Human red cell acid phosphatase (ACP1): the primary structure of the two pairs of isozymes encoded by the ACP1*A and ACP1*C alleles

doi:10.1016/0167-4838(92)90155-7

Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology

Volume 1121, Issue 3, 24 June 1992, Pages 261-268

https://doi.org/10.1016/0167-4838(92)90155-7 Get rights and content

The Af, As, Cf and Cs isozymes encoded by the human red cell acid phosphatase ACP1^*A and ACP1^*C alleles, respectively, have been sequenced. All four isozymes consist of a single non-glycosylated peptide chain (157 residues), acetylated at the amino-terminal alanine residue. Each f isozyme differs from the corresponding s isozyme over the sequence segment 40–73, while the remaining four-fifth of the molecules are identical. These findings are consistent with results for the Bf and Bs isozymes encoded by the common ACP1^*B allele and confirm that the presence of a specific f or s segment is a common property to ACP1 isozymes. This supports our hypothesis that f and s isozymes are generated by alternative splicing of exons in the primary RNA transcript. Cf and Cs are identical in sequence with Bf and Bs, respectively. Thus, the ACP1^*B and ACP1^*C alleles encode exactly the same pair of isozymes, the only difference at the protein level being the ratio of f and s isozyme. Af and As differ from the Bf and Bs isozymes by a single substitution at residue 105; Arg and Gln, respectively. These observations explain the electrophoretic identity of the B and C isozyme pairs and the higher P_i of the A isozyme pair.

Reference (47)

DissingJ. et al.
Biochim. Biophys. Acta
(1990)
NaiduJ.M. et al.
Comp. Biochem. Physiol.
(1985)
PanaraF. et al.
Int. J. Biochem.
(1991)
BaxterJ.H. et al.
Arch. Biochem. Biophys.
(1985)
ZhangZ.-Y. et al.
Arch. Biochem. Biophys.
(1990)
DissingJ. et al.
J. Biol. Chem.
(1991)
TsuboiK.K. et al.
Arch. Biochem. Biophys.
(1955)
TsuboiK.K. et al.
Arch. Biochem. Biophys.
(1956)
ScottE.M.
J. Biol. Chem.
(1966)
SensabaughG.F.

TagaE.M. et al.

Arch. Biochem. Biophys.

(1982)

DiPietroD.L. et al.

J. Biol. Chem.

(1967)

HeinriksonR.L.

J. Biol. Chem.

(1969)

LawrenceG.L. et al.

Arch. Biochem. Biophys.

(1981)

ChaimovichH. et al.

Arch. Biochem. Biophys.

(1970)

WhiteI.N.H. et al.

Biochim. Biophys. Acta

(1971)

DiPietroD.L.

J. Biol. Chem.

(1968)

BoivinP. et al.

Biochem. Biophys. Res. Commun.

(1986)

DivallG.B.

Forensic Sci. Int.

(1981)

CamiciG. et al.

J. Biol. Chem.

(1989)

SwallowD.M. et al.

Ann. Hum. Genet.

(1973)

BlakeN.M. et al.

Jap. J. Hum. Genet.

(1973)

FujimotoS. et al.

Chem. Pharm. Bull.

(1988)

Cited by (29)

