The reference OMIM entry for this protein is 107280

Serpin peptidase inhibitor, clade a, member 3; serpina3
Alpha-1-antichymotrypsin; aact
Antichymotrypsin, alpha-1; act

DESCRIPTION

Alpha-1-antichymotrypsin is a plasma protease inhibitor synthesized in the liver. It is a single glycopeptide chain of about 68,000 daltons and belongs to the class of serine protease inhibitors. In man, the normal serum level is about one-tenth that of alpha-1-antitrypsin (PI; 107400), with which it shares nucleic acid and protein sequence homology (Chandra et al., 1983). Both are major acute phase reactants; their concentrations in plasma increase in response to trauma, surgery, and infection. Antithrombin III, which also is structurally similar to alpha-1-antitrypsin, shows less sequence homology to antichymotrypsin and is not an acute phase reactant.

CLONING

Kelsey et al. (1988) cloned and analyzed the AACT gene, partly because of the possibility that genetic variation in other protease inhibitors may influence the prognosis in AAT deficiency. They isolated the AACT gene on a series of cosmid clones, with restriction mapping of about 70 kb around the gene.

GENE FUNCTION

By yeast 2-hybrid analysis, Kroczynska et al. (2004) found that DNAJC1 (611207) interacted with AACT, and they confirmed the interaction by dot blot, native electrophoresis, and fluorescence studies. The second SANT domain of DNAJC1 (SANT2) was sufficient to bind AACT both in yeast and in vitro, and the interaction was disrupted by a trp520-to-ala mutation in SANT2. AACT bound to SANT2 had no inhibitory activity toward chymotrypsin (see 118890). SANT2 significantly slowed formation of the AACT-chymotrypsin acyl complex with no significant effect on the catalytic efficiency of chymotrypsin.

BIOCHEMICAL FEATURES

Eriksson et al. (1986) studied levels of antichymotrypsin in 229 patients with liver disease verified by biopsy. In a small subgroup with seronegative, chronic, active hepatitis, they found low ACT values. In 1 of these patients they found equally low AACT levels among first-degree relatives, prompting a study of other cases of partial deficiency, i.e., those with approximately 50% of normal plasma levels. Six of 8 AACT-deficient individuals, over 25 years of age, had liver manifestations and 3 of 8 had pulmonary defects, varying from severe disease to subtle laboratory abnormalities. The abnormal gene was inherited in an autosomal dominant manner, and its frequency was estimated to be 0.003.

MAPPING

Rabin et al. (1985) found by in situ hybridization that the AACT gene maps to 14q31-q32.3, which overlaps the region to which PI has been mapped (14q24.3-q32.1) by study of somatic cell hybrids. PI and AACT may constitute a gene cluster: in situ hybridization shows that both map to the 14q31-q32.3 region (Rabin et al., 1986). Indeed, Sefton et al. (1989) demonstrated that the PI and the AACT genes are located on the same 360-kb MluI restriction fragment by pulsed field gel electrophoresis. Sefton et al. (1990) concluded that the PI-PIL gene cluster is only 220 kb away from the AACT gene and that it is oriented in the opposite direction. (PIL refers to 'PI-like' and is also referred to as 'antitrypsin-related,' or ATR (107410).) The comparatively short interval between the genes came as a surprise given previous estimates of the level of genetic recombination between them.

MOLECULAR GENETICS

Kelsey et al. (1988) found that a common TaqI polymorphism was tightly linked to the PI gene (maximum lod score in males = 2.29 at theta = 0; in females 6.11 at theta = 0.032). PI-AACT haplotypes in 31 ... More on the omim web site

Subscribe to this protein entry history

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

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 107280 was added.