HIPK2
entrez
28996
canonical
uniprot
Q9H2X6
canonical
ensembl
ENSG00000064393
resolver
ensp
ENSP00000385571
resolver
ensp
ENSP00000413724
resolver
ensp
ENSP00000577466
resolver
genesymbol
HIPK2
resolver
hgnc
HGNC:14402
resolver
uniprot
Q75MR7
resolver
uniprot
Q8WWI4
resolver
uniprot
Q9H2Y1
resolver
uniprot_entry
HIPK2_HUMAN
resolver
uniprot_sec
Q75MR7
resolver
uniprot_sec
Q8WWI4
resolver
uniprot_sec
Q9H2Y1
resolver
amino_acid_sequence
MAPVYEGMASHVQVFSPHTLQSSAFCSVKKLKIEPSSNWDMTGYGSHSKVYSQSKNIPLSQPATTTVSTSLPVPNPSLPYEQTIVFPGSTGHIVVTSASSTSVTGQVLGGPHNLMRRSTVSLLDTYQKCGLKRKSEEIENTSSVQIIEEHPPMIQNNASGATVATATTSTATSKNSGSNSEGDYQLVQHEVLCSMTNTYEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILARLSTESADDYNFVRAYECFQHKNHTCLVFEMLEQNLYDFLKQNKFSPLPLKYIRPVLQQVATALMKLKSLGLIHADLKPENIMLVDPSRQPYRVKVIDFGSASHVSKAVCSTYLQSRYYRAPEIILGLPFCEAIDMWSLGCVIAELFLGWPLYPGASEYDQIRYISQTQGLPAEYLLSAGTKTTRFFNRDTDSPYPLWRLKTPDDHEAETGIKSKEARKYIFNCLDDMAQVNMTTDLEGSDMLVEKADRREFIDLLKKMLTIDADKRITPIETLNHPFVTMTHLLDFPHSTHVKSCFQNMEICKRRVNMYDTVNQSKTPFITHVAPSTSTNLTMTFNNQLTTVHNQAPSSTSATISLANPEVSILNYPSTLYQPSAASMAAVAQRSMPLQTGTAQICARPDPFQQALIVCPPGFQGLQASPSKHAGYSVRMENAVPIVTQAPGAQPLQIQPGLLAQQAWPSGTQQILLPPAWQQLTGVATHTSVQHATVIPETMAGTQQLADWRNTHAHGSHYNPIMQQPALLTGHVTLPAAQPLNVGVAHVMRQQPTSTTSSRKSKQHQSSVRNVSTCEVSSSQAISSPQRSKRVKENTPPRCAMVHSSPACSTSVTCGWGDVASSTTRERQRQTIVIPDTPSPTVSVITISSDTDEEEEQKHAPTSTVSKQRKNVISCVTVHDSPYSDSSSNTSPYSVQQRAGHNNANAFDTKGSLENHCTGNPRTIIVPPLKTQASEVLVECDSLVPVNTSHHSSSYKSKSSSNVTSTSGHSSGSSSGAITYRQQRPGPHFQQQQPLNLSQAQQHITTDRTGSHRRQQAYITPTMAQAPYSFPHNSPSHGTVHPHLAAAAAAAHLPTQPHLYTYTAPAALGSTGTVAHLVASQGSARHTVQHTAYPASIVHQVPVSMGPRVLPSPTIHPSQYPAQFAHQTYISASPASTVYTGYPLSPAKVNQYPYI
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
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, ZBTB4 and DAZAP2. 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. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). 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. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33591310}.
uniprot
proteins
mass_dalton
130966
uniprot
proteins
mutagenesis
MUTAGEN 228; /note="K->A: Locates in the nucleoplasm, no effect on interaction with RANBP9, but loss of kinase activity toward PML, RUNX1, EP300 and DAZAP2."; /evidence="ECO:0000269|PubMed:11267674, ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12220523, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:12907596, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:33591310"; MUTAGEN 228; /note="K->R: Abolishes enzymatic activity, no effect on interaction with TP53 and TP73 or on BMP-induced transcriptional activation. Enhances BMP-induced transcriptional activation; when associated with 359-AAF-361."; /evidence="ECO:0000269|PubMed:11267674, ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12220523, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:12907596, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:19015637"; MUTAGEN 359..361; /note="STY->AAF: Enhances BMP-induced transcriptional activation; when associated with R-228."; /evidence="ECO:0000269|PubMed:12874272"; MUTAGEN 803; /note="K->A: Impaired nuclear localization; when associated with A-805."; /evidence="ECO:0000269|PubMed:21145359"; MUTAGEN 805; /note="K->A: Impaired nuclear localization; when associated with A-803."; /evidence="ECO:0000269|PubMed:21145359"; MUTAGEN 833; /note="R->A: Impaired nuclear localization."; /evidence="ECO:0000269|PubMed:21145359"; MUTAGEN 835; /note="K->E: Impaired nuclear localization."; /evidence="ECO:0000269|PubMed:21145359"; MUTAGEN 885..892; /note="VSVITISS->KFMHFHRM: Loss of SUMO and CBX4 interaction, and impaired nuclear and PML-nuclear bodies localization."; /evidence="ECO:0000269|PubMed:21145359"; MUTAGEN 885..888; /note="VSVI->KSAK: Loss of SUMO interaction, and impaired nuclear and PML-nuclear bodies localization."; /evidence="ECO:0000269|PubMed:21192925"; MUTAGEN 892..895; /note="SDTD->ADTA: Loss of SUMO interaction, and impaired nuclear and PML-nuclear bodies localization."; /evidence="ECO:0000269|PubMed:21192925"; MUTAGEN 893..899; /note="DTDEEEE->NFNQQQQ: Loss of SUMO and CBX4 interaction, and impaired nuclear and PML-nuclear bodies localization."; /evidence="ECO:0000269|PubMed:21145359
uniprot
proteins
post_translational_modification
PTM: Autophosphorylation at Tyr-361 in the activation loop activates the kinase and promotes nuclear localization. {ECO:0000250}.; PTM: Sumoylated. When conjugated it is directed to nuclear speckles. Desumoylated by SENP1 (By similarity). Sumoylation on Lys-32 is promoted by the E3 SUMO-protein ligase CBX4. {ECO:0000250, ECO:0000269|PubMed:16253240, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:21145359, ECO:0000269|PubMed:21192925}.; PTM: Ubiquitinated by FBXO3, WSB1 and SIAH1, leading to rapid proteasome-dependent degradation. The degradation mediated by FBXO3, but not ubiquitination, is prevented in the presence of PML. The degradation mediated by WSB1 and SIAH1 is reversibly reduced upon DNA damage. {ECO:0000269|PubMed:18093972, ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:33591310}.; PTM: Cleaved at Asp-923 and Asp-984 by CASP6 in a p53/TP53-dependent manner. The cleaved form lacks the autoinhibitory C-terminal domain (AID), resulting in a hyperactive kinase, which potentiates p53/TP53 Ser-46 phosphorylation and subsequent activation of the cell death machinery. {ECO:0000269|PubMed:16601678}.
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
HIPK subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
11032752
uniprot
proteins
pubmed
11267674
uniprot
proteins
pubmed
11740489
uniprot
proteins
pubmed
11798164
uniprot
proteins
pubmed
11925430
uniprot
proteins
pubmed
12220523
uniprot
proteins
pubmed
12851404
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
12874272
uniprot
proteins
pubmed
12907596
uniprot
proteins
pubmed
14609633
uniprot
proteins
pubmed
14647468
uniprot
proteins
pubmed
14678985
uniprot
proteins
pubmed
16253240
uniprot
proteins
pubmed
16601678
uniprot
proteins
pubmed
17018294
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17960875
uniprot
proteins
pubmed
18093972
uniprot
proteins
pubmed
18536714
uniprot
proteins
pubmed
18695000
uniprot
proteins
pubmed
18809579
uniprot
proteins
pubmed
18974774
uniprot
proteins
pubmed
19015637
uniprot
proteins
pubmed
19046997
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19448668
uniprot
proteins
pubmed
19714248
uniprot
proteins
pubmed
19788416
uniprot
proteins
pubmed
20234185
uniprot
proteins
pubmed
20307497
uniprot
proteins
pubmed
20514025
uniprot
proteins
pubmed
20573984
uniprot
proteins
pubmed
20637728
uniprot
proteins
pubmed
20980392
uniprot
proteins
pubmed
21145359
uniprot
proteins
pubmed
21192925
uniprot
proteins
pubmed
22825850
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
27211601
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
33591310
uniprot
proteins
sequence_length
1198
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000269|PubMed:27211601, ECO:0000269|PubMed:33591310}. Cytoplasm {ECO:0000269|PubMed:33591310}. Cytoplasm, Stress granule {ECO:0000269|PubMed:33591310}. Note=Concentrated in PML/POD/ND10 nuclear bodies. Small amounts are cytoplasmic.
uniprot
proteins