The role of protein tyrosine phosphatases in colorectal cancer
2012, Biochimica et Biophysica Acta - Reviews on Cancer
Citation Excerpt :
There are three common ACP1 alleles; A, B, and C, which give rise to six phenotypes. Subsequent alternative splicing of the ACP1 mRNA results in two isoforms of the LMWPTP protein, a slow migrating form (S) and a fast migrating form (F) [54]. The different genotypes of LMWPTP show different enzymatic activities and other molecular properties.
Colorectal cancer is one of the most common oncogenic diseases in the Western world. Several cancer associated cellular pathways have been identified, in which protein phosphorylation and dephosphorylation, especially on tyrosine residues, are one of most abundant regulatory mechanisms. The balance between these processes is under tight control by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Aberrant activity of oncogenic PTKs is present in a large portion of human cancers. Because of the counteracting role of PTPs on phosphorylation-based activation of signal pathways, it has long been thought that PTPs must act as tumor suppressors. This dogma is now being challenged, with recent evidence showing that dephosphorylation events induced by some PTPs may actually stimulate tumor formation. As such, PTPs might form a novel attractive target for anticancer therapy. In this review, we summarize the action of different PTPs, the consequences of their altered expression in colorectal cancer, and their potential as target for the treatment of this deadly disease.
A study of acid phosphatase locus 1 in women with high fat content and normal body mass index
2009, Metabolism: Clinical and Experimental
De Lorenzo and coworkers have recently described a class of women with normal body mass index (BMI) and high fat content (normal weight obese syndrome [NWO]). This observation prompted us to study the possible role of acid phosphatase locus 1 (ACP₁) in the differentiation of this special class of obese subjects. Acid phosphatase locus 1 is a polymorphic gene associated with severe obesity and with total cholesterol and triglycerides levels. The enzyme is composed by 2 isoforms—F and S—that have different biochemical properties and probably different functions. The sample study was composed of 130 white women from the population of Rome. Total fat mass and percentage of fat mass were measured by dual-energy x-ray absorptiometry. Thirty-six women had a BMI less than 25 and percentage of fat mass greater than 30 (high fat, normal BMI [HFHB]), and 94 women showed a BMI greater than 25 and a percentage of fat mass greater than 30 (high fat, high BMI [HFHB]). In the whole sample, the proportion of low-activity ACP₁ genotypes (*A/*A and *B/*A) was higher than in controls. However, whereas HFNB showed a very high frequency of ACP₁ *A/*A genotype, high-fat, high-BMI women showed an increase of *B/*A genotype. These 2 genotypes differ in the concentration of F isoform and the F/S ratio, which are lower in ACP₁*A/*A genotype than in ACP₁*B/*A genotype. The genetic differentiation of the class of women with normal BMI and high fat content from the class showing a concordant level of the 2 parameters supports the hypothesis that HFNB class represents a special cluster of obese subjects not revealed by BMI evaluation. Because ACP₁ is present in adipocytes, the present observation suggests that F isoform may have a specific role in the regulation of quantity of adipose tissue.
Is there an association between uterine leiomyomas and acid phosphatase locus 1 polymorphism?
2009, American Journal of Obstetrics and Gynecology
Citation Excerpt :
Thus, it is very likely that the 2 isoforms have, at least partly, different substrates and functions in intact cells. The amino acid sequence of LMPTP7,8 revealed that the 2 isoforms are encoded by a single gene and arise through a pre–messenger ribonucleic acid (mRNA) splicing process, in which either exon 3 or exon 4 is excised and the other retained.9,10 Therefore, the 2 isoforms are identical to each other outside the 40 amino acid region, called the variable loop, which is encoded by exon 4 in the S isoform and by exon 3 in the F isoform.
Platelet derived growth factor (PDGF) is involved in the development of leiomyomas. The low-molecular-weight phosphoprotein-tyrosine–phosphatase (LMWPTP), controlled by the highly polymorphic acid phosphatase locus 1 (ACP1), is able to dephosphorylate the PDGF receptor. Therefore, we searched for a possible association between ACP1 and leiomyomas.
We studied 172 women hospitalized for symptomatic leiomyomas requiring surgical intervention and 164 healthy women without clinical evidence of leiomyomas from the same white population. The χ² test of independence, Pearson correlation, analysis of variance, and post hoc test for difference between means were performed.
The distribution of ACP1 genotypes among patients does not differ significantly from that of healthy women. However, leiomyoma size was negatively correlated with ACP1 F isoform concentrations. Leiomyoma size was smaller among carriers of the *B/*B genotype, which has the highest concentration of the F isoform, than among carriers of *A/*A, *C/*B, and *C/*C genotypes, which have the lowest concentration of the F isoform.
High ACP1 F isoform concentration, through dephosphorylation of the PDGF receptor, may negatively regulate cell proliferation and growth of leiomyomas.
