ACAN

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0007417 central nervous system development	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Aggrecan contributes to the extracellular environment of developing neural circuits through perineuronal nets. The broad CNS-development IBA is biologically defensible but less informative than its matrix-binding and structural activities, so it remains non-core. The cached PAINT IBD places this inherited process at PTN000515588. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000515588 · PTN000515588 SUPPORTS TRANSFER Cached PTHR22804 PAINT data place the IBD for GO:0007417 at PTN000515588 (dated 20230603). The IBA follows descent from this ancestral assertion; no target-specific loss or erroneous node placement is established. Supporting Evidence: PMID:25701227 Aggrecan is also expressed in the brain, and unlike other hyalectans, is expressed primarily in the perineuronal nets
GO:0045202 synapse	IBA GO_REF:0000033	MODIFY	Summary: Recombinant human G1 and G1-G2 fragments bind perineuronal nets in mouse cortical neuron cultures, and the proteoglycan review identifies these nets as the principal brain localization of aggrecan. Perineuronal net specifies the characterized neural matrix compartment more precisely than synapse. Reason: Prefer GO:0072534 for the directly characterized aggrecan-rich neural matrix. The refinement concerns compartment specificity; the cached ancestral assertion remains biologically plausible. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN008374273 · PTN008374273 SUPPORTS TRANSFER Cached PTHR22804 PAINT data place the IBD for GO:0045202 at PTN008374273 (dated 20230603). The IBA follows descent from this ancestral assertion; no target-specific loss or erroneous node placement is established. Proposed replacements: perineuronal net Supporting Evidence: PMID:25701227 Aggrecan is also expressed in the brain, and unlike other hyalectans, is expressed primarily in the perineuronal nets PMID:40273987 both fragments of ACAN bound highly and very specifically to PNNs on cultured cortical neurons
GO:0072534 perineuronal net	IBA GO_REF:0000033	ACCEPT	Summary: Perineuronal net is a well-supported extracellular location of aggrecan. PMID:40273987 directly assays recombinant human G1 and G1-G2 fragments added to pre-existing nets in mouse cortical neuron cultures. Hyaluronan-binding-null mutants retain weaker net binding, indicating an additional anchoring interaction. This supports the inherited localization without claiming that the experiment measured endogenous human brain expression or de novo net assembly. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008374273 · PTN008374273 SUPPORTS TRANSFER Cached PTHR22804 PAINT data place the IBD for GO:0072534 at PTN008374273 (dated 20230111). The IBA follows descent from this ancestral assertion; no target-specific loss or erroneous node placement is established. Supporting Evidence: PMID:40273987 both fragments of ACAN bound highly and very specifically to PNNs on cultured cortical neurons PMID:40273987 Thus, these results suggest that ACAN can be recruited into PNNs independently of its HA-binding activity. PMID:25701227 Aggrecan is also expressed in the brain, and unlike other hyalectans, is expressed primarily in the perineuronal nets
GO:0001501 skeletal system development	IBA GO_REF:0000033	MODIFY	Summary: Aggrecan supplies the hydrated structural matrix required during cartilage development and skeletal growth. Cartilage development is a useful refinement of the broader skeletal-system term. Aggrecan-deficient animal models have severe cartilage defects and lethality; human variants cause distinct dominant or recessive skeletal disorders. The PAINT IBD is consistent with this conserved structural role. Reason: GO:0051216 specifies the cartilage developmental contribution supported by aggrecan structural biology, animal models, and human skeletal phenotypes. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000515588 · PTN000515588 SUPPORTS TRANSFER Cached PTHR22804 PAINT data place the IBD for GO:0001501 at PTN000515588 (dated 20200808). The IBA follows descent from this ancestral assertion; no target-specific loss or erroneous node placement is established. Proposed replacements: cartilage development Supporting Evidence: PMID:25701227 In both mutant animals, there is little or no aggrecan in cartilage leading to shortened long bones and lethality PMID:35338222 The cartilage aggrecan proteoglycan is crucial for both skeletal growth and articular cartilage function.
