Primary Information
BoMiProt ID	Bomi152
Protein Name	Alpha-1-acid glycoprotein
Organism	Bos taurus
Uniprot ID	Q3SZR3
Milk Fraction	Whey
Ref Sequence ID	NP_001035592.1
Aminoacid Length	202
Molecular Weight	23182
FASTA Sequence	Download
Gene Name	ORM1
Gene ID	497200
Protein Existence Status	Reviewed: Experimental evidence at transcript level
Secondary Information
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) N-glycosylation, O-glycosylation, Phosphorylation
Predicted Disorder Regions	NA
DisProt Annotation
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 (Bubalus bubalis). Asian-Australasian Journal of Animal Sciences, 26(6), 788–794. https://doi.org/10.5713/ajas.2012.12261. 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.