Q9QZR5 (HIPK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeodomain-interacting protein kinase 2
EC=2.7.11.1

Alternative name(s):
Nuclear body-associated kinase 1
Sialophorin tail-associated nuclear serine/threonine-protein kinase

Gene names

Name:	Hipk2
Synonyms:	Nbak1, Stank

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1196 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 phoyphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Ref.8 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.18 Ref.19 Ref.20 Ref.21
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with CREB1, SIAH1, WSB1, CBX4, TRADD, p53/TP53, TP73, TP63, CREBBP, DAXX, P53DINP1, SKI, SMAD1, SMAD2 and SMAD3, but not SMAD4 By similarity. Interacts with ATF1, PML, RUNX1, EP300, NKX1-2, NKX2-5, SPN/CD43, UBE2I, HMGA1, CTBP1, AXIN1, NLK, MYB, POU4F1, POU4F2, POU4F3, UBE2I, UBL1 and ZBTB4. Probably part of a complex consisting of p53/TP53, HIPK2 and AXIN1. Ref.1 Ref.2 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
Subcellular location	Nucleus › PML body. Cytoplasm By similarity Ref.1 Ref.2 Ref.4 Ref.7 Ref.21. Isoform 2: Nucleus. Cytoplasm. Note: Isoform 2 seems to be both nuclear and cytoplasmic. Ref.1 Ref.2 Ref.4 Ref.7 Ref.21
Tissue specificity	Ubiquitous. Abundant in muscle, heart, small intestine, stomach, kidney and brain; and low in testis, skin and lung. Ref.2 Ref.4 Ref.9
Developmental stage	At E15-E17, mainly in the developing retina, telencephalon and myoblasts. At E12.5, detected in the developing trigeminal and dorsal root ganglia, and in the developing spinal cord (at protein level). Highly induced during primary fetal liver erythropoiesis. Expressed in the inner retina during late embryogenesis, in nucleus. Highest levels at E14.5 for isoform 2 and P12.5 for isoform 1. Ref.9 Ref.14 Ref.20 Ref.21
Induction	During T-cell activation. Ref.2 Ref.17
Post-translational modification	Sumoylated. When conjugated it is directed to nuclear speckles. Desumoylated by SENP1. Sumoylation on Lys-32 is promoted by the E3 SUMO-protein ligase CBX4 By similarity. Ref.7 Autophosphorylated. Phosphorylated on tyrosines. Ref.8 Ref.10 Ref.16 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 By similarity. 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.
Disruption phenotype	Inhibited terminal erythroid cell proliferation and terminal enucleation, as well as reduced accumulation of hemoglobin. Impaired transcription of many genes involved in cell proliferation and apoptosis, and of erythroid-specific genes involved in hemoglobin biosynthesis, such as HBA and SLC25A37/MFRN. Enhanced stability of CTNNB1; accumulation of beta-catenin leading to the potentiation of beta-catenin-mediated cell proliferation and tumor formation. Small eyes with deficient lens, abnormal retinal lamination, and thickened retinas. Ref.18 Ref.20 Ref.21
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence AAC63011.1 differs from that shown. Reason: Frameshift at position 2.

