ACP1 explained

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]

Further reading

• Junien C, Kaplan JC, Bernheim A, Berger R . Regional assignment of red cell acid phosphatase locus to band 2p25 . Human Genetics . 48 . 1 . 17–21 . April 1979 . 457131 . 10.1007/BF00273269 . 422040 .
• Sensabaugh GF, Golden VL . Phenotype dependence in the inhibition of red cell acid phosphatase (ACP) by folates . American Journal of Human Genetics . 30 . 5 . 553–560 . September 1978 . 736044 . 1685602 .
• Shekels LL, Smith AJ, Van Etten RL, Bernlohr DA . Identification of the adipocyte acid phosphatase as a PAO-sensitive tyrosyl phosphatase . Protein Science . 1 . 6 . 710–721 . June 1992 . 1304913 . 2142247 . 10.1002/pro.5560010603 .
• Wo YY, McCormack AL, Shabanowitz J, Hunt DF, Davis JP, Mitchell GL, Van Etten RL . Sequencing, cloning, and expression of human red cell-type acid phosphatase, a cytoplasmic phosphotyrosyl protein phosphatase . The Journal of Biological Chemistry . 267 . 15 . 10856–10865 . May 1992 . 10.1016/S0021-9258(19)50097-7 . 1587862 . free .
• Dissing J, Johnsen AH . Human red cell acid phosphatase (ACP1): the primary structure of the two pairs of isozymes encoded by the ACP1*A and ACP1*C alleles . Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology . 1121 . 3 . 261–268 . June 1992 . 1627603 . 10.1016/0167-4838(92)90155-7 .
• Dissing J, Johnsen AH, Sensabaugh GF . Human red cell acid phosphatase (ACP1). The amino acid sequence of the two isozymes Bf and Bs encoded by the ACP1*B allele . The Journal of Biological Chemistry . 266 . 31 . 20619–20625 . November 1991 . 10.1016/S0021-9258(18)54754-2 . 1939112 . free .
• Wakita Y, Narahara K, Takahashi Y, Kikkawa K, Kimura S, Oda M, Kimoto H . Duplication of 2p25: confirmation of the assignment of soluble acid phosphatase (ACP1) locus to 2p25 . Human Genetics . 71 . 3 . 259–260 . 1986 . 4065897 . 10.1007/BF00284586 . 10610694 .
• Blake NM, Kirk RL, Barnes KR, Thompson JM . Expression of human red cell acid phosphatase activity in placenta and other tissues . Jinrui Idengaku Zasshi. The Japanese Journal of Human Genetics . 18 . 1 . 10–23 . June 1973 . 4356849 .
• Sensabaugh GF, Lazaruk KA . A TaqI site identifies the *A allele at the ACP1 locus . Human Molecular Genetics . 2 . 7 . 1079 . July 1993 . 8364553 . 10.1093/hmg/2.7.1079-a .
• Bryson GL, Massa H, Trask BJ, Van Etten RL . Gene structure, sequence, and chromosomal localization of the human red cell-type low-molecular-weight acid phosphotyrosyl phosphatase gene, ACP1 . Genomics . 30 . 2 . 133–140 . November 1995 . 8586411 . 10.1006/geno.1995.9893 .
• Tailor P, Gilman J, Williams S, Couture C, Mustelin T . Regulation of the low molecular weight phosphotyrosine phosphatase by phosphorylation at tyrosines 131 and 132 . The Journal of Biological Chemistry . 272 . 9 . 5371–5374 . February 1997 . 9038134 . 10.1074/jbc.272.9.5371 . free .
• Stein E, Lane AA, Cerretti DP, Schoecklmann HO, Schroff AD, Van Etten RL, Daniel TO . Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses . Genes & Development . 12 . 5 . 667–678 . March 1998 . 9499402 . 316584 . 10.1101/gad.12.5.667 .
• Modesti A, Marzocchini R, Raugei G, Chiti F, Sereni A, Magherini F, Ramponi G . Cloning, expression and characterisation of a new human low Mr phosphotyrosine protein phosphatase originating by alternative splicing . FEBS Letters . 431 . 1 . 111–115 . July 1998 . 9684876 . 10.1016/S0014-5793(98)00732-7 . 38383291 . free .
• Zhang M, Stauffacher CV, Lin D, Van Etten RL . Crystal structure of a human low molecular weight phosphotyrosyl phosphatase. Implications for substrate specificity . The Journal of Biological Chemistry . 273 . 34 . 21714–21720 . August 1998 . 9705307 . 10.1074/jbc.273.34.21714 . free .
• Tailor P, Gilman J, Williams S, Mustelin T . A novel isoform of the low molecular weight phosphotyrosine phosphatase, LMPTP-C, arising from alternative mRNA splicing . European Journal of Biochemistry . 262 . 2 . 277–282 . June 1999 . 10336608 . 10.1046/j.1432-1327.1999.00353.x . free .
• Huang L, Sankar S, Lin C, Kontos CD, Schroff AD, Cha EH, Feng SM, Li SF, Yu Z, Van Etten RL, Blanar MA, Peters KG . 6 . HCPTPA, a protein tyrosine phosphatase that regulates vascular endothelial growth factor receptor-mediated signal transduction and biological activity . The Journal of Biological Chemistry . 274 . 53 . 38183–38188 . December 1999 . 10608891 . 10.1074/jbc.274.53.38183 . free .
• Nicolas G, Fournier CM, Galand C, Malbert-Colas L, Bournier O, Kroviarski Y, Bourgeois M, Camonis JH, Dhermy D, Grandchamp B, Lecomte MC . 6 . Tyrosine phosphorylation regulates alpha II spectrin cleavage by calpain . Molecular and Cellular Biology . 22 . 10 . 3527–3536 . May 2002 . 11971983 . 133798 . 10.1128/MCB.22.10.3527-3536.2002 .
• Bottini N, Stefanini L, Williams S, Alonso A, Jascur T, Abraham RT, Couture C, Mustelin T . 6 . Activation of ZAP-70 through specific dephosphorylation at the inhibitory Tyr-292 by the low molecular weight phosphotyrosine phosphatase (LMPTP) . The Journal of Biological Chemistry . 277 . 27 . 24220–24224 . July 2002 . 11976341 . 10.1074/jbc.M202885200 . free .
• Bottini N, Ammendola M, Gloria-Bottini F . ACP1 is associated with allergy . Allergy . 57 . 7 . 651–652 . July 2002 . 12100313 . 10.1034/j.1398-9995.2002.23722.x . 42578825 .
• Kikawa KD, Vidale DR, Van Etten RL, Kinch MS . 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 . 12167657 . 10.1074/jbc.M207127200 . free .

