Difference between revisions of "Phosphatase Subfamily DSP12"

Revision as of 21:25, 1 July 2015

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP12

DSP12 is a subfamily conserved throughout unikonts, but its function is poorly understood.

Evolution

DSP12 is conserved throughout unikonts and usually a single copy in each genome.

Domain

DSP12 has two domains: phosphatase domain and C-terminal Zinc binding domain. Zinc binding domain is dispensable for in vitro phosphatase activity but is essential for function in vivo. There is a phosphorylation site in Zinc binding domain, serine 335. The phosphorylation regulates subcellular targeting of hYVH1 and augments the DUSP12 G2/M phenotype [1]. The Zinc binding domain may act as a redox sensor to impede the active site cysteine from inactivating oxidation [2].

Function

The function of human DUSP12 is poorly understood, particularly in the aspect of its substrate. It interacts with Hsp70 and prevents heat-shock-induced cell death. This function is dependent on its phosphatase catalytic activity, since catalytically inactive DUSP12 is unable to interact with Hsp70 [3]. Human DUSP12 modulates cell cycle progression, which is mediated by its C-terminal zinc-binding domain. Similarly, in yeast, YVH1 which is human DUSP12 orthologs, regulates cell growth and morphogenesis [4], and these functions do not map to the phosphatase domain, but to the C-terminal Zinc binding domain [4, 5, 6]. Yeast YVH1 participates in 60S ribosome maturation in a phosphatase-independent manner [7, 8].

In addition, human DUSP12 has been shown to be a putative oncogene [6] and contribute to type 2 diabetes susceptibility in Caucasians [9].

YVH1, yeast's DSP12, is required for pre-autophagosomal structure formation after TORC1 inactivation [10].

References

1. Error fetching PMID 21521943: [Kozarova11]
2. Error fetching PMID 19567874: [Bonham09]
3. Error fetching PMID 18973475: [Sharda09]
4. Error fetching PMID 10852885: [Beeser00]
5. Error fetching PMID 10446167: [Muda99]
6. Error fetching PMID 21556130: [Cain11]
7. Error fetching PMID 19797079: [Kemmler09]
8. Error fetching PMID 19797078: [Lo09]
9. Error fetching PMID 16936214: [Das06]
10. Error fetching PMID 26125457: [Yeasmin15]