Brevican processing and fragments formed by ADAMTS cleavage. Schematic representation of brevican, its endogenous proteolytic fragments and their interaction with other components of brain ECM: (A) Secreted brevican core protein which bears 1–3 chondroitin sulfate chains (MW > 145 kD). (B) Secreted brevican core protein without chondroitin sulfate chains (MW = 145 kD). When cleaved by extracellular glutamyl-endopeptidases, the ADAMTSs (arrows in A and B), an N-terminal, 55 kD fragment is formed (C) that contains a unique C-terminal murine (Ms) epitope sequence "EAMESE", homologous to the rat (Rt) "EAVESE" which are selectively recognized by respective neoepitope antibodies, anti-EAMESE or anti-EAVESE (C). A larger C-terminal fragment is formed upon ADAMTS cleavage (D). The > 145 kD and 145 kD isoforms of brevican or other lecticans in matrix form an tertiary aggregate complex with hyaluronan and tenascin-R (E) and when cleaved by ADAMTSs, the proteolytic degradation of brevican "loosens" the ECM complex (F).