Phosphatase Subfamily ACP5
Phosphatase Classification: Fold PPPL: Superfamily PPPL: Family PAP: ACP5
ACP5 subfamily is found in most eukaryotes. Human ACP5 hydrolyzes a variety of phosphomonoesters at acid pH in vitro. It also show phosphatase activity towards protein osteopontin, and mannose 6-phosphate modification on lysosomal proteins.
Evolution
ACP5 is present in most eukaryotic groups, such as animals and plants. It is found in few fungi, though. ACP5 is also observed in some prokaryotes. ACP5 subfamily has a single member in human genome, which is also called tartrate resistant acid phosphatase (TRAP) or uteroferrin. Fruit fly has a single ACP5 gene (CG1637), which encodes at least five protein isoforms. C. elegans, nematostella, sponge, monosiga and dicty have multiple ACP5 genes; some but not all locate close to each other, even in the form of tandem duplications.
One monosiga ACP5 ([Phosphatase_Sequence_MbreP089_AA]) has an additional SapB (Sphingolipid Activator Protein, B) domain. The unusual domain combination is also found in Salpingoeca rosetta, Capsaspora owczarzaki and Thecamonas trahens, suggesting it probably emerged in the common ancestor between Apusomonadida and Opisthokonta.
Domain
ACP5 has a purple acid phosphatase N-terminal domain, a phosphatase domain, and purple acid phosphatase C-terminal domain. The boundary of the phosphatase domain is defined according to the crystal structures [1, 2].
Function
Human ACP5 hydrolyzes a variety of phosphomonoesters at acid pH in vitro. ACP5 also acts as an osteopontin phosphatase [3]. Osteopontin is a protein that in humans is encoded by the SPP1 gene (secreted phosphoprotein 1). Osteopontin is involved in many biological processes including biomineralization, bone remodeling, immune functions in heart, chemotaxis, cell activation, apoptosis.
ACP5 also dephosphorylate mannose 6-phosphate modification on lysosomal proteins. Most newly synthesized proteins destined for the lysosome reach this location via a specific intracellular pathway. In the Golgi, a phosphotransferase specifically labels lysosomal proteins with mannose 6-phosphate (Man-6-P). This modification is recognized by receptors that target the lysosomal proteins to the lysosome where, in most cell types, the Man-6-P recognition marker is rapidly removed [4].
References
- Uppenberg J, Lindqvist F, Svensson C, Ek-Rylander B, and Andersson G. Crystal structure of a mammalian purple acid phosphatase. J Mol Biol. 1999 Jul 2;290(1):201-11. DOI:10.1006/jmbi.1999.2896 |
- Guddat LW, McAlpine AS, Hume D, Hamilton S, de Jersey J, and Martin JL. Crystal structure of mammalian purple acid phosphatase. Structure. 1999 Jul 15;7(7):757-67. DOI:10.1016/s0969-2126(99)80100-2 |
- Andersson G, Ek-Rylander B, Hollberg K, Ljusberg-Sjölander J, Lång P, Norgård M, Wang Y, and Zhang SJ. TRACP as an osteopontin phosphatase. J Bone Miner Res. 2003 Oct;18(10):1912-5. DOI:10.1359/jbmr.2003.18.10.1912 |
- Sun P, Sleat DE, Lecocq M, Hayman AR, Jadot M, and Lobel P. Acid phosphatase 5 is responsible for removing the mannose 6-phosphate recognition marker from lysosomal proteins. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16590-5. DOI:10.1073/pnas.0807472105 |