ACP1 and offspring sex ratio in smoking puerperae: A study at population level
2007, Early Human Development
Data from previous study by our group suggest that in smoking women sex ratio of offspring is higher in newborns carrying ACP1⁎C allele than in other ACP1 genotypes, suggesting that differences observed among human population concerning the effect of smoking may depend in part on this genetic factor.
In order to further explore this issue we have studied another population and have analysed the relationship between sex ratio and ACP1⁎C gene frequency at population level.
The analysis includes 719 consecutive births from Central Italy considered in a previous paper and 5510 consecutive births from Sardinia. Data from English and Japanese populations have also been considered in the analysis.
Among newborns not carrying ACP1⁎C there is a decrease of SR among the offspring of smoking mothers, while among newborns carrying the ACP1⁎C allele there is an increase of SR among the offspring of smoking mothers relative to non-smoking mothers. Considering Sardinian, Italian, English and Japanese population there is a linear positive relationship between ⁎C allele frequency and SR in smoking mothers.
The present observation suggests an interaction between smoking and ACP1 regarding their effects on sex ratio, by which the presence of the ACP1⁎C allele appears to counteract the effect of smoking. This suggests that genetic background may modify the effects of toxic environmental factors on gamete production and functionality and/or on intrauterine survival.
Evolutionary aspects of the gene for the classical enzyme polymorphism, ACP1
2003, International Congress Series
The gene for the classical polymorphic marker, ACP1, contains an unusual construction, two alternative exons, 3F and 3S, interspaced by a short 41-bp non-coding sequence, too short to function as a normal intron. During processing, two different mRNAs are produced, one containing 3F, the other 3S, resulting in the expression of two isoforms of the enzyme in human tissues. The fast and slow isoforms have different enzymatic properties and may have different physiological functions. This low molecular weight enzyme seems to function as a protein phosphotyrosine phosphatase (LMPTP). The LMPTP gene is highly conserved through evolution and has been found all the way back to yeasts, however, these express only one isoform. The ability to generate two functionally different isoforms by alternative splicing may be of evolutionary significance. We have analysed various species for LMPTP isoforms and gene structure. Two isoforms with different properties were observed in mammals and in fish, even in the evolutionary old shark. Exons similar to the human 3F and 3S were detected in cow, pig and cod, however, the intron between them is longer, 47 bp in cow and pig and 56 bp in cod.
Association of the acid phosphatase (ACP1) gene with triglyceride levels in obese women
2002, Molecular Genetics and Metabolism
The acid phosphatase (ACP1) locus codes for a low molecular weight protein tyrosine phosphatase (LMPTP) that is found ubiquitously in human tissues. The ^*A allele of the ACP1 gene is associated with lower total enzymatic activity than the ^*B and ^*C alleles. An association between the ^*A allele and extreme values of body-mass-index (BMI) and dyslipidemia has previously been described in several samples of obese subjects from the Italian population. In the present study, we investigated the relationship between ACP1 ^*A allele genotypes (^*A/^*A, ^*A/^*B, and ^*A/^*C) and non-^*A allele genotypes (^*B/^*B, ^*B/^*C, and ^*C/^*C) and metabolic variables in 277 Caucasian post-menopausal subjects consisting of 82 non-obese subjects (BMI⩽29), 60 moderately obese (BMI 30–34) and 135 very obese (BMI⩾35) subjects. ACP1 genotypes were found to be significantly associated with total cholesterol (p⩽0.002) and triglyceride (p⩽0.001) levels in the obese and very obese women only. The significantly lower levels of triglycerides in ^*A carriers in this group suggest a protective effect of the ^*A allele against hypertriglyceridemia. It has been unclear why some individuals who gain weight develop dyslipidemia and other aspects of the metabolic syndrome while others do not. The present study suggests that those who gain weight and carry the ACP1 ^*A allele may be partially protected against developing the metabolic syndrome. The confirmation of ACP1 as a modifier gene of the metabolic complications could open the door to the prevention of the lethal complications of obesity.

View all citing articles on Scopus

View full text

Human red cell acid phosphatase (ACP1): the primary structure of the two pairs of isozymes encoded by the ACP1*A and ACP1*C alleles

Biochim. Biophys. Acta

Comp. Biochem. Physiol.

Int. J. Biochem.

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

J. Biol. Chem.

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

J. Biol. Chem.

Arch. Biochem. Biophys.

J. Biol. Chem.

J. Biol. Chem.

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

Biochim. Biophys. Acta

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Forensic Sci. Int.

J. Biol. Chem.

Ann. Hum. Genet.

Jap. J. Hum. Genet.

Chem. Pharm. Bull.

Human red cell acid phosphatase (ACP1): the primary structure of the two pairs of isozymes encoded by the ACP1^A and ACP1^C alleles