Ontologies

Keywords
Biological process	Apoptosis DNA damage Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Tumor suppressor
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	adult walking behavior Inferred from mutant phenotype. Source: MGI anterior/posterior pattern specification Inferred from genetic interaction. Source: MGI apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW embryonic camera-type eye morphogenesis Inferred from mutant phenotype Ref.21. Source: DFLAT embryonic retina morphogenesis in camera-type eye Inferred from mutant phenotype Ref.21. Source: DFLAT iris morphogenesis Inferred from mutant phenotype Ref.21. Source: DFLAT lens induction in camera-type eye Inferred from mutant phenotype Ref.21. Source: DFLAT negative regulation of neuron apoptosis Inferred from mutant phenotype. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.1. Source: UniProtKB neuron differentiation Inferred from mutant phenotype Ref.21. Source: DFLAT positive regulation of DNA binding Inferred from direct assay Ref.1. Source: UniProtKB positive regulation of JNK cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from genetic interaction. Source: MGI positive regulation of transforming growth factor beta receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB retina layer formation Inferred from mutant phenotype Ref.21. Source: DFLAT smoothened signaling pathway Inferred from genetic interaction. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transforming growth factor beta receptor signaling pathway Inferred from mutant phenotype. Source: MGI voluntary musculoskeletal movement Inferred from mutant phenotype. Source: MGI
Cellular component	PML body Traceable author statement. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW transcription corepressor activity Inferred from direct assay Ref.1. Source: UniProtKB virion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Myb	P06876	2	EBI-366905,EBI-366934
Nlk	O54949	2	EBI-366905,EBI-366894
WSB1	Q9Y6I7	5	EBI-366905,EBI-1171494	From a different organism.

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9QZR5-1)

Also known as: Nbak1b; b;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9QZR5-2)

Also known as: Nbak1a; a;

The sequence of this isoform differs from the canonical sequence as follows:
     594-620: Missing.

Isoform 3 (identifier: Q9QZR5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: Missing.
     369-1196: Missing.

Isoform 4 (identifier: Q9QZR5-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: Missing.
     594-620: Missing.

Isoform 5 (identifier: Q9QZR5-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-480: Missing.
     595-605: APTTSSATLSL → KSQLIGLSPES
     606-1196: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1196	1196	Homeodomain-interacting protein kinase 2		PRO_0000085997
Regions
	Domain	199 – 527	329	Protein kinase
	Nucleotide binding	205 – 213	9	ATP Probable
	Region	97 – 230	134	Transcriptional corepression
	Region	189 – 520	332	Interaction with DAXX By similarity
	Region	539 – 844	306	Interaction with SKI and SMAD1 By similarity
	Region	752 – 897	146	Interaction with POU4F1
	Region	774 – 876	103	Interaction with CTBP1
	Region	787 – 897	111	Interaction with HMGA1
	Region	802 – 805	4	Nuclear localization signal 1 (NLS1) By similarity
	Region	832 – 835	4	Nuclear localization signal 2 (NLS2) By similarity
	Region	839 – 934	96	Interaction with TP53 and TP73
	Region	873 – 980	108	Localization to nuclear speckles
	Region	873 – 980	108	Required for localization to nuclear speckles By similarity
	Region	873 – 907	35	Interaction with UBE2I
	Region	884 – 908	25	SUMO interaction motifs (SIM); required for nuclear localization and kinase activity By similarity
	Region	935 – 1050	116	Interaction with AXIN1
	Region	984 – 1196	213	Autoinhibitory domain (AID) By similarity
	Compositional bias	1089 – 1092	4	Poly-Ala
Sites
	Active site	324	1	Proton acceptor Probable
	Binding site	228	1	ATP Probable
	Site	923 – 924	2	Cleavage; by CASP6 By similarity
	Site	984 – 985	2	Cleavage; by CASP6 By similarity
Amino acid modifications
	Modified residue	361	1	Phosphotyrosine Ref.16
	Modified residue	827	1	Phosphoserine By similarity
	Modified residue	838	1	Phosphothreonine By similarity
	Cross-link	32		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	1189		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Natural variations
	Alternative sequence	1 – 480	480	Missing in isoform 5.		VSP_013136
	Alternative sequence	1 – 7	7	Missing in isoform 3 and isoform 4.		VSP_013135
	Alternative sequence	369 – 1196	828	Missing in isoform 3.		VSP_013137
	Alternative sequence	594 – 620	27	Missing in isoform 2 and isoform 4.		VSP_004808
	Alternative sequence	595 – 605	11	APTTSSATLSL → KSQLIGLSPES in isoform 5.		VSP_013138
	Alternative sequence	606 – 1196	591	Missing in isoform 5.		VSP_013139
Experimental info
