Homeodomain-interacting protein kinase 1

Names and origin

Protein names

Recommended name:
    Homeodomain-interacting protein kinase 1
    EC=2.7.11.1
Alternative name(s):
    Protein kinase Myak
    Nuclear body-associated kinase 2

Gene names

Name:	Hipk1
Synonyms:	Kiaa0630, Myak, Nbak2

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

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Protein attributes

Sequence length	1210 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	May play a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. May be involved in malignant squamous cell tumor formation. Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with Nkx1-2, Nkx2-5, DAXX, and TP53. Ref.6 Ref.1 Ref.5
Subcellular location	Nucleus. Cytoplasm. Note= Predominantly nuclear. Ref.5
Tissue specificity	Ubiquitously expressed, with high levels in reproductive tissues. Expressed in the epithelial layer of mammary gland, uterus and epididymis, in the corpus luteum, and in post-meiotic round spermatids. Ref.5 Ref.2
Developmental stage	Highest at E12, where it is expressed primarily in the central nervous system. Ref.2
Post-translational modification	Phosphorylated and activated by JNK1 By similarity. Autophosphorylated.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily. Contains 1 protein kinase domain.

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Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis Inferred from genetic interaction. Source: MGI anterior/posterior pattern formation Inferred from genetic interaction. Source: MGI negative regulation of transcription from RNA polymerase II promoter Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of DNA binding Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from genetic interaction. Source: MGI protein amino acid phosphorylation Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB smoothened signaling pathway Inferred from genetic interaction. Source: MGI
Cellular component	PML body Ref.5 Inferred from direct assay. Source: MGI cytoplasm Ref.5 Inferred from direct assay. Source: MGI nuclear speck Ref.5 Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro protein serine/threonine kinase activity Inferred from electronic annotation. Source: InterPro transcription corepressor activity Ref.1 Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAXX	Q9UER7	1	EBI-692945,EBI-77321	From a different organism.
Daxx	O35613	2	EBI-692945,EBI-77304

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Alternative products

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

Isoform 1 (identifier: O88904-1) Also known as: 2b; Myak-L; 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: O88904-2) Also known as: 2a; The sequence of this isoform differs from the canonical sequence as follows: 702-746: Missing.

Isoform 3 (identifier: O88904-3) Also known as: Myak-S; The sequence of this isoform differs from the canonical sequence as follows: 661-719: TGLQATTKHS...ATLHPQVATI → KSEQAEGNEG...KAFWIPCEDG 720-1209: Missing.

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1210

1210

Homeodomain-interacting protein kinase 1

PRO_0000085994

Regions

Domain

190 – 518

329

Protein kinase

Nucleotide binding

196 – 204

9

ATP Probable

Region

885 – 1093

209

Interaction with TP53

Sites

Active site

315

1

Proton acceptor Probable

Binding site

219

1

ATP Probable

Amino acid modifications

Modified residue

352

1

Phosphotyrosine Ref.7 Ref.8

Natural variations

Alternative sequence

661 – 719

59

TGLQA…QVATI → KSEQAEGNEGLGETESSPGG QESGSGVSQGETTGGAQEQI HNPWTTSNNKAFWIPCEDG in isoform 3.

VSP_013132

Alternative sequence

702 – 746

45

Missing in isoform 2.

VSP_013133

Alternative sequence

720 – 1209

490

Missing in isoform 3.

