Cartilage oligomeric matrix protein (COMP/thrombospondin-5) is a pentameric extracellular matrix glycoprotein of the thrombospondin family that functions primarily as a structural constituent organizing ECM components in load-bearing tissues. The mature protein consists of an N-terminal oligomerization domain, four EGF-like repeats (two Ca2+-binding), eight TSP type-3 repeats that each bind two calcium ions, and a C-terminal globular domain that binds collagen and aggrecan. COMP forms homopentamers via disulfide-linked N-terminal coiled-coil regions, creating a multivalent scaffold that bridges collagens (types I, II, IX), matrilins (MATN1, MATN3, MATN4), fibronectin, aggrecan, and integrins (alpha5beta1, alphaVbeta3). It promotes collagen fibrillogenesis, supports cartilage ECM integrity, mediates chondrocyte attachment through integrin receptors, and suppresses apoptosis via induction of IAP family survival proteins. Expressed abundantly in cartilage, tendon, ligament, and synovium, with additional expression in blood vessels and adipose tissue. Mutations cause pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia type 1 (EDM1) through ER retention of misfolded protein and activation of the unfolded protein response. Also implicated as a biomarker in osteoarthritis and as a prognostic factor in certain cancers.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0031012 extracellular matrix | IBA GO_REF:0000033 | ACCEPT | Summary: COMP is a major extracellular matrix component in cartilage, tendon, ligament, and other load-bearing tissues. IBA annotations represent phylogenetically-informed annotations that have undergone extensive review. This annotation correctly captures COMP's primary cellular compartment where it functions as a structural organizer. Reason: This is the core localization for COMP's primary function as an ECM structural constituent. Supported by extensive literature showing COMP expression and function in the ECM of multiple tissues. IBA evidence is robust and this matches experimental evidence. Supporting Evidence: PMID:18285447 ECM incorporation as insoluble punctate deposits is an evolutionarily conserved property of TSPs. ECM retention of TSP1 is mediated by the C-terminal region in trimeric form PMID:7713493 Cartilage oligomeric matrix protein (COMP) is a 524,000-Da protein that is expressed at high levels in the territorial matrix of chondrocytes file:human/COMP/COMP-deep-research-falcon.md See deep research file for comprehensive analysis |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: COMP is a calcium-binding protein, with 11-14 calcium ions bound per subunit. The eight TSP type-3 repeats each bind two calcium ions, and the C-terminal domain binds three additional calcium ions. Calcium binding is essential for COMP conformation and collagen-binding activity. Reason: This annotation is well-supported by multiple experimental studies demonstrating calcium binding by COMP. The InterPro EGF-Ca-binding domains (IPR001881) correctly predict this function, validated by direct experimental evidence. Supporting Evidence: PMID:10852928 Cartilage oligomeric matrix protein is a calcium-binding protein, and a mutation in its type 3 repeats causes conformational changes PMID:11084047 Mutations in cartilage oligomeric matrix protein causing pseudoachondroplasia and multiple epiphyseal dysplasia affect binding of calcium and collagen I, II, and IX UniProt:P49747 Binds 11-14 calcium ions per subunit |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: COMP is a secreted protein localized to the extracellular region. This is a parent term of extracellular matrix where COMP actually functions. Reason: Correct annotation but redundant with the more specific extracellular matrix annotation. COMP is secreted and deposited into the ECM. Acceptable as IEA provides broad coverage. Supporting Evidence: UniProt:P49747 SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix |
| GO:0006915 apoptotic process | IEA GO_REF:0000120 | MODIFY | Summary: COMP is involved in regulating apoptosis - specifically it suppresses apoptotic processes. The annotation to 'apoptotic process' is too vague; COMP acts as a suppressor, not a general participant. Reason: COMP suppresses apoptosis by blocking caspase-3 activation and inducing IAP family survival proteins. The generic 'apoptotic process' term is inaccurate; should be annotated to negative regulation of apoptotic process. Proposed replacements: negative regulation of apoptotic process Supporting Evidence: PMID:17993464 Cartilage oligomeric matrix protein protects cells against death by elevating members of the IAP family of survival proteins UniProt:P49747 Potent suppressor of apoptosis in both primary chondrocytes and transformed cells. Suppresses apoptosis by blocking the activation of caspase-3 and by inducing the IAP family of survival proteins |
