Prostatic Acid Phosphatase (ACPP) Enzyme

This gene encodes an enzyme that catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is synthesized under androgen regulation and is secreted by the epithelial cells of the prostate gland. An alternatively spliced transcript variant encoding a longer isoform has been found for this gene. This isoform contains a transmembrane domain and is localized in the plasma membrane-endosomal-lysosomal pathway. [provided by RefSeq, Sep 2008]

Function: A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins. Has lipid phosphatase activity and inactivates lysophosphatidic acid in seminal plasma. Ref.11 Ref.13 Ref.15 Ref.18Isoform 2: the cellular form also has ecto-5'-nucleotidase activity in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP which acts as a pain suppressor. Acts as a tumor suppressor of prostate cancer through dephosphorylation of ERBB2 and deactivation of MAPK-mediated signaling. Ref.11 Ref.13 Ref.15 Ref.18

Catalytic activity: A phosphate monoester + H2O = an alcohol + phosphate. Ref.11A 5'-ribonucleotide + H2O = a ribonucleoside + phosphate. Ref.11

Enzyme regulation: Phosphatase activity inhibited by L+-tartrate, and by its derivative, alpha-benzylaminobenzylphosphonic acid. Ref.10

Subunit structure: Homodimer; dimer formation is required for phosphatase activity

By similarity.

Subcellular location: Isoform 1: Secreted Ref.12 Ref.14. Isoform 2: Cell membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane protein. Note: Appears to shuttle between the cell membrane and intracellular vesicles. Colocalizes with FLOT1 at cell membrane and in intracellular vesicles. Colocalizes with LAMP2 on the lysosome membrane. Ref.12 Ref.14

Tissue specificity: Highly expressed in the prostate, restricted to glandular and ductal epithelial cells. Also expressed in bladder, kidney, pancreas, lung, cervix, testis and ovary. Weak expression in a subset of pancreatic islet cells, squamous epithelia, the pilosebaceous unit, colonic neuroendocrine cells and skin adnexal structures. Isoform 2 also expressed in the sarcolemma of skeletal muscle. Levels of this cellular isoform decreased in prostate cancer. Ref.12 Ref.19

Post-translational modification: N-glycosylated. High mannose content, partially sialylated and fucosylated biantennary complex. Also fucosylated with partially sialylated triantennary complex oligosaccharides. Ref.9 Ref.21 Ref.22Proteolytically cleaved in seminal fluid to produce several peptides. Peptide PAPf39, the most prominent, forms amyloid beta-sheet fibrils, SEVI (semen-derived enhancer of viral infection) which entrap HIV virions, attach them to target cells and enhance infection. SEVI amyloid fibrils are degraded by polyphenol epigallocatechin-3-gallate (EGCG), a constituent of green tea. Target cell attachment and enhancement of HIV infection is inhibited by surfen. Also similarly boosts XMRV (xenotropic murine leukemia virus-related virus) infection. Ref.13 Ref.15

Miscellaneous: Used as a diagnostic tool for staging metastatic prostatic cancer.

Sequence similarities: Belongs to the histidine acid phosphatase family.