Reviewed, UniProtKB/Swiss-Prot Q9H2X6 (HIPK2_HUMAN)

Names and origin

Protein names

Recommended name:
    Homeodomain-interacting protein kinase 2
      Short name=hHIPk2
    EC=2.7.11.1

Gene names

Name:

HIPK2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1198 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Protein kinase acting as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Inhibits cell growth and promotes apoptosis. Involved in transcriptional activation of TP53 and TP73. Phosphorylation of TP53 may be mediated by a TP53-HIPK2-AXIN1 complex. In response to TGFB, cooperates with DAXX to activate JNK. Phosphorylates the antiapoptotic factor CTBP1 and promotes its proteasomal degradation. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between TAK1 and NLK to promote the proteasomal degradation of MYB By similarity. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with TRADD, TP53, TP73, TP63, CREBBP, DAXX, P53DINP1, SKI, SMAD1, SMAD2 and SMAD3, but not SMAD4. Interacts with NKX1-2, NKX2-5, SPN/CD43, UBE2I, HMGA1, CTBP1, AXIN1, NLK, MYB, POU4F1, POU4F2, POU4F3, UBE2I, UBL1. Probably part of a complex consisting of TP53, HIPK2 and AXIN1 By similarity. Interacts with CBX4.
Subcellular location	Nucleus. Cytoplasm. Note: Concentrated in PML/POD/ND10 nuclear bodies. Small amounts are cytoplasmic. Ref.1 Ref.7 Ref.9 Ref.10 Ref.12
Tissue specificity	Highly expressed in heart, muscle and kidney. Weakly expressed in a ubiquitous way. Down-regulated in several thyroid and breast tumors. Ref.1 Ref.6
Induction	By UV. Ref.9
Post-translational modification	Phosphorylated on tyrosines By similarity. Autophosphorylated. 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.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Apoptosis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Inferred from direct assay. Source: UniProtKB apoptosis Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis by intracellular signals Non-traceable author statement. Source: UniProtKB positive regulation of JNK cascade Ref.11 Inferred from mutant phenotype. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from mutant phenotype. Source: UniProtKB positive regulation of transforming growth factor beta receptor signaling pathway Ref.11 Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro transcription Inferred from electronic annotation. Source: UniProtKB-KW virus-host interaction Non-traceable author statement. Source: UniProtKB
Cellular component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nuclear body Traceable author statement. Source: UniProtKB
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 Traceable author statement. Source: ProtInc virion binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BAT1	Q13838	1	EBI-348345,EBI-348622
HMGA1	P17096-1	1	EBI-348345,EBI-746854
HMGA1	P17096-2	1	EBI-348345,EBI-746858
MYB	P10242	1	EBI-348345,EBI-298355
WSB1	Q9Y6I7	1	EBI-348345,EBI-1171494

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q9H2X6-1)

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: Q9H2X6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     808-907: Missing.
     989-1018: VNTSHHSSSYKSKSSSNVTSTSGHSSGSSS → GNLGPGQGRNLSLESGFPAFLLLEMLLYGS
     1019-1198: Missing.

