Aggrecan fragments recovered from human synovial fluid all begin at a single new N-terminus, generated by cleavage of the aggrecan core protein at the Glu373-Ala374 bond in the interglobular domain between G1 and G2.

The cleavage is attributed to a cartilage proteinase acting on aggrecan, so aggrecan is the substrate of the proteolytic event, not its agent.

COMP binds aggrecan directly in a solid-phase assay, dependent on COMP's calcium-replete conformation and mediated in part through aggrecan's glycosaminoglycan side chains.

The interaction is partly glycosaminoglycan-mediated, which is why it is best expressed as extracellular matrix binding rather than as bare protein binding.

A heterozygous V2303M substitution in the aggrecan G3 C-type lectin causes dominant familial osteochondritis dissecans and abolishes binding of the recombinant G3 domain to fibulin-1, fibulin-2 and tenascin-R.

The study explains that guanidine-HCl extraction solubilizes tightly bound extracellular matrix components, including aggregating proteoglycans. This methodological statement alone is not an aggrecan-specific identification result.

Aggrecan aggregates with hyaluronan and link protein into complexes exceeding 200 MDa and is the principal load-bearing proteoglycan of cartilage.

The G1-hyaluronan-link protein ternary complex immobilises aggrecan into large aggregates that provide cartilage with its mechanical properties.

The aggregates form a densely packed hydrated gel within the collagen fibril network.

The G3 domain binds tenascins, fibulins and sulfated glycolipids, integrating aggrecan into the wider matrix.

Unlike the other lecticans, aggrecan's brain expression is concentrated in perineuronal nets.

The interglobular region between G1 and G2 carries the protease-sensitive sites responsible for aggrecan degradation in arthritis.

Animals lacking cartilage aggrecan have shortened long bones and die perinatally, establishing that aggrecan is required for cartilage development.

Aggrecan's negatively charged glycans attract water and thereby confer resistance to compression.

Aggrecan is present in normal venous tissue and is lost in varicose veins at both protein and transcript level.

This study is the first identification of aggrecan in venous tissue.

The network combines systematic yeast two-hybrid screening with literature interactions. The available abstract does not establish the validation status or functional significance of the specific ACAN-APP pair.

Aggrecan is required for both skeletal growth and articular cartilage function.

Missense variants in the G3 C-type lectin repeat reduce secretion of both recombinant variant protein and full-length aggrecan from heterozygous patient cartilage.

The same variants reduce binding to known cartilage extracellular matrix ligands, establishing the G3 C-type lectin as a matrix-binding module.

The cocrystal structure of the human ACAN G1 region with a hyaluronan decasaccharide shows the immunoglobulin domain and two Link modules acting as a single structural unit, with hyaluronan clamped in a groove spanning the tandem Link domains.

Human ACAN G1 binds immobilised hyaluronan with an affinity of 234 nM measured by biolayer interferometry, agreeing with an earlier surface plasmon resonance determination.

Recombinant human G1 and G1-G2 fragments added to mouse cortical neuron cultures bind pre-existing perineuronal nets with high specificity.

Abolishing hyaluronan binding by point mutation only reduces, rather than prevents, incorporation into perineuronal nets, so a hyaluronan-independent anchoring activity also operates.