GO:0005540 hyaluronic acid binding	IEA GO_REF:0000002	ACCEPT	Summary: Hyaluronan binding is a core activity of aggrecan G1. The inherited InterPro IEA remains valid. Independently, PMID:40273987 provides a human G1-hyaluronan crystal structure and biolayer-interferometry binding measurements with an affinity of 234 nM for immobilized hyaluronan. Direct experimental support does not invalidate or change the seeded IEA. Supporting Evidence: file:human/ACAN/ACAN-uniprot.txt CC resist compression in cartilage. It binds avidly to hyaluronic acid via PMID:40273987 We demonstrate that the single immunoglobulin domain and the two Link modules that comprise the G1 region form a single structural unit, and that HA is clamped inside a groove that spans the length of the tandem Link domains. PMID:40273987 In these experiments, ACAN binds to immobilized HA with an affinity of 234 nM, which is consistent with the value of 226 nM reported in an earlier study using surface plasmon resonance
GO:0005796 Golgi lumen	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: True but transitional. Aggrecan's keratan sulfate chains, chondroitin sulfate chains and N-glycans are all built in the Golgi lumen, so the core protein necessarily passes through that compartment on its way out of the chondrocyte. It does not function there - the mechanical function requires the mature, fully glycanated molecule in the extracellular matrix. This ARBA model annotation duplicates fourteen Reactome reaction-level rows for the same compartment. Supporting Evidence: file:human/ACAN/ACAN-uniprot.txt CC -!- PTM: Contains mostly chondroitin sulfate, but also keratan sulfate
GO:0007155 cell adhesion	IEA GO_REF:0000002	UNDECIDED	Summary: PMID:11222505 reports CD44-dependent cell binding to immobilized rat and bovine aggrecan through chondroitin sulfate chains. This supports an adhesion role for those preparations, but does not directly validate the human Link-domain mapping. The available primary abstract does not resolve that mechanistic and species scope; the complete study was not recovered. Reason: The human InterPro domain-to-process inference remains unresolved. The accessible nonhuman study implicates glycosaminoglycan chains rather than the Link domain, so its evidence neither establishes nor excludes the specific human annotation. Propagation Review Root cause: UNRESOLVED Sources checked: InterPro:IPR000538 · Link domain UNRESOLVED The domain-to-process mapping requires assessment of the role of the human target. The nonhuman CD44-aggrecan adhesion study implicates chondroitin sulfate chains, not the aggrecan Link domain; it neither validates this mapping nor supports categorical rejection.
GO:0043202 lysosomal lumen	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: A lysosomal pool is consistent with turnover of internalized keratan sulfate proteoglycans. Reactome models delivery to this compartment but explicitly leaves the uptake mechanism uncertain. Retain as a non-core catabolic location, without assigning a lysosomal catalytic activity to the aggrecan substrate.
GO:0140150 gel phase of interstitial matrix	IEA GO_REF:0000117	ACCEPT	Summary: Aggrecan-hyaluronan aggregates form the hydrated proteoglycan gel described in PMID:25701227. Live AmiGO identifies GO:0140150 as part_of interstitial matrix (GO:0005614), itself an extracellular matrix subtype, and cites PMID:25701227 among the gel-term definition sources. This hydrogel compartment supports the core compression-resisting activity. Reason: Retain this core location and include GO:0140150 in the compression-resistance core function. The IEA row uses located_in while the TAS row uses is_active_in; both identify the same compartment. Harmonizing these source relations to located_in would express the compartment claim consistently, without changing the preserved source qualifiers here. Supporting Evidence: PMID:25701227 These large aggregates generate a densely-packed, hydrated gel enmeshed in a network of reinforcing collagen fibrils and other proteoglycans PMID:27068509 To our knowledge, the present study is the first to report the identification of aggrecan in venous tissue.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: The annotation records an APP-aggrecan interaction from the neurodegeneration interactome study, and the cached UniProt record lists three experiments. The available abstract describes systematic screening plus literature integration; the pair-specific constructs, validation and biological mechanism were not recovered. Reason: Generic protein binding provides no informative molecular function, and the available evidence does not establish a specific replacement. Remove this uninformative annotation without denying the reported interaction or making a claim about its replication or quality. Supporting Evidence: PMID:32814053 is generated by systematic yeast two-hybrid interaction screening file:human/ACAN/ACAN-uniprot.txt CC P16112; P05067: APP; NbExp=3; IntAct=EBI-9076211, EBI-77613;
