SERPINA1 Recombinant Protein (RPPB4809)

Subcellular location: Secreted Ref.24. Short peptide from AAT: Secreted � extracellular space � extracellular matrix Ref.24.

Tissue specificity: Plasma.

Domain: The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.

Post-translational modification: Several isomers are observed, resulting from the combination of different N-linked glycan structures and mature N-terminus. N-linked glycan at Asn-107 is alternatively di-antennary, tri-antennary or tetra-antennary, whereas glycan at Asn-70 is di-antennary with trace amounts of tri-antennary, and glycan at Asn-271 is exclusively di-antennary. The structure of the antennas is Neu5Ac(alpha1-6)Gal(beta1-4)GlcNAc attached to the core structure Man(alpha1-6)[Man(alpha1-3)]Man(beta1-4)GlcNAc(beta1-4)GlcNAc. Some antennas are fucosylated, which forms a Lewis-X determinant.Proteolytic processing may yield the truncated form that ranges from Asp-30 to Lys-418.

Polymorphism: The sequence shown is that of the M1V allele which is the most common form of PI (44 to 49%). Other frequent alleles are: M1A 20 to 23%; M2 10 to 11%; M3 14 to 19%.

Involvement in Disease: Defects in SERPINA1 are the cause of alpha-1-antitrypsin deficiency (A1ATD) [

MIM:613490]. A disorder whose most common manifestation is emphysema, which becomes evident by the third to fourth decade. A less common manifestation of the deficiency is liver disease, which occurs in children and adults, and may result in cirrhosis and liver failure. Environmental factors, particularly cigarette smoking, greatly increase the risk of emphysema at an earlier age. Ref.58 Ref.60 Ref.62

Miscellaneous: The aberrant form is found in the plasma of chronic smokers, and persists after smoking is ceased. It can still be found ten years after smoking has ceased.

Sequence similarities: Belongs to the serpin family.

Sequence caution: The sequence CAD62334.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence CAD62585.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.