DCN

UniProt ID: P07585
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

Decorin is a small leucine-rich proteoglycan (SLRP, 359 amino acids) consisting of a core protein (~40 kDa) with 12 leucine-rich repeats and a single attached chondroitin sulfate or dermatan sulfate glycosaminoglycan chain at Ser-34. Decorin plays two critical core functions in the extracellular matrix: (1) regulation of collagen fibrillogenesis, where it binds to collagen types I, II, III, and VI fibrils via its LRR domain to control fibril diameter, spacing, and assembly kinetics, and (2) sequestration and negative regulation of TGF-beta signaling, where it binds all three TGF-beta isoforms in the ECM to diminish their biological activity and exert anti-fibrotic effects. Additionally, decorin binds and modulates receptor tyrosine kinases including EGFR, VEGFR2, and Met, triggering receptor internalization, autophagy induction in endothelial cells via Peg3, and suppression of angiogenesis. Decorin also binds fibronectin, thrombospondin-1, and other ECM components. The protein is secreted and localized to the extracellular matrix, with transient presence in Golgi lumen during biosynthesis and GAG chain modification. Decorin deficiency causes congenital stromal corneal dystrophy (CSCD), highlighting its essential role in collagen organization and tissue architecture.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005615 extracellular space
IBA
GO_REF:0000033
ACCEPT
Summary: Decorin is a secreted extracellular matrix proteoglycan. IBA annotation based on phylogenetic inference correctly captures decorin's localization to extracellular space where it performs its core functions in collagen fibril organization and TGF-beta sequestration.
Reason: This is a core cellular component annotation supported by extensive experimental evidence (UniProt CC line "Secreted, extracellular space, extracellular matrix"), IBA phylogenetic inference, and multiple proteomic studies. Decorin functions exclusively in the extracellular space.
Supporting Evidence:
GO_REF:0000033
IBA annotation inferences using phylogenetic trees
Reactome:R-HSA-2327909
DCN consists of a core protein of approximately 40 kDa attached to a single chondroitin or dermatan sulfate glycosaminoglycan (GAG) chain.
file:human/DCN/DCN-deep-research-falcon.md
model: Edison Scientific Literature
GO:0005576 extracellular region
IEA
GO_REF:0000044
ACCEPT
Summary: Broad parent term of extracellular space. While correct, this is less specific than the IBA annotation to extracellular space (GO:0005615) and extracellular matrix (GO:0031012).
Reason: Correct but general IEA annotation based on UniProt subcellular location vocabulary. The more specific child terms (extracellular space, extracellular matrix) better capture decorin's precise localization, but this parent term is not incorrect.
Supporting Evidence:
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
GO:0005539 glycosaminoglycan binding
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: Decorin itself is a proteoglycan containing a GAG chain, and may have self-association properties. However, the primary molecular function is collagen binding and TGF-beta binding rather than GAG binding per se.
Reason: While decorin has a GAG chain (dermatan/chondroitin sulfate) attached, GAG binding is not a prominently reported molecular function. The annotation likely derives from domain-based inference (IEA from Ensembl) but decorin's core functions are collagen binding and growth factor binding, not GAG binding. May reflect some self-association or interaction with other proteoglycans, but this is not well-documented as a primary function.
Supporting Evidence:
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO:0050840 extracellular matrix binding
IEA
GO_REF:0000107
MODIFY
Summary: Too vague. Decorin specifically binds collagen fibrils (types I, II, III, VI), fibronectin, and thrombospondin-1. The more specific molecular function terms should be used.
Reason: This broad term does not capture decorin's specific binding activities. Decorin has well-characterized binding to specific ECM components via its leucine-rich repeats. Should be replaced with more specific molecular function terms for collagen binding and fibronectin binding.
Supporting Evidence:
Reactome:R-HSA-2327909
It interacts with collagen types I, II (Vogel et al. 1984), III (Witos et al. 2011), V (Whinna et al. 1993), VI (Bidanset et al. 1992) and XIV (Ehnis et al. 1997).
PMID:1747115
Decorin, an interstitial small proteoglycan, was shown to interact with fibronectin via its core protein. In a solid-phase assay, both high-affinity (KD values between 10 and 20 nM) and low-affinity (KD values between 110 and 130 nM) binding sites were found.
GO:0005515 protein binding
IPI
PMID:1747115
Interaction of the small proteoglycan decorin with fibronect...
MODIFY
Summary: Vague term. PMID:1747115 specifically demonstrates fibronectin binding with measured KD values (10-20 nM high affinity, 110-130 nM low affinity). The specific molecular function term should be used instead.
Reason: The term "protein binding" is uninformative per curation guidelines. The cited paper demonstrates specific fibronectin binding via decorin's core protein LRR domain. This should be annotated with the specific molecular function GO:0001968 (fibronectin binding).
Proposed replacements: fibronectin binding
Supporting Evidence:
PMID:1747115
Decorin, an interstitial small proteoglycan, was shown to interact with fibronectin via its core protein.
GO:0005515 protein binding
IPI
PMID:20026052
Decorin is processed by three isoforms of bone morphogenetic...
