Alkaline phosphatase, placental type explained

Alkaline phosphatase, placental type also known as placental alkaline phosphatase (PLAP) is an allosteric enzyme that in humans is encoded by the ALPP gene.^{[1] [2] [3]}

Gene

There are at least four distinct but related alkaline phosphatases: intestinal (ALPI), placental (this enzyme), placental-like (ALPPL2), and liver/bone/kidney (ALPL) (tissue-nonspecific). The first three are located together on chromosome 2, whereas the tissue-nonspecific form is located on chromosome 1. The coding sequence for this form of alkaline phosphatase is unique in that the 3' untranslated region contains multiple copies of an Alu family repeat. In addition, this gene is polymorphic and three common alleles (type 1, type 2, and type 3) for this form of alkaline phosphatase have been well-characterized.^[3]

Function

Alkaline phosphatase, placental type is a membrane-bound glycosylated dimeric enzyme, also referred to as the heat-stable form, that is expressed primarily in the placenta, although it is closely related to the intestinal form of the enzyme as well as to the placental-like form.^[3]

Clinical significance

PLAP is a tumor marker, especially in seminoma^{[4] [5] [6]} and ovarian cancer (e.g., dysgerminoma).^[7] PLAP is reliable only in non-smokers, as smoking interferes with measurement of PLAP,^[8] since serum concentrations of PLAP are increased up to 10-fold in smokers and its measurement is therefore of little value in this group.^[9]

Further reading

• Nye KE, Riley GA, Pinching AJ . The defect seen in the phosphatidylinositol hydrolysis pathway in HIV-infected lymphocytes and lymphoblastoid cells is due to inhibition of the inositol 1,4,5-trisphosphate 1,3,4,5-tetrakisphosphate 5-phosphomonoesterase. . Clin. Exp. Immunol. . 89 . 1 . 89–93 . 1992 . 1321014 . 1554388 . 10.1111/j.1365-2249.1992.tb06883.x .
• Lowe ME . Site-specific mutations in the COOH-terminus of placental alkaline phosphatase: a single amino acid change converts a phosphatidylinositol-glycan-anchored protein to a secreted protein. . J. Cell Biol. . 116 . 3 . 799–807 . 1992 . 1730777 . 2289307 . 10.1083/jcb.116.3.799 .
• Micanovic R, Gerber LD, Berger J, Kodukula K, Udenfriend S . Selectivity of the cleavage/attachment site of phosphatidylinositol-glycan-anchored membrane proteins determined by site-specific mutagenesis at Asp-484 of placental alkaline phosphatase. . Proc. Natl. Acad. Sci. U.S.A. . 87 . 1 . 157–61 . 1990 . 2153284 . 53219 . 10.1073/pnas.87.1.157 . 1990PNAS...87..157M . free .
• Martin D, Spurr NK, Trowsdale J . RFLP of the human placental alkaline phosphatase gene (PLAP). . Nucleic Acids Res. . 15 . 21 . 9104 . 1988 . 2891112 . 306450 . 10.1093/nar/15.21.9104 .
• Knoll BJ, Rothblum KN, Longley M . Nucleotide sequence of the human placental alkaline phosphatase gene. Evolution of the 5' flanking region by deletion/substitution. . J. Biol. Chem. . 263 . 24 . 12020–7 . 1988 . 10.1016/S0021-9258(18)37887-6 . 3042787 . free .
• Micanovic R, Bailey CA, Brink L, Gerber L, Pan YC, Hulmes JD, Udenfriend S . Aspartic acid-484 of nascent placental alkaline phosphatase condenses with a phosphatidylinositol glycan to become the carboxyl terminus of the mature enzyme. . Proc. Natl. Acad. Sci. U.S.A. . 85 . 5 . 1398–402 . 1988 . 3422741 . 279778 . 10.1073/pnas.85.5.1398 . 1988PNAS...85.1398M . free .
• Knoll BJ, Rothblum KN, Longley M . Two gene duplication events in the evolution of the human heat-stable alkaline phosphatases. . Gene . 60 . 2–3 . 267–76 . 1988 . 3443302 . 10.1016/0378-1119(87)90235-6 .
• Ovitt CE, Strauss AW, Alpers DH, Chou JY, Boime I . Expression of different-sized placental alkaline phosphatase mRNAs in placenta and choriocarcinoma cells. . Proc. Natl. Acad. Sci. U.S.A. . 83 . 11 . 3781–5 . 1986 . 3459156 . 323607 . 10.1073/pnas.83.11.3781 . 1986PNAS...83.3781O . free .
• Millán JL . Molecular cloning and sequence analysis of human placental alkaline phosphatase. . J. Biol. Chem. . 261 . 7 . 3112–5 . 1986 . 10.1016/S0021-9258(17)35755-1 . 3512548 . free .
• Ezra E, Blacher R, Udenfriend S . Purification and partial sequencing of human placental alkaline phosphatase. . Biochem. Biophys. Res. Commun. . 116 . 3 . 1076–83 . 1984 . 6651840 . 10.1016/S0006-291X(83)80252-6 .
• Le Du MH, Stigbrand T, Taussig MJ, Menez A, Stura EA . Crystal structure of alkaline phosphatase from human placenta at 1.8 A resolution. Implication for a substrate specificity. . J. Biol. Chem. . 276 . 12 . 9158–65 . 2001 . 11124260 . 10.1074/jbc.M009250200 . free .
• Spurway TD, Dalley JA, High S, Bulleid NJ . Early events in glycosylphosphatidylinositol anchor addition. substrate proteins associate with the transamidase subunit gpi8p. . J. Biol. Chem. . 276 . 19 . 15975–82 . 2001 . 11278620 . 10.1074/jbc.M010128200 . free .
• Rump A, Kasper G, Hayes C, Wen G, Starke H, Liehr T, Lehmann R, Lagemann D, Rosenthal A . Complex arrangement of genes within a 220-kb region of double-duplicated DNA on human 2q37.1. . Genomics . 73 . 1 . 50–5 . 2001 . 11352565 . 10.1006/geno.2000.6504 .
• Wennberg C, Kozlenkov A, Di Mauro S, Fröhlander N, Beckman L, Hoylaerts MF, Millán JL . Structure, genomic DNA typing, and kinetic characterization of the D allozyme of placental alkaline phosphatase (PLAP/ALPP). . Hum. Mutat. . 19 . 3 . 258–67 . 2002 . 11857742 . 10.1002/humu.10052 . 44666573 .
• Kozlenkov A, Manes T, Hoylaerts MF, Millán JL . Function assignment to conserved residues in mammalian alkaline phosphatases. . J. Biol. Chem. . 277 . 25 . 22992–9 . 2002 . 11937510 . 10.1074/jbc.M202298200 . free .
• Tang J, Li W . [Methodological study on the assay of glycosylphosphatidylinositol-specific phospholipase D activity in serum] . Hunan Yi Ke da Xue Xue Bao . 24 . 2 . 119–22 . 2002 . 11938765 .
• Lehto MT, Sharom FJ . Proximity of the protein moiety of a GPI-anchored protein to the membrane surface: a FRET study. . Biochemistry . 41 . 26 . 8368–76 . 2002 . 12081485 . 10.1021/bi012038+.
• Le Du MH, Millan JL . Structural evidence of functional divergence in human alkaline phosphatases. . J. Biol. Chem. . 277 . 51 . 49808–14 . 2003 . 12372831 . 10.1074/jbc.M207394200 . free .
• Llinas P, Stura EA, Ménez A, Kiss Z, Stigbrand T, Millán JL, Le Du MH . Structural studies of human placental alkaline phosphatase in complex with functional ligands . J. Mol. Biol. . 350 . 3 . 441–51 . July 2005 . 15946677 . 10.1016/j.jmb.2005.04.068 .

