Phosphatase Subfamily ACP2
Phosphatase Classification: Fold HP: Superfamily HP (histidine phosphatase): Family HP, branch 2: Subfamily ACP2
Contents
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.
Functions
Human ACPP (acid phosphatase, prostate) is a prostate epithelium-specific differentiation antigen, 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 [1, 2]. His-12 and Asp-258 of ACPP, but not Cys-183 or Cys-281, are required for the phosphatase activity [3].
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 [4]. It is worthy pointing out ACPT is specifically expressed in testis rather than brain (see [5] and GTEx).
References
- 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 |
- 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 |
- 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 |
