Sgpl2O is a new plasma sialoglycoprotein of 120 kDa on which we have recently reported the isolation and partial characterization. This protein was co-isolated with the second component of human complement (C2) on C4b-Sepharose. While these proteins have features in common, the following important differences have been noted. Sgpl2O is present in plasma at 15x the concentration of C2. These proteins do not cross immunoprecipitate with polyclonal antisera. They are activated and cleaved by distinct mediator pathways: sgpl2O by the contact-activation system (CAS) and C2 by the classical complement pathway (CCP). The proteins have unique N-terminal amino acid sequences and a C-terminal stretch of 238 residues within sgpl2O as determined by cDNA cloning and sequencing is unrecognized in any of 55,000 screened protein sequences including C2, kallikrein and HMW kininogen. Affinity isolated sgpl2O (sgpl2O-A) represents a small % of the total available sgpl2O in plasma. Sgpl2O (sgpl2O-l) which doesn't bind to C4b can by isolated by conventional chromatography also contains a small % of sgpl2O-A. Although the two forms are immunochemically indistinguishable, produce similar fragments on kallikrein digestion and have identical N-terminal amino-acid sequences, by a number of criteria these two forms are distinct and in particular sgpl2O-A possess most if not all described biologic activities. Sgpl2O-A is slightly larger in size and has a more basic pl of 5.0. We have fully sequenced the initially identified and isolated clone that produces a fusion protein detectable by monospecific antibody to sgpl2O. The partial deduced 238 aa sequence contained the N-terminal peptide sequence derived from a C-terminal 25 kDa fragment derived from sgpl2O-A. We are in the process of completing the sequence of larger clones identified by 32-P labeled probe hybridization with cDNA from our initial clone.