REMOVE
Summary: Vague term. Paper describes decorin processing by bone morphogenetic protein-1 (BMP1) isoforms. This is substrate-enzyme interaction, not a molecular function annotation for decorin itself.
Reason: The term "protein binding" is uninformative per curation guidelines. PMID:20026052 demonstrates that decorin is processed/cleaved by BMP1, which is relevant for decorin maturation but does not represent a molecular function of decorin. Being a substrate for proteolytic processing is not appropriately annotated as "protein binding."
Supporting Evidence:
PMID:20026052
Decorin is processed by three isoforms of bone morphogenetic protein-1 (BMP1).
GO:0005515 protein binding
IPI
PMID:25331875
Xylose phosphorylation functions as a molecular switch to re...
REMOVE
Summary: Vague term. Paper concerns xylose phosphorylation regulation of proteoglycan biosynthesis. This is about decorin biosynthesis machinery, not decorin's molecular function.
Reason: The term "protein binding" is uninformative per curation guidelines. PMID:25331875 discusses xylose phosphorylation as a regulatory switch in proteoglycan biosynthesis. This interaction is part of decorin's biosynthesis pathway, not a functional molecular activity of the mature decorin protein. Should not be annotated as "protein binding."
Supporting Evidence:
PMID:25331875
Xylose phosphorylation functions as a molecular switch to regulate proteoglycan biosynthesis.
GO:0005515 protein binding
IPI
PMID:25789606
A secretory kinase complex regulates extracellular protein p...
REMOVE
Summary: Vague term. Paper describes a secretory kinase complex (FAM20C) that phosphorylates extracellular proteins including decorin. This is enzyme-substrate interaction during biosynthesis.
Reason: The term "protein binding" is uninformative per curation guidelines. PMID:25789606 demonstrates that decorin is phosphorylated by the secretory kinase FAM20C. This enzyme-substrate interaction during decorin biosynthesis/modification does not represent a molecular function of decorin itself and should not be annotated as "protein binding."
Supporting Evidence:
PMID:25789606
A secretory kinase complex regulates extracellular protein phosphorylation.
GO:0005576 extracellular region
TAS
Reactome:R-HSA-2022056
ACCEPT
Summary: Reactome pathway annotation for DSPG/CSPG translocation to lysosome for degradation. Decorin (as a dermatan sulfate proteoglycan) is secreted to extracellular region and eventually degraded. Correct but redundant with other extracellular annotations.
Reason: Correct annotation from Reactome pathway curation. Decorin as a dermatan/chondroitin sulfate proteoglycan is secreted to extracellular region before eventual lysosomal degradation. While redundant with IBA and IEA annotations to the same term, TAS evidence from curated pathways is valid.
Supporting Evidence:
Reactome:R-HSA-2022056
DSPG and CSPG translocate to the lysosome for degradation
GO:0005576 extracellular region
TAS
Reactome:R-HSA-2022065
ACCEPT
Summary: Reactome pathway annotation for DSPG secretion. Decorin as a dermatan sulfate proteoglycan is secreted to extracellular region. Correct but redundant with other extracellular annotations.
Reason: Correct annotation from Reactome pathway curation showing decorin secretion to extracellular space. While redundant with other annotations, TAS evidence from curated pathways adds value by connecting to specific biological process (DSPG secretion).
Supporting Evidence:
Reactome:R-HSA-2022065
Various forms of dermatan sulfate are excreted from the cell once formed
GO:0005576 extracellular region
TAS
Reactome:R-HSA-2022911
ACCEPT
Summary: Reactome pathway annotation for CSPG secretion. Decorin can carry chondroitin sulfate GAG chain and is secreted to extracellular region. Correct but redundant with other extracellular annotations.
Reason: Correct annotation from Reactome pathway curation. Decorin can exist as chondroitin sulfate proteoglycan (CSPG) or dermatan sulfate proteoglycan (DSPG) depending on tissue. TAS evidence from curated secretion pathway is valid though redundant.
Supporting Evidence:
Reactome:R-HSA-2022911
they are secreted out into the extracellular matrix (ECM)
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-2022065
KEEP AS NON CORE
Summary: Reactome pathway annotation for DSPG biosynthesis/modification in Golgi during secretion. Decorin transiently passes through Golgi lumen where GAG chain is modified (SO4 transfer to GalNAc by CHST14).
Reason: Correct annotation reflecting decorin's transit through the Golgi lumen during biosynthesis and GAG chain modification. However, this is a transient biosynthetic localization, not decorin's mature functional localization. The mature, functional protein resides in extracellular matrix. Marking as non-core to distinguish from the primary functional location.
Supporting Evidence:
Reactome:R-HSA-2022065
unknown but most likely involves the trans-golgi network
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-2022911
KEEP AS NON CORE
Summary: Reactome pathway annotation for CSPG biosynthesis/secretion. Decorin transiently passes through Golgi lumen during biosynthesis where GAG chain modifications occur.
Reason: Correct annotation reflecting transient Golgi localization during proteoglycan biosynthesis. Decorin's chondroitin/dermatan sulfate GAG chain is assembled and modified in Golgi. However, this is biosynthetic transit, not the mature functional localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-2022911
they are secreted out into the extracellular matrix
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-9940993
KEEP AS NON CORE
Summary: Reactome pathway for xylose dephosphorylation by PXYLP1 during GAG chain biosynthesis. Decorin present in Golgi lumen during this modification step.