VSP_013134

Experimental info

Mutagenesis

219

1

K → A: Abolishes enzymatic activity Ref.5

Sequence conflict

732

1

Missing in AAC63010. Ref.1

Sequence conflict

921

1

K → E in AAC63010. Ref.1

Sequence conflict

953

1

H → Y Ref.4

Sequence conflict

954

1

P → S Ref.1

Sequence conflict

954

1

P → S Ref.4

Sequence conflict

1134

1

S → F in AAC63010. Ref.1

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 (2b) (Myak-L) [UniParc]. Last modified March 15, 2005. Version 2. Checksum: 26D264B883220640 Show »	FASTA	1,210	130,723
10 20 30 40 50 60 MASQLQVFSP PSVSSSAFCS AKKLKIEPSG WDVSGQSSND KYYTHSKTLP ATQGQASSSH 70 80 90 100 110 120 QVANFNLPAY DQGLLLPAPA VEHIVVTAAD SSGSAATATF QSSQTLTHRS NVSLLEPYQK 130 140 150 160 170 180 CGLKRKSEEV ESNGSVQIIE EHPPLMLQNR TVVGAAATTT TVTTKSSSSS GEGDYQLVQH 190 200 210 220 230 240 EILCSMTNSY EVLEFLGRGT FGQVAKCWKR STKEIVAIKI LKNHPSYARQ GQIEVSILSR 250 260 270 280 290 300 LSSENADEYN FVRSYECFQH KNHTCLVFEM LEQNLYDFLK QNKFSPLPLK YIRPILQQVA 310 320 330 340 350 360 TALMKLKSLG LIHADLKPEN IMLVDPVRQP YRVKVIDFGS ASHVSKAVCS TYLQSRYYRA 370 380 390 400 410 420 PEIILGLPFC EAIDMWSLGC VIAELFLGWP LYPGASEYDQ IRYISQTQGL PAEYLLSAGT 430 440 450 460 470 480 KTTRFFNRDP NLGYPLWRLK TPEEHELETG IKSKEARKYI FNCLDDMAQV NMSTDLEGTD 490 500 510 520 530 540 MLAEKADRRE YIDLLKKMLT IDADKRITPL KTLNHQFVTM SHLLDFPHSS HVKSCFQNME 550 560 570 580 590 600 ICKRRVHMYD TVSQIKSPFT THVAPNTSTN LTMSFSNQLN TVHNQASVLA SSSTAAAATL 610 620 630 640 650 660 SLANSDVSLL NYQSALYPSS AAPVPGVAQQ GVSLQPGTTQ ICTQTDPFQQ TFIVCPPAFQ 670 680 690 700 710 720 TGLQATTKHS GFPVRMDNAV PIVPQAPAAQ PLQIQSGVLT QGSCTPLMVA TLHPQVATIT 730 740 750 760 770 780 PQYAVPFTLS CAAGRPALVE QTAAVLQAWP GGTQQILLPS AWQQLPGVAL HNSVQPAAVI 790 800 810 820 830 840 PEAMGSSQQL ADWRNAHSHG NQYSTIMQQP SLLTNHVTLA TAQPLNVGVA HVVRQQQSSS 850 860 870 880 890 900 LPSKKNKQSA PVSSKSSLEV LPSQVYSLVG SSPLRTTSSY NSLVPVQDQH QPIIIPDTPS 910 920 930 940 950 960 PPVSVITIRS DTDEEEDNKY KPNSSSLKAR SNVISYVTVN DSPDSDSSLS SPHPTDTLSA 970 980 990 1000 1010 1020 LRGNSGTLLE GPGRPAADGI GTRTIIVPPL KTQLGDCTVA TQASGLLSSK TKPVASVSGQ 1030 1040 1050 1060 1070 1080 SSGCCITPTG YRAQRGGASA VQPLNLSQNQ QSSSASTSQE RSSNPAPRRQ QAFVAPLSQA 1090 1100 1110 1120 1130 1140 PYAFQHGSPL HSTGHPHLAP APAHLPSQPH LYTYAAPTSA AALGSTSSIA HLFSPQGSSR 1150 1160 1170 1180 1190 1200 HAAAYTTHPS TLVHQVPVSV GPSLLTSASV APAQYQHQFA TQSYIGSSRG STIYTGYPLS 1210 PTKISQYSYL « Hide
Isoform 2 (2a). Checksum: C082CA8CD6BB206C Show »		1,165	126,144