Notes and References

1. Web site: Entrez Gene: ACP1 acid phosphatase 1, soluble.
2. Ruela-de-Sousa RR, Hoekstra E, Hoogland AM, Souza Queiroz KC, Peppelenbosch MP, Stubbs AP, Pelizzaro-Rocha K, van Leenders GJ, Jenster G, Aoyama H, Ferreira CV, Fuhler GM . 6 . Low-Molecular-Weight Protein Tyrosine Phosphatase Predicts Prostate Cancer Outcome by Increasing the Metastatic Potential . European Urology . 69 . 4 . 710–719 . April 2016 . 26159288 . 10.1016/j.eururo.2015.06.040 .
3. Faria AV, Yu B, Mommersteeg M, de Souza-Oliveira PF, Andrade SS, Spaander MC, de Maat MP, Peppelenbosch MP, Ferreira-Halder CV, Fuhler GM . 6 . 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 . 34610471 . 10.1016/j.bbadis.2021.166280 . free .
4. Faria AV, Tornatore TF, Milani R, Queiroz KC, Sampaio IH, Fonseca EM, Rocha-Brito KJ, Santos TO, Silveira LR, Peppelenbosch MP, Ferreira-Halder CV . 6 . Oncophosphosignaling Favors a Glycolytic Phenotype in Human Drug Resistant Leukemia . Journal of Cellular Biochemistry . 118 . 11 . 3846–3854 . November 2017 . 28387439 . 10.1002/jcb.26034 . 3915599 .
5. Fernandes GV, Cavagis AD, Ferreira CV, Olej B, Leão M, Yano CL, Peppelenbosch M, Granjeiro JM, Zambuzzi WF . 6 . Osteoblast adhesion dynamics: a possible role for ROS and LMW-PTP . Journal of Cellular Biochemistry . 115 . 6 . 1063–1069 . June 2014 . 24123071 . 10.1002/jcb.24691 . 7383008 .
6. Faria AV, Andrade SS, Reijm AN, Spaander MC, de Maat MP, Peppelenbosch MP, Ferreira-Halder CV, Fuhler GM . 6 . Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients . Journal of Clinical Medicine . 8 . 7 . 936 . June 2019 . 31261776 . 10.3390/jcm8070936 . free . 6678874 .
7. Kikawa KD, Vidale DR, Van Etten RL, Kinch MS . 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 . 12167657 . 10.1074/jbc.M207127200 . free .
8. Stein E, Lane AA, Cerretti DP, Schoecklmann HO, Schroff AD, Van Etten RL, Daniel TO . Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses . Genes & Development . 12 . 5 . 667–678 . March 1998 . 9499402 . 316584 . 10.1101/gad.12.5.667 .
9. Zambuzzi WF, Granjeiro JM, Parikh K, Yuvaraj S, Peppelenbosch MP, Ferreira CV . Modulation of Src activity by low molecular weight protein tyrosine phosphatase during osteoblast differentiation . Cellular Physiology and Biochemistry . 22 . 5–6 . 497–506 . 2008 . 19088431 . 10.1159/000185506 . free .