PRG4

Proteoglycan 4 or lubricin is a is_associated_with::proteoglycan that in humans is encoded by the PRG4 is_associated_with::gene. This proteoglycan acts as a is_associated_with::joint/boundary lubricant.

Function
Lubricin is present in is_associated_with::synovial fluid and on the surface (superficial layer) of articular is_associated_with::cartilage and therefore plays an important role in is_associated_with::joint lubrication and synovial is_associated_with::homeostasis. When first isolated, cartilage lubricin was called "superficial zone protein" (SZP). Lubricin, MSF and SZP are now collectively known as Proteoglycan 4 (hence PRG4 for the gene nomenclature). The expression of lubricin has also been detected and the protein localized in is_associated_with::tendon, is_associated_with::meniscus, is_associated_with::lung, is_associated_with::liver, is_associated_with::heart, is_associated_with::bone, is_associated_with::ligament, is_associated_with::muscle, and is_associated_with::skin.

Structure
The protein encoded by this gene is a is_associated_with::proteoglycan of approximately 345 kDa specifically synthesized by is_associated_with::chondrocytes located at the surface of is_associated_with::articular cartilage, and also by some synovial lining cells. The cDNA encodes a protein of 1,404 amino acids (human A isoform) with a somatomedin B homology domain, is_associated_with::heparin-binding domains, multiple is_associated_with::mucin-like repeats, a is_associated_with::hemopexin domain, and an aggregation domain. There are 3 consensus sequences for N-glycosylation and 1 chondroitin sulfate substitution site.

Lubricin is a large, water-soluble is_associated_with::glycoprotein with a molecular weight of 206,000 Daltons and consists of approximately equal proportions of is_associated_with::protein and oligosaccharides. is_associated_with::Electron microscope measurements show that the lubricin molecule is a partially extended flexible rod and, in solution, occupies a smaller spatial domain than would be expected from structural predictions. This characteristic may aid in the molecule's boundary lubricating ability.

Clinical significance
Lubricin, as MSF, was detected in the urine of patients undergoing is_associated_with::bone marrow transplantation during a period of acute is_associated_with::thrombocytopenia. Depletion of lubricin function has also been associated with is_associated_with::camptodactyly-is_associated_with::arthropathy-is_associated_with::coxa vara-is_associated_with::pericarditis syndrome (CACP), an is_associated_with::arthritis-like is_associated_with::autosomal recessive disorder.

The locus for autosomal recessive camptodactyly-arthropathy-coxa vara-pericarditis syndrome maps to chromosome 1q25-q31 where the PRG4 gene is located. Cell overgrowth may be primary to the pathogenesis of this protein.

Lubricin’s role in improving is_associated_with::tendon gliding has also been studied. While adding lubricin alone fails to have an impact on the tendon gliding resistance, the addition of is_associated_with::cd-gelatin plus lubricin significantly lowered the gliding resistance of the tendons. This research can aid in improving the gliding ability of tendon grafts done clinically.