cartilage oligomeric matrix protein; thrombospondin 5 (COMP, EDM1, PSACH, TSP5)

Function

• may play a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens & fibronectin
• can mediate the interaction of chondrocytes with the cartilage extracellular matrix through interaction with cell surface integrin receptors
• could play a role in the pathogenesis of osteoarthritis
• potent suppressor of apoptosis in both primary chondrocytes & transformed cells
• suppresses apoptosis by blocking activation of caspase-3 & by inducing the IAP family of survival proteins (BIRC3, BIRC2, BIRC5 & XIAP)
• essential for maintaining a vascular smooth muscle cells contractile/differentiated phenotype under physiological & pathological stimuli
  • maintains this phenotype by interacting with ITGA7 (putative)
• exists in a more compact conformation in the presence of Ca+2 & shows a more extended conformation in the absence of Ca+2
• interacts with ITGB3, ITGA5 & FN1
• binding to FN1 requires the presence of divalent cations (Ca+2, Mg+2 or Mn+2)
• the greatest amount of binding is seen in the presence of Mn+2
• interacts with MATN1, MATN3, MATN4 & ACAN
• binds heparin, heparan sulfate & chondroitin sulfate
• EDTA diminishes significantly its binding to ACAN & abolishes its binding to MATN3, MATN4 & chondroitin sulfate
• interacts with collagen 1, collagen 2 & collagen 9
  • interaction with thesecollagens is dependent on the presence of Zn+2
• interacts with ADAMTS12
• nteracts with ITGA7 (putative)

Cofactor: binds 11-14 Ca+2 per subunit

Structure

• pentamer; disulfide-linked
• the cell attachment motif
  • mediates attachment to chondrocytes
  • mediates induction of both the IAP family of survival proteins & the antiapoptotic response
• the TSP C-terminal domain mediates interaction with FN1 & ACAN
• belongs to the thrombospondin family
• contains 4 EGF-like domains
• contains 1 TSP C-terminal (TSPC) domain
• contains 8 TSP type-3 repeats

Compartment

• secreted, extracellular space, extracellular matrix

Expression

• abundantly expressed in chondrocyte extracellular matrix
• also found in bone, tendon, ligament, synovium & blood vessels
• present during the earliest stages of limb maturation & is later found in regions where the joints develop

Pathology

• defects are the cause of:
  • multiple epiphyseal dysplasia 1
  • pseudoachondroplasia
• increased amounts are produced during late stages of osteoarthritis in the area adjacent to the main defect

Laboratory

• cartilage oligomeric matrix protein in serum

More general terms

• matrix protein
• oligomerizing protein

Additional terms

• multiple epiphyseal dysplasia (EDM)
• pseudoachondroplasia

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1311
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1311
• OMIM: https://mirror.omim.org/entry/132400
• OMIM: https://mirror.omim.org/entry/177170
• OMIM: https://mirror.omim.org/entry/600310
• UniProt: http://www.uniprot.org/uniprot/P49747.html