SERPINA1

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.

Function

Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin.

Short peptide from AAT

reversible chymotrypsin inhibitor. It also inhibits elastase, but not trypsin. Its major physiological function is the protection of the lower respiratory tract against proteolytic destruction by human leukocyte elastase (HLE).

Involvement in disease

Alpha-1-antitrypsin deficiency

A1ATD

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

N-glycosylated. Differential glycosylation produces a number of isoforms. N-linked glycan at Asn-107 is alternatively di-antennary, tri-antennary or tetra-antennary. The glycan at Asn-70 is di-antennary with trace amounts of tri-antennary. Glycan at Asn-271 is exclusively di-antennary. Structure of glycans at Asn-70 and Asn-271 is Hex5HexNAc4. The structure of the antennae 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 antennae are fucosylated, which forms a Lewis-X determinant.

Proteolytic processing may yield the truncated form that ranges from Asp-30 to Lys-418.

(Microbial infection) Proteolytically processed by Staphylococcus aureus seryl, cysteinyl, and metallo-proteases.

Sequence similarities

Belongs to the serpin family.

Tissue specificity

Ubiquitous. Expressed in leukocytes and plasma.

Cellular localization

• Secreted
• Endoplasmic reticulum
• The S and Z allele are not secreted effectively and accumulate intracellularly in the endoplasmic reticulum.
• Short peptide from AAT
• Secreted
• Extracellular space
• Extracellular matrix

Alternative names

• Alpha-1-antitrypsin
• Alpha-1 protease inhibitor
• Alpha-1-antiproteinase
• Serpin A1
• SERPINA1
• AAT
• PI
• PRO0684
• PRO2209

Database links

• entrezGene:5265
• omim:107400
• swissprot:P01009

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Molecular weight

46737Da