| GO:0007155 cell adhesion | IEA GO_REF:0000120 | ACCEPT | Summary: COMP mediates chondrocyte attachment to the cartilage ECM through interaction with integrin receptors. This supports cell adhesion function. Reason: COMP supports chondrocyte attachment through interaction with integrins (ITGA5, ITGB3), consistent with cell adhesion function. This is a secondary function to its primary ECM structural role. Supporting Evidence: PMID:16051604 Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte attachment through interaction with integrins UniProt:P49747 Can mediate the interaction of chondrocytes with the cartilage extracellular matrix through interaction with cell surface integrin receptors |
| GO:0008201 heparin binding | IEA GO_REF:0000120 | ACCEPT | Summary: COMP binds heparin, heparan sulfate, and chondroitin sulfate proteoglycans, as demonstrated experimentally. Reason: Heparin binding is experimentally validated for COMP. This reflects its ability to interact with glycosaminoglycans as part of its ECM organizing function. Supporting Evidence: PMID:17588949 Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan UniProt:P49747 Binds heparin, heparan sulfate and chondroitin sulfate |
| GO:0005515 protein binding | IPI PMID:16611630 ADAMTS-12 associates with and degrades cartilage oligomeric ... | MODIFY | Summary: This reference demonstrates COMP interaction with ADAMTS-12. The generic 'protein binding' term is uninformative; COMP has specific binding partners. Reason: ADAMTS-12 is a metalloprotease that degrades COMP. A more specific annotation such as 'protease binding' would be more informative. Proposed replacements: protease binding Supporting Evidence: PMID:16611630 ADAMTS-12 associates with and degrades cartilage oligomeric matrix protein |
| GO:0005515 protein binding | IPI PMID:17588949 Interaction of cartilage oligomeric matrix protein/thrombosp... | MODIFY | Summary: This reference demonstrates COMP interaction with aggrecan (ACAN). The generic 'protein binding' is uninformative. Reason: COMP binds aggrecan specifically through its C-terminal domain. A more specific annotation to proteoglycan binding is warranted. Proposed replacements: proteoglycan binding Supporting Evidence: PMID:17588949 Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan UniProt:P49747 Interacts with MATN1, MATN3, MATN4 and ACAN |
| GO:0005515 protein binding | IPI PMID:18485748 Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilag... | MODIFY | Summary: This reference discusses inhibition of ADAMTS-7 and ADAMTS-12 degradation of COMP by alpha-2-macroglobulin. The protein binding annotation relates to protease interactions. Reason: The interaction is specifically with proteases ADAMTS-7 and ADAMTS-12. Protease binding is more appropriate. Proposed replacements: protease binding Supporting Evidence: PMID:18485748 Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: High-throughput interactome study. Generic protein binding from large-scale screen. Reason: High-throughput study provides evidence for protein interactions but lacks mechanistic detail. Acceptable as background annotation but not informative for core function. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Study on genetic variants affecting protein interactions. High-throughput data. Reason: Population-level study of variant effects on interactions. Not informative for core molecular function annotation. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Reference map of human binary protein interactome. High-throughput data. Reason: Large-scale interactome study. Generic protein binding annotation is minimally informative. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0001501 skeletal system development | IEA GO_REF:0000107 | ACCEPT | Summary: COMP is essential for skeletal development. Mutations cause pseudoachondroplasia and multiple epiphyseal dysplasia, demonstrating its critical role in skeletal system development. Reason: COMP's role in skeletal development is well-established through disease genetics and expression studies. Present during earliest stages of limb maturation and in joint development regions. Supporting Evidence: PMID:7670472 Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene PMID:16542502 Cartilage oligomeric matrix protein is involved in human limb development and in the pathogenesis of osteoarthritis UniProt:P49747 Present during the earliest stages of limb maturation and is later found in regions where the joints develop |
| GO:0001503 ossification | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP is involved in endochondral ossification, but this is secondary to its primary role in cartilage ECM organization. Reason: COMP affects bone formation indirectly through its effects on cartilage template organization during endochondral ossification. This is downstream of its primary ECM function. Supporting Evidence: PMID:7670472 Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene |
| GO:0002020 protease binding | IEA GO_REF:0000107 | ACCEPT | Summary: COMP is cleaved by metalloproteases ADAMTS-4, ADAMTS-1, ADAMTS-7, and ADAMTS-12. Protease binding reflects COMP's role as a substrate for these enzymes. Reason: COMP interaction with ADAMTS proteases is experimentally validated. This binding is relevant to COMP turnover in cartilage homeostasis and disease. Supporting Evidence: PMID:16611630 ADAMTS-12 associates with and degrades cartilage oligomeric matrix protein PMID:18485748 Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin UniProt:P49747 Proteolytically cleaved by metalloproteases ADAMTS4 and ADAMTS1 with ADAMTS4 showing more potent activity |
| GO:0002063 chondrocyte development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP is expressed by chondrocytes and supports their function, but there is limited direct evidence for a role in chondrocyte development per se versus maintenance. Reason: COMP's primary role is in ECM organization rather than chondrocyte differentiation. Its expression in cartilage supports chondrocyte function but evidence for developmental role is indirect. Supporting Evidence: PMID:7713493 Cartilage oligomeric matrix protein (COMP) is a 524,000-Da protein that is expressed at high levels in the territorial matrix of chondrocytes |
| GO:0003416 endochondral bone growth | IEA GO_REF:0000107 | ACCEPT | Summary: COMP mutations cause growth plate abnormalities in PSACH and EDM1, indicating a role in endochondral bone growth. Reason: COMP defects disrupt growth plate cartilage and endochondral ossification, leading to short stature in PSACH/EDM1 patients. This supports involvement in endochondral bone growth. Supporting Evidence: PMID:7670472 Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene UniProt:P49747 A skeletal dysplasia usually manifesting in the second year of life and characterized by moderate to severe disproportionate short stature |
| GO:0003417 growth plate cartilage development | IEA GO_REF:0000107 | ACCEPT | Summary: COMP is expressed in growth plate cartilage and mutations cause growth plate abnormalities in skeletal dysplasias. Reason: COMP is essential for normal growth plate function as demonstrated by the pathology in PSACH/EDM1 where mutant COMP accumulates in chondrocyte ER and disrupts growth plate organization. Supporting Evidence: PMID:7670472 Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene PMID:16542502 Cartilage oligomeric matrix protein is involved in human limb development |
| GO:0005178 integrin binding | IEA GO_REF:0000107 | ACCEPT | Summary: COMP binds integrins alpha5beta1 and alphaVbeta3 to mediate chondrocyte attachment and cell signaling. Reason: Integrin binding is experimentally validated. COMP mediates cell-matrix interactions through these integrin receptors. Supporting Evidence: PMID:16051604 Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte attachment through interaction with integrins UniProt:P49747 Interacts with ITGB3, ITGA5 Reactome:R-HSA-2426259 COMP binds Integrin alpha5beta1, Integrin alphaVbeta3, CD47 |
| GO:0005615 extracellular space | IEA GO_REF:0000107 | ACCEPT | Summary: COMP is secreted into the extracellular space and incorporated into the ECM. This is redundant with extracellular matrix annotation. Reason: Accurate annotation for a secreted protein. COMP is found both in the ECM and in body fluids (synovial fluid, serum) as a biomarker. Supporting Evidence: UniProt:P49747 SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix |
| GO:0006986 response to unfolded protein | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Mutant COMP causes ER stress and activates the unfolded protein response. However, COMP itself is not a component of the UPR; rather, its misfolding triggers the response. Reason: This annotation conflates COMP's role as a trigger of UPR (when mutated) with participation in the UPR pathway. Wild-type COMP does not function in the UPR; only pathogenic variants cause ER stress. Supporting Evidence: UniProt:P49747 Potent suppressor of apoptosis in both primary chondrocytes and transformed cells. Suppresses apoptosis by blocking the activation of caspase-3 and by inducing the IAP family of survival proteins |
| GO:0007596 blood coagulation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This annotation may derive from COMP's relationship to the thrombospondin family, some members of which function in coagulation. However, COMP/TSP-5 is not a major participant in blood coagulation. Reason: Unlike TSP-1 which has documented roles in platelet function and coagulation, COMP/TSP-5 is primarily an ECM protein in cartilage. This may be inappropriate transfer from other thrombospondins. Supporting Evidence: UniProt:P49747 Abundantly expressed in the chondrocyte extracellular matrix, and is also found in bone, tendon, ligament and synovium and blood vessels |