10 20 30 40 50 60 MASQLQVFSP PSVSSSAFCS AKKLKIEPSG WDVSGQSSND KYYTHSKTLP ATQGQASSSH 70 80 90 100 110 120 QVANFNLPAY DQGLLLPAPA VEHIVVTAAD SSGSAATATF QSSQTLTHRS NVSLLEPYQK 130 140 150 160 170 180 CGLKRKSEEV ESNGSVQIIE EHPPLMLQNR TVVGAAATTT TVTTKSSSSS GEGDYQLVQH 190 200 210 220 230 240 EILCSMTNSY EVLEFLGRGT FGQVAKCWKR STKEIVAIKI LKNHPSYARQ GQIEVSILSR 250 260 270 280 290 300 LSSENADEYN FVRSYECFQH KNHTCLVFEM LEQNLYDFLK QNKFSPLPLK YIRPILQQVA 310 320 330 340 350 360 TALMKLKSLG LIHADLKPEN IMLVDPVRQP YRVKVIDFGS ASHVSKAVCS TYLQSRYYRA 370 380 390 400 410 420 PEIILGLPFC EAIDMWSLGC VIAELFLGWP LYPGASEYDQ IRYISQTQGL PAEYLLSAGT 430 440 450 460 470 480 KTTRFFNRDP NLGYPLWRLK TPEEHELETG IKSKEARKYI FNCLDDMAQV NMSTDLEGTD 490 500 510 520 530 540 MLAEKADRRE YIDLLKKMLT IDADKRITPL KTLNHQFVTM SHLLDFPHSS HVKSCFQNME 550 560 570 580 590 600 ICKRRVHMYD TVSQIKSPFT THVAPNTSTN LTMSFSNQLN TVHNQASVLA SSSTAAAATL 610 620 630 640 650 660 SLANSDVSLL NYQSALYPSS AAPVPGVAQQ GVSLQPGTTQ ICTQTDPFQQ TFIVCPPAFQ 670 680 690 700 710 720 TGLQATTKHS GFPVRMDNAV PIVPQAPAAQ PLQIQSGVLT QQAWPGGTQQ ILLPSAWQQL 730 740 750 760 770 780 PGVALHNSVQ PAAVIPEAMG SSQQLADWRN AHSHGNQYST IMQQPSLLTN HVTLATAQPL 790 800 810 820 830 840 NVGVAHVVRQ QQSSSLPSKK NKQSAPVSSK SSLEVLPSQV YSLVGSSPLR TTSSYNSLVP 850 860 870 880 890 900 VQDQHQPIII PDTPSPPVSV ITIRSDTDEE EDNKYKPNSS SLKARSNVIS YVTVNDSPDS 910 920 930 940 950 960 DSSLSSPHPT DTLSALRGNS GTLLEGPGRP AADGIGTRTI IVPPLKTQLG DCTVATQASG 970 980 990 1000 1010 1020 LLSSKTKPVA SVSGQSSGCC ITPTGYRAQR GGASAVQPLN LSQNQQSSSA STSQERSSNP 1030 1040 1050 1060 1070 1080 APRRQQAFVA PLSQAPYAFQ HGSPLHSTGH PHLAPAPAHL PSQPHLYTYA APTSAAALGS 1090 1100 1110 1120 1130 1140 TSSIAHLFSP QGSSRHAAAY TTHPSTLVHQ VPVSVGPSLL TSASVAPAQY QHQFATQSYI 1150 1160 GSSRGSTIYT GYPLSPTKIS QYSYL « Hide
Isoform 3 (Myak-S). Checksum: FEEEFF23976995DD Show »		720	79,448
10 20 30 40 50 60 MASQLQVFSP PSVSSSAFCS AKKLKIEPSG WDVSGQSSND KYYTHSKTLP ATQGQASSSH 70 80 90 100 110 120 QVANFNLPAY DQGLLLPAPA VEHIVVTAAD SSGSAATATF QSSQTLTHRS NVSLLEPYQK 130 140 150 160 170 180 CGLKRKSEEV ESNGSVQIIE EHPPLMLQNR TVVGAAATTT TVTTKSSSSS GEGDYQLVQH 190 200 210 220 230 240 EILCSMTNSY EVLEFLGRGT FGQVAKCWKR STKEIVAIKI LKNHPSYARQ GQIEVSILSR 250 260 270 280 290 300 LSSENADEYN FVRSYECFQH KNHTCLVFEM LEQNLYDFLK QNKFSPLPLK YIRPILQQVA 310 320 330 340 350 360 TALMKLKSLG LIHADLKPEN IMLVDPVRQP YRVKVIDFGS ASHVSKAVCS TYLQSRYYRA 370 380 390 400 410 420 PEIILGLPFC EAIDMWSLGC VIAELFLGWP LYPGASEYDQ IRYISQTQGL PAEYLLSAGT 430 440 450 460 470 480 KTTRFFNRDP NLGYPLWRLK TPEEHELETG IKSKEARKYI FNCLDDMAQV NMSTDLEGTD 490 500 510 520 530 540 MLAEKADRRE YIDLLKKMLT IDADKRITPL KTLNHQFVTM SHLLDFPHSS HVKSCFQNME 550 560 570 580 590 600 ICKRRVHMYD TVSQIKSPFT THVAPNTSTN LTMSFSNQLN TVHNQASVLA SSSTAAAATL 610 620 630 640 650 660 SLANSDVSLL NYQSALYPSS AAPVPGVAQQ GVSLQPGTTQ ICTQTDPFQQ TFIVCPPAFQ 670 680 690 700 710 720 KSEQAEGNEG LGETESSPGG QESGSGVSQG ETTGGAQEQI HNPWTTSNNK AFWIPCEDGL « Hide

