Homeodomain-interacting protein kinase 2 is an enzyme that in humans is encoded by the HIPK2 gene. HIPK2 can be categorized as a Serine/Threonine Protein kinase, specifically one that interacts with homeodomain transcription factors. It belongs to a family of protein kinases known as the DYRK kinases. Within this family HIPK2 belongs to a group of homeodomain-interacting protein kinases (HIPKs), including HIPK1 and HIPK3. HIPK2 can be found in a wide variety of species and its functions in gene expression and apoptosis are regulated by several different mechanisms. Discovery HIPK2 was discovered concurrently with HIPKs 1 and 3 in 1998. The HIPKs were discovered during an experiment that tried to identify genes that when expressed, yielded products that interacted with transcription factors related to the NK homeodomain . HIPKs were discovered using a technique called Two-hybrid screening. Two-hybrid screening is in conjunction with cDNA cloning, in which embryonic mouse cDNA libraries were used with mouse homeoprotein Nkx-1.2 to find genes involved with homeodomain transcription factors. The researchers found two clones that were similar in protein sequence, demonstrated a strong interaction with the homeoprotein, and an active site characteristic of protein kinases. These characteristics led to the name "HIPK". In 2000, the location of the HIPK2 gene was discovered to be on the long arm of Chromosome 7 (human) in the human genome. In mice, HIPK2 was discovered to be on Chromosome 6. Homology There is evidence to suggest that HIPKs including HIPK2 are evolutionarily conserved proteins across a wide array of species. The human sequence shares a close similarity to a sequence from the genome of Caenorhabditis elegans. HIPKs also share a close similarity with YAK1 in yeast and are in the same family as a kinase from Dictyostelium. Furthermore, HIPKs are able to interact with homeoproteins from other species, such as NK-1 and NK-3 in Drosophila as well as Nkx-2.5 in mice. HIPK2 can also be found in dogs, cats, sheep, and zebrafish as well as many other species. Localization Expression in tissues HIPK2 is expressed in nearly all tissue types, however it is highly expressed in the heart, muscle and kidneys. HIPK2 has been shown to be expressed at the highest levels in the brain and neuronal tissues. In addition to adult tissues, HIPK2 is also expressed late in the development of the Human embryo, specifically in the retina, muscles, and neural tissues. Sub-cellular localization HIPK2 is found in