COMPLETE CODING SEQUENCE, DEDUCED PRIMARY STRUCTURE, CHROMOSOMAL LOCALIZATION, AND STRUCTURAL-ANALYSIS OF MURINE AGGRECAN

We have isolated and sequenced overlapping cDNA clones encoding the en tire core protein of aggrecan (the large aggregating chondroitin sulfa te/keratan sulfate proteoglycan of cartilage) from three chondrocyte c DNA libraries of BALB/c mice and localized the aggrecan gene in mouse chromosome 7. We determined 7386 bp of the cDNA sequence, including 13 2 and 854 nucleotides of 5' and 3' untranslated regions, respectively. The core protein precursor is 2132 amino acids long (M(r) 222,008), i ncluding a 19-residue secretory signal peptide. The overall amino acid sequence of the mouse aggrecan shows 91.6% identity to rat and 72.5% to human aggrecan. Comparison of the amino acid sequences of various d omains and subdomain structures of mouse aggrecan to known sequences o f other species and related proteins (versican, neurocan, link protein , and lymphocyte homing receptor CD44) revealed high levels of identit y of the G1, G2, and G3 globular domains and relatively less conserved structures in the interglobular and glycosaminoglycan-attachment regi ons. Epidermal growth factor (EGF)-like module was detected in only a minor fraction of aggrecan clones, while the complement regulatory pro tein (CRP)-like domain was regularly expressed in all samples. (C) 199 4 Academic Press, inc.