Asporin (ASPN, also PLAP-1) is a secreted extracellular matrix protein of the small leucine-rich repeat family. Unlike related SLRPs, it lacks a glycosaminoglycan attachment site, and it carries a polymorphic N-terminal aspartate repeat that binds calcium. It binds type I collagen, competing with decorin, and binds TGF-beta, inhibiting TGF-beta-induced chondrogenesis and matrix gene expression in articular cartilage. The D14 repeat allele, which inhibits most strongly, is associated with osteoarthritis. In the periodontal ligament it blocks BMP-2 binding to its type IB receptor, preventing ligament mineralization. In osteoblast cultures it promotes collagen mineralization.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005509 calcium ion binding | IDA PMID:19589127 Asporin competes with decorin for collagen binding, binds ca... | ACCEPT | Summary: Calcium ion binding (IDA). The polyaspartate stretch of asporin binds calcium and regulates hydroxyapatite formation in vitro. Accepted. Reason: [PMID:19589127 "We demonstrate that the polyaspartate domain binds calcium and regulates hydroxyapatite formation in vitro."] Supporting Evidence: PMID:19589127 We demonstrate that the polyaspartate domain binds calcium and regulates hydroxyapatite formation in vitro. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Extracellular region (IBA). Asporin is a secreted extracellular matrix protein of the small leucine-rich repeat family. Accepted. Reason: [file:human/ASPN/ASPN-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular"] [PMID:19589127 "Here, we show that asporin binds collagen type I."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002542430 SUPPORTS TRANSFER SLRP family node seeded by many characterized secreted leucine-rich repeat proteins, human ASPN (Q9BXN1) among them; extracellular location is conserved. Supporting Evidence: file:human/ASPN/ASPN-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular PMID:19589127 Here, we show that asporin binds collagen type I. |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | RCA PMID:20551380 Proteomics characterization of extracellular space component... | MARK AS OVER ANNOTATED | Summary: Extracellular matrix structural constituent conferring compression resistance (RCA, from an extracellular-space proteomics study). Matrisome pipelines assign this term to proteoglycans, whose glycosaminoglycan chains give compression resistance. Asporin has no glycosaminoglycan attachment site and is probably not a proteoglycan; its known ECM role is binding collagen and growth factors. The term overstates its structural role; marked as over-annotated. Reason: [file:human/ASPN/ASPN-uniprot.txt "CC attachment of O-linked glycosaminoglycans and this is probably not a"] [PMID:19589127 "Here, we show that asporin binds collagen type I."] Supporting Evidence: file:human/ASPN/ASPN-uniprot.txt CC attachment of O-linked glycosaminoglycans and this is probably not a PMID:19589127 Here, we show that asporin binds collagen type I. |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | MARK AS OVER ANNOTATED | Summary: Extracellular matrix structural constituent conferring compression resistance (RCA, from a colon cancer ECM proteomics study). Matrisome pipelines assign this term to proteoglycans, whose glycosaminoglycan chains give compression resistance. Asporin has no glycosaminoglycan attachment site and is probably not a proteoglycan; its known ECM role is binding collagen and growth factors. The term overstates its structural role; marked as over-annotated. Reason: [file:human/ASPN/ASPN-uniprot.txt "CC attachment of O-linked glycosaminoglycans and this is probably not a"] [PMID:19589127 "Here, we show that asporin binds collagen type I."] Supporting Evidence: file:human/ASPN/ASPN-uniprot.txt CC attachment of O-linked glycosaminoglycans and this is probably not a PMID:19589127 Here, we show that asporin binds collagen type I. |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | RCA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | MARK AS OVER ANNOTATED | Summary: Extracellular matrix structural constituent conferring compression resistance (RCA, from a venous ECM proteomics study). Matrisome pipelines assign this term to proteoglycans, whose glycosaminoglycan chains give compression resistance. Asporin has no glycosaminoglycan attachment site and is probably not a proteoglycan; its known ECM role is binding collagen and growth factors. The term overstates its structural role; marked as over-annotated. Reason: [file:human/ASPN/ASPN-uniprot.txt "CC attachment of O-linked glycosaminoglycans