Isoform 3 (identifier: Q9H2X6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     595-621: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1198	1198	Homeodomain-interacting protein kinase 2		PRO_0000085995
Regions
	Domain	199 – 527	329	Protein kinase
	Nucleotide binding	205 – 213	9	ATP Probable
	Region	97 – 230	134	Transcriptional corepression By similarity
	Region	189 – 520	332	Interaction with DAXX
	Region	539 – 844	306	Interaction with SKI and SMAD1
	Region	752 – 897	146	Interaction with POU4F1 By similarity
	Region	774 – 876	103	Interaction with CTBP1 By similarity
	Region	787 – 897	111	Interaction with HMGA1 By similarity
	Region	846 – 941	96	Interaction with TP53 and TP73
	Region	873 – 980	108	Required for localization to nuclear speckles By similarity
	Region	873 – 907	35	Interaction with UBE2I By similarity
	Region	935 – 1049	115	Interaction with AXIN1 By similarity
	Compositional bias	1088 – 1094	7	Poly-Ala
Sites
	Active site	324	1	Proton acceptor Probable
	Binding site	228	1	ATP Probable
Amino acid modifications
	Modified residue	361	1	Phosphotyrosine Ref.16
	Cross-link	32		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.15
	Cross-link	1191		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Natural variations
	Alternative sequence	595 – 621	27	Missing in isoform 3.		VSP_004804
	Alternative sequence	808 – 907	100	Missing in isoform 2.		VSP_004805
	Alternative sequence	989 – 1018	30	VNTSH…SGSSS → GNLGPGQGRNLSLESGFPAF LLLEMLLYGS in isoform 2.		VSP_004806
	Alternative sequence	1019 – 1198	180	Missing in isoform 2.		VSP_004807
	Natural variant	792	1	R → Q Ref.17		VAR_040547
	Natural variant	1027	1	R → Q Ref.17		VAR_040548
Experimental info
	Mutagenesis	228	1	K → A: Locates in the nucleoplasm, no effect on interaction with RANBP9. Ref.1 Ref.7 Ref.9 Ref.10 Ref.8 Ref.11 Ref.13
	Mutagenesis	228	1	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. Ref.1 Ref.7 Ref.9 Ref.10 Ref.8 Ref.11 Ref.13
	Mutagenesis	359 – 361	3	STY → AAF: Enhances BMP-induced transcriptional activation; when associated with R-228. Ref.13
	Sequence conflict	33	1	I → V in AAG41236. Ref.1
	Sequence conflict	59	1	L → P in AAG41236. Ref.1
	Sequence conflict	64	1	T → S in AAG41236. Ref.1
	Sequence conflict	169	1	S → F in AAG35710. Ref.4
	Sequence conflict	187	1	V → S in AAG35710. Ref.4
	Sequence conflict	202	1	L → S in AAG35710. Ref.4
	Sequence conflict	233	1	H → R in AAG41236. Ref.1
	Sequence conflict	471	1	N → I in AAL37371. Ref.2
	Sequence conflict	669	1	P → S in AAG35710. Ref.4
	Sequence conflict	711	1	T → N in AAG35710. Ref.4
	Sequence conflict	717 – 719	3	PPA → SPT in AAG35710. Ref.4
	Sequence conflict	724	1	T → D in AAG35710. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 6, 2002. Version 2. Checksum: 6022D5710E8D2D93	FASTA	1,198	130,966
