Alpha-1 antitrypsin

SERPINA1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ATU, 1D5S, 1EZX, 1HP7, 1IZ2, 1KCT, 1OO8, 1OPH, 1PSI, 1QLP, 1QMB, 2D26, 2QUG, 3CWL, 3CWM, 3DRM, 3DRU, 3NDD, 3NDF, 3NE4, 3T1P, 7API, 8API, 9API, 4PYW, 5IO1
Identifiers
Aliases	SERPINA1, A1A, A1AT, AAT, PI, PI1, PRO2275, alpha1AT, serpin family A member 1, nNIF
External IDs	OMIM: 107400; MGI: 891968; HomoloGene: 20103; GeneCards: SERPINA1; OMA:SERPINA1 - orthologs
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q32.13 Start 94,376,747 bp[1] End 94,390,693 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12 E|12 52.98 cM Start 103,729,853 bp[2] End 103,739,851 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver blood islet of Langerhans monocyte granulocyte gallbladder duodenum human kidney upper lobe of left lung appendix Top expressed in proximal tubule hepatobiliary system liver right kidney human kidney Hindgut lobe of liver yolk sac midgut islet of Langerhans More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase inhibitor activity protease binding protein binding identical protein binding serine-type endopeptidase inhibitor activity Cellular component Golgi apparatus endoplasmic reticulum lumen COPII-coated ER to Golgi transport vesicle extracellular exosome endoplasmic reticulum-Golgi intermediate compartment membrane platelet alpha granule lumen extracellular region endoplasmic reticulum Golgi membrane extracellular space intracellular membrane-bounded organelle ficolin-1-rich granule lumen collagen-containing extracellular matrix Biological process hemostasis negative regulation of peptidase activity platelet degranulation endoplasmic reticulum to Golgi vesicle-mediated transport COPII vesicle coating acute-phase response negative regulation of endopeptidase activity blood coagulation neutrophil degranulation post-translational protein modification Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5265 20703 Ensembl ENSG00000197249 ENSG00000277377 ENSMUSG00000071177 UniProt P01009 Q00897 P07758 RefSeq (mRNA) NM_001127707 NM_000295 NM_001002235 NM_001002236 NM_001127700 NM_001127701 NM_001127702 NM_001127703 NM_001127704 NM_001127705 NM_001127706 NM_009246 RefSeq (protein) NP_000286 NP_001002235 NP_001002236 NP_001121172 NP_001121173 NP_001121174 NP_001121175 NP_001121176 NP_001121177 NP_001121178 NP_001121179 NP_033272 NP_001239498 NP_033269 Location (UCSC) Chr 14: 94.38 – 94.39 Mb Chr 12: 103.73 – 103.74 Mb PubMed search [3] [4]
Wikidata
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Alpha-1 antitrypsin or α₁-antitrypsin (A1AT, α₁AT, A1A, or AAT) is a protein belonging to the serpin superfamily. It is encoded in humans by the SERPINA1 gene. A protease inhibitor, it is also known as alpha₁–proteinase inhibitor (A1PI) or alpha₁-antiproteinase (A1AP) because it inhibits various proteases (not just trypsin).^[5] In older biomedical literature it was sometimes called serum trypsin inhibitor (STI, dated terminology), because its capability as a trypsin inhibitor was a salient feature of its early study. As a type of enzyme inhibitor, it protects tissues from enzymes of inflammatory cells, especially neutrophil elastase, and has a reference range in blood of 0.9–2.3 g/L (in the US the reference range is expressed as mg/dL or micromoles), but the concentration can rise manyfold upon acute inflammation.^[6]

When the blood contains inadequate amounts of A1AT or functionally defective A1AT (such as in alpha-1 antitrypsin deficiency), neutrophil elastase is excessively free to break down elastin, degrading the elasticity of the lungs, which results in respiratory complications, such as chronic obstructive pulmonary disease, in adults. Normally, A1AT leaves its site of origin, the liver, and joins the systemic circulation; defective A1AT can fail to do so, building up in the liver, which results in cirrhosis in either adults or children.

In addition to binding to neutrophil elastase released by inflammatory cells, A1AT also binds to elastase localized on the cell surface in which case elastase does not act as an enzyme, but instead acts to signal cells to undergo locomotion.^[7] Besides liver cells, A1PI is produced in bone marrow, by lymphocytic and monocytic cells in lymphoid tissue, and by the Paneth cells of the gut.^[8]

Inactivation of A1AT by enzymes other than elastase due to inflammation/infection causes the migration of T cells to halt precisely at the site where the pathologic insult exists. This suggests a role for α1PI not only in locomotion of lymphocytes through tissue, but as a consequence of infection, a primary role as a sentinel in immune vigilance.^[9]

A1AT is both an endogenous protease inhibitor and an exogenous one used as medication. The pharmaceutical form is purified from human donor blood and is sold under the nonproprietary name alpha₁–proteinase inhibitor (human) and under various trade names (including Aralast NP, Glassia, Prolastin, Prolastin-C, and Zemaira). Recombinant versions are also available but are currently used in medical research more than as medication.