Phosphatase Subfamily ACP2

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

ACP2 is a phosphatase subfamily that is found in most eukaryotes. Human has three copies with different tissue specificity.

Evolution

ACP2 is found in holozoa, amoebozoa and some protists, but is absent from some fungi and most plants. Amoebozoan ACP2s are quite divergent from holozoan ACP2s in sequence. There are usually multiple copies per genome. Human, Drosophila, and C elegans have 3, 5 and 21 copies, respectively.

Domain Structure

ACP2 has either a transmembrane region or signal peptide at the N terminus. Vertebrate ACP2 has a C-terminal YRHV motif that is necessary and sufficient to mediate recycling between endosome and lysosome [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 its expression is decreased in prostate carcinomas. It has been shown to downregulate prostate cell growth by dephosphorylating phosphotyrosine on the oncoprotein ErbB2 [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 with the tyrosine phosphatase inhibitor, pervanadate [7]. Curiously, ACPT transcript appears to be expressed almost exclusively in testis ([8] and GTEx).

Human ACP2 (acid phosphatase2, lysosomal) removes phosphate from protein residues that have been modified with mannose-6-phosphate (M6P) on their arrival at the lysosome. M6P is a trafficking signal to direct proteins to the lysosome. This activity is also carried out by ACP5, from the PPPL fold [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 14, 15, 16, 16, 16, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 45, 46, 46, 46, 46, 46, 46, 46, 46, 47, 48, 49, 50, 51, 52, 53, 54]