Human alpha 2-HS-glycoprotein: the A and B chains with a connecting sequence are encoded by a single mRNA transcript.

Abstract

The a2-HS-glycoprotein (AHSG) is a plasma protein reported to play roles in bone mineralization and in the immune response. It is composed of two subunits, the A and B chains. Recombinant plasmids containing human cDNA AHSG have been isolated by screening an adult human liver library with a mixed oligonucleotide probe. The cDNA clones containing AHSG inserts span approximately 1.5 kiobase pairs and include the entire AHSG coding sequence, demonstrating that the A and B chains are encoded by a single mRNA transcript. The cDNA sequence predicts an 18-amino-acid signal peptide, followed by the A-chain sequence of AHSG. A heretofore unseen connecting sequence of 40 amino acids was deduced between the A-and B-chain sequences. The connecting sequence demonstrates the unique amino acid doublets and collagen triplets found in the A and B chains; it is not homologous with other reported amino acid sequences. The connecting sequence may be cleaved in a posttranslational step by limited proteolysis before mature AHSG is released into the circulation or may vary in its presence because of alternative processing. The AHSG cDNA was utilized for mapping the AHSG gene to the 3q21-*qter region of human chromosome 3. The availability of the AHSG cDNA clone will facilitate the analysis of its genetic control and gene expression during development and bone formation.The human a2-HS-glycoprotein (AHSG) is a plasma protein that consists of two subunits, an A chain of 282 amino acids and a B chain of 27 amino acids (1, 2). The A chain and B chain are linked through a disulfide bond. The molecule has interesting and unique features; there are 29 amino acid doublets in circulating AHSG with Ala-Ala or Ala-Ala-Ala

Friends and relations of the cystatin superfamily—new members and their evolution

“…A genomic clone was also isolated (Delbridge & Kelly, 1990). As has been observed elsewhere in the superfamily (e.g., Lee et al, 1987), the gene appeared to be polymorphic (Delbridge & Kelly, 1990). The authors further noted that the cDNA sequence was most closely related to that of oryzacystatin I (Kondo et al, 1989), demonstrating approximately 22% sequence identity (Delbridge & Kelly, 1990).…”

“…These two hairpin loops and the largely unstructured amino terminus of the protein form a wedge that fits into the protease (Bode et al, 1988;Stubbs et al, 1990;Machleidt et al, 1995; Auerswald et al, 1996). In the fetuins and HRGs, these sequences have been extensively altered, making it unlikely that they are viable cysteine protease inhibitors.Conserved sequences around the cysteine at the carboxylterminus of the fetuins, HMW kininogen, and HRG As Elzanowski et al (Elzanowski et al, 1988) noted, the sequence immediately surrounding the last cysteine residue, pro-pro-_cys-pro-gly-arg in human fetuin (Gejyo et al, 1983;Lee et al, 1987) shares significant homology with the same region of human prolys-*-pro-gly-arg (Ohkubo et al, 1984;Kitamura et al, 1985;Salvesen et al, 1986;Kellermann et al, 1986Kellermann et al, , 1987, and bovine pro-lys-%-pro-ser-arg Kitamura et al, 1983;Sueyoshi et al, 1984Sueyoshi et al, , 1985 high-molecular weight kininogen, suggesting a possible common origin of the carboxyl-terminal regions of the two proteins. Furthermore, the sequence around the last cysteine in bovine glu-ser-cys-pro-gly-thr (Sorensen et al, 1993) and human glu-ser-cys-pro-gly-lys (Koide et al, 1986) histidine-rich glycoprotein is also similar.…”

Haplotype analysis of the human α2‐HS glycoprotein (fetuin) gene

“…The molecule consists of two polypeptide chains produced through post-translational cleavage from a single polypeptide by enzymatic proteolysis ; the two chains are linked by a disulfide bond (Lee et al 1987 ;Nawratil et al 1996). AHSG is a member of the cystatin superfamily which includes kininogen and…”

cDNA Sequencing of Guinea Pig a2-HS Glycoprotein, Its Expression in Various Tissues and Acute Phase Expression

“…It is clear now that AHSG is the human homolog of fetuin (Christie et al, 1987;Dziegielewska et al, 1990). Protein and/or DNA sequences have been reported for human (Lee et al, 1987), cow (Dziegielewska et al, 1990), sheep and pig , rat (Ohnishi et al, 1993), mouse (Yamamoto and Sinohara, 1993;Yang et al, 1992), Mongolian gerbil (Goto et al, 1997), rabbit (Osawa et al, 1997), and Habu snake (Yamakawa and Omori-Satoh, 1992) fetuins. AHSG is also one of the few negative acute phase reactants in humans (Lebreton et al, 1979) and rats (Daveau et al, 1990), whereas fetuin is a positive acute phase protein in cattle and mice (Yang et al, 1992).…”