The reference OMIM entry for this protein is 107400

Serpin peptidase inhibitor, clade a, member 1; serpina1
Alpha-1-antitrypsin; aat
Protease inhibitor 1; pi
Pi1
Anti-elastase
Antitrypsin

DESCRIPTION

The SERPINA1 gene encodes alpha-1-antitrypsin (AAT), also known as protease inhibitor (PI), a major plasma serine protease inhibitor. AAT complexes predominantly with elastase, but also with trypsin, chymotrypsin, thrombin, and bacterial proteases. The most important inhibitory action of AAT is that against neutrophil elastase (ELANE, or HLE; 130130), a protease that degrades elastin of the alveolar walls as well as other structural proteins of a variety of tissues (review by Cox, 2001).

CLONING

Kurachi et al. (1981) cloned a nearly full-length baboon AAT cDNA (approximately 1,352 bp) and a partial human AAT cDNA (approximately 306 bp). They found more than 96% homology between the cDNA and predicted amino acid sequences of AAT in the 2 species. Comparison of baboon AAT, human antithrombin III (107300), and chicken ovalbumin indicated about 30% homology of amino acid sequence. Long et al. (1984) cloned a full-length human AAT cDNA from a liver cDNA library. Sequence analysis revealed a precursor molecule containing a 24-amino acid signal peptide and a mature protein of 394 amino acids. AAT is primarily synthesized in the liver. Crystal (1990) noted that hepatocytes are the major source of AAT, but that the gene is also expressed in mononuclear phagocytes and neutrophils.

GENE STRUCTURE

Lai et al. (1983) showed that the AAT gene contains 3 introns in the peptide-coding region. Long et al. (1984) found that the genomic length of the PI gene is 10.2 kb with a 1,434-bp coding region. The gene has 4 introns; exon 1, the 5-prime portion of exon 2, and the 3-prime portion of exon 5 are noncoding regions. The first intron, 5.3 kb long, contains a 143-amino acid open reading frame (which does not appear to be an actual protein coding region), an Alu family sequence, and a pseudotranscription initiation region. Perlino et al. (1987) found that the AAT gene in macrophages is transcribed from a macrophage-specific promoter located about 2,000 bp upstream of the hepatocyte-specific promoter. Transcription from the 2 AAT promoters is mutually exclusive; the macrophage promoter is silent in hepatocytes and the hepatocyte promoter is silent in macrophages. In macrophages, 2 distinct mRNAs are generated by alternative splicing. Hafeez et al. (1992) demonstrated that the AAT gene has 3 macrophage-specific transcriptional initiation sites upstream from a single hepatocyte-specific transcriptional initiation site. Macrophages use these sites during basal and modulated expression. Hepatoma cells use the hepatocyte-specific transcriptional initiation site during basal and modulated expression but also switch on transcription from the upstream macrophage transcriptional initiation sites during modulation by the acute phase mediator interleukin-6 (IL6; 147620). Soutoglou and Talianidis (2002) analyzed the ordered recruitment of factors to the human alpha-1-antitrypsin promoter around the initial activation of the gene during enterocyte differentiation. They found that a complete preinitiation complex, including phosphorylated RNA Pol II (180660), was assembled at the promoter long before transcriptional activation. The histone acetyltransferases CBP (600140) and P/CAF (602303) were recruited subsequently, but local histone hyperacetylation was delayed. After transient recruitment of the human Brahma homolog BRM (600014), remodeling of the neighboring nucleosome coincided with transcription initiation. Soutoglou and ... More on the omim web site

Subscribe to this protein entry history

June 29, 2020: Protein entry updated
Automatic update: OMIM entry 107400 was added.

Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).