GO:0140150 gel phase of interstitial matrix	TAS PMID:25701227 Proteoglycan form and function: A comprehensive nomenclature...	ACCEPT	Summary: Aggrecan-hyaluronan aggregates form the hydrated proteoglycan gel described in PMID:25701227. Live AmiGO identifies GO:0140150 as part_of interstitial matrix (GO:0005614), itself an extracellular matrix subtype, and cites PMID:25701227 among the gel-term definition sources. This hydrogel compartment supports the core compression-resisting activity. Reason: Retain this core location and include GO:0140150 in the compression-resistance core function. The IEA row uses located_in while the TAS row uses is_active_in; both identify the same compartment. Harmonizing these source relations to located_in would express the compartment claim consistently, without changing the preserved source qualifiers here. Supporting Evidence: PMID:25701227 These large aggregates generate a densely-packed, hydrated gel enmeshed in a network of reinforcing collagen fibrils and other proteoglycans
GO:0005576 extracellular region	TAS Reactome:R-HSA-2046180	MODIFY	Summary: Reactome R-HSA-2046180 explicitly describes secretion of keratan sulfate proteoglycans into the extracellular matrix. Although the exported compartment is extracellular region, the source narrative resolves the destination as matrix. Reason: Refine to GO:0031012 using the stated ECM destination. The reaction describes aggrecan biosynthetic transit; source-specific location resolution, rather than the importance of the reaction, justifies the refinement. Proposed replacements: extracellular matrix Supporting Evidence: file:human/ACAN/ACAN-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
GO:0005576 extracellular region	TAS Reactome:R-HSA-2046239	KEEP AS NON CORE	Summary: Reactome R-HSA-2046239 represents an extracellular keratan sulfate proteoglycan pool before lysosomal delivery. Its input is labeled extracellular region, and the narrative leaves uptake uncertain, including endocytosis or autophagy. Unlike the matrix-assembly and ECM-secretion records, this record does not specify whether the material entering turnover remains matrix-associated. Reason: Retain the supported broad extracellular compartment as non-core turnover context. The input pool is not resolved sufficiently to refine this particular location to matrix; aggrecan can originate in ECM without every extracellular degradation or uptake pool remaining matrix-bound.
GO:0005576 extracellular region	TAS Reactome:R-HSA-2318623	MODIFY	Summary: Reactome R-HSA-2318623 represents aggrecan binding hyaluronan and HAPLN1 into an extracellular matrix aggregate. Extracellular matrix is the informative location of this core binding event. Reason: Refine to GO:0031012 because the source identifies an extracellular matrix aggregate or interaction between matrix constituents. This location refinement follows the resolved compartment of the represented material. Proposed replacements: extracellular matrix Supporting Evidence: PMID:25701227 The G1/hyaluronan/link protein ternary complex is very stable thereby immobilizing the aggrecan into enormous complexes that maintain a stable network and provide mechanical properties to cartilage.
GO:0005576 extracellular region	TAS Reactome:R-HSA-2424246	MODIFY	Summary: Reactome R-HSA-2424246 represents tenascin binding to lecticans, including aggrecan. Its source summary explicitly identifies TNC and TNR as aggrecan partners in the extracellular matrix; the human G3 binding studies independently support this interaction. Reason: Refine to GO:0031012 because the source identifies an extracellular matrix aggregate or interaction between matrix constituents. This location refinement follows the resolved compartment of the represented material. Proposed replacements: extracellular matrix Supporting Evidence: PMID:25701227 Moreover, the G3 domain of aggrecan interacts with tenascins, fibulins and sulfated glycolipids Reactome:R-HSA-2424246 TNC and TNR bind to members of the lectican family, a class of extracellular chondroitin sulfate proteoglycans consisting of aggrecan, versican, brevican and neurocan.