	Mutagenesis	228	1	K → R: No enzymatic activity, but still interacts with TP53 and NLK. Blocks the ability to induce cell growth arrest. Decreases corepressor activity. Ref.1 Ref.8 Ref.10 Ref.13
	Mutagenesis	1189	1	K → R: Inhibits localization to nuclear speckles. Ref.7
	Sequence conflict	460	1	I → T in AAC63011. Ref.1
	Sequence conflict	479	1	V → G in AAC63011. Ref.1
	Sequence conflict	705	1	Missing in AAG41237. Ref.3
	Sequence conflict	705	1	Missing in AAK07649. Ref.4
	Sequence conflict	719	1	A → T in AAC63011. Ref.1
	Sequence conflict	1120	1	A → R in AAC63011. Ref.1
	Sequence conflict	1132	1	T → A in AAK07650. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Nbak1b) (b) [UniParc]. Last modified April 27, 2001. Version 2. Checksum: 5C863BE377F3AAEF	FASTA	1,196	130,498
	10 20 30 40 50 60 MAPVYEGMAS HVQVFSPHTL QSSAFCSVKK LKVEPSSNWD MTGYGSHSKV YSQSKNIPPS 70 80 90 100 110 120 QPASTTVSTS LPIPNPSLPY EQTIIFPGST GHIVVTSASS TSVTGQVLGG PHNLMRRSTV 130 140 150 160 170 180 SLLDTYQKCG LKRKSEEIEN TSSVQIIEEH PPMIQNNASG ATVATATTST ATSKNSGSNS 190 200 210 220 230 240 EGDYQLVQHE VLCSMTNTYE VLEFLGRGTF GQVVKCWKRG TNEIVAIKIL KNHPSYARQG 250 260 270 280 290 300 QIEVSILARL STESADDYNF VRAYECFQHK NHTCLVFEML EQNLYDFLKQ NKFSPLPLKY 310 320 330 340 350 360 IRPVLQQVAT ALMKLKSLGL IHADLKPENI MLVDPSRQPY RVKVIDFGSA SHVSKAVCST 370 380 390 400 410 420 YLQSRYYRAP EIILGLPFCE AIDMWSLGCV IAELFLGWPL YPGASEYDQI RYISQTQGLP 430 440 450 460 470 480 AEYLLSAGTK TTRFFNRDTD SPYPLWRLKT PDDHEAETGI KSKEARKYIF NCLDDMAQVN 490 500 510 520 530 540 MTTDLEGSDM LVEKADRREF IDLLKKMLTI DADKRVTPIE TLNHPFVTMT HLLDFPHSAH 550 560 570 580 590 600 VKSCFQNMEI CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQAPTTSS 610 620 630 640 650 660 ATLSLANPEV SILNYQSALY QPSAASMAAV APRSMPLQTG TAQICARPDP FQQALIVCPP 670 680 690 700 710 720 GFQGLQASPS KHAGYSVRME NAVPIVTQAP GAQPLQIQPG LLAQQAWPGG AQQILLPPAW 730 740 750 760 770 780 QQLTGVATHT SVQHAAVIPE TMAGTQQLAD WRNTHAHGSH YNPIMQQPAL LTGHVTLPAA 790 800 810 820 830 840 QPLNVGVAHV MRQQPTSTTS SRKSKQHQSS VRNVSTCEVT SSQAISSPQR SKRVKENTPP 850 860 870 880 890 900 RCAMVHSSPA CSTSVTCGWG DVASSTTRER QRQTIVIPDT PSPTVSVITI SSDTDEEEEQ 910 920 930 940 950 960 KHAPTSTVSK QRKNVISCVT VHDSPYSDSS SNTSPYSVQQ RTGHNGTNTL DTKGGLENHC 970 980 990 1000 1010 1020 TGNPRTIIVP PLKTQASEVL VECDSLGPAI SASHHSSSFK SKSSSTVTST SGHSSGSSSG 1030 1040 1050 1060 1070 1080 AIAYRQQRPG PHFQQQQPLN LSQAQQHMAA DRTGSHRRQQ AYITPTMAQA PYTFPHNSPS 1090 1100 1110 1120 1130 1140 HGTVHPHLAA AAHLPTQPHL YTYTAPTALG STGTVAHLVA SQGSARHTVQ HTAYPASIVH 1150 1160 1170 1180 1190 QVPVSMGPRV LPSPTIHPSQ YPAQFAHQTY ISASPASTVY TGYPLSPAKV NQYPYI
