Difference between revisions of "Phosphatase Subfamily ACP5"
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ACP5 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 <cite>sun08</cite>. This function is shared by the unrelated phosphatase [[Phosphatase_Subfamily_ACP2|ACP2]]. The loss of the ACP5 subfamily in yeast may parallel their lack of M6P-based sorting <cite>Li</cite>, though plants are also believed to lack M6P sorting, yet have ACP5 members. | ACP5 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 <cite>sun08</cite>. This function is shared by the unrelated phosphatase [[Phosphatase_Subfamily_ACP2|ACP2]]. The loss of the ACP5 subfamily in yeast may parallel their lack of M6P-based sorting <cite>Li</cite>, though plants are also believed to lack M6P sorting, yet have ACP5 members. | ||
| − | Human ACP5 also acts as an osteopontin phosphatase <cite>andersson03</cite>. [http://en.wikipedia.org/wiki/Osteopontin Osteopontin] is an extracellular phosphoprotein involved in biomineralization and bone remodeling, as well as immune functions in heart, chemotaxis, cell activation, apoptosis. It is phosphorylated by the Golgi-resident kinase, [http://kinase.com/wiki/index.php/Kinase_Family_GASK FAM20]. | + | Human ACP5 also acts as an osteopontin phosphatase <cite>andersson03</cite>. [http://en.wikipedia.org/wiki/Osteopontin Osteopontin] is an extracellular phosphoprotein involved in biomineralization and bone remodeling, as well as immune functions in heart, chemotaxis, cell activation, apoptosis. It is phosphorylated by the Golgi-resident kinase, [http://kinase.com/wiki/index.php/Kinase_Family_GASK FAM20]. ACP5 modulates the ability of osteopontin to cause osteoclast migration <cite>Ek-Rylander</cite> ACP5 is also secreted and may have roles in dendritic cell and macrophage activation<cite>Esfandiari, Raisanen</cite>, fetal erythropoesis <cite>Ying</cite> and adipogenesis <cite>Lang</cite>. Other reported ACP substrates include osteonectin, bone sialoprotein, gastrin, and casein<cite><Andersson95</cite>. |
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=== References === | === References === | ||
<biblio> | <biblio> | ||
| + | #Andersson95 pmid=8553850 | ||
#andersson03 pmid=14584906 | #andersson03 pmid=14584906 | ||
| + | #Ek-Rylander pmid=19854170 | ||
| + | #Esfandiari pmid=16939395 | ||
#Guddat99 pmid=10425678 | #Guddat99 pmid=10425678 | ||
| + | #Lang pmid=18320034 | ||
#Li pmid=18786576 | #Li pmid=18786576 | ||
| + | #Raisanen pmid=15845367 | ||
#sun08 pmid=18940929 | #sun08 pmid=18940929 | ||
#Uppenberg99 pmid=10388567 | #Uppenberg99 pmid=10388567 | ||
| + | #Ying pmid=25093463 | ||
</biblio> | </biblio> | ||
Revision as of 16:26, 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]. The single human member, ACP5 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].
Functions
ACP5 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 [4]. This function is shared by the unrelated phosphatase ACP2. The loss of the ACP5 subfamily in yeast may parallel their lack of M6P-based sorting [1], though plants are also believed to lack M6P sorting, yet have ACP5 members.
Human ACP5 also acts as an osteopontin phosphatase [5]. Osteopontin is an extracellular phosphoprotein involved in biomineralization and bone remodeling, as well as immune functions in heart, chemotaxis, cell activation, apoptosis. It is phosphorylated by the Golgi-resident kinase, FAM20. ACP5 modulates the ability of osteopontin to cause osteoclast migration [6] ACP5 is also secreted and may have roles in dendritic cell and macrophage activation[7, 8], fetal erythropoesis [9] and adipogenesis [10]. Other reported ACP substrates include osteonectin, bone sialoprotein, gastrin, and casein[11].
References
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