GO:0005576 extracellular region	TAS Reactome:R-HSA-2424252	MODIFY	Summary: Reactome R-HSA-2424252 represents COMP binding to aggrecan within the extracellular matrix. The aggrecan-COMP interaction is directly supported by PMID:17588949 and implicates aggrecan glycosaminoglycan chains. Reason: Refine to GO:0031012 because the source identifies an extracellular matrix aggregate or interaction between matrix constituents. This location refinement follows the resolved compartment of the represented material. Proposed replacements: extracellular matrix Supporting Evidence: PMID:17588949 Using a solid-phase binding assay, we have shown that COMP/TSP5 can bind aggrecan. Reactome:R-HSA-2424252 In adult cartilage, COMP is located primarily in the inter-territorial matrix between chondrocytes
GO:0005576 extracellular region	TAS Reactome:R-HSA-8855825	MODIFY	Summary: Reactome R-HSA-8855825 places HTRA1-mediated aggrecan cleavage within degradation of the extracellular matrix and explicitly describes that matrix-turnover role. The source therefore supports extracellular matrix as the more precise compartment of the represented cleavage event. Reason: Refine to GO:0031012 based on the source ECM-degradation context. Aggrecan remains the substrate in this reaction; refining its location does not assign proteolytic activity to it. Proposed replacements: extracellular matrix
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2025724	KEEP AS NON CORE	Summary: Biosynthetic transit compartment, one of fourteen identical Golgi lumen rows. This row comes from the reaction in which B3GNT enzymes add GlcNAc to build the keratan chain on the aggrecan core protein. Correct, but it records where aggrecan is glycanated, not where it acts.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2046175	KEEP AS NON CORE	Summary: Duplicate Golgi lumen row, from CHST1 sulfating galactose on the keratan chain. Biosynthetic transit, not a site of function.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2046180	KEEP AS NON CORE	Summary: Duplicate Golgi lumen row, from the secretion step of keratan sulfate proteoglycan. The same Reactome reaction also generates one of the six extracellular region rows, which is how a single secretion event yields two GOA compartment statements.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2046222	KEEP AS NON CORE	Summary: Duplicate Golgi lumen row, from CHST2/3/5/6 sulfating GlcNAc on the keratan chain. Biosynthetic transit, not a site of function.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2046265	KEEP AS NON CORE	Summary: Duplicate Golgi lumen row, from B4GALT enzymes transferring galactose to the keratan chain. Biosynthetic transit, not a site of function.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2046285	KEEP AS NON CORE	Summary: Duplicate Golgi lumen row, from ST3GAL enzymes optionally capping the keratan chain with sialic acid. Biosynthetic transit, not a site of function.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2046298	KEEP AS NON CORE	Summary: Duplicate Golgi lumen row, from B4GALT enzymes transferring galactose to a keratan branch. Biosynthetic transit, not a site of function.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3656230	KEEP AS NON CORE	Summary: Reactome models defective B4GALT1 and failure of galactose transfer to a keratan chain in the Golgi. Aggrecan is represented among the proteoglycan acceptors. This places the proteoglycan acceptor in the Golgi during biosynthesis; retain that non-core location. The named modifying enzyme is the catalyst.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3656258	KEEP AS NON CORE	Summary: Reactome models defective ST3GAL3 and failure of sialic acid transfer to keratan in the Golgi. Aggrecan is represented among the proteoglycan acceptors. This places the proteoglycan acceptor in the Golgi during biosynthesis; retain that non-core location. The named modifying enzyme is the catalyst.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3656269	KEEP AS NON CORE	Summary: Reactome models defective CHST6 and failure of GlcNAc sulfation on keratan in the Golgi. Aggrecan is represented among the proteoglycan acceptors. This places the proteoglycan acceptor in the Golgi during biosynthesis; retain that non-core location. The named modifying enzyme is the catalyst.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-9035950	KEEP AS NON CORE	Summary: Reactome models defective B4GALT1 and failure of galactose transfer to a keratan branch in the Golgi. Aggrecan is represented among the proteoglycan acceptors. This places the proteoglycan acceptor in the Golgi during biosynthesis; retain that non-core location. The named modifying enzyme is the catalyst.
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1793217	KEEP AS NON CORE	Summary: Catabolic compartment, from the reaction in which an unidentified endo-beta-galactosidase cleaves the keratan chain inside the lysosome. Correct as the site where aggrecan is degraded, not a functional location.
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-2046239	KEEP AS NON CORE	Summary: Duplicate lysosomal lumen row, from the translocation of extracellular keratan sulfate proteoglycan to the lysosome for degradation. The same Reactome reaction also generates one of the six extracellular region rows.
GO:0030021 extracellular matrix structural constituent conferring compression resistance	RCA PMID:20551380 Proteomics characterization of extracellular space component...	ACCEPT	Summary: Compression resistance is a core activity. The aortic proteomics paper describes negatively charged proteoglycans attracting water and resisting compression as a class-level property. Aggrecan-specific support is supplied independently by PMID:27068509 and the proteoglycan review. Retain the seeded RCA rather than interpreting the evidence code as a direct mechanical assay. Supporting Evidence: PMID:20551380 Proteoglycans, because of their negative charge, attract water and confer resistance to compression. PMID:25701227 is the principal load-bearing proteoglycan of cartilage file:human/ACAN/ACAN-uniprot.txt CC resist compression in cartilage. It binds avidly to hyaluronic acid via
GO:0030021 extracellular matrix structural constituent conferring compression resistance	RCA PMID:27068509 Extracellular matrix remodelling in response to venous hyper...	ACCEPT	Summary: Same core molecular function, and this reference states it for aggrecan specifically rather than for proteoglycans in general. The varicose vein proteomics study identified aggrecan in venous matrix, found it depleted in varicose veins at both protein and transcript level, and explains the loss in terms of aggrecan's water-attracting, compression-resisting glycans. A duplicate of the preceding row, but the better-supported of the two. Supporting Evidence: PMID:27068509 Negatively charged glycans on the surface of aggrecan attract water and therefore confer resistance to compression. PMID:27068509 Extracellular matrix remodelling in varicose veins was characterized by a loss of aggrecan and several small leucine-rich proteoglycans
GO:0031012 extracellular matrix	HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper...	ACCEPT	Summary: Aggrecan was identified by mass spectrometry in the guanidine-HCl extracellular matrix fraction of human saphenous vein and confirmed by targeted MRM. This directly supports a core matrix location in vascular tissue, in addition to the well-characterized cartilage pool. Supporting Evidence: PMID:27068509 To our knowledge, the present study is the first to report the identification of aggrecan in venous tissue. file:human/ACAN/ACAN-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
GO:0031012 extracellular matrix	HDA PMID:20551380 Proteomics characterization of extracellular space component...	ACCEPT	Summary: Extracellular matrix is the appropriate core compartment. The curated HDA from human aorta is consistent with the established aggrecan matrix localization and independent venous proteomics in PMID:27068509. The quoted aortic-paper passage describes the extraction method and expected proteoglycan class, not an aggrecan-specific result table; it should not be presented as direct identification evidence on its own. Reason: The compartment is supported. The source qualifier colocalizes_with is weaker than located_in in the independent venous HDA row and the established matrix residence of aggrecan. Recommend harmonization to located_in while preserving the exported qualifier in this review. Supporting Evidence: PMID:20551380 Guanidine HCl extractions were developed more than 40 years ago as a very effective way to solubilize most of the strongly bound ECM components, including large aggregating proteoglycans (versican, aggrecan, etc.) file:human/ACAN/ACAN-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular PMID:27068509 To our knowledge, the present study is the first to report the identification of aggrecan in venous tissue.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2025723	KEEP AS NON CORE	Summary: Duplicate Golgi lumen row, from B4GALT enzymes transferring galactose to the N-glycan precursor that keratan chains are built on. Biosynthetic transit, not a site of function.
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-9035949	KEEP AS NON CORE	Summary: Reactome models defective B4GALT1 and failure of galactose transfer to the N-glycan precursor in the Golgi. Aggrecan is represented among the proteoglycan acceptors. This places the proteoglycan acceptor in the Golgi during biosynthesis; retain that non-core location. The named modifying enzyme is the catalyst.