	Isoform 2 (Nbak1a) (a) [UniParc]. Checksum: F8C5ED0ADE4CFE4F	FASTA	1,169	127,676
	10 20 30 40 50 60 MAPVYEGMAS HVQVFSPHTL QSSAFCSVKK LKVEPSSNWD MTGYGSHSKV YSQSKNIPPS 70 80 90 100 110 120 QPASTTVSTS LPIPNPSLPY EQTIIFPGST GHIVVTSASS TSVTGQVLGG PHNLMRRSTV 130 140 150 160 170 180 SLLDTYQKCG LKRKSEEIEN TSSVQIIEEH PPMIQNNASG ATVATATTST ATSKNSGSNS 190 200 210 220 230 240 EGDYQLVQHE VLCSMTNTYE VLEFLGRGTF GQVVKCWKRG TNEIVAIKIL KNHPSYARQG 250 260 270 280 290 300 QIEVSILARL STESADDYNF VRAYECFQHK NHTCLVFEML EQNLYDFLKQ NKFSPLPLKY 310 320 330 340 350 360 IRPVLQQVAT ALMKLKSLGL IHADLKPENI MLVDPSRQPY RVKVIDFGSA SHVSKAVCST 370 380 390 400 410 420 YLQSRYYRAP EIILGLPFCE AIDMWSLGCV IAELFLGWPL YPGASEYDQI RYISQTQGLP 430 440 450 460 470 480 AEYLLSAGTK TTRFFNRDTD SPYPLWRLKT PDDHEAETGI KSKEARKYIF NCLDDMAQVN 490 500 510 520 530 540 MTTDLEGSDM LVEKADRREF IDLLKKMLTI DADKRVTPIE TLNHPFVTMT HLLDFPHSAH 550 560 570 580 590 600 VKSCFQNMEI CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQPSAASM 610 620 630 640 650 660 AAVAPRSMPL QTGTAQICAR PDPFQQALIV CPPGFQGLQA SPSKHAGYSV RMENAVPIVT 670 680 690 700 710 720 QAPGAQPLQI QPGLLAQQAW PGGAQQILLP PAWQQLTGVA THTSVQHAAV IPETMAGTQQ 730 740 750 760 770 780 LADWRNTHAH GSHYNPIMQQ PALLTGHVTL PAAQPLNVGV AHVMRQQPTS TTSSRKSKQH 790 800 810 820 830 840 QSSVRNVSTC EVTSSQAISS PQRSKRVKEN TPPRCAMVHS SPACSTSVTC GWGDVASSTT 850 860 870 880 890 900 RERQRQTIVI PDTPSPTVSV ITISSDTDEE EEQKHAPTST VSKQRKNVIS CVTVHDSPYS 910 920 930 940 950 960 DSSSNTSPYS VQQRTGHNGT NTLDTKGGLE NHCTGNPRTI IVPPLKTQAS EVLVECDSLG 970 980 990 1000 1010 1020 PAISASHHSS SFKSKSSSTV TSTSGHSSGS SSGAIAYRQQ RPGPHFQQQQ PLNLSQAQQH 1030 1040 1050 1060 1070 1080 MAADRTGSHR RQQAYITPTM AQAPYTFPHN SPSHGTVHPH LAAAAHLPTQ PHLYTYTAPT 1090 1100 1110 1120 1130 1140 ALGSTGTVAH LVASQGSARH TVQHTAYPAS IVHQVPVSMG PRVLPSPTIH PSQYPAQFAH 1150 1160 QTYISASPAS TVYTGYPLSP AKVNQYPYI
	Isoform 3 [UniParc]. Checksum: F1F5B6095C8BCDA5	FASTA	361	39,990
