Link_domain_CSPGs_modules_2_4; this link domain is found in the second and fourth link modules of the chondroitin sulfate proteoglycan core protein (CSPG) aggrecan and, in the second link module of three other CSPGs: versican, neurocan, and brevican. The link domain is a hyaluronan (HA)-binding domain. CSPGs are characterized by an N-terminal globular domain (G1 domain) containing two contiguous link modules (modules 1 and 2). Both link modules of the G1 domain of aggrecan are involved in interaction with HA. Aggrecan in addition contains a second globular domain (G2) having link modules 3 and 4 which lack HA-binding activity. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggregan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.
Feature 1:putative hyaluronan binding site [chemical binding site]
Evidence:
Comment:For CSPGs link module 2 (G1 domain) and aggrecan link module 4 (G2 domain), these two putative HA- binding sites are not well conserved.
Comment:HA-binding residues were identified in TSG-6 and CD44 by site-directed mutagenesis.
Comment:These two HA-binding residues are found at equivalent sequence positions in TSG-6 and CD44 . None of the other HA-binding residues identified were found at equivalent sequence positions in the two proteins.
Jiyao W et al.(2023). "The conserved domain database in 2023.",