GO:0005515 protein binding	IPI PMID:17588949 Interaction of cartilage oligomeric matrix protein/thrombosp...	MODIFY	Summary: PMID:17588949 directly demonstrates aggrecan binding to COMP in solid-phase assays. Binding depends on the calcium-replete conformation of COMP and involves aggrecan glycosaminoglycan side chains; the mapped signature domain belongs to COMP. Since COMP is a matrix constituent, extracellular matrix binding is more informative than generic protein binding. This mechanism is distinct from aggrecan G3 binding to tenascins and fibulins. Reason: GO:0050840 describes binding to an extracellular matrix constituent without misassigning the COMP interaction to aggrecan G3 or claiming an untested matrilin interaction. Proposed replacements: extracellular matrix binding Supporting Evidence: PMID:17588949 Using a solid-phase binding assay, we have shown that COMP/TSP5 can bind aggrecan. PMID:17588949 Soluble glycosaminoglycans (GAGs) partially inhibited binding, suggesting that the interaction was mediated in part through aggrecan GAG side chains. file:human/ACAN/ACAN-uniprot.txt CC (By similarity). Interacts with COMP (PubMed:17588949). PMID:20137779 Binding studies with recombinant mutated and wild-type G3 proteins showed loss of fibulin-1, fibulin-2, and tenascin-R interactions for the V2303M protein.
GO:0001501 skeletal system development	NAS PMID:1569188 The structure of aggrecan fragments in human synovial fluid....	MODIFY	Summary: Aggrecan supplies a structural component of developing cartilage, making cartilage development a useful refinement of skeletal system development. PMID:1569188 is available as an abstract about cleavage of aggrecan; its complete discussion was not recovered. Independent developmental and human skeletal evidence in PMID:25701227 and PMID:35338222 supports the refinement. Reason: The cartilage-specific process states the established developmental contribution more precisely. Preserve the source NAS and PMID while documenting the additional evidence supporting this refinement. Proposed replacements: cartilage development Supporting Evidence: PMID:25701227 In both mutant animals, there is little or no aggrecan in cartilage leading to shortened long bones and lethality PMID:35338222 The cartilage aggrecan proteoglycan is crucial for both skeletal growth and articular cartilage function.
GO:0005201 extracellular matrix structural constituent	TAS PMID:1569188 The structure of aggrecan fragments in human synovial fluid....	MODIFY	Summary: Compression resistance is the specific structural contribution of aggrecan: fixed charges on its glycosaminoglycans attract water and generate swelling pressure within cartilage matrix. GO:0030021 captures this activity more precisely than the broad structural-constituent term. Reason: Refine to the supported child term GO:0030021, which specifies the mechanical contribution described in PMID:25701227 and PMID:27068509. Proposed replacements: extracellular matrix structural constituent conferring compression resistance Supporting Evidence: PMID:25701227 is the principal load-bearing proteoglycan of cartilage PMID:27068509 Negatively charged glycans on the surface of aggrecan attract water and therefore confer resistance to compression.
GO:0006508 proteolysis	NAS PMID:1569188 The structure of aggrecan fragments in human synovial fluid....	REMOVE	Summary: The cited abstract establishes aggrecan as the cleaved substrate: synovial-fluid fragments have a new terminus generated at the interglobular Glu373-Ala374 bond by a cartilage proteinase. Aggrecan supplies matrix structure and is degraded during turnover; the available evidence does not assign it catalytic, scaffold, or cofactor work in the proteolytic step. The protease performs that step. Reason: The NAS assertion assigns proteolysis to its substrate rather than to the entity doing the cleavage. Aggrecanases ADAMTS4 and ADAMTS5, HTRA1, and matrix metalloproteinases perform proteolytic steps; the 1992 abstract itself leaves the relevant cartilage proteinase unidentified. Reactome R-HSA-8855825 represents the HTRA1 activity with aggrecan as its substrate. Supporting Evidence: PMID:1569188 This NH2 terminus results from cleavage of the human aggrecan core protein at the Glu 373-Ala 374 bond within the interglobular domain between the G1 and G2 domains. PMID:1569188 is promoted by the action of a normal cartilage proteinase which cleaves the Glu 373-Ala 374 bond of the interglobular domain file:human/ACAN/ACAN-uniprot.txt CC stages of human osteoarthritis is the result of cleavage by PMID:25701227 An interglobular region, between G1 and G2, has a rod-like structure and harbors several protease-sensitive sites involved in the partial degradation of aggrecan in arthritis and other inflammatory diseases.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Affinage

📚 Additional Documentation

Notes

📄 View Raw YAML