Eisspeedway

ACP1

ACP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesACP1, HAAP, LMW-PTP, acid phosphatase 1, soluble, LMWPTP, acid phosphatase 1
External IDsOMIM: 171500; MGI: 87881; HomoloGene: 38274; GeneCards: ACP1; OMA:ACP1 - orthologs
EC number3.1.3.2
Orthologs
SpeciesHumanMouse
Entrez

52

11431

Ensembl

ENSG00000143727

ENSMUSG00000044573

UniProt

P24666

Q9D358

RefSeq (mRNA)

NM_001040649
NM_004300
NM_007099
NM_177554

NM_001110239
NM_021330

RefSeq (protein)

NP_001035739
NP_004291
NP_009030

NP_001103709
NP_067305

Location (UCSC)Chr 2: 0.26 – 0.28 MbChr 12: 30.94 – 30.96 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5]

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.[6] Also in other cancers, e.g. colon cancer, high ACP1 protein levels are linked to aggressive disease.[7] 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.[8] 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,[9] while its inhibition appears useful for counteracting experimental [venous thromboembolism].[10] Currently, there are no clinically approved inhibitors that allow targeting ACP1 in patients.

Interactions

ACP1 has been shown to interact with EPH receptor A2[11] and EPH receptor B1.[12] The proto-oncogene Src has been suggested to be a direct target for ACP1 tyrosine phosphatase activity, but this has not been formally proven.[13]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000143727 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000044573 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: ACP1 acid phosphatase 1, soluble".
  6. ^ Ruela-de-Sousa RR, Hoekstra E, Hoogland AM, Souza Queiroz KC, Peppelenbosch MP, Stubbs AP, et al. (April 2016). "Low-Molecular-Weight Protein Tyrosine Phosphatase Predicts Prostate Cancer Outcome by Increasing the Metastatic Potential". European Urology. 69 (4): 710–719. doi:10.1016/j.eururo.2015.06.040. PMID 26159288.
  7. ^ Faria AV, Yu B, Mommersteeg M, de Souza-Oliveira PF, Andrade SS, Spaander MC, et al. (January 2022). "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. doi:10.1016/j.bbadis.2021.166280. PMID 34610471.
  8. ^ Faria AV, Tornatore TF, Milani R, Queiroz KC, Sampaio IH, Fonseca EM, et al. (November 2017). "Oncophosphosignaling Favors a Glycolytic Phenotype in Human Drug Resistant Leukemia". Journal of Cellular Biochemistry. 118 (11): 3846–3854. doi:10.1002/jcb.26034. PMID 28387439. S2CID 3915599.
  9. ^ Fernandes GV, Cavagis AD, Ferreira CV, Olej B, Leão M, Yano CL, et al. (June 2014). "Osteoblast adhesion dynamics: a possible role for ROS and LMW-PTP". Journal of Cellular Biochemistry. 115 (6): 1063–1069. doi:10.1002/jcb.24691. PMID 24123071. S2CID 7383008.
  10. ^ Faria AV, Andrade SS, Reijm AN, Spaander MC, de Maat MP, Peppelenbosch MP, et al. (June 2019). "Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients". Journal of Clinical Medicine. 8 (7): 936. doi:10.3390/jcm8070936. PMC 6678874. PMID 31261776.
  11. ^ Kikawa KD, Vidale DR, Van Etten RL, Kinch MS (October 2002). "Regulation of the EphA2 kinase by the low molecular weight tyrosine phosphatase induces transformation". The Journal of Biological Chemistry. 277 (42): 39274–39279. doi:10.1074/jbc.M207127200. PMID 12167657.
  12. ^ Stein E, Lane AA, Cerretti DP, Schoecklmann HO, Schroff AD, Van Etten RL, Daniel TO (March 1998). "Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses". Genes & Development. 12 (5): 667–678. doi:10.1101/gad.12.5.667. PMC 316584. PMID 9499402.
  13. ^ Zambuzzi WF, Granjeiro JM, Parikh K, Yuvaraj S, Peppelenbosch MP, Ferreira CV (2008). "Modulation of Src activity by low molecular weight protein tyrosine phosphatase during osteoblast differentiation". Cellular Physiology and Biochemistry. 22 (5–6): 497–506. doi:10.1159/000185506. PMID 19088431.
  • 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


Quelle: https://en.wikipedia.org/wiki/ACP1