Phosphatase Subfamily ACP2

Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): Family HP, branch 2: Subfamily ACP2

Evolution

ACP2 is found in holozoa, amoebozoa and some protists, but is absent from some fungi and most plants. There are usually multiple copies per genome. For example, human and fruit fly have 3 and 5 copies, respectively.

Domain

ACP2 has either transmembrane region or signal peptide cleavage site at N terminus. Some members have predicted C-terminal transmembrane regions, which may contain targeting sequence. For example, the membrane-proximal 12 residues of the human ACP2 tail are necessary and sufficient to mediate recycling and that the tyrosine motif of ACP2 (YRHV) is the critical sequence element mediating recycling [1].

Posttranslational modification

Human ACPP, prostatic acid phosphatase, is glycosylated at three asparagine residues (N62, N188, N301) and has potent antinociceptive effects when administered to mice [2].

Functions

Human ACPP (acid phosphatase, prostate) is a prostate epithelium-specific differentiation antigen (see GTEx), and is decreased in prostate carcinomas. It has been show to downregulate prostate cell growth by dephosphorylating phosphotyrosine on c-ErbB-2, an oncoprotein in prostate cells [3, 4]. His-12 and Asp-258 of ACPP, but not Cys-183 or Cys-281, are required for the phosphatase activity [5]. Though ACPP is supposed to be prostate specific, one of its isoforms is found in a broad of tissues [6].

Human ACPT (acid phosphatase, testicular) can act as a tyrosine phosphatase to modulate signals mediated by ErbB4 that are important for neuronal development and synaptic plasticity. ACPT and ErbB4 are both expressed in the brain where they are enriched at post-synaptic sites. ACPT can inhibit basal and neuregulin-induced tyrosine phosphorylation of ErbB4. ACPT-dependent dephosphorylation can regulate the proteolytic cleavage of ErbB4, and this process can be reversed by applying the tyrosine phosphatase inhibitor, pervanadate [7]. It is worthy pointing out ACPT is specifically expressed in testis rather than brain (see [8] and GTEx).

References

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