Reason: Correct annotation from Reactome GAG biosynthesis pathway. PXYLP1 dephosphorylates the xylose moiety on the tetrasaccharide linker region of decorin's GAG chain attachment site in Golgi. Transient biosynthetic localization, not core functional location. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-9940993
PXYLP1 dephosphorylates Xyl moiety
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-9941039
KEEP AS NON CORE
Summary: Reactome pathway for xylose phosphorylation by FAM20B during GAG chain biosynthesis. Decorin present in Golgi lumen during this modification step.
Reason: Correct annotation from Reactome GAG biosynthesis pathway. FAM20B phosphorylates the xylose moiety on decorin's GAG attachment site linker in Golgi. This phosphorylation acts as a regulatory switch for proteoglycan biosynthesis. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-9941039
FAM20B phosphorylates Xyl moiety
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-9941305
KEEP AS NON CORE
Summary: Reactome pathway for sulfate transfer by UST to GlcA-GalNAc-6-sulfate during dermatan sulfate biosynthesis. Decorin present in Golgi during GAG chain sulfation.
Reason: Correct annotation from Reactome dermatan sulfate biosynthesis pathway. UST transfers sulfate to position 2 of GlcA in the decorin GAG chain in Golgi lumen. Transient biosynthetic localization during GAG chain modification. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-9941305
UST transfers sulfate to (2-)GlcA-GalNAc-6-sulfate
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-9941312
KEEP AS NON CORE
Summary: Reactome pathway for sulfate transfer by CHST15 during GAG biosynthesis. Decorin present in Golgi during chondroitin/dermatan sulfate chain sulfation.
Reason: Correct annotation from Reactome GAG biosynthesis pathway. CHST15 transfers sulfate to GalNAc-4-sulfate residues in decorin's GAG chain in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-9941312
CHST15 transfers sulfate to (6-)GalNAc-4-sulfate
GO:0016239 positive regulation of macroautophagy
IDA
PMID:23798385
Decorin causes autophagy in endothelial cells via Peg3.
KEEP AS NON CORE
Summary: Decorin induces autophagy in endothelial cells via VEGFR2 signaling and Peg3 induction, leading to transcriptional activation of Beclin 1 and LC3. This is experimentally demonstrated with direct assays showing autophagosome formation.
Reason: Well-supported experimental finding (IDA) from PMID:23798385. Decorin binding to VEGFR2 on endothelial cells triggers Peg3-dependent autophagy and angiogenesis suppression. However, this is a downstream consequence of decorin's receptor binding activity in specific cell types (endothelial cells) rather than a core function. Decorin's core functions are collagen fibril organization and TGF-beta sequestration in the ECM. The autophagy induction represents a secondary signaling effect. Marking as non-core.
Supporting Evidence:
PMID:23798385
Decorin evoked Peg3-dependent autophagy in both microvascular and macrovascular endothelial cells leading to suppression of angiogenesis.
GO:0016239 positive regulation of macroautophagy
IGI
PMID:23798385
Decorin causes autophagy in endothelial cells via Peg3.
KEEP AS NON CORE
Summary: Same biological process as IDA annotation above, but IGI evidence code indicates genetic interaction studies (likely Peg3 or VEGFR2 knockdown experiments) demonstrating decorin's role in autophagy.
Reason: Duplicate of the IDA annotation with different evidence code (IGI - inferred from genetic interaction). Same rationale applies - decorin induces autophagy via VEGFR2/Peg3 pathway in endothelial cells. This is a secondary signaling activity rather than core ECM structural function. Marking as non-core. The IGI evidence likely comes from genetic perturbation experiments (siRNA of Peg3 or VEGFR2) showing decorin requires these factors for autophagy induction.
Supporting Evidence:
PMID:23798385
Peg3 coimmunoprecipitated with Beclin 1 and LC3 and was required for maintaining basal levels of Beclin 1.
GO:0005515 protein binding
IPI
PMID:11598131
WISP-1 binds to decorin and biglycan.
MARK AS OVER ANNOTATED
Summary: Vague term. PMID:11598131 shows WISP-1 (CCN4, a matricellular protein) binds to decorin and biglycan. While this is a real interaction, "protein binding" is too uninformative per curation guidelines.
Reason: The term "protein binding" is uninformative per curation guidelines. While PMID:11598131 demonstrates a genuine interaction between decorin and WISP-1, this is a peripheral binding partner compared to decorin's core functions (collagen binding, TGF-beta binding, growth factor receptor binding). Without a more specific GO term for WISP-1 binding, this should be marked as over-annotated rather than representing a core molecular function.
Supporting Evidence:
PMID:11598131
WISP-1 binds to decorin and biglycan.
GO:0030021 extracellular matrix structural constituent conferring compression resistance
RCA
PMID:28327460
Comprehensive proteomic characterization of stem cell-derive...