and this is probably not a"] [PMID:19589127 "Here, we show that asporin binds collagen type I."] Supporting Evidence: file:human/ASPN/ASPN-uniprot.txt CC attachment of O-linked glycosaminoglycans and this is probably not a PMID:19589127 Here, we show that asporin binds collagen type I. |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | RCA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | MARK AS OVER ANNOTATED | Summary: Extracellular matrix structural constituent conferring compression resistance (RCA, from a muscle ECM glycoproteomics study). Matrisome pipelines assign this term to proteoglycans, whose glycosaminoglycan chains give compression resistance. Asporin has no glycosaminoglycan attachment site and is probably not a proteoglycan; its known ECM role is binding collagen and growth factors. The term overstates its structural role; marked as over-annotated. Reason: [file:human/ASPN/ASPN-uniprot.txt "CC attachment of O-linked glycosaminoglycans and this is probably not a"] [PMID:19589127 "Here, we show that asporin binds collagen type I."] Supporting Evidence: file:human/ASPN/ASPN-uniprot.txt CC attachment of O-linked glycosaminoglycans and this is probably not a PMID:19589127 Here, we show that asporin binds collagen type I. |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | RCA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | MARK AS OVER ANNOTATED | Summary: Extracellular matrix structural constituent conferring compression resistance (RCA, from a matrisome proteomics atlas of normal and diseased tissues). Matrisome pipelines assign this term to proteoglycans, whose glycosaminoglycan chains give compression resistance. Asporin has no glycosaminoglycan attachment site and is probably not a proteoglycan; its known ECM role is binding collagen and growth factors. The term overstates its structural role; marked as over-annotated. Reason: [file:human/ASPN/ASPN-uniprot.txt "CC attachment of O-linked glycosaminoglycans and this is probably not a"] [PMID:19589127 "Here, we show that asporin binds collagen type I."] Supporting Evidence: file:human/ASPN/ASPN-uniprot.txt CC attachment of O-linked glycosaminoglycans and this is probably not a PMID:19589127 Here, we show that asporin binds collagen type I. |
| GO:0030282 bone mineralization | IDA PMID:19589127 Asporin competes with decorin for collagen binding, binds ca... | KEEP AS NON CORE | Summary: Bone mineralization (IDA). Asporin binds calcium through its polyaspartate domain and increases collagen nodule formation and osteoblast markers in culture. Its effect on mineralization is context-dependent, as it inhibits periodontal ligament mineralization. Kept as non-core. Reason: [PMID:19589127 "We demonstrate that the polyaspartate domain binds calcium and regulates hydroxyapatite formation in vitro."] [PMID:19589127 "In the presence of asporin, the number of collagen nodules, and mRNA of osteoblastic markers Osterix and Runx2, were increased."] [PMID:17522060 "We report that PLAP-1/asporin is also expressed specifically and predominantly in the periodontal ligament (PDL) and that it negatively regulates the mineralization of PDL cells."] Supporting Evidence: PMID:19589127 We demonstrate that the polyaspartate domain binds calcium and regulates hydroxyapatite formation in vitro. PMID:19589127 In the presence of asporin, the number of collagen nodules, and mRNA of osteoblastic markers Osterix and Runx2, were increased. PMID:17522060 We report that PLAP-1/asporin is also expressed specifically and predominantly in the periodontal ligament (PDL) and that it negatively regulates the mineralization of PDL cells. |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | IDA PMID:17827158 Mechanisms for asporin function and regulation in articular ... | ACCEPT | Summary: Negative regulation of transforming growth factor beta receptor signaling pathway (IDA). Asporin binds TGF-beta directly and inhibits TGF-beta-induced matrix gene expression and chondrogenesis in human articular chondrocytes. It acts by sequestering the ligand from its receptor. Core process. Reason: [PMID:15640800 "In vitro binding assays showed a direct interaction between asporin and TGF-beta."] [PMID:17827158 "Asporin inhibits TGF-beta/Smad signaling upstream of TGF-beta type I receptor activation in vivo by co-localizing with TGF-beta1 on the cell surface and blocking its interaction with the TGF-beta type II receptor."] [PMID:17827158 "Asporin blocks chondrogenesis and inhibits TGF-beta1-induced expression of matrix genes and the resulting chondrocyte phenotypes."] Supporting Evidence: PMID:15640800 In vitro binding assays showed a direct interaction between asporin and TGF-beta. PMID:17827158 Asporin inhibits TGF-beta/Smad signaling upstream of TGF-beta type I receptor activation in vivo by co-localizing with TGF-beta1 on the cell surface and blocking its interaction with the TGF-beta type II receptor. PMID:17827158 Asporin blocks chondrogenesis and inhibits TGF-beta1-induced expression of matrix genes and the resulting chondrocyte phenotypes. |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Negative regulation of transforming growth factor beta receptor signaling pathway (IEA). Asporin binds TGF-beta directly and inhibits TGF-beta-induced matrix gene expression and chondrogenesis in human articular chondrocytes. It acts by sequestering the ligand from its receptor. Core process. Reason: [PMID:15640800 "In vitro binding assays showed a direct interaction between asporin and TGF-beta."] [PMID:17827158 "Asporin inhibits TGF-beta/Smad signaling upstream of TGF-beta type I receptor activation in vivo by co-localizing with TGF-beta1 on the cell surface and blocking its interaction with the TGF-beta type II receptor."] [PMID:17827158 "Asporin blocks chondrogenesis and inhibits TGF-beta1-induced expression of matrix genes and the resulting chondrocyte phenotypes."] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q99MQ4 SUPPORTS TRANSFER Mouse Aspn (UniProtKB:Q99MQ4); human ASPN has its own IDA (PMID:17827158). Supporting Evidence: PMID:15640800 In vitro binding assays showed a direct interaction between asporin and TGF-beta. PMID:17827158 Asporin inhibits TGF-beta/Smad signaling upstream of TGF-beta type I receptor activation in vivo by co-localizing with TGF-beta1 on the cell surface and blocking its interaction with the TGF-beta type II receptor. PMID:17827158 Asporin blocks chondrogenesis and inhibits TGF-beta1-induced expression of matrix genes and the resulting chondrocyte phenotypes. |
| GO:0031012 extracellular matrix | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Extracellular matrix (HDA; detected in an extracellular-space proteomics study). Asporin is an ECM component of cartilage and periodontal ligament that binds type I collagen. Core location. Reason: [PMID:19589127 "Here, we show that asporin binds collagen type I."] [file:human/ASPN/ASPN-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular"] Supporting Evidence: PMID:19589127 Here, we show that asporin binds collagen type I. file:human/ASPN/ASPN-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: Extracellular matrix (HDA; detected in a colon cancer ECM proteomics study). Asporin is an ECM component of cartilage and periodontal ligament that binds type I collagen. Core location. Reason: [PMID:19589127 "Here, we show that asporin binds collagen type I."] [file:human/ASPN/ASPN-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular"] Supporting Evidence: PMID:19589127 Here, we show that asporin binds collagen type I. file:human/ASPN/ASPN-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular |
| GO:0031012 extracellular matrix | HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | ACCEPT | Summary: Extracellular matrix (HDA; detected in a venous ECM proteomics study). Asporin is an ECM component of cartilage and periodontal ligament that binds type I collagen. Core location. Reason: [PMID:19589127 "Here, we show that asporin binds collagen type I."] [file:human/ASPN/ASPN-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular"] Supporting Evidence: PMID:19589127 Here, we show that asporin binds collagen type I. file:human/ASPN/ASPN-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular |
| GO:0031012 extracellular matrix | HDA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: Extracellular matrix (HDA; detected in a muscle ECM glycoproteomics study). Asporin is an ECM component of cartilage and periodontal ligament that binds type I collagen. Core location. Reason: [PMID:19589127 "Here, we show that asporin binds collagen type I."] [file:human/ASPN/ASPN-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular"] Supporting Evidence: PMID:19589127 Here, we show that asporin binds collagen type I. file:human/ASPN/ASPN-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: Extracellular matrix (HDA; detected in a matrisome proteomics atlas of normal and diseased tissues). Asporin is an ECM component of cartilage and periodontal ligament that binds type I collagen. Core location. Reason: [PMID:19589127 "Here, we show that asporin binds collagen type I."] [file:human/ASPN/ASPN-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular"] Supporting Evidence: PMID:19589127 Here, we show that asporin binds collagen type I. file:human/ASPN/ASPN-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular |
| GO:0031012 extracellular matrix | IDA PMID:17827158 Mechanisms for asporin function and regulation in articular ... | ACCEPT | Summary: Extracellular matrix (IDA; shown in human articular cartilage). Asporin is an ECM component of cartilage and periodontal ligament that binds type I collagen. Core location. Reason: [PMID:19589127 "Here, we show that asporin binds collagen type I."] [file:human/ASPN/ASPN-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular"] Supporting Evidence: PMID:19589127 Here, we show that asporin binds collagen type I. file:human/ASPN/ASPN-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular |
| GO:0031012 extracellular matrix | IEA GO_REF:0000107 | ACCEPT | Summary: Extracellular matrix (IEA; projected from mouse Aspn). Asporin is an ECM component of cartilage and periodontal ligament that binds type I collagen. Core location. Reason: [PMID:19589127 "Here, we show that asporin binds collagen type I."] [file:human/ASPN/ASPN-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular"] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q99MQ4 SUPPORTS TRANSFER Mouse Aspn (UniProtKB:Q99MQ4); human ASPN has its own ECM evidence. Supporting Evidence: PMID:19589127 Here, we show that asporin binds collagen type I. file:human/ASPN/ASPN-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular |
| GO:0070171 negative regulation of tooth mineralization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of tooth mineralization (IEA, from mouse Aspn). Asporin (PLAP-1) is expressed predominantly in the periodontal ligament and inhibits mineralization of PDL cells by blocking BMP-2 access to its receptor, keeping the ligament unossified. A tissue-specific outcome of its BMP antagonism; kept as non-core. Reason: [PMID:17522060 "We report that PLAP-1/asporin is also expressed specifically and predominantly in the periodontal ligament (PDL) and that it negatively regulates the mineralization of PDL cells."] [PMID:18407830 "Recombinant PLAP-1/asporin inhibited BMP-2-induced cytodifferentiation of PDL cells and competitively prevented BMP-2 from binding to the BMP receptor-IB (BMPR-IB), resulting in inhibition of BMP-dependent activation of Smad proteins."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q99MQ4 SUPPORTS TRANSFER Mouse Aspn (UniProtKB:Q99MQ4); periodontal ligament mineralization. Supporting Evidence: PMID:17522060 We report that PLAP-1/asporin is also expressed specifically and predominantly in the periodontal ligament (PDL) and that it negatively regulates the mineralization of PDL cells. PMID:18407830 Recombinant PLAP-1/asporin inhibited BMP-2-induced cytodifferentiation of PDL cells and competitively prevented BMP-2 from binding to the BMP receptor-IB (BMPR-IB), resulting in inhibition of BMP-dependent activation of Smad proteins. |
| GO:0070171 negative regulation of tooth mineralization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of tooth mineralization (ISS, from mouse Aspn). Asporin (PLAP-1) is expressed predominantly in the periodontal ligament and inhibits mineralization of PDL cells by blocking BMP-2 access to its receptor, keeping the ligament unossified. A tissue-specific outcome of its BMP antagonism; kept as non-core. Reason: [PMID:17522060 "We report that PLAP-1/asporin is also expressed specifically and predominantly in the periodontal ligament (PDL) and that it negatively regulates the mineralization of PDL cells."] [PMID:18407830 "Recombinant PLAP-1/asporin inhibited BMP-2-induced cytodifferentiation of PDL cells and competitively prevented BMP-2 from binding to the BMP receptor-IB (BMPR-IB), resulting in inhibition of BMP-dependent activation of Smad proteins."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q99MQ4 SUPPORTS TRANSFER Mouse Aspn (UniProtKB:Q99MQ4); periodontal ligament mineralization. Supporting Evidence: PMID:17522060 We report that PLAP-1/asporin is also expressed specifically and predominantly in the periodontal ligament (PDL) and that it negatively regulates the mineralization of PDL cells. PMID:18407830 Recombinant PLAP-1/asporin inhibited BMP-2-induced cytodifferentiation of PDL cells and competitively prevented BMP-2 from binding to the BMP receptor-IB (BMPR-IB), resulting in inhibition of BMP-dependent activation of Smad proteins. |
