|Protein Name||Alpha-1-acid glycoprotein|
|Ref Sequence ID||NP_001035592.1|
|Protein Existence Status||Reviewed: Experimental evidence at transcript level|
|Protein Function||Belongs to the “lipocalins” family,a group of proteins that are deputed to the binding and transport of small hydrophobic molecules; classified as immunocalins, a subfamily of proteins that may also immunomodulate the inflammatory reaction; acute Phase Proteins, structurally un-related group of mainly liverderived plasma proteins that are associated with an acute phase reaction. Alpha-1-acid glycoprotein (AGP, also known as AAG or orosomucoid) is an important plasma protein involved in the binding and transport of many drugs, especially basic compounds.|
|Biochemical Properties||In humans - all-beta protein that is dominated by a single eight-stranded antiparallel beta-sheet with a hydrophobic interior; one of the most acidic plasma proteins with a pI of 3.2-3.6 because of sialylation; Desialylation reduces the number of isoforms detectable within this pH range from ten to three or four with a pI of 4.2-4.7; two molecular forms, AGP-1 and AGP - 2; AGP-1 contains four and AGP-2 five cysteine residues; Vibrational spectroscopy confirmed details of the secondary structure and the structure content predicted by homology modeling of the protein moiety, i.e., 15% a-helices, 41% β-sheets, 12% β-turns, 8% bands, and 24% unordered structure at pH 7.4|
|Significance in milk||A predicted role in milk: an immunomodulatory molecule; could play several roles during inflammatory challenges in the mammary gland; inhibit several activities of neutrophils that can cause severe cell and tissue damages in the mammary gland; in humans, the protein significantly inhibits the proliferation of peripheral blood T-cells , induces the expression of several pro- and anti-inflammatory cytokines by monocytes and can directly antagonise the capillary leakage induced by some inflammatory mediators, such as histamine, platelet activating factor and bradykinin; physiological amount may be increased during mastitis|
|PTMs||A glycoprotein; carbohydrate moiety accounting for 26.6% of its molecular weight; presence of sialic acid-containing diantennary oligosaccharides which is composed of only N-glycolylneuraminic acid as reported in bovine milk; presence of 2 isoforms in milk, one from mammary galnd and another from somatic cells; isoforms share a similar content of sialic acid a(2-3)- and a(2-6)-linked to galactose; somatic cells produce AGP isoforms that are strongly fucosylated and contain an elevated number of diantennary glycans; in humans the protein has five N-linked glycans; different degrees of branching; structurally heterogeneous due to the great diversity of the terminating sugars;|
| Site(s) of PTM(s) |
|Predicted Disorder Regions||NA|
|TM Helix Prediction||No TM helices|
|Significance of PTMs||Reported in bovine: immunomodulatory function of is dependent on both its fucosylation and its branching degree; hyperfucosylated AGP from somatic cells is anti-inflammatory, since it can reduce the local inflammatory reaction by both ameliorating neutrophilsmediated damage and by reducing the complement activation|
|Additional Comments||AGP is an acute phase protein and the concentration of AGP in plasma can significantly increase in various diseases (such as cancer and inflammatory diseases) or following trauma (burns, surgery).|
|Bibliography||1. Ceciliani, F., Pocacqua, V., Lecchi, C., Fortin, R., Rebucci, R., Avallone, G., … Sartorelli, P. (2007). Differential expression and secretion of α1-acid glycoprotein in bovine milk. Journal of Dairy Research, 74(03), 374. https://doi.org/10.1017/S0022029907002646. |
2. Guha, A., Guha, R., & Gera, S. (2013). Comparison of α1-Antitrypsin, α1-Acid Glycoprotein, Fibrinogen and NOx as Indicator of Subclinical Mastitis in Riverine Buffalo (
3. Ceciliani, F., Pocacqua, V., Provasi, E., Comunian, C., Bertolini, A., Bronzo, V., … Sartorelli, P. (2005). Identification of the bovine α 1-acid glycoprotein in colostrum and milk. Veterinary Research, 36(5–6), 735–746. https://doi.org/10.1051/vetres:2005029.
4. Guha, A., Guha, R., & Gera, S. (2013). Comparison of α1-Antitrypsin, α1-Acid Glycoprotein, Fibrinogen and NOx as Indicator of Subclinical Mastitis in Riverine Buffalo (Bubalus bubalis). Asian-Australasian Journal of Animal Sciences, 26(6), 788–794. https://doi.org/10.5713/ajas.2012.12261.
5. Lijima, S., Shiba, K., Kimura, M., Nagai, K., & Iwai, T. (2000). Changes of α1-acid glycoprotein microheterogeneity in acute inflammation stages analyzed by isoelectric focusing using serum obtained postoperatively. Electrophoresis, 21(4), 753–759. https://doi.org/10.1002/(SICI)1522-2683(20000301)21:4<753::AID-ELPS753>3.0.CO;2-Y.
6. Eap, C. B., Cuendet, C., & Baumann, P. (1988). Orosomucoid (alpha-1 acid glycoprotein) phenotyping by use of immobilized pH gradients with 8 M urea and immunoblotting - A new variant encountered in a population study. Human Genetics, 80(2), 183–185. https://doi.org/10.1007/BF00702865. 7.Huang Z, Ung T. Effect of alpha-1-acid glycoprotein binding on pharmacokinetics and pharmacodynamics. Curr Drug Metab. 2013 Feb;14(2):226-38. PMID: 23092311.