	10 20 30 40 50 60 MASHVQVFSP HTLQSSAFCS VKKLKVEPSS NWDMTGYGSH SKVYSQSKNI PPSQPASTTV 70 80 90 100 110 120 STSLPIPNPS LPYEQTIIFP GSTGHIVVTS ASSTSVTGQV LGGPHNLMRR STVSLLDTYQ 130 140 150 160 170 180 KCGLKRKSEE IENTSSVQII EEHPPMIQNN ASGATVATAT TSTATSKNSG SNSEGDYQLV 190 200 210 220 230 240 QHEVLCSMTN TYEVLEFLGR GTFGQVVKCW KRGTNEIVAI KILKNHPSYA RQGQIEVSIL 250 260 270 280 290 300 ARLSTESADD YNFVRAYECF QHKNHTCLVF EMLEQNLYDF LKQNKFSPLP LKYIRPVLQQ 310 320 330 340 350 360 VATALMKLKS LGLIHADLKP ENIMLVDPSR QPYRVKVIDF GSASHVSKAV CSTYLQSRYY R
	Isoform 4 [UniParc]. Checksum: 7478F6F1DAF75DE1	FASTA	1,162	126,928
	10 20 30 40 50 60 MASHVQVFSP HTLQSSAFCS VKKLKVEPSS NWDMTGYGSH SKVYSQSKNI PPSQPASTTV 70 80 90 100 110 120 STSLPIPNPS LPYEQTIIFP GSTGHIVVTS ASSTSVTGQV LGGPHNLMRR STVSLLDTYQ 130 140 150 160 170 180 KCGLKRKSEE IENTSSVQII EEHPPMIQNN ASGATVATAT TSTATSKNSG SNSEGDYQLV 190 200 210 220 230 240 QHEVLCSMTN TYEVLEFLGR GTFGQVVKCW KRGTNEIVAI KILKNHPSYA RQGQIEVSIL 250 260 270 280 290 300 ARLSTESADD YNFVRAYECF QHKNHTCLVF EMLEQNLYDF LKQNKFSPLP LKYIRPVLQQ 310 320 330 340 350 360 VATALMKLKS LGLIHADLKP ENIMLVDPSR QPYRVKVIDF GSASHVSKAV CSTYLQSRYY 370 380 390 400 410 420 RAPEIILGLP FCEAIDMWSL GCVIAELFLG WPLYPGASEY DQIRYISQTQ GLPAEYLLSA 430 440 450 460 470 480 GTKTTRFFNR DTDSPYPLWR LKTPDDHEAE TGIKSKEARK YIFNCLDDMA QVNMTTDLEG 490 500 510 520 530 540 SDMLVEKADR REFIDLLKKM LTIDADKRVT PIETLNHPFV TMTHLLDFPH SAHVKSCFQN 550 560 570 580 590 600 MEICKRRVNM YDTVNQSKTP FITHVAPSTS TNLTMTFNNQ LTTVHNQPSA ASMAAVAPRS 610 620 630 640 650 660 MPLQTGTAQI CARPDPFQQA LIVCPPGFQG LQASPSKHAG YSVRMENAVP IVTQAPGAQP 670 680 690 700 710 720 LQIQPGLLAQ QAWPGGAQQI LLPPAWQQLT GVATHTSVQH AAVIPETMAG TQQLADWRNT 730 740 750 760 770 780 HAHGSHYNPI MQQPALLTGH VTLPAAQPLN VGVAHVMRQQ PTSTTSSRKS KQHQSSVRNV 790 800 810 820 830 840 STCEVTSSQA ISSPQRSKRV KENTPPRCAM VHSSPACSTS VTCGWGDVAS STTRERQRQT 850 860 870 880 890 900 IVIPDTPSPT VSVITISSDT DEEEEQKHAP TSTVSKQRKN VISCVTVHDS PYSDSSSNTS 910 920 930 940 950 960 PYSVQQRTGH NGTNTLDTKG GLENHCTGNP RTIIVPPLKT QASEVLVECD SLGPAISASH 970 980 990 1000 1010 1020 HSSSFKSKSS STVTSTSGHS SGSSSGAIAY RQQRPGPHFQ QQQPLNLSQA QQHMAADRTG 1030 1040 1050 1060 1070 1080 SHRRQQAYIT PTMAQAPYTF PHNSPSHGTV HPHLAAAAHL PTQPHLYTYT APTALGSTGT 1090 1100 1110 1120 1130 1140 VAHLVASQGS ARHTVQHTAY PASIVHQVPV SMGPRVLPSP TIHPSQYPAQ FAHQTYISAS 1150 1160 PASTVYTGYP LSPAKVNQYP YI
	Isoform 5 [UniParc]. Checksum: 7052092228D50AD5	FASTA	125	14,279
	10 20 30 40 50 60 MTTDLEGSDM LVEKADRREF IDLLKKMLTI DADKRVTPIE TLNHPFVTMT HLLDFPHSAH 70 80 90 100 110 120 VKSCFQNMEI CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQKSQLIG LSPES

