Difference between revisions of "Phosphatase Subfamily ACP5"

Revision as of 15:21, 15 May 2016

Phosphatase Classification: Fold PPPL: Superfamily PPPL: Family PAP: ACP5

ACP5 is found in most eukaryotes. It removes the mannose-6-phosphate trafficking signal in lysosomal proteins and is also reported to have protein substrates, including osteopontin.

Evolution

ACP5 is present in some prokaryotes, and most eukaryotes, though absent from many fungi, which lack mannose-6-phosphate lysosomal targetting [1]. 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 Dictyostelium have multiple ACP5 genes; some are chromosomal neighbors, indicating recent duplication..

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. The human SapB, produced by the cleavage of human PSAP gene activates many enzymes through interaction with the substrates.

Another Monosiga ACP5 (Phosphatase_Sequence_MbreP088_AA) has an additional GBP (Guanylate-binding protein) domain; One Nematostella ACP5 has two tandem phosphatase domains. Neither of these domain combinations are conserved, and may be gene prediction artefacts.

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 [2, 3].

Function

Human ACP5 hydrolyzes a variety of phosphomonoesters at acid pH in vitro. ACP5 also acts as an osteopontin phosphatase [4]. 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 dephosphorylates mannose 6-phosphate (M6P) modification on lysosomal proteins. Most newly synthesized lysosomal proteins are labelled with M6P by a Golgi-resisdent phosphotransferase. This modification is recognized by receptors that target the lysosomal proteins to the lysosome where, in most cell types, the M6P recognition marker is rapidly removed [5]. This function is shared by the unrelated phosphatase ACP2.

References

1. Li SC and Kane PM. The yeast lysosome-like vacuole: endpoint and crossroads. Biochim Biophys Acta. 2009 Apr;1793(4):650-63. DOI:10.1016/j.bbamcr.2008.08.003 | PubMed ID:18786576 | HubMed [Li]
2. 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 | PubMed ID:10388567 | HubMed [Uppenberg99]
3. 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 | PubMed ID:10425678 | HubMed [Guddat99]
4. 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 | PubMed ID:14584906 | HubMed [andersson03]
5. 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 | PubMed ID:18940929 | HubMed [sun08]