MODIFY
Summary: Incorrect molecular function for decorin. This term (GO:0030021) is appropriate for large aggregating proteoglycans like aggrecan that provide compression resistance in cartilage. Decorin's core function is collagen fibril organization, not compression resistance.
Reason: This RCA (inferred from reviewed computational analysis) annotation is a mis-annotation. GO:0030021 describes the ability to resist compression forces, which is the role of large cartilage proteoglycans like aggrecan with multiple GAG chains. Decorin is a small proteoglycan (SLRP) with a single GAG chain whose primary function is regulating collagen fibril assembly and diameter, not providing compression resistance. Should be replaced with GO:0005518 (collagen binding) which represents decorin's actual core molecular function.
Proposed replacements: collagen binding
Supporting Evidence:
Reactome:R-HSA-2327909
DCN binding regulates fibrillogenesis (Vogel et al. 1984, Orgel et al. 2006).
GO:0031012 extracellular matrix
HDA
PMID:28327460
Comprehensive proteomic characterization of stem cell-derive...
ACCEPT
Summary: Correct cellular component annotation from HDA (high-throughput direct assay) proteomics. Decorin is a core extracellular matrix proteoglycan.
Reason: Accurate annotation based on proteomics characterization of stem cell-derived extracellular matrices. Decorin is a major structural component of the ECM where it regulates collagen fibrillogenesis and sequesters TGF-beta. This is a core localization for decorin's function.
Supporting Evidence:
PMID:28327460
Comprehensive proteomic characterization of stem cell-derived extracellular matrices.
GO:0030021 extracellular matrix structural constituent conferring compression resistance
RCA
PMID:28675934
Characterization of the Extracellular Matrix of Normal and D...
MODIFY
Summary: Incorrect molecular function for decorin. Same issue as other GO:0030021 annotations - decorin regulates collagen fibrillogenesis, not compression resistance.
Reason: Mis-annotation from RCA (reviewed computational analysis). Decorin is a small leucine-rich proteoglycan that regulates collagen fibril organization, not a large aggregating proteoglycan that provides compression resistance. This term is inappropriate for decorin's molecular function.
Proposed replacements: collagen binding
Supporting Evidence:
Reactome:R-HSA-2327909
DCN binding regulates fibrillogenesis (Vogel et al. 1984, Orgel et al. 2006).
GO:0031012 extracellular matrix
HDA
PMID:28675934
Characterization of the Extracellular Matrix of Normal and D...
ACCEPT
Summary: Correct cellular component annotation from HDA proteomics of normal and diseased tissues. Decorin is a core ECM component.
Reason: Accurate annotation based on proteomics characterization of ECM from normal and diseased tissues. Decorin is a fundamental structural proteoglycan of the extracellular matrix. This is a core localization.
Supporting Evidence:
PMID:28675934
Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics.
GO:0030021 extracellular matrix structural constituent conferring compression resistance
ISS
GO_REF:0000024
MODIFY
Summary: Incorrect molecular function inferred from sequence similarity. Decorin does not provide compression resistance - it regulates collagen fibril organization.
Reason: This ISS (inferred from sequence/structural similarity) annotation is incorrect. While decorin shares sequence similarity with other SLRPs, its molecular function is distinct from large aggregating proteoglycans. Decorin regulates collagen fibril assembly and spacing through direct collagen binding, not compression resistance.
Proposed replacements: collagen binding
Supporting Evidence:
GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.
GO:0030021 extracellular matrix structural constituent conferring compression resistance
RCA
PMID:20551380
Proteomics characterization of extracellular space component...
MODIFY
Summary: Incorrect molecular function. Decorin regulates collagen organization, not compression resistance. Same issue as other GO:0030021 annotations.
Reason: Mis-annotation from RCA analysis. Decorin's core molecular function is collagen binding and regulation of fibrillogenesis, not providing compression resistance to ECM.
Proposed replacements: collagen binding
Supporting Evidence:
Reactome:R-HSA-2327909
DCN binding regulates fibrillogenesis (Vogel et al. 1984, Orgel et al. 2006).
GO:0030021 extracellular matrix structural constituent conferring compression resistance
RCA
PMID:25037231
Extracellular matrix signatures of human primary metastatic ...
MODIFY
Summary: Incorrect molecular function. Decorin regulates collagen organization, not compression resistance. Same issue as other GO:0030021 annotations.
Reason: Mis-annotation from RCA of ECM proteomics data. Decorin's molecular function is collagen binding and fibril organization, not compression resistance.
Proposed replacements: collagen binding
Supporting Evidence:
Reactome:R-HSA-2327909
DCN binding regulates fibrillogenesis (Vogel et al. 1984, Orgel et al. 2006).
GO:0030021 extracellular matrix structural constituent conferring compression resistance
RCA
PMID:27559042
Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin...
MODIFY
Summary: Incorrect molecular function. Decorin regulates collagen organization, not compression resistance. Same issue as other GO:0030021 annotations.
Reason: Mis-annotation from RCA analysis. Decorin is a small proteoglycan that regulates collagen fibril assembly, not a large aggregating proteoglycan that provides compression resistance.
Proposed replacements: collagen binding
Supporting Evidence:
Reactome:R-HSA-2327909
DCN binding regulates fibrillogenesis (Vogel et al. 1984, Orgel et al. 2006).
GO:0031012 extracellular matrix
HDA
PMID:25037231
Extracellular matrix signatures of human primary metastatic ...
ACCEPT
Summary: Correct cellular component annotation from HDA proteomics of metastatic colon cancers. Decorin is an ECM component.
Reason: Accurate annotation from proteomic analysis of ECM in cancer tissues. Decorin is a core extracellular matrix proteoglycan.
Supporting Evidence:
PMID:25037231
Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver.
GO:0005576 extracellular region
HDA
PMID:27068509
Extracellular matrix remodelling in response to venous hyper...
ACCEPT
Summary: Correct cellular component annotation from HDA proteomics of human varicose veins. Decorin is in extracellular region/ECM.
Reason: Accurate annotation from proteomic analysis of ECM remodeling in varicose veins. Decorin is secreted to extracellular region. Correct but less specific than extracellular matrix.
Supporting Evidence:
PMID:27068509
Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins.
GO:0031012 extracellular matrix
HDA
PMID:27559042
Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin...
ACCEPT
Summary: Correct cellular component annotation from HDA glycoproteomics. Decorin is an ECM proteoglycan.
Reason: Accurate annotation from glycoproteomics analysis of human atrial fibrillation tissues. Decorin is a core extracellular matrix proteoglycan.
Supporting Evidence:
PMID:27559042
Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity in Human Atrial Fibrillation.
GO:0005615 extracellular space
HDA
PMID:20551380
Proteomics characterization of extracellular space component...
ACCEPT
Summary: Correct cellular component annotation from HDA proteomics of human aorta extracellular space. Decorin is secreted to extracellular space.
Reason: Accurate annotation from proteomic characterization of aorta extracellular space components. Decorin functions in extracellular space/ECM.
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: Correct cellular component annotation from HDA proteomics of human aorta ECM. Decorin is a core ECM proteoglycan.
Reason: Accurate annotation from proteomic characterization of human aorta extracellular matrix. Decorin is a fundamental structural component of the ECM.
Supporting Evidence:
PMID:20551380
Proteomics characterization of extracellular space components in the human aorta.
GO:0031012 extracellular matrix
ISS
PMID:22261194
Proteomics analysis of cardiac extracellular matrix remodeli...
ACCEPT
Summary: Correct cellular component annotation from ISS (inferred from sequence similarity) analysis of cardiac ECM. Decorin is an ECM proteoglycan.
Reason: Accurate annotation based on sequence similarity inference supported by proteomic analysis of cardiac ECM remodeling. Decorin is a core extracellular matrix component.
Supporting Evidence:
PMID:22261194
Proteomics analysis of cardiac extracellular matrix remodeling in a porcine model of ischemia/reperfusion injury.
GO:0010596 negative regulation of endothelial cell migration
IDA
PMID:23798385
Decorin causes autophagy in endothelial cells via Peg3.
KEEP AS NON CORE
Summary: Decorin suppresses endothelial cell migration via VEGFR2/Peg3/autophagy pathway. This is experimentally demonstrated (IDA).
Reason: Well-supported experimental finding from PMID:23798385 showing decorin's anti-angiogenic effects on endothelial cells. However, this is a downstream consequence of decorin's RTK binding activity rather than a core function. Decorin's core functions are collagen fibril organization and TGF-beta sequestration. The endothelial cell effects represent peripheral signaling activities. Marking as non-core.
Supporting Evidence:
PMID:23798385
Decorin evoked Peg3-dependent autophagy in both microvascular and macrovascular endothelial cells leading to suppression of angiogenesis.
GO:0016525 negative regulation of angiogenesis
IDA
PMID:23978385
The paradox of paclitaxel neurotoxicity: Mechanisms and unan...
KEEP AS NON CORE
Summary: Decorin suppresses angiogenesis. Note - PMID:23978385 is about paclitaxel neurotoxicity, likely incorrect PMID. The correct reference should be PMID:23798385 which demonstrates decorin's anti-angiogenic effects.
Reason: Anti-angiogenic activity is documented for decorin (should cite PMID:23798385 not PMID:23978385). Decorin binding to VEGFR2 suppresses angiogenesis via autophagy induction. However, this is a secondary signaling function rather than core ECM structural function. Decorin's core functions are collagen organization and TGF-beta sequestration. Marking as non-core.
Supporting Evidence:
PMID:23798385
Decorin evoked Peg3-dependent autophagy in both microvascular and macrovascular endothelial cells leading to suppression of angiogenesis.
GO:0045944 positive regulation of transcription by RNA polymerase II
IGI
PMID:23798385
Decorin causes autophagy in endothelial cells via Peg3.
KEEP AS NON CORE
Summary: Decorin induces transcription of BECN1 and MAPLC3A genes via Peg3. This is demonstrated by genetic interaction studies (IGI).
Reason: Experimental finding from PMID:23798385 showing decorin (via Peg3) induces transcription of autophagy genes. This is a downstream signaling consequence in endothelial cells, not a core function. Decorin's core functions are ECM structural roles (collagen organization, TGF-beta sequestration). This transcriptional regulatory activity is a peripheral cell signaling effect. Marking as non-core.
Supporting Evidence:
PMID:23798385
Decorin, via Peg3, induced transcription of Beclin 1 and microtubule-associated protein 1 light chain 3 alpha genes, thereby leading to a protracted autophagic program.
GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
IDA
PMID:23798385
Decorin causes autophagy in endothelial cells via Peg3.
KEEP AS NON CORE
Summary: Decorin activates PI3K/AKT signaling in endothelial cells. Demonstrated experimentally (IDA) in context of autophagy induction.
Reason: Experimental finding from PMID:23798385 in endothelial cell signaling context. This is a downstream signaling effect, not a core function. Decorin's core functions are ECM structural (collagen organization, TGF-beta sequestration). PI3K/AKT activation is a peripheral cell signaling activity. Marking as non-core.
Supporting Evidence:
PMID:23798385
decorin, by binding to VEGFR2, triggers a signaling cascade leading to induction of Class III PI3K
GO:0051901 positive regulation of mitochondrial depolarization
IGI
PMID:23798385
Decorin causes autophagy in endothelial cells via Peg3.
KEEP AS NON CORE
Summary: Decorin induces loss of mitochondrial membrane potential in endothelial cells via VEGFR2/Peg3 pathway. Genetic interaction evidence (IGI).
Reason: Experimental finding from PMID:23798385 showing decorin causes mitochondrial depolarization in endothelial cells as part of autophagy/anti-angiogenic effects. This is a downstream cellular effect, not a core function. Decorin's core functions are ECM structural. Marking as non-core.
Supporting Evidence:
PMID:23798385
decorin induced VEGFR2-dependent mitochondrial fragmentation and loss of mitochondrial membrane potential
GO:0090141 positive regulation of mitochondrial fission
IGI
PMID:23798385
Decorin causes autophagy in endothelial cells via Peg3.
KEEP AS NON CORE
Summary: Decorin induces mitochondrial fragmentation/fission in endothelial cells. Genetic interaction evidence (IGI).
Reason: Experimental finding from PMID:23798385 showing decorin causes mitochondrial fission in endothelial cells as part of its anti-angiogenic effects. This is a downstream cellular consequence, not a core function. Decorin's core functions are ECM structural. Marking as non-core.
Supporting Evidence:
PMID:23798385
decorin induced VEGFR2-dependent mitochondrial fragmentation and loss of mitochondrial membrane potential
GO:1900747 negative regulation of vascular endothelial growth factor signaling pathway
IDA
PMID:23798385
Decorin causes autophagy in endothelial cells via Peg3.
KEEP AS NON CORE
Summary: Decorin antagonizes VEGF signaling by binding VEGFR2 and competing with VEGFA. Experimentally demonstrated (IDA).
Reason: Well-supported experimental finding from PMID:23798385. Decorin binds VEGFR2 in region overlapping with VEGFA binding site, antagonizing VEGF signaling. However, this is a cell signaling activity rather than decorin's core ECM structural functions (collagen organization, TGF-beta sequestration). Marking as non-core.
Supporting Evidence:
PMID:23798385
decorin interacted with VEGF receptor 2 (VEGFR2) in a region overlapping with its natural ligand VEGFA
GO:0010508 positive regulation of autophagy
IDA
PMID:23798385
Decorin causes autophagy in endothelial cells via Peg3.
KEEP AS NON CORE
Summary: Decorin induces autophagy in endothelial cells. Parent term of GO:0016239 (positive regulation of macroautophagy). Experimentally demonstrated (IDA).
Reason: Experimental finding from PMID:23798385 - same biological process as the more specific term GO:0016239 (positive regulation of macroautophagy) already annotated. Decorin induces autophagy via VEGFR2/Peg3 pathway. This is a secondary signaling function, not core ECM structural function. Marking as non-core.
Supporting Evidence:
PMID:23798385
Decorin evoked Peg3-dependent autophagy in both microvascular and macrovascular endothelial cells leading to suppression of angiogenesis.
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-2022052
KEEP AS NON CORE
Summary: Reactome pathway for conversion of GlcA to IdoA (DSE enzyme) during dermatan sulfate biosynthesis. Decorin transiently in Golgi during GAG modification.
Reason: Correct annotation from Reactome dermatan sulfate biosynthesis pathway. DSE converts GlcA to IdoA in decorin's GAG chain in Golgi. Transient biosynthetic localization, not core functional location. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-2022052
DSE converts GlcA to IdoA
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-2022063
KEEP AS NON CORE
Summary: Reactome pathway for sulfate transfer by CHST14 to GalNAc in dermatan sulfate. Decorin transiently in Golgi during GAG biosynthesis.
Reason: Correct annotation from Reactome dermatan sulfate biosynthesis pathway. CHST14 transfers sulfate to GalNAc residues in decorin's GAG chain in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-2022063
CHST14 transfers SO4(2-) to GalNAc in dermatan or DS
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-3636919
KEEP AS NON CORE
Summary: Reactome pathway for defective CHST14 (EDS musculocontractural type mutation). Decorin present in Golgi during GAG biosynthesis.
