Search by BoMiProt ID - Bomi317

Primary Information

BoMiProt ID Bomi317
Protein Name Alkaline phosphatase, tissue-nonspecific isozyme
Organism Bos taurus
Uniprot IDP09487
Milk FractionWhey, MFGM, Exosome
Ref Sequence ID NP_789828.2
Aminoacid Length 524
Molecular Weight 57193
FASTA Sequence Download
Gene Name ALPL
Gene ID 280994
Protein Existence Status Reviewed: Experimental evidence at protein level

Secondary Information

Protein Function hydrolysis of phosphate monoesters at basic pH values; bone isoenzyme may be involved in mammalian bone calcification and the intestinal isoenzyme is thought to play a role in the transport of phosphate into epithelial cells of the intestine; alkaline phosphatase is an important serum analyte and its elevation in serum is correlated with the presence of bone,liver, and other diseases. Alkaline phosphatase (ALP) is a ubiquitous membrane-bound glycoprotein capable of providing inorganic phosphate by catalyzing the hydrolysis of organic phosphate esters, or removing inorganic pyrophosphate that inhibits calcification.
Biochemical Properties highest activity was obtained in ethanolamine buffer (pH 8.2 to 10.49); In CAPS [3-(cyclohexylamino)-I-propanesulfonic acid[ buffer, activity was maximum between pH 10.5 and 11.1]; The maximum activity in diethanolamine buffer occurred from pH 10.1 to 10.7; The optimal pH for alkaline phosphatase activity is affected by a number of variables: the type of buffer, the specific substrate used, the concentration of the substrate, and the stability of the enzyme at high pH; Activation of alkaline phosphatase is observed with Co 2+, Mn2+, and Mg2+, whereas Zn ions are inhibitory. Calcium ions have little effect on activity; The highest activities were obtained at pH 10.1 with four substrates containing aromatic groups: a-naphthyl phosphate, pNPP, methylumbelliferyl phosphate, and phosphotyrosine. The alkaline phosphatase hydrolyzed 10 substrates with maximum activity at pH 9.0. ß Casein, which is a poor substrate, showed maximum hydrolysis at pH 8.1;Levamisole is a potent inhibitor of mammalian alkaline phosphatases found in liver, kidney and bone; Homoarginine inhibits the alkaline phosphatase from fat globule membranes, microsomes and liver to a much greater extent than the intestinal alkaline phosphatase
Significance in milk covalently bound to bovine mammary microsomal membranes and milk fat globule membranes through linkage to phosphatidylinositol; has been found in the mammary gland of rat, cow, cat, rabbit, goat, mare, dog, sheep, and human; as detected in humans, AP decresed from colustrum to mature milk; ALP can dephosphorylate casein, phosphoprotein, under suitable conditions
PTMs Disulfide bond formation,N-Linked Glycosylation at Asn, GPI-anchor formation, Lipoprotein formation, Phosphorylation at Ser
Site(s) of PTM(s)

N-glycosylation, O-glycosylation,
Predicted Disorder Regions NA
DisProt Annotation
TM Helix Prediction No TM helices
Significance of PTMs N-glycosylation is absolutely essential for TNAP activity, but not for that of the placental or intestinal enzymes.Asn-213 is a possible N-glycosylation site, and it suggests that this sugar chain plays a key role in enzyme regulation.
Bibliography 1. Bingham, E. W. and Malin, E. L. (1992) ‘Alkaline phosphatase in the lactating bovine mammary gland and the milk fat globule membrane. Release by phosphatidylinositol-specific phospholipase C’, Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 102(2), pp. 213–218. doi: 10.1016/0305-0491(92)90113-6.
2. Bingham, E. W., Garver, K. and Powlen, D. (1992) ‘Purification and properties of alkaline phosphatase in the lactating bovine mammary gland.’, Journal of dairy science, 75(12), pp. 3394–401. doi: 10.3168/jds.S0022-0302(92)78115-6.
3. Hamilton, T. A., Górnicki, S. Z. and Sussman, H. H. (1979) ‘Alkaline phosphates from human milk. Comparison with isoenzymes from placenta and liver’, Biochemical Journal, 177(1), pp. 197–201. doi: 10.1042/bj1770197. 4.Sato M, Saitoh I, Kiyokawa Y, Iwase Y, Kubota N, Ibano N, Noguchi H, Yamasaki Y, Inada E. Tissue-Nonspecific Alkaline Phosphatase, a Possible Mediator of Cell Maturation: Towards a New Paradigm. Cells. 2021 Nov 28;10(12):3338. doi: 10.3390/cells10123338. PMID: 34943845; PMCID: PMC8699127. 5.Nosjean O, Koyama I, Goseki M, Roux B, Komoda T. Human tissue non-specific alkaline phosphatases: sugar-moiety-induced enzymic and antigenic modulations and genetic aspects. Biochem J. 1997 Jan 15;321 ( Pt 2)(Pt 2):297-303. doi: 10.1042/bj3210297. PMID: 9020858; PMCID: PMC1218068.