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors." Kim Y.H., Choi C.Y., Lee S.-J., Conti M.A., Kim Y. J. Biol. Chem. 273:25875-25879(1998) [PubMed: 9748262] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, INTERACTION WITH NKX1-2 AND NKX2-5, MUTAGENESIS OF LYS-228. Strain: BALB/c.
[2]	"Identification and cloning of a CD43-associated serine/threonine kinase." Wang W., Link V., Green J.M. Cell. Immunol. 205:34-39(2000) [PubMed: 11078605] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH SPN, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INDUCTION. Strain: BALB/c. Tissue: Heart.
[3]	"Isolation and characterization of cDNAs for the protein kinase HIPK2." Wang Y., Hofmann T.G., Runkel L., Haaf T., Schaller H., Debatin K.-M., Hug H. Biochim. Biophys. Acta 1518:168-172(2001) [PubMed: 11267674] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[4]	"US11 of herpes simplex virus type 1 interacts with HIPK2 and antagonizes HIPK2-induced cell growth arrest." Giraud S., Diaz-Latoud C., Hacot S., Textoris J., Bourette R.P., Diaz J.-J. J. Virol. 78:2984-2993(2004) [PubMed: 14990717] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, SUBCELLULAR LOCATION. Tissue: Heart.
[5]	"Protein kinases associated with PML/CBP nuclear bodies and filamentous threads regulate transcription and inhibit cell growth." Sather S.L., Johnson N.L., Johnson G.L. Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[6]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 5). Strain: C57BL/6J. Tissue: Testis.
[7]	"Covalent modification of the homeodomain-interacting protein kinase 2 (HIPK2) by the ubiquitin-like protein SUMO-1." Kim Y.H., Choi C.Y., Kim Y. Proc. Natl. Acad. Sci. U.S.A. 96:12350-12355(1999) [PubMed: 10535925] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH UBE2I, SUMOYLATION, MUTAGENESIS OF LYS-1189.
[8]	"High mobility group I (Y) proteins bind HIPK2, a serine-threonine kinase protein which inhibits cell growth." Pierantoni G.M., Fedele M., Pentimalli F., Benvenuto G., Pero R., Viglietto G., Santoro M., Chiariotti L., Fusco A. Oncogene 20:6132-6141(2001) [PubMed: 11593421] [Abstract] Cited for: INTERACTION WITH HMGA1, FUNCTION, PHOSPHORYLATION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-228.
[9]	"The homeodomain-interacting protein kinase 2 gene is expressed late in embryogenesis and preferentially in retina, muscle, and neural tissues." Pierantoni G.M., Bulfone A., Pentimalli F., Fedele M., Iuliano R., Santoro M., Chiariotti L., Ballabio A., Fusco A. Biochem. Biophys. Res. Commun. 290:942-947(2002) [PubMed: 11798164] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[10]	"Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis." D'Orazi G., Cecchinelli B., Bruno T., Manni I., Higashimoto Y., Saito S., Gostissa M., Coen S., Marchetti A., Del Sal G., Piaggio G., Fanciulli M., Appella E., Soddu S. Nat. Cell Biol. 4:11-19(2002) [PubMed: 11780126] [Abstract] Cited for: FUNCTION, INTERACTION WITH TP53, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-228.
[11]	"Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP." Zhang Q., Yoshimatsu Y., Hildebrand J., Frisch S.M., Goodman R.H. Cell 115:177-186(2003) [PubMed: 14567915] [Abstract] Cited for: FUNCTION, INTERACTION WITH CTBP1.
[12]	"Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation." Rui Y., Xu Z., Lin S., Li Q., Rui H., Luo W., Zhou H.-M., Cheung P.-Y., Wu Z., Ye Z., Li P., Han J., Lin S.-C. EMBO J. 23:4583-4594(2004) [PubMed: 15526030] [Abstract] Cited for: INTERACTION WITH AXIN1, IDENTIFICATION IN A COMPLEX WITH TP53 AND AXIN1.
[13]	"Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK." Kanei-Ishii C., Ninomiya-Tsuji J., Tanikawa J., Nomura T., Ishitani T., Kishida S., Kokura K., Kurahashi T., Ichikawa-Iwata E., Kim Y., Matsumoto K., Ishii S. Genes Dev. 18:816-829(2004) [PubMed: 15082531] [Abstract] Cited for: FUNCTION IN WNT SIGNALING, INTERACTION WITH NLK AND MYB, MUTAGENESIS OF LYS-228.
[14]	"Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival." Wiggins A.K., Wei G., Doxakis E., Wong C., Tang A.A., Zang K., Luo E.J., Neve R.L., Reichardt L.F., Huang E.J. J. Cell Biol. 167:257-267(2004) [PubMed: 15492043] [Abstract] Cited for: FUNCTION, INTERACTION WITH POU4F1; POU4F2 AND POU4F3, DEVELOPMENTAL STAGE.
