MGI.
 GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IEA:Compara.
 GO:0048596; P:embryonic camera-type eye morphogenesis; IMP:DFLAT.
 GO:0060059; P:embryonic retina morphogenesis in camera-type eye; IMP:DFLAT.
 GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IGI:MGI.
 GO:0061072; P:iris morphogenesis; IMP:DFLAT.
 GO:0060235; P:lens induction in camera-type eye; IMP:DFLAT.
 GO:0030514; P:negative regulation of BMP signaling pathway; IEA:Compara.
 GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0030182; P:neuron differentiation; IMP:DFLAT.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
 GO:0018107; P:peptidyl-threonine phosphorylation; IDA:BHF-UCL.
 GO:0045766; P:positive regulation of angiogenesis; IEA:Compara.
 GO:0008284; P:positive regulation of cell proliferation; IGI:MGI.
 GO:0043388; P:positive regulation of DNA binding; IDA:UniProtKB.
 GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB.
 GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
 GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
 GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
 GO:0010842; P:retina layer formation; IMP:DFLAT.
 GO:0060395; P:SMAD protein signal transduction; IEA:Compara.
 GO:0007224; P:smoothened signaling pathway; IGI:MGI.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:MGI.
 GO:0050882; P:voluntary musculoskeletal movement; IMP:MGI. 
Interpro
 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 
SMART
 SM00220; S_TKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS