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Gene Review

COMP  -  cartilage oligomeric matrix protein

Homo sapiens

Synonyms: Cartilage oligomeric matrix protein, EDM1, EPD1, MED, PSACH, ...
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Disease relevance of COMP

  • Moreover, the COMP heptamer was preferentially recognized by circulating IgG in RA (n = 22) compared with osteoarthritis patients (n = 24) or age-matched healthy controls (n = 20; both p < 0.0001) [1].
  • Thus, increased COMP levels in body fluids may be indicative of active synovitis as well as of accelerated joint erosion [2].
  • TSP-1 and COMP were also detected in areas of microcalcification in atherosclerotic lesions and TSP-1 was detected adjacent to areas of calcification in calciphylaxis [3].
  • Clinical and radiographic features of multiple epiphyseal dysplasia not linked to the COMP or type IX collagen genes [4].
  • Normal human chondrocytes were transfected with wildtype (wt-) COMP or with mutant COMP (D469del; mt-) recombinant adenoviruses and grown in a nonattachment redifferentiating culture system that provides an environment allowing formation of a differentiated chondrocyte nodule [5].
  • Genetic variations of the COMP gene may account for some subgroups of benign joint hypermobility [6].

Psychiatry related information on COMP

  • When adjustment was made for markers of sexual risk taking, only genital warts remained significantly (p = 0.05) associated with SFM as compared to both SSM and COMP [7].
  • The D2-like antagonist haloperidol produced a dose-related decrease in locomotor activity when administered alone, and blocked the hyperactivity effects of PCP over the same dose-range (minimal effective dose, MED = 0.3 mg/kg for both effects) [8].
  • The distribution of profiles containing the m2-muscarinic acetylcholine receptor within the aged human basal forebrain and its relationship to cholinergic and noncholinerigc neurons and alterations in Alzheimer's disease (AD) was investigated by using an m2-specific monoclonal antibody (Levey et al. [1995] J. Comp. Neurol. 351:339-356) [9].
  • Hemolin is also developmentally regulated as suggested by changes in its concentration during larval and pupal ecdysis (Trenczek, T., 1998. Endogenous defense mechanisms of insects. Zoology 101, 298-315; Lanz-Mendoza, H., Faye, I., 1999. Physiological aspects of the immunoglobulin superfamily in invertebrates. Dev. Comp. Immunol. 23, 359-374) [10].
  • METHODS: They randomly assigned 34 (largely chronically) depressed individuals age 60 and older to receive 28 weeks of antidepressant medication plus clinical management, either alone (MED) or with the addition of dialectical behavior therapy skills-training and scheduled telephone coaching sessions (MED+DBT) [11].

High impact information on COMP


Chemical compound and disease context of COMP


Biological context of COMP


Anatomical context of COMP

  • Compared with a matched normal population, increased concentrations of cartilage oligomeric matrix protein (COMP) were found in all patients who developed rapid hip joint destruction [23].
  • RESULTS: COMP was synthesized and secreted by synovial cells as well as by articular chondrocytes in culture [2].
  • COMP was not detected in culture media of skin or fetal lung fibroblasts, either in the absence or the presence of TGFbeta1 [2].
  • The demonstration of COMP expression in surgical specimens of synovial tissues suggests that the inflamed synovium may provide an additional source for the elevated levels of COMP observed in arthritis [2].
  • Because COMP exists as a homopentamer, only one mutant COMP subunit may result in an abnormal complex that is accumulated in expanded rough endoplasmic reticulum (rER) cisternae, a hallmark of PSACH [24].

Associations of COMP with chemical compounds


Physical interactions of COMP


Regulatory relationships of COMP

  • RA SF presented more cell surface integrins, and monoclonal antibodies against CD51 inhibited the adhesion to COMP by 80% [34].
  • These results indicate that COMP expression within these cells is regulated in a unique manner that differs from the expression of other extracellular matrix genes [21].
  • CONCLUSION: COMP is highly expressed within the tumor cells of HCC, suggesting that COMP might play a role in the pathophysiology of this disease [35].

