Zhang et al. (2005) reported 13 exons that span around 60 kb; however, up to 15 exons are listed in different databases.

Around 15 kb mRNA (full-length); 3594 bp open reading frame.
At least two alternative transcripts.
Entrez Nucleotide:
[NM_022740.4] Homo sapiens HIPK2, transcript variant 1; 15245 bp linear mRNA; full-length isoform,
[NM_001113239.2] Homo sapiens HIPK2, transcript variant 2; 15164 bp linear mRNA; this variant lacks an internal segment in the CDS, the resulting isoform is shorter.
UniProtHB/Swiss-Prot [Q9H2X6]:
[Q9H2X6-1] full-length isoform (1),
[Q9H2X6-2] isoform (2),
[Q9H2X6-3] isoform (3).
Ensemble Gene [ENSG00000064393]; 4 transcripts:
HIPK2-001 [ENST00000406875]; 15049 bp linear mRNA; 1198 amino acids,
HIPK2-002 [ENST00000428878]; 3969 bp linear mRNA; 1171 amino acids,
HIPK2-201 [ENST00000263551]; 14953 bp linear mRNA; 1198 amino acids,
HIPK2-202 [ENST00000342645]; 2757 bp linear mRNA; 918 amino acids.

Nothing known.

HIPK2 is a protein kinase of 1198 amino acids (131 kDa); posttranslational modifications: phosphorylation, ubiquitination, sumoylation at K25, caspase cleavage at D916 and D977.
Contains several motifs and domains (from N- to C-terminus): a nuclear localisation signal (NLS)1 (97-157), a kinase domain (192-520), an interaction domain for homeodomain transcription factors (583-798), a NLS2 (780-840) and a NLS3 within a speckle-retention signal (SRS) (860-967), a PEST sequence (839-934) and an autoinhibitory domain (935-1050).

HIPK2 is ubiquitously expressed (high mRNA levels in neuronal tissues, heart, muscle and kidney); but barely detectable at protein levels in unstressed cells. Protein levels increase upon genotoxic stress.

Mainly nuclear localisation, in nuclear bodies; but also found in nucleoplasm and cytoplasm.

HIPK2 is a potential tumour suppressor; in vivo data suggest at least a role as an haploinsufficient tumour suppressor in the skin of mice.
HIPK2 is a protein kinase that interacts with numerous transcription factors (such as p53, AML1(RUNX1), PAX6, c-MYB or NK3) as well as transcriptional regulators (such as CBP, p300, Groucho, CtBP, HMGA1 or Smads). In this way HIPK2 can activate or repress transcription and thereby influence differentiation, development and the DNA damage response.
HIPK2 is an unstable protein in unstressed cells. It is constantly degraded via the ubiquitin-proteasome system (mediated by the E3 ubiquitin ligases SIAH1/SIAH2, WSB1 and MDM2). Various types of DNA damage (e.g. UV, IR or chemotherapeutics) lead to stabilisation of the kinase and an HIPK2-mediated induction of apoptosis or presumably also senescence.
HIPK2 can promote the apoptotic program via p53-dependent and -independent pathways through phosphorylation of p53 at Ser46 or phosphorylation of the anti-apoptotic co-repressor CtBP at Ser422 (both actions leading to the transcription of pro-apoptotic target genes).
HIPK2 plays a role in the transcriptional regulation at low oxigen concentrations (hypoxia).
Interestingly, HIPK2 also seems to have pro-survival functions, at least in dopamine neurons.

HIPK2 is conserved from flies to man.

HIPK2 is rarely mutated (2 out of 130 cases) in acute myeloid leukemia (AML) and myelodyplastic syndrome (MDS) patients. Two missense mutations (R868W and N958I) within the speckle-retention signal (SRS) were reported. These mutations led to a changed nuclear localisation of HIPK2 and a decreased transactivation potential in AML1- and p53-dependent transcription. The mutants showed dominant-negative effects (Li et al., 2007).