Proteoglycan 4

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PRG4
PRG4.pdf
Identifiers
Aliases PRG4, CACP, HAPO, JCAP, MSF, SZP, bG174L6.2, proteoglycan 4
External IDs HomoloGene: 130465 GeneCards: PRG4
RNA expression pattern
PBB GE PRG4 206007 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005807
NM_001127708
NM_001127709
NM_001127710
NM_001303232

n/a

RefSeq (protein)

NP_001121180
NP_001121181
NP_001121182
NP_001290161
NP_005798

n/a

Location (UCSC) Chr 1: 186.3 – 186.31 Mb n/a
PubMed search [1] n/a
Wikidata
View/Edit Human

Proteoglycan 4 or lubricin is a proteoglycan that in humans is encoded by the PRG4 gene.[2][3][4] This proteoglycan acts as a joint/boundary lubricant.[4]

Function[edit]

Lubricin is present in synovial fluid and on the surface (superficial layer) of articular cartilage and therefore plays an important role in joint lubrication and synovial homeostasis. When first isolated, cartilage lubricin was called "superficial zone protein" (SZP).[5][6] 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 tendon,[7] meniscus,[8] lung, liver, heart, bone,[9] ligament, muscle, and skin.[10]

Structure[edit]

The protein encoded by this gene is a proteoglycan of approximately 345 kDa[11] specifically synthesized by chondrocytes located at the surface of 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, heparin-binding domains, multiple mucin-like repeats, a hemopexin domain, and an aggregation domain. There are 3 consensus sequences for N-glycosylation and 1 chondroitin sulfate substitution site.[4]

Lubricin is a large, water-soluble glycoprotein with a molecular weight of 206,000 Daltons and consists of approximately equal proportions of protein and oligosaccharides. 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.[12] This characteristic may aid in the molecule's boundary lubricating ability.

Clinical significance[edit]

Lubricin, as MSF, was detected in the urine of patients undergoing bone marrow transplantation during a period of acute thrombocytopenia.[13] Depletion of lubricin function has also been associated with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), an arthritis-like autosomal recessive disorder.[14]

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.[4]

Lubricin’s role in improving tendon gliding has also been studied. While adding lubricin alone fails to affect the tendon gliding resistance, the addition of 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.[15] Extracorporeal shockwave therapy application has been shown to induce an increased lubricin expression in tendons and septa of rat hindlimbs, which might suggest a beneficial lubricanting effect for joints and tissues prone to wear and tear degradation. [16]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ Marcelino J, Carpten JD, Suwairi WM, Gutierrez OM, Schwartz S, Robbins C, Sood R, Makalowska I, Baxevanis A, Johnstone B, Laxer RM, Zemel L, Kim CA, Herd JK, Ihle J, Williams C, Johnson M, Raman V, Alonso LG, Brunoni D, Gerstein A, Papadopoulos N, Bahabri SA, Trent JM, Warman ML (Dec 1999). "CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome". Nat Genet. 23 (3): 319–22. doi:10.1038/15496. PMID 10545950. 
  3. ^ Flannery CR, Hughes CE, Schumacher BL, Tudor D, Aydelotte MB, Kuettner KE, Caterson B (Mar 1999). "Articular cartilage superficial zone protein (SZP) is homologous to megakaryocyte stimulating factor precursor and Is a multifunctional proteoglycan with potential growth-promoting, cytoprotective, and lubricating properties in cartilage metabolism". Biochem Biophys Res Commun. 254 (3): 535–41. doi:10.1006/bbrc.1998.0104. PMID 9920774. 
  4. ^ a b c d "Entrez Gene: PRG4 proteoglycan 4". 
  5. ^ Schumacher BL, Block JA, Schmid TM, Aydelotte MB, Kuettner KE (1994). "A novel proteoglycan synthesized and secreted by chondrocytes of the superficial zone of articular cartilage.". Arch Biochem Biophys. 311 (1): 144–52. doi:10.1006/abbi.1994.1219. PMID 8185311. 
  6. ^ Jay GD, et al. (2000). "Lubricin is a product of megakaryocyte stimulating factor gene expression by human synovial fibroblasts.". J Rheumatol. 27 (3): 594–600. PMID 10743795. 
  7. ^ Rees; Davies, JR; Tudor, D; Flannery, CR; Hughes, CE; Dent, CM; Caterson, B; et al. (2002). "Immunolocalisation and expression of proteoglycan 4 (cartilage superficial zone proteoglycan) in tendon". Matrix Biol. 21 (7): 593–602. doi:10.1016/S0945-053X(02)00056-2. PMID 12475643. 
  8. ^ Schumacher BL, et al. (2005). "Proteoglycan 4 (PRG4) synthesis and immunolocalization in bovine meniscus.". J Orthop Res. 23 (3): 562–568. doi:10.1016/j.orthres.2004.11.011. PMID 15885476. .
  9. ^ Ikegawa S, et al. (2000). "Isolation, characterization and mapping of the mouse and human PRG4 (proteoglycan 4) genes.". Cytogenet Cell Genet. 90 (3-4): 291–297. doi:10.1159/000056791. PMID 11124536. 
  10. ^ Sun Y, et al. (2006). "Mapping lubricin in canine musculoskeletal tissues.". Connect Tissue Res. 47 (4): 215–221. doi:10.1080/03008200600846754. PMID 16987753. .
  11. ^ Su JL, Schumacher BL, Lindley KM, et al. (June 2001). "Detection of superficial zone protein in human and animal body fluids by cross-species monoclonal antibodies specific to superficial zone protein". Hybridoma. 20 (3): 149–57. doi:10.1089/027245701750293475. PMID 11461663. 
  12. ^ Swann DA, et al. (1981). "The molecular structure of lubricating glycoprotein-I, the boundary lubricant for articular cartilage.". J Biol Chem. 256 (11): 5921–5925. PMID 7240180. 
  13. ^ Merberg DM et al. (1993) Comparison of vitronectin and megakaryocyte stimulating factor. In Biology of Vitronectins and their Receptors. (Preissner et al., eds) pp45-52 (Elsevier Science, Amsterdam).
  14. ^ Marcelino J, et al. (1999). "CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome.". Nat Genet. 23 (3): 319–322. doi:10.1038/15496. PMID 10545950. .
  15. ^ Taguchi M, Jay GD, et al. (Jan 2008). "Lubricin Surface Modification Improves Extrasynovial Tendon Gliding in a Canine Model in Vitro". The Journal of Bone and Joint Surgery. 90 (1): 129–135. doi:10.2106/JBJS.G.00045. PMID 18171967. 
  16. ^ Zhang D, Kearney CJ et al. (Jan 2011). "Extracorporeal shockwave-induced expression of lubricin in tendons and septa". Cell and Tissue Research. 346 (2): 255–263. doi:10.1007/s00441-011-1258-7. PMID 22009294. 

Further reading[edit]

External links[edit]