dbPTM

HIPK2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	HIPK2_MOUSE
UniProt AC	Q9QZR5
Protein Name	Homeodomain-interacting protein kinase 2
Gene Name	Hipk2
Organism	Mus musculus (Mouse).
Sequence Length	1196
Subcellular Localization	Nucleus, PML body . Cytoplasm. Isoform 2: Nucleus. Cytoplasm. Isoform 2 seems to be both nuclear and cytoplasmic.
Protein 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..
Protein Sequence	MAPVYEGMASHVQVFSPHTLQSSAFCSVKKLKVEPSSNWDMTGYGSHSKVYSQSKNIPPSQPASTTVSTSLPIPNPSLPYEQTIIFPGSTGHIVVTSASSTSVTGQVLGGPHNLMRRSTVSLLDTYQKCGLKRKSEEIENTSSVQIIEEHPPMIQNNASGATVATATTSTATSKNSGSNSEGDYQLVQHEVLCSMTNTYEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILARLSTESADDYNFVRAYECFQHKNHTCLVFEMLEQNLYDFLKQNKFSPLPLKYIRPVLQQVATALMKLKSLGLIHADLKPENIMLVDPSRQPYRVKVIDFGSASHVSKAVCSTYLQSRYYRAPEIILGLPFCEAIDMWSLGCVIAELFLGWPLYPGASEYDQIRYISQTQGLPAEYLLSAGTKTTRFFNRDTDSPYPLWRLKTPDDHEAETGIKSKEARKYIFNCLDDMAQVNMTTDLEGSDMLVEKADRREFIDLLKKMLTIDADKRVTPIETLNHPFVTMTHLLDFPHSAHVKSCFQNMEICKRRVNMYDTVNQSKTPFITHVAPSTSTNLTMTFNNQLTTVHNQAPTTSSATLSLANPEVSILNYQSALYQPSAASMAAVAPRSMPLQTGTAQICARPDPFQQALIVCPPGFQGLQASPSKHAGYSVRMENAVPIVTQAPGAQPLQIQPGLLAQQAWPGGAQQILLPPAWQQLTGVATHTSVQHAAVIPETMAGTQQLADWRNTHAHGSHYNPIMQQPALLTGHVTLPAAQPLNVGVAHVMRQQPTSTTSSRKSKQHQSSVRNVSTCEVTSSQAISSPQRSKRVKENTPPRCAMVHSSPACSTSVTCGWGDVASSTTRERQRQTIVIPDTPSPTVSVITISSDTDEEEEQKHAPTSTVSKQRKNVISCVTVHDSPYSDSSSNTSPYSVQQRTGHNGTNTLDTKGGLENHCTGNPRTIIVPPLKTQASEVLVECDSLGPAISASHHSSSFKSKSSSTVTSTSGHSSGSSSGAIAYRQQRPGPHFQQQQPLNLSQAQQHMAADRTGSHRRQQAYITPTMAQAPYTFPHNSPSHGTVHPHLAAAAHLPTQPHLYTYTAPTALGSTGTVAHLVASQGSARHTVQHTAYPASIVHQVPVSMGPRVLPSPTIHPSQYPAQFAHQTYISASPASTVYTGYPLSPAKVNQYPYI