| GO:0009306 protein secretion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP facilitates collagen secretion from the ER, representing an intracellular chaperone-like function distinct from its extracellular structural role. Reason: COMP has been shown to facilitate collagen secretion, but this is not its primary function. The main role is as an ECM structural constituent after secretion. Supporting Evidence: UniProt:P49747 Plays a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Limited direct evidence that COMP regulates gene expression. May be an over-annotation based on downstream effects of signaling. Reason: No strong evidence that COMP directly regulates gene expression. Any effects would be indirect through integrin signaling or other downstream pathways. |
| GO:0014829 vascular associated smooth muscle contraction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP maintains vascular smooth muscle cell phenotype through ITGA7 interaction. Reason: COMP's role in VSMC phenotype maintenance is documented but based on similarity evidence. This is a secondary tissue expression role, not core cartilage function. Supporting Evidence: UniProt:P49747 Essential for maintaining a vascular smooth muscle cells (VSMCs) contractile/differentiated phenotype under physiological and pathological stimuli. Maintains this phenotype of VSMCs by interacting with ITGA7 (By similarity) |
| GO:0016485 protein processing | IEA GO_REF:0000107 | REMOVE | Summary: COMP undergoes proteolytic processing (signal peptide cleavage, protease cleavage by ADAMTS enzymes), but it does not function as a protein processing enzyme. Reason: This annotation is incorrect. COMP is processed, not a processor. It undergoes cleavage by ADAMTS proteases but does not participate in processing other proteins. Supporting Evidence: UniProt:P49747 Proteolytically cleaved by metalloproteases ADAMTS4 and ADAMTS1 |
| GO:0030199 collagen fibril organization | IEA GO_REF:0000107 | ACCEPT | Summary: COMP promotes collagen fibrillogenesis and organizes collagen fibrils in the ECM. This is a core molecular function. Reason: COMP catalyzes collagen fibrillogenesis and stabilizes ECM networks. This is a primary function of COMP in cartilage and other load-bearing tissues. Supporting Evidence: PMID:11084047 Mutations in cartilage oligomeric matrix protein causing pseudoachondroplasia and multiple epiphyseal dysplasia affect binding of calcium and collagen I, II, and IX UniProt:P49747 Plays a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens |
| GO:0030282 bone mineralization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Bone mineralization defects are seen in COMP-related skeletal dysplasias, but COMP's role is likely indirect through effects on cartilage template. Reason: COMP mutations affect bone development but COMP is not directly involved in the mineralization process. Effects are secondary to cartilage ECM disorganization. Supporting Evidence: UniProt:P49747 Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers |
| GO:0030500 regulation of bone mineralization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Similar to bone mineralization, any role would be indirect. Reason: Indirect effect through cartilage template organization rather than direct regulation of mineralization. |
| GO:0030509 BMP signaling pathway | IEA GO_REF:0000107 | UNDECIDED | Summary: COMP may bind BMPs based on domain predictions but direct participation in BMP signaling is not well-documented. Reason: Limited direct experimental evidence for COMP participation in BMP signaling pathway. The annotation may be based on domain predictions rather than functional data. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | ACCEPT | Summary: COMP forms homopentameric complexes and interacts with multiple ECM proteins. Reason: COMP forms stable pentameric complexes and is part of larger ECM supramolecular assemblies with collagens, matrilins, and proteoglycans. Supporting Evidence: UniProt:P49747 Pentamer; disulfide-linked ComplexPortal:CPX-1791 Thrombospondin 5 complex |
| GO:0035264 multicellular organism growth | IEA GO_REF:0000107 | ACCEPT | Summary: COMP mutations cause short stature, demonstrating involvement in organismal growth. Reason: COMP deficiency causes disproportionate short stature in PSACH, demonstrating its essential role in normal growth. Supporting Evidence: UniProt:P49747 characterized by moderate to severe disproportionate short stature PMID:7670472 Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene |
| GO:0035988 chondrocyte proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP associates with granulin-epithelin precursor to potentiate chondrocyte proliferation. Reason: COMP may influence chondrocyte proliferation but this is not its primary function. The main role is ECM organization. |
| GO:0035989 tendon development | IEA GO_REF:0000107 | ACCEPT | Summary: COMP is expressed in tendons and contributes to tendon ECM organization. Reason: COMP is abundantly expressed in tendons and ligaments as well as cartilage. Its ECM organizing function is relevant to tendon structure. Supporting Evidence: UniProt:P49747 Abundantly expressed in the chondrocyte extracellular matrix, and is also found in bone, tendon, ligament and synovium and blood vessels |
