Phosphatase Subfamily MINPP1

Phosphatase Classification: Fold HP: Superfamily HP: Family HP, branch 2: MINPP1

MINPP1 is a non-protein phosphatase found in a broad of eukaryotes, including most metazoan and amoebazoan.

Evolution

MINPP1 is found broadly in eukaryotes but absent from many genomes, such as C elegans. Human has a single copy, but yeast have as many as five copies.

Domain

MINPP1 has a phosphatase domain, N-terminal signal peptide. A C-terminal xDEL has been hypothesized as an ER-retention signal, similar to KDEL [1]. However, the xDEL at the C-terminal is found only in vertebrates.

Functions

Human MIPP1 does not display any phosphoglycerate mutase activity. MINPP1 is the only hitherto known InsP6 (aka phytate) phosphatase [2] and is involved in cancer metabolism [3]. It has been shown to be predominantly localized in the lumen of the ER (endoplasmatic reticulum) [2, 4].

Human MIPP1 has biologically significant 2,3-BPG phosphatase activity [5]. Dictyostelium Mipp1 also shows 2,3-BPG phosphatase activity in vitro and in vivo [5]. TIGAR of HP2 family also dephosphorylates 2,3-BPG [6].

Yeast has as many as five MINPP1s, including PHO3, PHO5, PHO11, PHO12 and DIA3. The first four have been known to be involved in phosphate metabolism.

References

1. Romano PR, Wang J, O'Keefe RJ, Puzas JE, Rosier RN, and Reynolds PR. HiPER1, a phosphatase of the endoplasmic reticulum with a role in chondrocyte maturation. J Cell Sci. 1998 Mar;111 ( Pt 6):803-13. DOI:10.1242/jcs.111.6.803 |
2. Chi H, Yang X, Kingsley PD, O'Keefe RJ, Puzas JE, Rosier RN, Shears SB, and Reynolds PR. Targeted deletion of Minpp1 provides new insight into the activity of multiple inositol polyphosphate phosphatase in vivo. Mol Cell Biol. 2000 Sep;20(17):6496-507. DOI:10.1128/MCB.20.17.6496-6507.2000 |
3. Windhorst S, Lin H, Blechner C, Fanick W, Brandt L, Brehm MA, and Mayr GW. Tumour cells can employ extracellular Ins(1,2,3,4,5,6)P(6) and multiple inositol-polyphosphate phosphatase 1 (MINPP1) dephosphorylation to improve their proliferation. Biochem J. 2013 Feb 15;450(1):115-25. DOI:10.1042/BJ20121524 |
4. Ali N, Craxton A, and Shears SB. Hepatic Ins(1,3,4,5)P4 3-phosphatase is compartmentalized inside endoplasmic reticulum. J Biol Chem. 1993 Mar 25;268(9):6161-7.
5. Cho J, King JS, Qian X, Harwood AJ, and Shears SB. Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory capacity of the Rapoport-Luebering glycolytic shunt. Proc Natl Acad Sci U S A. 2008 Apr 22;105(16):5998-6003. DOI:10.1073/pnas.0710980105 |
6. Gerin I, Noël G, Bolsée J, Haumont O, Van Schaftingen E, and Bommer GT. Identification of TP53-induced glycolysis and apoptosis regulator (TIGAR) as the phosphoglycolate-independent 2,3-bisphosphoglycerate phosphatase. Biochem J. 2014 Mar 15;458(3):439-48. DOI:10.1042/BJ20130841 |