	10 20 30 40 50 60 MAPVYEGMAS HVQVFSPHTL QSSAFCSVKK LKIEPSSNWD MTGYGSHSKV YSQSKNIPLS 70 80 90 100 110 120 QPATTTVSTS LPVPNPSLPY EQTIVFPGST 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 DADKRITPIE TLNHPFVTMT HLLDFPHSTH 550 560 570 580 590 600 VKSCFQNMEI CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQAPSSTS 610 620 630 640 650 660 ATISLANPEV SILNYPSTLY QPSAASMAAV AQRSMPLQTG TAQICARPDP FQQALIVCPP 670 680 690 700 710 720 GFQGLQASPS KHAGYSVRME NAVPIVTQAP GAQPLQIQPG LLAQQAWPSG TQQILLPPAW 730 740 750 760 770 780 QQLTGVATHT SVQHATVIPE TMAGTQQLAD WRNTHAHGSH YNPIMQQPAL LTGHVTLPAA 790 800 810 820 830 840 QPLNVGVAHV MRQQPTSTTS SRKSKQHQSS VRNVSTCEVS SSQAISSPQR SKRVKENTPP 850 860 870 880 890 900 RCAMVHSSPA CSTSVTCGWG DVASSTTRER QRQTIVIPDT PSPTVSVITI SSDTDEEEEQ 910 920 930 940 950 960 KHAPTSTVSK QRKNVISCVT VHDSPYSDSS SNTSPYSVQQ RAGHNNANAF DTKGSLENHC 970 980 990 1000 1010 1020 TGNPRTIIVP PLKTQASEVL VECDSLVPVN TSHHSSSYKS KSSSNVTSTS GHSSGSSSGA 1030 1040 1050 1060 1070 1080 ITYRQQRPGP HFQQQQPLNL SQAQQHITTD RTGSHRRQQA YITPTMAQAP YSFPHNSPSH 1090 1100 1110 1120 1130 1140 GTVHPHLAAA AAAAHLPTQP HLYTYTAPAA LGSTGTVAHL VASQGSARHT VQHTAYPASI 1150 1160 1170 1180 1190 VHQVPVSMGP RVLPSPTIHP SQYPAQFAHQ TYISASPAST VYTGYPLSPA KVNQYPYI
	Isoform 2. Checksum: BA34005E15CFC5CD	FASTA	918	101,013
	10 20 30 40 50 60 MAPVYEGMAS HVQVFSPHTL QSSAFCSVKK LKIEPSSNWD MTGYGSHSKV YSQSKNIPLS 70 80 90 100 110 120 QPATTTVSTS LPVPNPSLPY EQTIVFPGST 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 DADKRITPIE TLNHPFVTMT HLLDFPHSTH 550 560 570 580 590 600 VKSCFQNMEI CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQAPSSTS 610 620 630 640 650 660 ATISLANPEV SILNYPSTLY QPSAASMAAV AQRSMPLQTG TAQICARPDP FQQALIVCPP 670 680 690 700 710 720 GFQGLQASPS KHAGYSVRME NAVPIVTQAP GAQPLQIQPG LLAQQAWPSG TQQILLPPAW 730 740 750 760 770 780 QQLTGVATHT SVQHATVIPE TMAGTQQLAD WRNTHAHGSH YNPIMQQPAL LTGHVTLPAA 790 800 810 820 830 840 QPLNVGVAHV MRQQPTSTTS SRKSKQHVSK QRKNVISCVT VHDSPYSDSS SNTSPYSVQQ 850 860 870 880 890 900 RAGHNNANAF DTKGSLENHC TGNPRTIIVP PLKTQASEVL VECDSLVPGN LGPGQGRNLS 910 LESGFPAFLL LEMLLYGS
	Isoform 3. Checksum: C38A3241948C7D66	FASTA	1,171	128,158
	10 20 30 40 50 60 MAPVYEGMAS HVQVFSPHTL QSSAFCSVKK LKIEPSSNWD MTGYGSHSKV YSQSKNIPLS 70 80 90 100 110 120 QPATTTVSTS LPVPNPSLPY EQTIVFPGST 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 DADKRITPIE TLNHPFVTMT HLLDFPHSTH 550 560 570 580 590 600 VKSCFQNMEI CKRRVNMYDT VNQSKTPFIT HVAPSTSTNL TMTFNNQLTT VHNQPSAASM 610 620 630 640 650 660 AAVAQRSMPL QTGTAQICAR PDPFQQALIV CPPGFQGLQA SPSKHAGYSV RMENAVPIVT 670 680 690 700 710 720 QAPGAQPLQI QPGLLAQQAW PSGTQQILLP PAWQQLTGVA THTSVQHATV IPETMAGTQQ 730 740 750 760 770 780 LADWRNTHAH GSHYNPIMQQ PALLTGHVTL PAAQPLNVGV AHVMRQQPTS TTSSRKSKQH 790 800 810 820 830 840 QSSVRNVSTC EVSSSQAISS PQRSKRVKEN TPPRCAMVHS SPACSTSVTC GWGDVASSTT 850 860 870 880 890 900 RERQRQTIVI PDTPSPTVSV ITISSDTDEE EEQKHAPTST VSKQRKNVIS CVTVHDSPYS 910 920 930 940 950 960 DSSSNTSPYS VQQRAGHNNA NAFDTKGSLE NHCTGNPRTI IVPPLKTQAS EVLVECDSLV 970 980 990 1000 1010 1020 PVNTSHHSSS YKSKSSSNVT STSGHSSGSS SGAITYRQQR PGPHFQQQQP LNLSQAQQHI 1030 1040 1050 1060 1070 1080 TTDRTGSHRR QQAYITPTMA QAPYSFPHNS PSHGTVHPHL AAAAAAAHLP TQPHLYTYTA 1090 1100 1110 1120 1130 1140 PAALGSTGTV AHLVASQGSA RHTVQHTAYP ASIVHQVPVS MGPRVLPSPT IHPSQYPAQF 1150 1160 1170 AHQTYISASP ASTVYTGYPL SPAKVNQYPY I

