Cartilage oligomeric matrix protein explained

Cartilage oligomeric matrix protein (COMP), also known as thrombospondin-5, is an extracellular matrix (ECM) protein primarily present in cartilage. In humans it is encoded by the COMP gene.^{[1] [2] [3]}

Function

The protein encoded by this gene is a noncollagenous extracellular matrix (ECM) protein.^[4] It consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. Oligomerization results from formation of a five-stranded coiled coil and disulfide bonds. Binding to other ECM proteins such as collagen appears to depend on divalent cations. Mutations can cause the osteochondrodysplasias pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED).

COMP is a marker of cartilage turnover.^[5] It is present in high quantities in fibrotic scars and systemic sclerosis, and it appears to have a role in vascular wall remodeling.^[6]

Further reading

• Unger S, Hecht JT . Pseudoachondroplasia and multiple epiphyseal dysplasia: New etiologic developments . American Journal of Medical Genetics . 106 . 4 . 244–50 . 2002 . 11891674 . 10.1002/ajmg.10234 .
• Liu C . Transcriptional mechanism of COMP gene expression and chondrogenesis . Journal of Musculoskeletal & Neuronal Interactions . 5 . 4 . 340–1 . 2006 . 16340129 . 9089272 .
• Morozzi G, Fabbroni M, Bellisai F, Pucci G, Galeazzi M . Cartilage oligomeric matrix protein level in rheumatic diseases: potential use as a marker for measuring articular cartilage damage and/or the therapeutic efficacy of treatments . Annals of the New York Academy of Sciences . 1108 . 1 . 398–407 . Jun 2007 . 17894003 . 10.1196/annals.1422.041 . 2007NYASA1108..398M . 23534917 .
• Månsson B, Carey D, Alini M, Ionescu M, Rosenberg LC, Poole AR, Heinegård D, Saxne T . Cartilage and bone metabolism in rheumatoid arthritis. Differences between rapid and slow progression of disease identified by serum markers of cartilage metabolism . The Journal of Clinical Investigation . 95 . 3 . 1071–7 . Mar 1995 . 7533784 . 441442 . 10.1172/JCI117753 .
• Hecht JT, Nelson LD, Crowder E, Wang Y, Elder FF, Harrison WR, Francomano CA, Prange CK, Lennon GG, Deere M . Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia . Nature Genetics . 10 . 3 . 325–9 . Jul 1995 . 7670471 . 10.1038/ng0795-325 . 29506849 .
• Briggs MD, Hoffman SM, King LM, Olsen AS, Mohrenweiser H, Leroy JG, Mortier GR, Rimoin DL, Lachman RS, Gaines ES . Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene . Nature Genetics . 10 . 3 . 330–6 . Jul 1995 . 7670472 . 10.1038/ng0795-330 . 43867448 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Oehlmann R, Summerville GP, Yeh G, Weaver EJ, Jimenez SA, Knowlton RG . Genetic linkage mapping of multiple epiphyseal dysplasia to the pericentromeric region of chromosome 19 . American Journal of Human Genetics . 54 . 1 . 3–10 . Jan 1994 . 8279467 . 1918067 .
• Briggs MD, Rasmussen IM, Weber JL, Yuen J, Reinker K, Garber AP, Rimoin DL, Cohn DH . Genetic linkage of mild pseudoachondroplasia (PSACH) to markers in the pericentromeric region of chromosome 19 . Genomics . 18 . 3 . 656–60 . Dec 1993 . 8307576 . 10.1016/S0888-7543(05)80369-6 .
• Ballo R, Briggs MD, Cohn DH, Knowlton RG, Beighton PH, Ramesar RS . Multiple epiphyseal dysplasia, ribbing type: a novel point mutation in the COMP gene in a South African family . American Journal of Medical Genetics . 68 . 4 . 396–400 . Feb 1997 . 9021009 . 10.1002/(SICI)1096-8628(19970211)68:4<396::AID-AJMG4>3.0.CO;2-K .
• Susic S, McGrory J, Ahier J, Cole WG . Multiple epiphyseal dysplasia and pseudoachondroplasia due to novel mutations in the calmodulin-like repeats of cartilage oligomeric matrix protein . Clinical Genetics . 51 . 4 . 219–24 . Apr 1997 . 9184241 . 10.1111/j.1399-0004.1997.tb02458.x . 35871300 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Briggs MD, Mortier GR, Cole WG, King LM, Golik SS, Bonaventure J, Nuytinck L, De Paepe A, Leroy JG, Biesecker L, Lipson M, Wilcox WR, Lachman RS, Rimoin DL, Knowlton RG, Cohn DH . Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum . American Journal of Human Genetics . 62 . 2 . 311–9 . Feb 1998 . 9463320 . 1376889 . 10.1086/301713 .
• Rosenberg K, Olsson H, Mörgelin M, Heinegård D . Cartilage oligomeric matrix protein shows high affinity zinc-dependent interaction with triple helical collagen . The Journal of Biological Chemistry . 273 . 32 . 20397–403 . Aug 1998 . 9685393 . 10.1074/jbc.273.32.20397 . free .
• Hecht JT, Deere M, Putnam E, Cole W, Vertel B, Chen H, Lawler J . Characterization of cartilage oligomeric matrix protein (COMP) in human normal and pseudoachondroplasia musculoskeletal tissues . Matrix Biology . 17 . 4 . 269–78 . Aug 1998 . 9749943 . 10.1016/S0945-053X(98)90080-4 .
• Délot E, King LM, Briggs MD, Wilcox WR, Cohn DH . Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene . Human Molecular Genetics . 8 . 1 . 123–8 . Jan 1999 . 9887340 . 10.1093/hmg/8.1.123 . free .
• Ikegawa S, Ohashi H, Nishimura G, Kim KC, Sannohe A, Kimizuka M, Fukushima Y, Nagai T, Nakamura Y . Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations in pseudoachondroplasia and multiple epiphyseal dysplasia . Human Genetics . 103 . 6 . 633–8 . Dec 1998 . 9921895 . 10.1007/s004390050883 . 22099443 .
• Deere M, Sanford T, Francomano CA, Daniels K, Hecht JT . Identification of nine novel mutations in cartilage oligomeric matrix protein in patients with pseudoachondroplasia and multiple epiphyseal dysplasia . American Journal of Medical Genetics . 85 . 5 . 486–90 . Aug 1999 . 10405447 . 10.1002/(SICI)1096-8628(19990827)85:5<486::AID-AJMG10>3.0.CO;2-O .
• Thur J, Rosenberg K, Nitsche DP, Pihlajamaa T, Ala-Kokko L, Heinegård D, Paulsson M, Maurer P . Mutations in cartilage oligomeric matrix protein causing pseudoachondroplasia and multiple epiphyseal dysplasia affect binding of calcium and collagen I, II, and IX . The Journal of Biological Chemistry . 276 . 9 . 6083–92 . Mar 2001 . 11084047 . 10.1074/jbc.M009512200 . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Pseudoachondroplasia
• GeneReviews/NCBI/NIH/UW entry on Multiple Epiphyseal Dysplasia, Dominant