| GO:0036122 BMP binding | IEA GO_REF:0000107 | UNDECIDED | Summary: BMP binding is predicted from domain structure but lacks strong experimental validation for COMP specifically. Reason: Limited direct experimental evidence for BMP binding by COMP. Annotation may be based on domain predictions. |
| GO:0043588 skin development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP is expressed in skin according to HPA data, but its role in skin development is not well characterized. Reason: Expression in skin is documented but functional role in skin development is not established. This is a secondary expression site. Supporting Evidence: HPA:ENSG00000105664 Tissue enhanced (adipose tissue, heart muscle, skin) |
| GO:0048844 artery morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP is expressed in blood vessels and affects VSMC phenotype, potentially contributing to vascular development. Reason: COMP expression in blood vessels and effects on VSMC are documented by similarity, but this is not a core function compared to cartilage ECM role. Supporting Evidence: UniProt:P49747 Abundantly expressed in the chondrocyte extracellular matrix, and is also found in bone, tendon, ligament and synovium and blood vessels |
| GO:0050881 musculoskeletal movement | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP in cartilage, tendon, and ligament supports musculoskeletal function, but this is a very high-level process term. Reason: This is too general. COMP's contribution to musculoskeletal movement is through its structural role in load-bearing tissues, not a direct function in movement. |
| GO:0050905 neuromuscular process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: No clear evidence for COMP involvement in neuromuscular processes specifically. Reason: COMP is an ECM protein without documented roles in neuromuscular junction or neuromuscular transmission. Likely an over-annotation. |
| GO:0051216 cartilage development | IEA GO_REF:0000107 | ACCEPT | Summary: COMP is essential for cartilage development and function, as demonstrated by PSACH/EDM1 phenotypes. Reason: COMP is a major cartilage ECM protein essential for normal cartilage development and maintenance. Core function. Supporting Evidence: PMID:7713493 Cartilage oligomeric matrix protein (COMP) is a 524,000-Da protein that is expressed at high levels in the territorial matrix of chondrocytes PMID:16542502 Cartilage oligomeric matrix protein is involved in human limb development and in the pathogenesis of osteoarthritis |
| GO:0051260 protein homooligomerization | IEA GO_REF:0000107 | ACCEPT | Summary: COMP forms homopentamers via its N-terminal domain and disulfide bonds. Reason: COMP pentamerization is essential for its function and well-documented structurally. The pentameric assembly creates the multivalent scaffold for ECM bridging. Supporting Evidence: UniProt:P49747 Pentamer; disulfide-linked |
| GO:0055001 muscle cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP affects VSMC phenotype but general muscle cell development role is not well established. Reason: VSMC phenotype maintenance is documented by similarity but broad muscle cell development role is not COMP's primary function. Supporting Evidence: UniProt:P49747 Essential for maintaining a vascular smooth muscle cells (VSMCs) contractile/differentiated phenotype under physiological and pathological stimuli |
| GO:0060173 limb development | IEA GO_REF:0000107 | ACCEPT | Summary: COMP is expressed during limb development and mutations cause limb abnormalities. Reason: COMP is present during earliest stages of limb maturation and later in joint development regions. Essential for normal limb development. Supporting Evidence: PMID:16542502 Cartilage oligomeric matrix protein is involved in human limb development UniProt:P49747 Present during the earliest stages of limb maturation and is later found in regions where the joints develop |
| GO:0060349 bone morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP mutations affect bone shape (morphogenesis) through effects on cartilage template. Reason: Bone morphogenesis defects in PSACH/EDM1 are secondary to cartilage abnormalities. COMP's primary role is in cartilage ECM. |
| GO:0070527 platelet aggregation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Unlike other thrombospondins, COMP/TSP-5 is not a major participant in platelet aggregation. Reason: COMP is primarily a cartilage ECM protein. Platelet aggregation role may be inappropriately transferred from other thrombospondin family members like TSP-1. |
| GO:0090398 cellular senescence | IEA GO_REF:0000107 | UNDECIDED | Summary: Limited evidence for COMP involvement in cellular senescence specifically. Reason: No clear experimental evidence for COMP role in cellular senescence. May be an over-annotation. |
| GO:0097084 vascular associated smooth muscle cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP maintains VSMC phenotype through ITGA7 interaction. Reason: Documented by similarity but not a core function of COMP. Primary role is in cartilage/tendon ECM. Supporting Evidence: UniProt:P49747 Essential for maintaining a vascular smooth muscle cells (VSMCs) contractile/differentiated phenotype under physiological and pathological stimuli |
