The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PRG4  -  proteoglycan 4

Homo sapiens

Synonyms: CACP, FLJ32635, HAPO, JCAP, Lubricin, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PRG4

  • We have studied the autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP; MIM 208250) to identify biological pathways that lead to synoviocyte hyperplasia, the principal pathological feature of this syndrome [1].
  • METHODS: Lubricin was purified from pooled synovial fluid aliquots with normal lubricating activity obtained from patients with osteoarthritis [2].
  • Modifications to the structure of SZP, coupled with inhibition of SZP synthesis during inflammation, may account for the attachment and invasion of pannus observed in inflammatory joint diseases [3].
  • Migration-stimulating factor (MSF) is a 70-kDa motogenic protein previously reported to be expressed by fetal and cancer patient fibroblasts cultured in vitro and present in the serum of breast cancer patients [4].
  • Furthermore, an association between MSF expression and invasive capacity is observed in various breast adenocarcinoma cell lines [5].

High impact information on PRG4

  • The CACP protein, which has previously been identified as both 'megakaryocyte stimulating factor precursor' and 'superficial zone protein', contains domains that have homology to somatomedin B, heparin-binding proteins, mucins and haemopexins [1].
  • In addition to expression in joint synovium and cartilage, CACP is expressed in non-skeletal tissues including liver and pericardium [1].
  • The availability of MSF obtained from cancer patient fibroblasts provides a potential means with which to examine the complex cellular interactions contributing to this process as well as develop a screening regime for identifying individuals at elevated risk of developing cancer [6].
  • Data are now presented indicating that MSF present in the conditioned medium of fetal and cancer patient fibroblasts is precipitated at 10% saturation ammonium sulfate and binds to heparin and cation-exchange resins [6].
  • Purified MSF has an estimated molecular mass of 70 kDa; amino acid analysis reveals a relatively high level of proline (13.34 residues per 100) [6].

Biological context of PRG4


Anatomical context of PRG4

  • OBJECTIVE: To determine whether the synovial fluid (SF) constituents hyaluronan (HA), proteoglycan 4 (PRG4), and surface-active phospholipids (SAPL) contribute to boundary lubrication, either independently or additively, at an articular cartilage-cartilage interface [10].
  • Structural modifications to SZP, together with a reduction in synthesis during tendon inflammation with injury and disease may account for the formation of tendon adhesions and contribute to the overall dysfunction of the tissue [11].
  • CONCLUSION: Lubricin is secreted by synovial fibroblasts via expression of the MSF gene [2].
  • 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 [3].
  • Articular cartilage provides a low-friction surface for joint articulation, with boundary lubrication facilitated by proteoglycan 4 (PRG4), which is secreted by chondrocytes of the superficial zone [8].

Associations of PRG4 with chemical compounds

  • OBJECTIVE: The boundary lubricating ability of human synovial fluid has been attributed to lubricin, a mucinous glycoprotein [2].
  • Lubricating ability of lubricin was assayed in a friction apparatus that oscillates natural latex against a ring of polished glass [2].
  • Courses 1, 3, and 5 consisted of fluorouracil as a 120-hour infusion (5FU-I) with cisplatin (CACP) as an intravenous (IV) bolus [12].
  • We have previously reported that this difference in behaviour results from the secretion by fetal fibroblasts of a 'migration stimulating factor' (MSF) which is not made by their normal adult counterparts, and that MSF appears to act by stimulating the synthesis of hyaluronic acid (HA) [13].
  • The human knee lubricin had a similar carbohydrate composition to bovine knee lubricin except for the higher glucosamine content, and the amino acid composition differed slightly [14].
  • TNFalpha levels showed a significant negative relationship with log2 lubricin levels [15].

Regulatory relationships of PRG4

  • Conversely, treatment with transforming growth factor-beta (TGF-beta) significantly upregulates lubricin synthesis, secretion and cartilage boundary association [16].

