UniProt Accession

 HIPK2_HUMAN; Q9H2X6; Q75MR7; Q8WWI4; Q9H2Y1 

Genbank Protein ID

 AF208291; AF326592; AC005531; AC073184; AC006021; AC141932; AF207702 

Genbank Nucleotide ID

 AAG41236.1; AAL37371.1; AAS00368.1; AAG35710.1 

Protein Name

 Homeodomain-interacting protein kinase 2 

Protein Synonyms/Alias

 hHIPk2 

Gene Name

 HIPK2 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
29	SSAFCSVKKLKIEPS	acetylation	[1]
32	FCSVKKLKIEPSSNW	sumoylation	[2]
128	SLLDTYQKCGLKRKS	acetylation	[1]
430	YLLSAGTKTTRFFNR	acetylation	[1]
449	PYPLWRLKTPDDHEA	acetylation	[1]
803	TSTTSSRKSKQHQSS	acetylation	[1]
805	TTSSRKSKQHQSSVR	acetylation	[1]
910	APTSTVSKQRKNVIS	acetylation	[1]
953	NANAFDTKGSLENHC	acetylation	[1]
973	TIIVPPLKTQASEVL	acetylation	[1]
1001	HSSSYKSKSSSNVTS	acetylation	[1]
1191	GYPLSPAKVNQYPYI	sumoylation	[3]

Reference

 [1] A redox-regulated SUMO/acetylation switch of HIPK2 controls the survival threshold to oxidative stress.
 de la Vega L, Grishina I, Moreno R, Krüger M, Braun T, Schmitz ML.
 Mol Cell. 2012 May 25;46(4):472-83. [PMID: 22503103]
 [2] 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]
 [3] Sumoylation of topoisomerase I is involved in its partitioning between nucleoli and nucleoplasm and its clearing from nucleoli in response to camptothecin.
 Rallabhandi P, Hashimoto K, Mo YY, Beck WT, Moitra PK, D'Arpa P.
 J Biol Chem. 2002 Oct 18;277(42):40020-6. [PMID: 12149243] 

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 (By
 REGION 189 520 Interaction with DAXX.
 REGION 539 844 Interaction with SKI and SMAD1.
 REGION 752 897 Interaction with POU4F1 (By similarity).
 REGION 774 876 Interaction with CTBP1 (By similarity).
 REGION 787 897 Interaction with HMGA1 (By similarity).
 REGION 802 805 Nuclear localization signal 1 (NLS1).
 REGION 832 835 Nuclear localization signal 2 (NLS2).
 REGION 846 941 Interaction with TP53 and TP73.
 REGION 873 980 Required for localization to nuclear
 REGION 873 907 Interaction with UBE2I (By similarity).
 REGION 884 908 SUMO interaction motifs (SIM); required
 REGION 935 1049 Interaction with AXIN1 (By similarity).
 REGION 984 1198 Autoinhibitory domain (AID).
 ACT_SITE 324 324 Proton acceptor (Probable).
 BINDING 228 228 ATP (Probable).
 MOD_RES 16 16 Phosphoserine.
 MOD_RES 118 118 Phosphoserine.
 MOD_RES 135 135 Phosphoserine.
 MOD_RES 141 141 Phosphothreonine.
 MOD_RES 252 252 Phosphothreonine.
 MOD_RES 273 273 Phosphothreonine.
 MOD_RES 361 361 Phosphotyrosine; by autocatalysis.
 MOD_RES 441 441 Phosphoserine.
 MOD_RES 482 482 Phosphothreonine.
 MOD_RES 517 517 Phosphothreonine.
 MOD_RES 566 566 Phosphothreonine.
 MOD_RES 634 634 Phosphoserine.
 MOD_RES 668 668 Phosphoserine.
 MOD_RES 687 687 Phosphothreonine.
 MOD_RES 815 815 Phosphoserine.
 MOD_RES 827 827 Phosphoserine.
 MOD_RES 934 934 Phosphoserine.
 MOD_RES 992 992 Phosphoserine.
 MOD_RES 1041 1041 Phosphoserine.
 MOD_RES 1155 1155 Phosphoserine.
 MOD_RES 1188 1188 Phosphoserine.
 CROSSLNK 32 32 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 1191 1191 Glycyl lysine isopeptide (Lys-Gly)  

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

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1198 AA 

Protein Sequence

Gene Ontology

 GO:0005813; C:centrosome; IDA:HPA.
 GO:0005737; C:cytoplasm; ISS:UniProtKB.
 GO:0016604; C:nuclear body; IDA:UniProtKB.
 GO:0031965; C:nuclear membrane; IDA:HPA.
 GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004674; F:protein serine/threonine kinase activity; ISS:BHF-UCL.
 GO:0001102; F:RNA polymerase II activating transcription factor binding; ISS:BHF-UCL.
 GO:0001105; F:RNA polymerase II transcription coactivator activity; IEA:Compara.
 GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
 GO:0046790; F:virion binding; IPI:UniProtKB.
 GO:0007628; P:adult walking behavior; IEA:Compara.
 GO:0009952; P:anterior/posterior pattern specification; IEA:Compara.
 GO:0071456; P:cellular response to hypoxia; TAS:UniProtKB.
 GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IDA:BHF-UCL.
 GO:0048596; P:embryonic camera-type eye morphogenesis; IEA:Compara.
 GO:0060059; P:embryonic retina morphogenesis in camera-type eye; IEA:Compara.
 GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
 GO:0001654; P:eye development; ISS:UniProtKB.
 GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; TAS:UniProtKB.
 GO:0061072; P:iris morphogenesis; IEA:Compara.
 GO:0060235; P:lens induction in camera-type eye; IEA:Compara.
 GO:0030514; P:negative regulation of BMP signaling pathway; IMP:UniProtKB.
 GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Compara.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0030182; P:neuron differentiation; IEA:Compara.
 GO:0018105; P:peptidyl-serine phosphorylation; ISS:BHF-UCL.
 GO:0018107; P:peptidyl-threonine phosphorylation; ISS:BHF-UCL.
 GO:0030578; P:PML body organization; TAS:UniProtKB.
 GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; IEA:Compara.
 GO:0043388; P:positive regulation of DNA binding; IEA:Compara.
 GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB.
 GO:0032092; P:positive regulation of protein binding; ISS:BHF-UCL.
 GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; ISS:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL.
 GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
 GO:0051726; P:regulation of cell cycle; TAS:UniProtKB.
 GO:0010842; P:retina layer formation; IEA:Compara.
 GO:0060395; P:SMAD protein signal transduction; IDA:UniProtKB.
 GO:0007224; P:smoothened signaling pathway; IEA:Compara.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Compara.
 GO:0019048; P:virus-host interaction; NAS:UniProtKB.
 GO:0050882; P:voluntary musculoskeletal movement; IEA:Compara. 

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