| GO:0140150 gel phase of interstitial matrix | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Gel phase of interstitial matrix (IEA). This term denotes the hydrated aggrecan-hyaluronan gel of the interstitial matrix, built from glycosaminoglycan-bearing proteoglycans. Asporin has no glycosaminoglycan attachment site and is a collagen-fibril-binding protein, so it belongs with the fibrillar rather than the gel phase. The placement comes from a family-level proteoglycan grouping; marked as over-annotated. Reason: [file:human/ASPN/ASPN-uniprot.txt "CC attachment of O-linked glycosaminoglycans and this is probably not a"] [PMID:19589127 "Here, we show that asporin binds collagen type I."] Supporting Evidence: file:human/ASPN/ASPN-uniprot.txt CC attachment of O-linked glycosaminoglycans and this is probably not a PMID:19589127 Here, we show that asporin binds collagen type I. |
| GO:0140150 gel phase of interstitial matrix | TAS PMID:25701227 Proteoglycan form and function: A comprehensive nomenclature... | MARK AS OVER ANNOTATED | Summary: Gel phase of interstitial matrix (TAS). This term denotes the hydrated aggrecan-hyaluronan gel of the interstitial matrix, built from glycosaminoglycan-bearing proteoglycans. Asporin has no glycosaminoglycan attachment site and is a collagen-fibril-binding protein, so it belongs with the fibrillar rather than the gel phase. The placement comes from a family-level proteoglycan grouping; marked as over-annotated. Reason: [file:human/ASPN/ASPN-uniprot.txt "CC attachment of O-linked glycosaminoglycans and this is probably not a"] [PMID:19589127 "Here, we show that asporin binds collagen type I."] Supporting Evidence: file:human/ASPN/ASPN-uniprot.txt CC attachment of O-linked glycosaminoglycans and this is probably not a PMID:19589127 Here, we show that asporin binds collagen type I. |
| GO:1902617 response to fluoride | IEA GO_REF:0000107 | UNDECIDED | Summary: Response to fluoride (IEA, from rat). An Ensembl orthology projection of a rat observation that cannot be checked from the cached sources. At most it reflects transcript regulation, with no known role for the protein in a fluoride response. Undecided. Reason: The row is an Ensembl orthology projection from rat; no cached evidence connects asporin to a fluoride response. Propagation Review Root cause: SOURCE WEAK OR INFERRED Sources checked: UniProtKB:A0A1W2Q6A1 SOURCE WEAK OR INFERRED Rat Aspn projection; source evidence not available in the cache. |
| GO:0050431 transforming growth factor beta binding | IDA PMID:15640800 An aspartic acid repeat polymorphism in asporin inhibits cho... | NEW | Summary: Transforming growth factor beta binding (NEW, IDA). In vitro binding assays show a direct interaction between asporin and TGF-beta, and the D14 repeat allele inhibits TGF-beta activity most strongly. This binding is the basis of its inhibition of TGF-beta signalling. Comparators: other non-receptor TGF-beta-sequestering proteins carry this term, including LTBP1, LTBP3, LTBP4, LRRC32 (GARP) and WFIKKN2 (QuickGO, 2026-10-05). Reason: [PMID:15640800 "In vitro binding assays showed a direct interaction between asporin and TGF-beta."] [PMID:15640800 "Asporin suppresses TGF-beta-mediated expression of the genes aggrecan (AGC1) and type II collagen (COL2A1) and reduced proteoglycan accumulation in an in vitro model of chondrogenesis."] Supporting Evidence: PMID:15640800 In vitro binding assays showed a direct interaction between asporin and TGF-beta. PMID:15640800 Asporin suppresses TGF-beta-mediated expression of the genes aggrecan (AGC1) and type II collagen (COL2A1) and reduced proteoglycan accumulation in an in vitro model of chondrogenesis. |
| GO:0005518 collagen binding | IDA PMID:19589127 Asporin competes with decorin for collagen binding, binds ca... | NEW | Summary: Collagen binding (NEW, IDA). Asporin binds type I collagen through its leucine-rich repeats 10-12, competing with decorin. Reason: [PMID:19589127 "Here, we show that asporin binds collagen type I."] Supporting Evidence: PMID:19589127 Here, we show that asporin binds collagen type I. |
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Download this section (compressed HTML)Q: Does asporin's sequestration of BMP-2 from BMPR-IB, shown in periodontal ligament cells, operate in human tissues, and should negative regulation of BMP signaling be annotated once human evidence is available?
Q: How does the aspartate-repeat length tune asporin's binding of TGF-beta, BMP-2 and calcium, and which of these underlies the osteoarthritis association?
Experiment: Compare D13 and D14 asporin for TGF-beta and BMP-2 binding affinity and for calcium-dependent collagen mineralization in chondrocyte and PDL cultures.
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