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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), INTERACTION WITH NKX1-2 AND NKX2-5. Strain: BALB/c.
[2]	"Murine Myak, a member of a family of yeast YAK1-related genes, is highly expressed in hormonally modulated epithelia in the reproductive system and in the embryonic central nervous system." Shang E., Wang X., Huang J., Yoshida W., Kuroiwa A., Wolgemuth D.J. Mol. Reprod. Dev. 55:372-378(2000) [PubMed: 10694743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Strain: CD-1. Tissue: Testis.
[3]	"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).
[4]	"Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H. DNA Res. 10:35-48(2003) [PubMed: 12693553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 608-1209 (ISOFORM 1). Tissue: Brain.
[5]	"Homeodomain-interacting protein kinase 1 modulates Daxx localization, phosphorylation, and transcriptional activity." Ecsedy J.A., Michaelson J.S., Leder P. Mol. Cell. Biol. 23:950-960(2003) [PubMed: 12529400] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH DAXX, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-219.
[6]	"Characterization of cells and gene-targeted mice deficient for the p53-binding kinase homeodomain-interacting protein kinase 1 (HIPK1)." Kondo S., Lu Y., Debbas M., Lin A.W., Sarosi I., Itie A., Wakeham A., Tuan J., Saris C., Elliott G., Ma W., Benchimol S., Lowe S.W., Mak T.W., Thukral S.K. Proc. Natl. Acad. Sci. U.S.A. 100:5431-5436(2003) [PubMed: 12702766] [Abstract] Cited for: INTERACTION WITH TP53, AUTOPHOSPHORYLATION, FUNCTION.
[7]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-352, MASS SPECTROMETRY.
[8]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-352, MASS SPECTROMETRY. Tissue: Brain cortex.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	AF077658 mRNA. Translation: AAC63010.1. AF071070 mRNA. Translation: AAD41592.1. AF071071 mRNA. Translation: AAD41593.1. AF170303 mRNA. Translation: AAD52568.1. AF170304 mRNA. Translation: AAD52569.1. AK122333 mRNA. Translation: BAC65615.1.
PIR	T14357.
RefSeq	NP_034562.2.
UniGene	Mm.20827 Mm.469359
3D structure databases
HSSP	HSSP built from PDB template 1LEZ based on UniProtKB P47811.
ModBase	Search...
Protein-protein interaction databases
IntAct	O88904. 3 interactions.
PTM databases
PhosphoSite	O88904.
Genome annotation databases
Ensembl	ENSMUSG00000008730. Mus musculus. [Contig view]
GeneID	15257.
KEGG	mmu:15257.
Organism-specific databases
MGI	MGI:1314873. Hipk1.
Rouge	Search...
Phylogenomic databases
HOGENOM	O88904.
HOVERGEN	O88904.
Gene expression databases
ArrayExpress	O88904.
CleanEx	MM_HIPK1.
GermOnline	ENSMUSG00000008730. Mus musculus.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. 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	287873.
SOURCE	Search...

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Entry information

Entry name

HIPK1_MOUSE

Accession

Primary (citable) accession number: O88904
Secondary accession number(s): Q80TV5

Q9WVN7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 29, 2003
Last sequence update:	March 15, 2005
Last modified:	December 16, 2008
This is version 79 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents