Phosphatase Subfamily AP

Phosphatase Classification: Fold AP: Superfamily AP: Family AP: Subfamily AP(Alkaline phosphatase)

Alkaline phosphatase is a conserved phosphatase that has a broad of substrates, including proteins. It is used in clinical lab test, diary industry and biomedical research.

Evolution

Alkaline phosphatases are found in metazoa except nematodes, fungi, some protists, and bacteria, but are absent from most plants (see internal database). They belong to the alkaline phosphatase-like fold (SCOP), which contains other enzymes, such as phosphoesterases and sulfatases. Human has four APs. Three of them (ALPP, ALPPL2, ALPI) locates in a quasi-tandem way at 1q36.

APs were lost from most nematodes except a few individual species of different nematode lineages, as shown by BLASTing human and fruit fly AP against NR database. APs were also lost in monosiga and sponge.

Domain

APs have single phosphatase domain, and an N-terminal signal peptide.

Functions

Alkaline phosphatases are a superfamily (Pfam) with a wide variety of substrates, possibly including phosphoproteins. There are four human alkaline phosphatases, named by their tissue expression: ALPI (alkaline phosphatase, intestinal), ALPP (alkaline phosphatase, placental), ALPPL2 (alkaline phosphatase, placental-like 2), and ALPL (alkaline phosphatase, liver/bone/kidneytissue). Early reports found that ALPL and ALPI can dephosphorylate Histone H2A [1, 2] and that PLAP is a protein tyrosine phosphatase [3], but their physiological relevance as protein phosphatases is still unclear.

AP as biomarker

• Alkaline phosphatase (ALP) together with lactate dehydrogenase (LDH) was independent prognostic factors for overall survival of esophageal squamous cell carcinoma. A combination of the two indexes might contribute to further identification of survival differences in esophageal squamous cell carcinoma [4].

Serum alkaline phosphatase negatively affects endothelium-dependent vasodilation in naïve hypertensive patients [5].

References

1. Swarup G, Cohen S, and Garbers DL. Selective dephosphorylation of proteins containing phosphotyrosine by alkaline phosphatases. J Biol Chem. 1981 Aug 10;256(15):8197-201.
2. Chan JR and Stinson RA. Dephosphorylation of phosphoproteins of human liver plasma membranes by endogenous and purified liver alkaline phosphatases. J Biol Chem. 1986 Jun 15;261(17):7635-9.
3. Telfer JF and Green CD. Placental alkaline phosphatase activity is inversely related to cell growth rate in HeLaS3 cervical cancer cells. FEBS Lett. 1993 Aug 30;329(3):238-44. DOI:10.1016/0014-5793(93)80229-n |
4. Wei XL, Zhang DS, He MM, Jin Y, Wang DS, Zhou YX, Bai L, Li ZZ, Luo HY, Wang FH, and Xu RH. The predictive value of alkaline phosphatase and lactate dehydrogenase for overall survival in patients with esophageal squamous cell carcinoma. Tumour Biol. 2016 Feb;37(2):1879-87. DOI:10.1007/s13277-015-3851-y |
5. Perticone F, Perticone M, Maio R, Sciacqua A, Andreucci M, Tripepi G, Corrao S, Mallamaci F, Sesti G, and Zoccali C. Serum alkaline phosphatase negatively affects endothelium-dependent vasodilation in naïve hypertensive patients. Hypertension. 2015 Oct;66(4):874-80. DOI:10.1161/HYPERTENSIONAHA.115.06117 |