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-228. Tissue: Liver and Testis.
[2]	"Sequencing of hHIPk2, a human homolog of mouse homeodomain interacting protein kinase 2." Stukart G.C., Dias-Neto E. Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Frontal cortex.
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Pierantoni G.M., Benvenuto G., Chiariotti L., Fusco A. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-1198 (ISOFORM 2).
[5]	"The serine/threonine kinase HIPK2 interacts with TRADD, but not with CD95 or TNF-R1 in 293T cells." Li X., Wang Y., Debatin K.-M., Hug H. Biochem. Biophys. Res. Commun. 277:513-517(2000) [PubMed: 11032752] [Abstract] Cited for: INTERACTION WITH TRADD.
[6]	"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.
[7]	"HIPK2 associates with RanBPM." Wang Y., Marion Schneider E., Li X., Duttenhoefer I., Debatin K.-M., Hug H. Biochem. Biophys. Res. Commun. 297:148-153(2002) [PubMed: 12220523] [Abstract] Cited for: INTERACTION WITH RANBP9, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-228.
[8]	"Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo." Kim E.-J., Park J.-S., Um S.-J. J. Biol. Chem. 277:32020-32028(2002) [PubMed: 11925430] [Abstract] Cited for: INTERACTION WITH TP73; TP53 AND TP63, MUTAGENESIS OF LYS-228, FUNCTION.
[9]	"Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2." Hofmann T.G., Moeller A., Sirma H., Zentgraf H., Taya Y., Droege W., Will H., Schmitz M.L. Nat. Cell Biol. 4:1-10(2002) [PubMed: 11740489] [Abstract] Cited for: SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, INTERACTION WITH TP53 AND CREBBP, MUTAGENESIS OF LYS-228, FUNCTION, INDUCTION.
[10]	"PML is required for homeodomain-interacting protein kinase 2 (HIPK2)-mediated p53 phosphorylation and cell cycle arrest but is dispensable for the formation of HIPK domains." Moeller A., Sirma H., Hofmann T.G., Rueffer S., Klimczak E., Droege W., Will H., Schmitz M.L. Cancer Res. 63:4310-4314(2003) [PubMed: 12907596] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-228.
[11]	"HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal kinase activation and apoptosis in human hepatoma cells." Hofmann T.G., Stollberg N., Schmitz M.L., Will H. Cancer Res. 63:8271-8277(2003) [PubMed: 14678985] [Abstract] Cited for: FUNCTION, INTERACTION WITH DAXX, MUTAGENESIS OF LYS-228.
[12]	"TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity." Tomasini R., Samir A.A., Carrier A., Isnardon D., Cecchinelli B., Soddu S., Malissen B., Dagorn J.-C., Iovanna J.L., Dusetti N.J. J. Biol. Chem. 278:37722-37729(2003) [PubMed: 12851404] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH P53DINP1.
[13]	"Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation." Harada J., Kokura K., Kanei-Ishii C., Nomura T., Khan M.M., Kim Y., Ishii S. J. Biol. Chem. 278:38998-39005(2003) [PubMed: 12874272] [Abstract] Cited for: FUNCTION, INTERACTION WITH SKI; SMAD1; SMAD2 AND SMAD3, MUTAGENESIS OF LYS-228 AND 359-SER--TYR-361.
[14]	"Desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) through the cytoplasmic-nuclear shuttling of the SUMO-specific protease SENP1." Kim Y.H., Sung K.S., Lee S.-J., Kim Y.-O., Choi C.Y., Kim Y. FEBS Lett. 579:6272-6278(2005) [PubMed: 16253240] [Abstract] Cited for: DESUMOYLATION.
[15]	"Phosphorylation-dependent control of Pc2 SUMO E3 ligase activity by its substrate protein HIPK2." Roscic A., Moeller A., Calzado M.A., Renner F., Wimmer V.C., Gresko E., Luedi K.S., Schmitz M.L. Mol. Cell 24:77-89(2006) [PubMed: 17018294] [Abstract] Cited for: INTERACTION WITH CBX4, SUMOYLATION AT LYS-32, FUNCTION.
[16]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-361, MASS SPECTROMETRY.
[17]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-792 AND GLN-1027.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF208291 mRNA. Translation: AAG41236.1. AF326592 mRNA. Translation: AAL37371.1. AC005531 Genomic DNA. Translation: AAS00368.1. AC073184 Genomic DNA. No translation available. AC006021 Genomic DNA. No translation available. AC141932 Genomic DNA. No translation available. AF207702 mRNA. Translation: AAG35710.1.
IPI	IPI00215949. IPI00215950. IPI00289892.
RefSeq	NP_001106710.1. NP_073577.3.
UniGene	Hs.397465 Hs.632033
3D structure databases
HSSP	HSSP built from PDB template 1H0V based on UniProtKB P24941.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H2X6. 5 interactions.
PTM databases
PhosphoSite	Q9H2X6.
Proteomic databases
PRIDE	Q9H2X6.
Genome annotation databases
Ensembl	ENSG00000064393. Homo sapiens. [Contig view]
GeneID	28996.
KEGG	hsa:28996.
Organism-specific databases
GeneCards	GC07M138907. GC07M138908.
H-InvDB	HIX0007135. HIX0033770.
HGNC	HGNC:14402. HIPK2.
MIM	606868. gene.
PharmGKB	PA29291.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9H2X6.
HOVERGEN	Q9H2X6.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Gene expression databases
ArrayExpress	Q9H2X6.
Bgee	Q9H2X6.
CleanEx	HS_HIPK2.
GermOnline	ENSG00000064393. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	51926.
PMAP-CutDB	Q9H2X6.
SOURCE	Search...

Entry information

Entry name

HIPK2_HUMAN

Accession

Primary (citable) accession number: Q9H2X6
Secondary accession number(s): Q75MR7, Q8WWI4, Q9H2Y1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	June 6, 2002
Last modified:	June 16, 2009
This is version 89 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)