| GO:0098868 bone growth | IEA GO_REF:0000107 | ACCEPT | Summary: COMP mutations cause short stature reflecting impaired bone growth. Reason: COMP deficiency causes growth failure, demonstrating its essential role in normal bone growth through cartilage template organization. Supporting Evidence: UniProt:P49747 characterized by moderate to severe disproportionate short stature |
| GO:1900047 negative regulation of hemostasis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: No clear evidence for COMP involvement in hemostasis regulation. Reason: COMP/TSP-5 is not documented to regulate hemostasis. May be inappropriate transfer from TSP-1 which has hemostatic roles. |
| GO:1902732 positive regulation of chondrocyte proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: COMP may influence chondrocyte proliferation through its ECM interactions. Reason: Some evidence for effects on chondrocyte proliferation but not the primary function of COMP. |
| GO:1990079 cartilage homeostasis | IEA GO_REF:0000107 | ACCEPT | Summary: COMP is essential for cartilage homeostasis, maintaining ECM integrity in load-bearing tissues. Reason: Cartilage homeostasis is a core function of COMP. Its role in maintaining ECM organization and responding to mechanical load supports cartilage health. Supporting Evidence: PMID:16542502 Cartilage oligomeric matrix protein is involved in human limb development and in the pathogenesis of osteoarthritis UniProt:P49747 Could play a role in the pathogenesis of osteoarthritis |
| GO:0031012 extracellular matrix | IDA PMID:18285447 Extracellular matrix retention of thrombospondin 1 is contro... | ACCEPT | Summary: Direct experimental evidence for COMP localization in ECM. Reason: IDA evidence confirming ECM localization. This is the core cellular compartment for COMP function. Supporting Evidence: PMID:18285447 ECM incorporation as insoluble punctate deposits is an evolutionarily conserved property of TSPs |
| GO:0005576 extracellular region | IDA PMID:32747625 Author Correction: Mutations in COMP cause familial carpal t... | ACCEPT | Summary: Direct evidence for secretion and extracellular localization from study of COMP mutations in carpal tunnel syndrome. Reason: IDA evidence confirming COMP secretion and extracellular localization. Supporting Evidence: PMID:32747625 Mutations in COMP cause familial carpal tunnel syndrome |
| GO:0051260 protein homooligomerization | IDA PMID:32747625 Author Correction: Mutations in COMP cause familial carpal t... | ACCEPT | Summary: Direct evidence for COMP pentamerization from CTS2 study. Reason: IDA evidence demonstrating COMP pentamerization and effects of mutations on oligomerization. Supporting Evidence: UniProt:P49747 Pentamer; disulfide-linked |
| GO:1990079 cartilage homeostasis | IDA PMID:32747625 Author Correction: Mutations in COMP cause familial carpal t... | ACCEPT | Summary: Direct experimental evidence for COMP role in cartilage homeostasis. Reason: IDA evidence supporting cartilage homeostasis function. Supporting Evidence: PMID:32747625 Mutations in COMP cause familial carpal tunnel syndrome |
| GO:0043394 proteoglycan binding | IDA PMID:29030641 Lubricin binds cartilage proteins, cartilage oligomeric matr... | ACCEPT | Summary: Direct evidence for COMP binding to proteoglycans including lubricin at cartilage surface. Reason: IDA evidence for proteoglycan binding. COMP interacts with aggrecan and other proteoglycans as part of its ECM organizing function. Supporting Evidence: PMID:29030641 Lubricin binds cartilage proteins, cartilage oligomeric matrix protein, fibronectin and collagen II at the cartilage surface |
| GO:0005201 extracellular matrix structural constituent | RCA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Reviewed computational analysis supporting COMP as an ECM structural constituent. Reason: This is the core molecular function of COMP - serving as a structural organizer in the ECM. RCA evidence is appropriate. Supporting Evidence: PMID:20551380 Proteomics characterization of extracellular space components in the human aorta UniProt:P49747 Plays a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins |
| GO:0005576 extracellular region | HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | ACCEPT | Summary: High-throughput data analysis supporting extracellular localization from varicose vein proteomics. Reason: HDA evidence confirming secreted/extracellular localization of COMP. Supporting Evidence: PMID:27068509 Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins |
| GO:0005615 extracellular space | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: High-throughput proteomics data supporting extracellular space localization. Reason: HDA evidence for extracellular space localization from aorta proteomics. Supporting Evidence: PMID:20551380 Proteomics characterization of extracellular space components in the human aorta |
