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, usually with multiple copies per genome. 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. For example, human, fruit fly, 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) hydrolyzes orthophosphoric monoesters to alcohol and phosphate, and is not known to have protein substrates. Mouse phenotypes for ACP2 include deformed bones alterations, lysosomal storage defects in the kidneys and central nervous system, and an increase in seizures.
References
- Obermüller S, Kiecke C, von Figura K, and Höning S. The tyrosine motifs of Lamp 1 and LAP determine their direct and indirect targetting to lysosomes. J Cell Sci. 2002 Jan 1;115(Pt 1):185-94. DOI:10.1242/jcs.115.1.185 |
- Hurt JK, Fitzpatrick BJ, Norris-Drouin J, and Zylka MJ. Secretion and N-linked glycosylation are required for prostatic acid phosphatase catalytic and antinociceptive activity. PLoS One. 2012;7(2):e32741. DOI:10.1371/journal.pone.0032741 |
- Meng TC and Lin MF. Tyrosine phosphorylation of c-ErbB-2 is regulated by the cellular form of prostatic acid phosphatase in human prostate cancer cells. J Biol Chem. 1998 Aug 21;273(34):22096-104. DOI:10.1074/jbc.273.34.22096 |
- Chuang TD, Chen SJ, Lin FF, Veeramani S, Kumar S, Batra SK, Tu Y, and Lin MF. Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth. J Biol Chem. 2010 Jul 30;285(31):23598-606. DOI:10.1074/jbc.M109.098301 |
- Zhang XQ, Lee MS, Zelivianski S, and Lin MF. Characterization of a prostate-specific tyrosine phosphatase by mutagenesis and expression in human prostate cancer cells. J Biol Chem. 2001 Jan 26;276(4):2544-50. DOI:10.1074/jbc.M006661200 |
- Quintero IB, Araujo CL, Pulkka AE, Wirkkala RS, Herrala AM, Eskelinen EL, Jokitalo E, Hellström PA, Tuominen HJ, Hirvikoski PP, and Vihko PT. Prostatic acid phosphatase is not a prostate specific target. Cancer Res. 2007 Jul 15;67(14):6549-54. DOI:10.1158/0008-5472.CAN-07-1651 |
- Fleisig H, El-Din El-Husseini A, and Vincent SR. Regulation of ErbB4 phosphorylation and cleavage by a novel histidine acid phosphatase. Neuroscience. 2004;127(1):91-100. DOI:10.1016/j.neuroscience.2004.04.060 |
- Yousef GM, Diamandis M, Jung K, and Diamandis EP. Molecular cloning of a novel human acid phosphatase gene (ACPT) that is highly expressed in the testis. Genomics. 2001 Jun 15;74(3):385-95. DOI:10.1006/geno.2001.6556 |