[15]	"Roles of HIPK1 and HIPK2 in AML1- and p300-dependent transcription, hematopoiesis and blood vessel formation." Aikawa Y., Nguyen L.A., Isono K., Takakura N., Tagata Y., Schmitz M.L., Koseki H., Kitabayashi I. EMBO J. 25:3955-3965(2006) [PubMed: 16917507] [Abstract] Cited for: FUNCTION AS KINASE AND IN ANGIOGENESIS, INTERACTION WITH RUNX1 AND EP300.
[16]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-361, MASS SPECTROMETRY. Tissue: Brain.
[17]	"Targeting hypoxia in cancer cells by restoring homeodomain interacting protein-kinase 2 and p53 activity and suppressing HIF-1alpha." Nardinocchi L., Puca R., Sacchi A., Rechavi G., Givol D., D'Orazi G. PLoS ONE 4:E6819-E6819(2009) [PubMed: 19714248] [Abstract] Cited for: INDUCTION BY ZINC DURING HYPOXIA.
[18]	"Homeodomain-interacting protein kinase 2 (HIPK2) targets beta-catenin for phosphorylation and proteasomal degradation." Kim E.-A., Kim J.E., Sung K.S., Choi D.W., Lee B.J., Choi C.Y. Biochem. Biophys. Res. Commun. 394:966-971(2010) [PubMed: 20307497] [Abstract] Cited for: FUNCTION AS CTNNB1 KINASE, DISRUPTION PHENOTYPE.
[19]	"Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-269 is HIPK2-dependent and affects PDX1 subnuclear localization." An R., da Silva Xavier G., Semplici F., Vakhshouri S., Hao H.X., Rutter J., Pagano M.A., Meggio F., Pinna L.A., Rutter G.A. Biochem. Biophys. Res. Commun. 399:155-161(2010) [PubMed: 20637728] [Abstract] Cited for: FUNCTION AS PDX1 KINASE.
[20]	"Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation." Hattangadi S.M., Burke K.A., Lodish H.F. Blood 115:4853-4861(2010) [PubMed: 20231426] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
[21]	"Involvement of the Hipk family in regulation of eyeball size, lens formation and retinal morphogenesis." Inoue T., Kagawa T., Inoue-Mochita M., Isono K., Ohtsu N., Nobuhisa I., Fukushima M., Tanihara H., Taga T. FEBS Lett. 584:3233-3238(2010) [PubMed: 20579985] [Abstract] Cited for: FUNCTION IN EYE DEVELOPMENT, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF077659 mRNA. Translation: AAC63011.1. Frameshift. AF273680 mRNA. Translation: AAG02078.1. AF208292 mRNA. Translation: AAG41237.1. AF333791 mRNA. Translation: AAK07649.1. AF333792 mRNA. Translation: AAK07650.1. AF170301 mRNA. Translation: AAD52566.1. AF170302 mRNA. Translation: AAD52567.1. AK016742 mRNA. Translation: BAB30405.1. AK019821 mRNA. Translation: BAB31866.1.
IPI	IPI00134753. IPI00137890. IPI00228078. IPI00553731. IPI00553825.
PIR	T17088.
RefSeq	NP_001129537.1. NM_001136065.1. NP_034563.2. NM_010433.2.
UniGene	Mm.23790. Mm.391962.
3D structure databases
ProteinModelPortal	Q9QZR5.
SMR	Q9QZR5. Positions 174-529.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-31712N.
IntAct	Q9QZR5. 5 interactions.
STRING	Q9QZR5.
PTM databases
PhosphoSite	Q9QZR5.
Proteomic databases
PRIDE	Q9QZR5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000114856; ENSMUSP00000110506; ENSMUSG00000061436. ENSMUST00000160360; ENSMUSP00000125500; ENSMUSG00000061436. ENSMUST00000160962; ENSMUSP00000125572; ENSMUSG00000061436. ENSMUST00000161779; ENSMUSP00000124133; ENSMUSG00000061436. ENSMUST00000162359; ENSMUSP00000125150; ENSMUSG00000061436. ENSMUST00000164534; ENSMUSP00000131953; ENSMUSG00000061436.
GeneID	15258.
KEGG	mmu:15258.
UCSC	uc009bkw.2. mouse. uc009bkx.2. mouse. uc009blb.2. mouse.
Organism-specific databases
CTD	28996.
MGI	MGI:1314872. Hipk2.
Phylogenomic databases
eggNOG	roNOG05282.
GeneTree	ENSGT00550000074148.
HOVERGEN	HBG051908.
InParanoid	Q9QZR5.
OrthoDB	EOG4CVG63.
PhylomeDB	Q9QZR5.
Enzyme and pathway databases
BRENDA	2.7.11.1. 3474.
Gene expression databases
ArrayExpress	Q9QZR5.
Bgee	Q9QZR5.
CleanEx	MM_HIPK2.
Genevestigator	Q9QZR5.
GermOnline	ENSMUSG00000061436. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K08826.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	287877.
SOURCE	Search...

Entry information

Entry name

HIPK2_MOUSE

Accession

Primary (citable) accession number: Q9QZR5
Secondary accession number(s): O88905 , Q99P45, Q99P46, Q9D2E6, Q9D474, Q9EQL2, Q9QZR4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	April 27, 2001
Last modified:	January 25, 2012
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program