Other interactions of PRG4


Analytical, diagnostic and therapeutic context of PRG4


  1. CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Marcelino, J., Carpten, J.D., Suwairi, W.M., Gutierrez, O.M., Schwartz, S., Robbins, C., Sood, R., Makalowska, I., Baxevanis, A., Johnstone, B., Laxer, R.M., Zemel, L., Kim, C.A., Herd, J.K., Ihle, J., Williams, C., Johnson, M., Raman, V., Alonso, L.G., Brunoni, D., Gerstein, A., Papadopoulos, N., Bahabri, S.A., Trent, J.M., Warman, M.L. Nat. Genet. (1999) [Pubmed]
  2. Lubricin is a product of megakaryocyte stimulating factor gene expression by human synovial fibroblasts. Jay, G.D., Britt, D.E., Cha, C.J. J. Rheumatol. (2000) [Pubmed]
  3. 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. Flannery, C.R., Hughes, C.E., Schumacher, B.L., Tudor, D., Aydelotte, M.B., Kuettner, K.E., Caterson, B. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  4. Migration-stimulating factor: a genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells. Schor, S.L., Ellis, I.R., Jones, S.J., Baillie, R., Seneviratne, K., Clausen, J., Motegi, K., Vojtesek, B., Kankova, K., Furrie, E., Sales, M.J., Schor, A.M., Kay, R.A. Cancer Res. (2003) [Pubmed]
  5. Migration-stimulating factor displays HEXXH-dependent catalytic activity important for promoting tumor cell migration. Houard, X., Germain, S., Gervais, M., Michaud, A., van den Brûle, F., Foidart, J.M., Noël, A., Monnot, C., Corvol, P. Int. J. Cancer (2005) [Pubmed]
  6. Purification of the migration stimulating factor produced by fetal and breast cancer patient fibroblasts. Grey, A.M., Schor, A.M., Rushton, G., Ellis, I., Schor, S.L. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  7. Mapping lubricin in canine musculoskeletal tissues. Sun, Y., Berger, E.J., Zhao, C., An, K.N., Amadio, P.C., Jay, G. Connect. Tissue Res. (2006) [Pubmed]
  8. Tailoring secretion of proteoglycan 4 (PRG4) in tissue-engineered cartilage. Klein, T.J., Schumacher, B.L., Blewis, M.E., Schmidt, T.A., Voegtline, M.S., Thonar, E.J., Masuda, K., Sah, R.L. Tissue Eng. (2006) [Pubmed]
  9. The camptodactyly-arthropathy-coxa vara-pericarditis syndrome: clinical features and genetic mapping to human chromosome 1. Bahabri, S.A., Suwairi, W.M., Laxer, R.M., Polinkovsky, A., Dalaan, A.A., Warman, M.L. Arthritis Rheum. (1998) [Pubmed]
  10. Boundary lubrication of articular cartilage: role of synovial fluid constituents. Schmidt, T.A., Gastelum, N.S., Nguyen, Q.T., Schumacher, B.L., Sah, R.L. Arthritis Rheum. (2007) [Pubmed]
  11. Immunolocalisation and expression of proteoglycan 4 (cartilage superficial zone proteoglycan) in tendon. Rees, S.G., Davies, J.R., Tudor, D., Flannery, C.R., Hughes, C.E., Dent, C.M., Caterson, B. Matrix Biol. (2002) [Pubmed]
  12. An intensive, five course, alternating combination chemotherapy induction regimen used in patients with advanced, unresectable head and neck cancer. Ensley, J., Kish, J., Tapazoglou, E., Jacobs, J., Weaver, A., Atkinson, D., Ahmed, K., Mathog, R., Al-Sarraf, M. J. Clin. Oncol. (1988) [Pubmed]
  13. Antagonistic effects of TGF-beta 1 and MSF on fibroblast migration and hyaluronic acid synthesis. Possible implications for dermal wound healing. Ellis, I., Grey, A.M., Schor, A.M., Schor, S.L. J. Cell. Sci. (1992) [Pubmed]
  14. The molecular structure and lubricating activity of lubricin isolated from bovine and human synovial fluids. Swann, D.A., Silver, F.H., Slayter, H.S., Stafford, W., Shore, E. Biochem. J. (1985) [Pubmed]
  15. Decreased lubricin concentrations and markers of joint inflammation in the synovial fluid of patients with anterior cruciate ligament injury. Elsaid, K.A., Fleming, B.C., Oksendahl, H.L., Machan, J.T., Fadale, P.D., Hulstyn, M.J., Shalvoy, R., Jay, G.D. Arthritis Rheum. (2008) [Pubmed]
  16. Bioregulation of lubricin expression by growth factors and cytokines. Jones, A.R., Flannery, C.R. European cells & materials (2007) [Pubmed]
  17. Static and dynamic compression regulate cartilage metabolism of PRoteoGlycan 4 (PRG4). Nugent, G.E., Schmidt, T.A., Schumacher, B.L., Voegtline, M.S., Bae, W.C., Jadin, K.D., Sah, R.L. Biorheology. (2006) [Pubmed]
  18. Reduced expression and proteolytic susceptibility of lubricin/superficial zone protein may explain early elevation in the coefficient of friction in the joints of rats with antigen-induced arthritis. Elsaid, K.A., Jay, G.D., Chichester, C.O. Arthritis Rheum. (2007) [Pubmed]
  19. Differential gene expression in the periprosthetic membrane: lubricin as a new possible pathogenetic factor in prosthesis loosening. Morawietz, L., Gehrke, T., Frommelt, L., Gratze, P., Bosio, A., Möller, J., Gerstmayer, B., Krenn, V. Virchows Arch. (2003) [Pubmed]
WikiGenes - Universities