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
16	Phosphorylation	ASHVQVFSPHTLQSS HHCEEEECCHHHCCC	19.54	23485397
32	Sumoylation	FCSVKKLKVEPSSNW EEEEEEEEECCCCCC	54.13	-
51	Phosphorylation	YGSHSKVYSQSKNIP CCCCCCCEECCCCCC	12.53	22871156
52	Phosphorylation	GSHSKVYSQSKNIPP CCCCCCEECCCCCCC	30.85	22871156
54	Phosphorylation	HSKVYSQSKNIPPSQ CCCCEECCCCCCCCC	23.02	22871156
118	Phosphorylation	PHNLMRRSTVSLLDT HHHHHCHHHHHHHHH	23.85	23485397
135	Phosphorylation	KCGLKRKSEEIENTS HHCCCCCCHHCCCCC	44.49	23485397
141	Phosphorylation	KSEEIENTSSVQIIE CCHHCCCCCCCEEEC	15.02	23485397
252	Phosphorylation	SILARLSTESADDYN EEEEECCCCCCCCCC	38.25	23485397
273	Phosphorylation	CFQHKNHTCLVFEML HHHCCCCEEEHHHHH	19.54	23485397
359	Phosphorylation	HVSKAVCSTYLQSRY HHHHHHHHHHHHHCC	17.31	30635358
360	Phosphorylation	VSKAVCSTYLQSRYY HHHHHHHHHHHHCCC	24.11	25521595
361	Phosphorylation	SKAVCSTYLQSRYYR HHHHHHHHHHHCCCC	6.10	23485397
364	Phosphorylation	VCSTYLQSRYYRAPE HHHHHHHHCCCCCCH	21.47	21082442
430	Ubiquitination	YLLSAGTKTTRFFNR HHHCCCCCEEECCCC	47.16	-
441	Phosphorylation	FFNRDTDSPYPLWRL CCCCCCCCCCCCEEE	28.55	23485397
482	Phosphorylation	DMAQVNMTTDLEGSD HHHHCCCCCCCCCCC	16.38	23485397
517	Phosphorylation	IDADKRVTPIETLNH CCCCCCCCCHHHCCC	23.68	23485397
566	Phosphorylation	DTVNQSKTPFITHVA HHCCCCCCCCEEEEC	28.78	23485397
634	Phosphorylation	MAAVAPRSMPLQTGT HHHCCCCCCCCCCCC	24.56	23485397
668	Phosphorylation	GFQGLQASPSKHAGY CCCCCCCCCCCCCCE	19.42	23485397
687	Phosphorylation	ENAVPIVTQAPGAQP CCCEEEEECCCCCCC	21.52	23485397
815	Phosphorylation	QSSVRNVSTCEVTSS HHHCCCCEECEECCH	30.78	23485397
822	Phosphorylation	STCEVTSSQAISSPQ EECEECCHHHCCCCC	17.79	28066266
826	Phosphorylation	VTSSQAISSPQRSKR ECCHHHCCCCCHHHC	38.69	25619855
827	Phosphorylation	TSSQAISSPQRSKRV CCHHHCCCCCHHHCH	20.95	23485397
847	Phosphorylation	PRCAMVHSSPACSTS CCEEEECCCCCCCCE	26.97	-
924	Phosphorylation	SCVTVHDSPYSDSSS EEEEECCCCCCCCCC	15.74	-
934	Phosphorylation	SDSSSNTSPYSVQQR CCCCCCCCCCCEECC	26.54	23485397
991	Phosphorylation	DSLGPAISASHHSSS CCCCCCCEECCCCCC	26.31	23485397
993	Phosphorylation	LGPAISASHHSSSFK CCCCCEECCCCCCCC	18.23	23485397
1009	O-linked_Glycosylation	KSSSTVTSTSGHSSG CCCCEEEECCCCCCC	19.08	22517741
1042	Phosphorylation	QQQPLNLSQAQQHMA CCCCCCHHHHHHHHH	23.54	23485397
1153	Phosphorylation	MGPRVLPSPTIHPSQ CCCCCCCCCCCCHHH	30.43	23485397
1186	Phosphorylation	VYTGYPLSPAKVNQY EECCCCCCCHHCCCC	20.50	9748262
1189	Sumoylation	GYPLSPAKVNQYPYI CCCCCCHHCCCCCCC	45.14	-
1189	Sumoylation	GYPLSPAKVNQYPYI CCCCCCHHCCCCCCC	45.14	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
361	Y	Phosphorylation	Kinase	HIPK2	Q9H2X6	PSP
361	Y	Phosphorylation	Kinase	HIPK2	Q9QZR5	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	Mdm2	P23804	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
32	K	Sumoylation	-
Sumoylation on Lys-32 is promoted by the E3 SUMO-protein ligase CBX4 (By similarity).
46	S	Phosphorylation	-
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.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of HIPK2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
P53_MOUSE	Trp53	physical	15526030
AXIN1_MOUSE	Axin1	physical	15526030

Drug and Disease Associations

Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of HIPK2_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large-scale identification and evolution indexing of tyrosinephosphorylation sites from murine brain."; Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; J. Proteome Res. 7:311-318(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-361, AND MASSSPECTROMETRY.	18034455 [Abstract]

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