Other interactions of COMP

  • Because of the exclusion of the EDM1 and EDM2 loci in some families, the existence of a third locus has been postulated [36].
  • The analysis resulted in identification of three mutations in COMP and one in COL9A1, but none in the other two collagen IX genes [37].
  • Type IX collagen and matrilin-3 (MATN3), also accumulate in the rER cisternae of PSACH chondrocytes, but it is unknown how mutant COMP interacts with these proteins [24].
  • The elevated levels of COMP were similar to those found in joint injury or osteoarthritis, and the elevated levels of MIA were comparable to those reported in rheumatoid arthritis [38].
  • The COMP gene mutation (C348R), while not previously published, is typical of those in PSACH patients, whereas the COL2A1 mutation (T1370M) is somewhat atypical, as it predicts an amino acid change within the carboxyl-terminal region of the protein [39].
  • Our data indicate that COMP/TSP5 is an aggrecan-binding protein, and this interaction is regulated by the calcium-sensitive conformation of COMP/TSP5; interaction of COMP with aggrecan can be mediated through the GAG side chains on aggrecan and the "signature domain" of COMP/TSP5 [40].

Analytical, diagnostic and therapeutic context of COMP


  1. Human monoclonal rheumatoid synovial B lymphocyte hybridoma with a new disease-related specificity for cartilage oligomeric matrix protein. Souto-Carneiro, M.M., Burkhardt, H., Müller, E.C., Hermann, R., Otto, A., Kraetsch, H.G., Sack, U., König, A., Heinegård, D., Müller-Hermelink, H.K., Krenn, V. J. Immunol. (2001) [Pubmed]
  2. Regulation of cartilage oligomeric matrix protein synthesis in human synovial cells and articular chondrocytes. Recklies, A.D., Baillargeon, L., White, C. Arthritis Rheum. (1998) [Pubmed]
  3. The involvement of matrix glycoproteins in vascular calcification and fibrosis: an immunohistochemical study. Canfield, A.E., Farrington, C., Dziobon, M.D., Boot-Handford, R.P., Heagerty, A.M., Kumar, S.N., Roberts, I.S. J. Pathol. (2002) [Pubmed]
  4. Clinical and radiographic features of multiple epiphyseal dysplasia not linked to the COMP or type IX collagen genes. Mortier, G.R., Chapman, K., Leroy, J.L., Briggs, M.D. Eur. J. Hum. Genet. (2001) [Pubmed]
  5. Expression of mutant cartilage oligomeric matrix protein in human chondrocytes induces the pseudoachondroplasia phenotype. Merritt, T.M., Alcorn, J.L., Haynes, R., Hecht, J.T. J. Orthop. Res. (2006) [Pubmed]
  6. Inverse association of general joint hypermobility with hand and knee osteoarthritis and serum cartilage oligomeric matrix protein levels. Chen, H.C., Shah, S.H., Li, Y.J., Stabler, T.V., Jordan, J.M., Kraus, V.B. Arthritis Rheum. (2008) [Pubmed]
  7. Sexually transmitted diseases in Swedish women with experience of casual sex with men of foreign nationalities within Sweden. Arvidson, M., Hellberg, D., Mårdh, P.A. Acta obstetricia et gynecologica Scandinavica. (1995) [Pubmed]
  8. Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine and serotonin receptor subtype selective antagonists in mice. Gleason, S.D., Shannon, H.E. Psychopharmacology (Berl.) (1997) [Pubmed]
  9. m2 muscarinic acetylcholine receptor-immunoreactive neurons are not reduced within the nucleus basalis in Alzheimer's disease: relationship with cholinergic and galaninergic perikarya. Mufson, E.J., Jaffar, S., Levey, A.I. J. Comp. Neurol. (1998) [Pubmed]
  10. The insect immune protein hemolin is expressed during oogenesis and embryogenesis. Bettencourt, R., Assefaw-Redda, Y., Faye, I. Mech. Dev. (2000) [Pubmed]
  11. Dialectical behavior therapy for depressed older adults: a randomized pilot study. Lynch, T.R., Morse, J.Q., Mendelson, T., Robins, C.J. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. (2003) [Pubmed]