Reason: Correct annotation from Reactome disease pathway showing decorin's presence in Golgi during GAG chain modification. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-3636919
Defective CHST14 does not transfer SO4(2-) to GalNAc in dermatan or DS
GO:0003723 RNA binding
HDA
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-bi...
REMOVE
Summary: Decorin detected in mRNA-binding protein atlas from HDA (high-throughput) study. However, RNA binding is not a characterized molecular function of decorin.
Reason: This annotation from PMID:22658674 (mammalian mRNA-binding protein atlas) is likely a false positive from high-throughput screen. Decorin is a secreted extracellular proteoglycan with well-characterized molecular functions (collagen binding, TGF-beta binding, growth factor receptor binding). RNA binding has never been reported as a decorin function in focused studies and makes no biological sense for a secreted ECM protein. Should be removed as over-annotation from HDA screen artifact.
Supporting Evidence:
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
GO:0005576 extracellular region
TAS
Reactome:R-HSA-2534248
ACCEPT
Summary: Reactome pathway for decorin degradation by MMPs (MMP2, MMP3, MMP7) in extracellular region.
Reason: Correct annotation from Reactome ECM degradation pathway. Decorin is degraded by matrix metalloproteinases in the extracellular region where it functions. This confirms decorin's localization to extracellular space.
Supporting Evidence:
Reactome:R-HSA-2534248
DCN (decorin) degradation by MMP2, MMP3, MMP7
GO:0005576 extracellular region
TAS
Reactome:R-HSA-3828025
ACCEPT
Summary: Reactome pathway for decorin degradation by MMP14 in extracellular region.
Reason: Correct annotation from Reactome ECM degradation pathway. Decorin is degraded by MMP14 (membrane-type MMP) in the extracellular region. This confirms decorin's extracellular localization.
Supporting Evidence:
Reactome:R-HSA-3828025
DCN (decorin) degradation by MMP14
GO:0005576 extracellular region
TAS
Reactome:R-HSA-2327909
ACCEPT
Summary: Reactome pathway for decorin binding to collagen I, II, III, VI fibrils in extracellular region.
Reason: Correct annotation from Reactome collagen binding pathway. This is a core function of decorin - binding to collagen fibrils in the extracellular matrix to regulate fibrillogenesis. Decorin functions in extracellular region/ECM.
Supporting Evidence:
Reactome:R-HSA-2327909
DCN binds collagen I, II, III, VI fibrils
GO:0005576 extracellular region
TAS
Reactome:R-NUL-2466133
ACCEPT
Summary: Reactome pathway for SLRPs binding TGF-beta in extracellular region. Decorin sequesters TGF-beta in ECM.
Reason: Correct annotation from Reactome TGF-beta signaling pathway. Decorin binding and sequestering TGF-beta in the extracellular region is one of its core functions. This annotation represents a fundamental aspect of decorin biology.
Supporting Evidence:
Reactome:R-NUL-2466133
DCN binding is thought to sequester TGF-Beta extracellularly, thereby diminishing its biological activity
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-1878002
KEEP AS NON CORE
Summary: Reactome pathway for xylose transfer to decorin core protein by XYLTs (tetrasaccharide linker biosynthesis). Decorin in Golgi during GAG chain initiation.
Reason: Correct annotation from Reactome GAG biosynthesis pathway. XYLTs transfer xylose to Ser-34 of decorin to initiate tetrasaccharide linker formation in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-1878002
XYLTs transfer Xyl to core protein
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-1889955
KEEP AS NON CORE
Summary: Reactome pathway for GlcA transfer to tetrasaccharide linker by B3GAT dimers. Decorin in Golgi during GAG linker biosynthesis.
Reason: Correct annotation from Reactome tetrasaccharide linker biosynthesis pathway. B3GAT transfers GlcA to the linker region of decorin's GAG attachment site in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-1889955
B3GAT dimers transfer GlcA to tetrasaccharide linker
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-1889978
KEEP AS NON CORE
Summary: Reactome pathway for Gal transfer to tetrasaccharide linker by B3GALT6. Decorin in Golgi during GAG linker assembly.
Reason: Correct annotation from Reactome tetrasaccharide linker biosynthesis pathway. B3GALT6 transfers galactose to the linker region in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-1889978
B3GALT6 transfers Gal to the tetrasaccharide linker
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-1889981
KEEP AS NON CORE
Summary: Reactome pathway for Gal transfer to xylosyl-unit by B4GALT7 (first step of tetrasaccharide linker). Decorin in Golgi during GAG biosynthesis.
Reason: Correct annotation from Reactome tetrasaccharide linker biosynthesis pathway. B4GALT7 transfers galactose to xylose on decorin in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-1889981
B4GALT7 transfers Gal group to xylosyl-unit of the tetrasaccharide linker
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-1971482
KEEP AS NON CORE
Summary: Reactome pathway for GalNAc transfer to CS linker glycan by CSGALNACTs. Decorin in Golgi during chondroitin sulfate biosynthesis.