Notes and References

1. Newton G, Weremowicz S, Morton CC, Copeland NG, Gilbert DJ, Jenkins NA, Lawler J . Characterization of human and mouse cartilage oligomeric matrix protein . Genomics . 24 . 3 . 435–9 . Dec 1994 . 7713493 . 10.1006/geno.1994.1649 .
2. Briggs MD, Rasmussen IM, Weber JL, Yuen J, Reinker K, Garber AP, Rimoin DL, Cohn DH . Genetic linkage of mild pseudoachondroplasia (PSACH) to markers in the pericentromeric region of chromosome 19 . Genomics . 18 . 3 . 656–60 . Dec 1993 . 8307576 . 10.1016/S0888-7543(05)80369-6 .
3. Web site: Entrez Gene: COMP cartilage oligomeric matrix protein.
4. Paulsson M, Heinegård D . Purification and structural characterization of a cartilage matrix protein . The Biochemical Journal . 197 . 2 . 367–75 . Aug 1981 . 7325960 . 1163135 . 10.1042/bj1970367.
5. Petersen SG, Saxne T, Heinegard D, Hansen M, Holm L, Koskinen S, Stordal C, Christensen H, Aagaard P, Kjaer M . Glucosamine but not ibuprofen alters cartilage turnover in osteoarthritis patients in response to physical training . Osteoarthritis and Cartilage . 18 . 1 . 34–40 . Jan 2010 . 19679221 . 10.1016/j.joca.2009.07.004 . free .
6. Book: Halper J, Kjaer M . Progress in Heritable Soft Connective Tissue Diseases . Basic Components of Connective Tissues and Extracellular Matrix: Elastin, Fibrillin, Fibulins, Fibrinogen, Fibronectin, Laminin, Tenascins and Thrombospondins . Advances in Experimental Medicine and Biology . 802 . 31–47 . 2014 . 24443019 . 10.1007/978-94-007-7893-1_3 . 978-94-007-7892-4 .