| GO:0031012 extracellular matrix | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: High-throughput proteomics data supporting ECM localization. Reason: HDA evidence for ECM localization consistent with COMP's known function. Supporting Evidence: PMID:20551380 Proteomics characterization of extracellular space components in the human aorta |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: High-throughput proteomics data detecting COMP in exosomes. Reason: Exosome detection may reflect COMP release during tissue turnover rather than primary exosomal function. Not a core localization. Supporting Evidence: PMID:23533145 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine |
| GO:0002020 protease binding | IPI PMID:18485748 Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilag... | ACCEPT | Summary: Direct evidence for COMP interaction with ADAMTS proteases. Reason: IPI evidence for protease binding. COMP is a substrate for ADAMTS-7 and ADAMTS-12. Supporting Evidence: PMID:18485748 Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2424252 | ACCEPT | Summary: Reactome pathway annotation for COMP binding to ECM components. Reason: TAS evidence from curated Reactome pathway supporting extracellular localization. Supporting Evidence: Reactome:R-HSA-2424252 COMP binds collagen, fibronectin, aggrecan and matrilins |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2426259 | ACCEPT | Summary: Reactome pathway annotation for COMP integrin interactions. Reason: TAS evidence from curated Reactome pathway. Supporting Evidence: Reactome:R-HSA-2426259 COMP binds Integrin alpha5beta1, Integrin alphaVbeta3, CD47 |
| GO:0005509 calcium ion binding | IDA PMID:10852928 Cartilage oligomeric matrix protein is a calcium-binding pro... | ACCEPT | Summary: Direct experimental evidence that COMP binds calcium ions and mutations in type 3 repeats cause conformational changes. Reason: IDA evidence demonstrating COMP calcium binding. Each TSP type-3 repeat binds two calcium ions. Supporting Evidence: PMID:10852928 Cartilage oligomeric matrix protein is a calcium-binding protein, and a mutation in its type 3 repeats causes conformational changes |
| GO:0005509 calcium ion binding | IDA PMID:11084047 Mutations in cartilage oligomeric matrix protein causing pse... | ACCEPT | Summary: Direct evidence that PSACH/EDM1 mutations affect calcium binding. Reason: IDA evidence demonstrating calcium binding and effects of disease mutations on this function. Supporting Evidence: PMID:11084047 Mutations in cartilage oligomeric matrix protein causing pseudoachondroplasia and multiple epiphyseal dysplasia affect binding of calcium and collagen I, II, and IX |
| GO:0005515 protein binding | IPI PMID:12225811 Matrix-matrix interaction of cartilage oligomeric matrix pro... | MODIFY | Summary: Study demonstrating COMP interaction with fibronectin. Reason: COMP binds fibronectin specifically. A more informative annotation to fibronectin binding would be appropriate. Proposed replacements: fibronectin binding Supporting Evidence: PMID:12225811 Matrix-matrix interaction of cartilage oligomeric matrix protein and fibronectin |
| GO:0005515 protein binding | IPI PMID:15075323 Interactions between the cartilage oligomeric matrix protein... | KEEP AS NON CORE | Summary: Study demonstrating COMP interaction with matrilins. Reason: COMP binds matrilins (MATN1, MATN3, MATN4). Generic protein binding annotation is acceptable but not informative. Supporting Evidence: PMID:15075323 Interactions between the cartilage oligomeric matrix protein and matrilins. Implications for matrix assembly and the pathogenesis of chondrodysplasias |
| GO:0005515 protein binding | IPI PMID:16051604 Cartilage oligomeric matrix protein/thrombospondin 5 support... | MODIFY | Summary: Study demonstrating COMP interaction with integrins. Reason: COMP binds integrins alpha5beta1 and alphaVbeta3. Integrin binding is more specific and informative. Proposed replacements: integrin binding Supporting Evidence: PMID:16051604 Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte attachment through interaction with integrins |
| GO:0005518 collagen binding | IDA PMID:11084047 Mutations in cartilage oligomeric matrix protein causing pse... | ACCEPT | Summary: Direct evidence for COMP binding to collagens I, II, and IX in zinc-dependent manner. Reason: Collagen binding is a core molecular function of COMP. IDA evidence demonstrates binding to multiple collagen types. Supporting Evidence: PMID:11084047 Mutations in cartilage oligomeric matrix protein causing pseudoachondroplasia and multiple epiphyseal dysplasia affect binding of calcium and collagen I, II, and IX UniProt:P49747 Interacts with collagen I, II and IX, and interaction with these collagens is dependent on the presence of zinc ions |