  12. Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia. Hecht, J.T., Nelson, L.D., Crowder, E., Wang, Y., Elder, F.F., Harrison, W.R., Francomano, C.A., Prange, C.K., Lennon, G.G., Deere, M. Nat. Genet. (1995) [Pubmed]
  13. Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene. Briggs, M.D., Hoffman, S.M., King, L.M., Olsen, A.S., Mohrenweiser, H., Leroy, J.G., Mortier, G.R., Rimoin, D.L., Lachman, R.S., Gaines, E.S. Nat. Genet. (1995) [Pubmed]
  14. The crystal structure of a five-stranded coiled coil in COMP: a prototype ion channel? Malashkevich, V.N., Kammerer, R.A., Efimov, V.P., Schulthess, T., Engel, J. Science (1996) [Pubmed]
  15. Sensitivity to sunburn is associated with susceptibility to ultraviolet radiation-induced suppression of cutaneous cell-mediated immunity. Kelly, D.A., Young, A.R., McGregor, J.M., Seed, P.T., Potten, C.S., Walker, S.L. J. Exp. Med. (2000) [Pubmed]
  16. Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein. Senolt, L., Braun, M., Olejárová, M., Forejtová, S., Gatterová, J., Pavelka, K. Ann. Rheum. Dis. (2005) [Pubmed]
  17. The treatment of localized non-Hodgkin's lymphoma in children: a report from the Children's Cancer Study Group. Jenkin, R.D., Anderson, J.R., Chilcote, R.R., Coccia, P.F., Exelby, P.R., Kersey, J.H., Kushner, J.H., Meadows, A.T., Siegel, S.E., Sposto, R. J. Clin. Oncol. (1984) [Pubmed]
  18. Comparison of long-term outcome of children and adolescents with disseminated non-lymphoblastic non-Hodgkin lymphoma treated with COMP or daunomycin-COMP: A report from the Children's Cancer Group. Sposto, R., Meadows, A.T., Chilcote, R.R., Steinherz, P.G., Kjeldsberg, C., Kadin, M.E., Krailo, M.D., Termuhlen, A.M., Morse, M., Siegel, S.E. Med. Pediatr. Oncol. (2001) [Pubmed]
  19. CCNU, vincristine, methotrexate, and procarbazine treatment of relapsed small cell lung carcinoma. Poplin, E.A., Aisner, J., Van Echo, D.A., Whitacre, M., Wiernik, P.H. Cancer treatment reports. (1982) [Pubmed]
  20. COMP mutations, chondrocyte function and cartilage matrix. Hecht, J.T., Hayes, E., Haynes, R., Cole, W.G. Matrix Biol. (2005) [Pubmed]
  21. Analysis of the promoter region of human cartilage oligomeric matrix protein (COMP). Deere, M., Rhoades Hall, C., Gunning, K.B., LeFebvre, V., Ridall, A.L., Hecht, J.T. Matrix Biol. (2001) [Pubmed]
  22. Pseudoachondroplasia and multiple epiphyseal dysplasia: New etiologic developments. Unger, S., Hecht, J.T. Am. J. Med. Genet. (2001) [Pubmed]
  23. Cartilage and bone metabolism in rheumatoid arthritis. Differences between rapid and slow progression of disease identified by serum markers of cartilage metabolism. Månsson, B., Carey, D., Alini, M., Ionescu, M., Rosenberg, L.C., Poole, A.R., Heinegård, D., Saxne, T. J. Clin. Invest. (1995) [Pubmed]
  24. Unique matrix structure in the rough endoplasmic reticulum cisternae of pseudoachondroplasia chondrocytes. Merritt, T.M., Bick, R., Poindexter, B.J., Alcorn, J.L., Hecht, J.T. Am. J. Pathol. (2007) [Pubmed]
  25. Production of cartilage oligomeric matrix protein (COMP) by cultured human dermal and synovial fibroblasts. Dodge, G.R., Hawkins, D., Boesler, E., Sakai, L., Jimenez, S.A. Osteoarthr. Cartil. (1998) [Pubmed]
  26. Inhibitory effects of leflunomide therapy on the activity of matrixmetalloproteinase-9 and the release of cartilage oligomeric matrix protein in patients with rheumatoid arthritis. Kullich, W.C., Mur, E., Aglas, F., Niksic, F., Czerwenka, C. Clin. Exp. Rheumatol. (2006) [Pubmed]
  27. Expression of extracellular matrix molecules typical of articular cartilage in the human scapholunate interosseous ligament. Milz, S., Aktas, T., Putz, R., Benjamin, M. J. Anat. (2006) [Pubmed]
