PRG4

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Proteoglycan 4
PRG4.pdf
Identifiers
Symbols PRG4 ; CACP; HAPO; JCAP; MSF; SZP; bG174L6.2
External IDs OMIM604283 HomoloGene130465 GeneCards: PRG4 Gene
RNA expression pattern
PBB GE PRG4 206007 at tn.png
More reference expression data
Protein domains
PRG4.pdf
Orthologs
Species Human Mouse
Entrez 10216 96875
Ensembl ENSG00000116690 ENSMUSG00000006014
UniProt Q92954 Q9JM99
RefSeq (mRNA) NM_001127708 NM_001110146
RefSeq (protein) NP_001121180 NP_001103616
Location (UCSC) Chr 1:
186.27 – 186.28 Mb
Chr 1:
150.45 – 150.47 Mb
PubMed search [1] [2]

Proteoglycan 4 or lubricin is a proteoglycan that in humans is encoded by the PRG4 gene.[1][2][3] This proteoglycan acts as a joint/boundary lubricant.[3]

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).[4][5] 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,[6] meniscus,[7] lung, liver, heart, bone,[8] ligament, muscle, and skin.[9]

Structure[edit]

The protein encoded by this gene is a proteoglycan of approximately 345 kDa[10] 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.[3]

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.[11] 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.[12] Depletion of lubricin function has also been associated with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), an arthritis-like autosomal recessive disorder.[13]

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.[3]

Lubricin’s role in improving tendon gliding has also been studied. While adding lubricin alone fails to have an impact on 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.[14]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ a b c d "Entrez Gene: PRG4 proteoglycan 4". 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ Rees et al.; Davies, JR; Tudor, D; Flannery, CR; Hughes, CE; Dent, CM; Caterson, B (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. 
  7. ^ 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. .
  8. ^ 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. 
  9. ^ Sun Y et al. (2006). "Mapping lubricin in canine musculoskeletal tissues.". Connect Tissue Res 47 (4): 215–221. doi:10.1080/03008200600846754. PMID 16987753. .
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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).
  13. ^ 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. .
  14. ^ 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. 

Further reading[edit]

External links[edit]