Biology:ACP1

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Short description: Protein-coding gene in humans


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Generic protein structure example

Low molecular weight phosphotyrosine protein phosphatase is an enzyme that in humans is encoded by the ACP1 gene.

The product of this gene belongs to the phosphotyrosine protein phosphatase family of proteins. It functions as an acid phosphatase and a protein tyrosine phosphatase by hydrolyzing protein tyrosine phosphate to protein tyrosine and orthophosphate. This enzyme also hydrolyzes orthophosphoric monoesters to alcohol and orthophosphate. This gene is genetically polymorphic, and three common alleles segregating at the corresponding locus give rise to six phenotypes. Each allele appears to encode at least two electrophoretically different isozymes, Bf and Bs, which are produced in allele-specific ratios. Three transcript variants encoding distinct isoforms have been identified for this gene.[1]

Clinical significance

Clinically, increased expression of ACP1 is a biomarker for poor prognosis in prostate cancer has been linked to worse clinical behaviour of prostate cancer, possibly outperforming the widely used Gleason grading system with respect to this important parameter.[2] Also in other cancers, e.g. colon cancer, high ACP1 protein levels are linked to aggressive disease.[3] It has been suggested that ACP1 acts as a bona fide oncogene, but for now this notion remains unproven even if ACP1 overexpression drives cells towards a Warburg effect-like glycolytic phenotype.[4] Apart from cancer, ACP1 has also been linked to osteoporosis as the enzyme plays an important role in the interaction of the osteocyte with the bone environment,[5] while its inhibition appears useful for counteracting experimental [venous thromboembolism].[6] Currently, there are no clinically approved inhibitors that allow targeting ACP1 in patients.

Interactions

ACP1 has been shown to interact with EPH receptor A2[7] and EPH receptor B1.[8] The proto-oncogene Src has been suggested to be a direct target for ACP1 tyrosine phosphatase activity, but this has not been formally proven.[9]

References

  1. ↑ "Entrez Gene: ACP1 acid phosphatase 1, soluble". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=52. 
  2. ↑ "Low-Molecular-Weight Protein Tyrosine Phosphatase Predicts Prostate Cancer Outcome by Increasing the Metastatic Potential". European Urology 69 (4): 710–719. April 2016. doi:10.1016/j.eururo.2015.06.040. PMID 26159288. 
  3. ↑ "Platelet-dependent signaling and Low Molecular Weight Protein Tyrosine Phosphatase expression promote aggressive phenotypic changes in gastrointestinal cancer cells". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1868 (1): 166280. January 2022. doi:10.1016/j.bbadis.2021.166280. PMID 34610471. 
  4. ↑ "Oncophosphosignaling Favors a Glycolytic Phenotype in Human Drug Resistant Leukemia". Journal of Cellular Biochemistry 118 (11): 3846–3854. November 2017. doi:10.1002/jcb.26034. PMID 28387439. 
  5. ↑ "Osteoblast adhesion dynamics: a possible role for ROS and LMW-PTP". Journal of Cellular Biochemistry 115 (6): 1063–1069. June 2014. doi:10.1002/jcb.24691. PMID 24123071. 
  6. ↑ "Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients". Journal of Clinical Medicine 8 (7): 936. June 2019. doi:10.3390/jcm8070936. PMID 31261776. 
  7. ↑ "Regulation of the EphA2 kinase by the low molecular weight tyrosine phosphatase induces transformation". The Journal of Biological Chemistry 277 (42): 39274–39279. October 2002. doi:10.1074/jbc.M207127200. PMID 12167657. 
  8. ↑ "Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses". Genes & Development 12 (5): 667–678. March 1998. doi:10.1101/gad.12.5.667. PMID 9499402. 
  9. ↑ "Modulation of Src activity by low molecular weight protein tyrosine phosphatase during osteoblast differentiation". Cellular Physiology and Biochemistry 22 (5–6): 497–506. 2008. doi:10.1159/000185506. PMID 19088431. 

External links

  • Human ACP1 genome location and ACP1 gene details page in the UCSC Genome Browser.
  • Overview of all the structural information available in the PDB for UniProt: P24666 (Human Low molecular weight phosphotyrosine protein phosphatase) at the PDBe-KB.
  • Overview of all the structural information available in the PDB for UniProt: Q9D358 (Mouse Low molecular weight phosphotyrosine protein phosphatase) at the PDBe-KB.

Further reading




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