  28. Protection against cartilage and bone destruction by systemic interleukin-4 treatment in established murine type II collagen-induced arthritis. Joosten, L.A., Lubberts, E., Helsen, M.M., Saxne, T., Coenen-de Roo , C.J., Heinegård, D., van den Berg , W.B. Arthritis Res. (1999) [Pubmed]
  29. Cartilage oligomeric matrix protein protects cells against death by elevating members of the IAP family of survival proteins. Gagarina, V., Carlberg, A.L., Pereira-Mouries, L., Hall, D.J. J. Biol. Chem. (2008) [Pubmed]
  30. ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein. Liu, C.J., Kong, W., Ilalov, K., Yu, S., Xu, K., Prazak, L., Fajardo, M., Sehgal, B., Di Cesare, P.E. FASEB J. (2006) [Pubmed]
  31. Selective intracellular retention of extracellular matrix proteins and chaperones associated with pseudoachondroplasia. Vranka, J., Mokashi, A., Keene, D.R., Tufa, S., Corson, G., Sussman, M., Horton, W.A., Maddox, K., Sakai, L., Bächinger, H.P. Matrix Biol. (2001) [Pubmed]
  32. FTIR-Spectroscopy of multistranded coiled coil proteins. Heimburg, T., Schünemann, J., Weber, K., Geisler, N. Biochemistry (1999) [Pubmed]
  33. Role of TSP-5/COMP in pseudoachondroplasia. Posey, K.L., Hayes, E., Haynes, R., Hecht, J.T. Int. J. Biochem. Cell Biol. (2004) [Pubmed]
  34. Galectin-3 is induced in rheumatoid arthritis synovial fibroblasts after adhesion to cartilage oligomeric matrix protein. Neidhart, M., Zaucke, F., von Knoch, R., Jüngel, A., Michel, B.A., Gay, R.E., Gay, S. Ann. Rheum. Dis. (2005) [Pubmed]
  35. Cartilage oligomeric matrix protein expression in hepatocellular carcinoma and the cirrhotic liver. Xiao, Y., Kleeff, J., Guo, J., Gazdhar, A., Liao, Q., Di Cesare, P.E., Büchler, M.W., Friess, H. J. Gastroenterol. Hepatol. (2004) [Pubmed]
  36. COL9A3: A third locus for multiple epiphyseal dysplasia. Paassilta, P., Lohiniva, J., Annunen, S., Bonaventure, J., Le Merrer, M., Pai, L., Ala-Kokko, L. Am. J. Hum. Genet. (1999) [Pubmed]
  37. A mutation in COL9A1 causes multiple epiphyseal dysplasia: further evidence for locus heterogeneity. Czarny-Ratajczak, M., Lohiniva, J., Rogala, P., Kozlowski, K., Perälä, M., Carter, L., Spector, T.D., Kolodziej, L., Seppänen, U., Glazar, R., Królewski, J., Latos-Bielenska, A., Ala-Kokko, L. Am. J. Hum. Genet. (2001) [Pubmed]
  38. Increased serum levels of non-collagenous matrix proteins (cartilage oligomeric matrix protein and melanoma inhibitory activity) in marathon runners. Neidhart, M., Müller-Ladner, U., Frey, W., Bosserhoff, A.K., Colombani, P.C., Frey-Rindova, P., Hummel, K.M., Gay, R.E., Häuselmann, H., Gay, S. Osteoarthr. Cartil. (2000) [Pubmed]
  39. Double heterozygosity for pseudoachondroplasia and spondyloepiphyseal dysplasia congenita. Unger, S., Korkko, J., Krakow, D., Lachman, R.S., Rimoin, D.L., Cohn, D.H. Am. J. Med. Genet. (2001) [Pubmed]
  40. Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan. Chen, F.H., Herndon, M.E., Patel, N., Hecht, J.T., Tuan, R.S., Lawler, J. J. Biol. Chem. (2007) [Pubmed]
  41. Monoclonal antibodies to human cartilage oligomeric matrix protein: epitope mapping and characterization of sandwich ELISA. Vilím, V., Vobůrka, Z., Vytásek, R., Senolt, L., Tchetverikov, I., Kraus, V.B., Pavelka, K. Clin. Chim. Acta (2003) [Pubmed]
  42. Antibodies against cyclic citrullinated peptide (CCP) and levels of cartilage oligomeric matrix protein (COMP) in very early arthritis: relation to diagnosis and disease activity. Söderlin, M.K., Kastbom, A., Kautiainen, H., Leirisalo-Repo, M., Strandberg, G., Skogh, T. Scand. J. Rheumatol. (2004) [Pubmed]
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