Notes and References

1. Kam W, Clauser E, Kim YS, Kan YW, Rutter WJ . Cloning, sequencing, and chromosomal localization of human term placental alkaline phosphatase cDNA . Proc Natl Acad Sci U S A . 82 . 24 . 8715–9 . Feb 1986 . 3001717 . 391507 . 10.1073/pnas.82.24.8715 . free .
2. Henthorn PS, Knoll BJ, Raducha M, Rothblum KN, Slaughter C, Weiss M, Lafferty MA, Fischer T, Harris H . Products of two common alleles at the locus for human placental alkaline phosphatase differ by seven amino acids . Proc Natl Acad Sci U S A . 83 . 15 . 5597–601 . Sep 1986 . 3461452 . 386335 . 10.1073/pnas.83.15.5597 . 1986PNAS...83.5597H . free .
3. Web site: Entrez Gene: ALPP alkaline phosphatase, placental (Regan isozyme).
4. Web site: European Group on Tumor Markers. A European Based Expert Group on Tumor Markers. Germ cell cancer.. https://web.archive.org/web/20120426001713/http://www.egtm.eu/recommendations/tumour_markers_in_germ_cell_cancer.htm . dead . 2012-04-26 .
5. W. Albrecht . Testicular tumor markers: Corner-stones in the management of malignant germ cell tumors . J Lab Med . 28 . 2 . 109–115 . 2004 . https://web.archive.org/web/20110124210805/http://www.egtm.eu/PDF/Albrecht.pdf . dead . 2011-01-24 . 10.1515/labmed.2004.018 . 53781946 . etal .
6. Sturgeon C . Practice guidelines for tumor marker use in the clinic . Clin. Chem. . 48 . 8 . 1151–9 . August 2002 . 12142367 . 10.1093/clinchem/48.8.1151. free .
7. Fishman WH . Clinical and biological significance of an isozyme tumor marker--PLAP . Clin. Biochem. . 20 . 6 . 387–92 . December 1987 . 3325192 . 10.1016/0009-9120(87)90003-8.
8. Schmoll HJ, Souchon R, Krege S, etal . European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG) . Annals of Oncology . 15 . 9 . 1377–99 . September 2004 . 15319245 . 10.1093/annonc/mdh301 .
9. Web site: Tumor Markers in Testicular Cancers . https://web.archive.org/web/20101112074644/http://aacc.org/members/nacb/LMPG/OnlineGuide/PublishedGuidelines/major/Documents/TumorMarkersMajor10.pdf . dead . 2010-11-12 .