The full-length cDNA for a new plasma sialoglycoprotein (sgp120) was elucidated from two human fetal liver cDNA libraries by standard cloning and sequencing technologies. We have demonstrated that several forms of the gene that code for sgp120 exist due to spliced variants. The largest form expressed contains 893 amino acids including a 35 amino acid insert at residue 593. This information along with earlier biochemical and immunological data unequivocally confirms sgp120 as a new plasma protein. Sgp120 was first identified by its capacity to bind with the activated fourth component (C4b) of the classical complement pathway (CCP). Results to date support the idea that this form of the protein, sgp120-A, may regulate the activation of the CCP. Sgp120 is also cleaved by kallikrein of the intrinsic coagulation-kinin generating pathway to produce several protein fragments. Good pI agreement was obtained by computer prediction analysis of the translated amino acid sequence of the largest form containing the 35 amino acid splice region (pI = 6.54, 907 residues) and without (pI = 6.08, 872 residues) to that obtained by direct electrophoretic analysis of desialidated sgp120-A/I, pI = 6.3 and 5.8, respectively. This supports our hypothesis that the larger sgp120-A is a product of a spliced gene such as in clone D, the insert representing the C4b binding domain. Pigtryin (PT), a postulated analog of human inter-alpha-trypsin inhibitor (IATI) was shown to have a peptide match of 76% identity with 81% similarity to sgp120. Thus, PT is most likely the pig analog of human sgp120 and not IATI. The mRNA of PT, identified as an acute phase reactant in a pig model of cardiogenic shock, is increased > 5 fold. Using an ELISA for sgp120 protein we have identified 2-3 fold increases in the serum of burn patients suggesting that sgp120 is also an acute phase reactant. Sgp120 as well shows strong homology to each of the three mature heavy chains of IATI. Homology to HC3 was most significant with 51% identity and 71% similarity over the 5' 619 amino acid residues upstream from the splice region.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000595-04
Application #
3746595
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code