| GO:0008201 heparin binding | IDA PMID:17588949 Interaction of cartilage oligomeric matrix protein/thrombosp... | ACCEPT | Summary: Direct evidence for COMP heparin binding from aggrecan interaction study. Reason: IDA evidence for heparin binding. COMP binds heparin, heparan sulfate, and chondroitin sulfate. Supporting Evidence: PMID:17588949 Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan UniProt:P49747 Binds heparin, heparan sulfate and chondroitin sulfate |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:17993464 Cartilage oligomeric matrix protein protects cells against d... | ACCEPT | Summary: Direct evidence that COMP suppresses apoptosis by inducing IAP family survival proteins. Reason: IDA evidence for anti-apoptotic function. COMP blocks caspase-3 activation and induces BIRC2, BIRC3, BIRC5, and XIAP. Supporting Evidence: PMID:17993464 Cartilage oligomeric matrix protein protects cells against death by elevating members of the IAP family of survival proteins UniProt:P49747 Potent suppressor of apoptosis in both primary chondrocytes and transformed cells. Suppresses apoptosis by blocking the activation of caspase-3 and by inducing the IAP family of survival proteins |
| GO:0043395 heparan sulfate proteoglycan binding | IDA PMID:17588949 Interaction of cartilage oligomeric matrix protein/thrombosp... | ACCEPT | Summary: Direct evidence for COMP binding to heparan sulfate proteoglycans. Reason: IDA evidence for heparan sulfate proteoglycan binding. Part of COMP's GAG-binding activity. Supporting Evidence: PMID:17588949 Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with aggrecan UniProt:P49747 Binds heparin, heparan sulfate and chondroitin sulfate |
| GO:0060173 limb development | IDA PMID:16542502 Cartilage oligomeric matrix protein is involved in human lim... | ACCEPT | Summary: Direct evidence for COMP involvement in human limb development from developmental expression study. Reason: IDA evidence demonstrating COMP expression during limb development and involvement in osteoarthritis pathogenesis. Supporting Evidence: PMID:16542502 Cartilage oligomeric matrix protein is involved in human limb development and in the pathogenesis of osteoarthritis |
| GO:0009887 animal organ morphogenesis | TAS PMID:7713493 Characterization of human and mouse cartilage oligomeric mat... | KEEP AS NON CORE | Summary: Traceable author statement supporting role in organ morphogenesis from original characterization paper. Reason: This is a high-level process term. COMP's role is more specifically in cartilage/skeletal morphogenesis. Supporting Evidence: PMID:7713493 Characterization of human and mouse cartilage oligomeric matrix protein |
| GO:0001501 skeletal system development | TAS PMID:7670472 Pseudoachondroplasia and multiple epiphyseal dysplasia due t... | ACCEPT | Summary: Traceable author statement from paper demonstrating COMP mutations cause skeletal dysplasias. Reason: TAS evidence strongly supporting skeletal development role based on PSACH/EDM1 genetics. Supporting Evidence: PMID:7670472 Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene |
| GO:0005201 extracellular matrix structural constituent | TAS PMID:7713493 Characterization of human and mouse cartilage oligomeric mat... | ACCEPT | Summary: Traceable author statement from original characterization establishing COMP as ECM structural protein. Reason: This is the core molecular function of COMP. TAS evidence from foundational paper. Supporting Evidence: PMID:7713493 Characterization of human and mouse cartilage oligomeric matrix protein |
| GO:0005509 calcium ion binding | TAS PMID:7670472 Pseudoachondroplasia and multiple epiphyseal dysplasia due t... | ACCEPT | Summary: Traceable author statement for calcium binding from disease genetics paper. Reason: TAS evidence supporting calcium binding, later confirmed by IDA. Supporting Evidence: PMID:7670472 Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene |
| GO:0031012 extracellular matrix | TAS PMID:7713493 Characterization of human and mouse cartilage oligomeric mat... | ACCEPT | Summary: Traceable author statement for ECM localization from original characterization. Reason: TAS evidence for ECM localization from foundational paper. Supporting Evidence: PMID:7713493 Cartilage oligomeric matrix protein (COMP) is a 524,000-Da protein that is expressed at high levels in the territorial matrix of chondrocytes |
Loading supporting content…
Download this section (compressed HTML)Q: Does COMP have a true enzymatic activity in catalyzing collagen fibril assembly, or does it act purely as a scaffold/organizer?
Q: What is the relative contribution of COMP to ECM function in different tissues (cartilage vs tendon vs blood vessels)?
Q: What is the relationship between COMP and BMP signaling in cartilage development?
Experiment: Comparative analysis of COMP-null mouse phenotypes in different tissue-specific knockouts to distinguish cartilage-specific from systemic COMP functions.
Experiment: Direct biochemical measurement of BMP binding affinity by COMP to validate or refute the predicted BMP binding annotation.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)