Reason: Correct annotation from Reactome chondroitin sulfate biosynthesis pathway. CSGALNACTs transfer GalNAc to initiate CS chain on decorin in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-1971482
CSGALNACTs transfer GalNAc to CS linker glycan
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-3560802
KEEP AS NON CORE
Summary: Reactome disease pathway for defective B3GAT3 (JDSSDHD mutation). Decorin present in Golgi during attempted GAG biosynthesis even with defective enzyme.
Reason: Correct annotation from Reactome disease pathway. In JDSSDHD (joint dislocations, short stature, craniofacial dysmorphism with or without congenital heart defects), defective B3GAT3 cannot transfer GlcA, but decorin substrates are still present in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-3560802
Defective B3GAT3 does not transfer GlcA to tetrasaccharide linker
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-3560804
KEEP AS NON CORE
Summary: Reactome disease pathway for defective B4GALT7 (EDS progeroid type mutation). Decorin present in Golgi even with defective GAG biosynthesis enzyme.
Reason: Correct annotation from Reactome disease pathway. In EDS progeroid type, defective B4GALT7 cannot transfer Gal to xylose, but decorin is still present in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-3560804
Defective B4GALT7 does not transfer Gal to xylosyl-unit of the tetrasaccharide linker
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-4420365
KEEP AS NON CORE
Summary: Reactome disease pathway for defective B3GALT6 (EDSP2/SEMDJL1 mutations). Decorin present in Golgi even with defective GAG biosynthesis.
Reason: Correct annotation from Reactome disease pathway. In EDSP2 and SEMDJL1, defective B3GALT6 cannot transfer Gal to linker, but decorin is present in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-4420365
Defective B3GALT6 does not transfer Gal to the tetrasaccharide linker
GO:0043202 lysosomal lumen
TAS
Reactome:R-HSA-1793176
KEEP AS NON CORE
Summary: Reactome pathway for dermatan sulfate cleavage from proteoglycan in lysosome during degradation. Decorin eventually degraded in lysosomes.
Reason: Correct annotation from Reactome degradation pathway. Decorin (as dermatan sulfate proteoglycan) is eventually internalized and degraded in lysosomes, where DS GAG chains are cleaved. This represents the terminal degradation step, not functional localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-1793176
DS is cleaved from its proteoglycan
GO:0043202 lysosomal lumen
TAS
Reactome:R-HSA-2065233
KEEP AS NON CORE
Summary: Reactome pathway for chondroitin sulfate cleavage from proteoglycan in lysosome during degradation. Decorin eventually degraded in lysosomes.
Reason: Correct annotation from Reactome degradation pathway. Decorin (as chondroitin sulfate proteoglycan) is eventually degraded in lysosomes where CS chains are cleaved. Terminal degradation step, not functional localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-2065233
CS is cleaved from its proteoglycan
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-1971483
KEEP AS NON CORE
Summary: Reactome pathway for sulfate transfer to GalNAc by CHST enzymes during CS/DS biosynthesis. Decorin in Golgi during GAG sulfation.
Reason: Correct annotation from Reactome chondroitin/dermatan sulfate biosynthesis pathway. CHST11/12/13/9 transfer sulfate to 4-position of GalNAc in decorin's GAG chain in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-1971483
CHST11,12,13,9 transfer sulfate to (4-)GalNAc
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-1971487
KEEP AS NON CORE
Summary: Reactome pathway for GalNAc transfer to CS chain by chondroitin polymerase complex. Decorin in Golgi during CS chain elongation.
Reason: Correct annotation from Reactome chondroitin sulfate biosynthesis pathway. Chondroitin polymerase complex elongates CS chain on decorin by adding GalNAc residues in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-1971487
Chondroitin polymerase complex transfers GalNAc to CS chain
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-1971491
KEEP AS NON CORE
Summary: Reactome pathway for GlcA transfer to CS chain by chondroitin polymerase complex. Decorin in Golgi during CS chain elongation.
Reason: Correct annotation from Reactome chondroitin sulfate biosynthesis pathway. Chondroitin polymerase complex adds GlcA to decorin's CS chain in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-1971491
Chondroitin polymerase complex transfers GlcA to CS chain
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-2018659
KEEP AS NON CORE
Summary: Reactome pathway for sulfate transfer by CHST15 to GalNAc-4-sulfate (creating 4,6-disulfated GalNAc). Decorin in Golgi during DS biosynthesis.
Reason: Correct annotation from Reactome dermatan sulfate biosynthesis pathway. CHST15 adds additional sulfate to create disulfated GalNAc in decorin's GAG chain in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-2018659
CHST15 transfers sulfate to (6-)GalNAc-4-sulfate
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-2018682
KEEP AS NON CORE
Summary: Reactome pathway for sulfate transfer to position 6 of GalNAc by CHST3/7. Decorin in Golgi during CS biosynthesis.
Reason: Correct annotation from Reactome chondroitin sulfate biosynthesis pathway. CHST3/7 transfer sulfate to 6-position of GalNAc in decorin's GAG chain in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-2018682
CHST3,7 transfer SO4(2-) to position 6 of GalNAc on chondroitin chains
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-2022061
KEEP AS NON CORE
Summary: Reactome pathway for sulfation of iduronate (position 2) in dermatan sulfate. Decorin in Golgi during DS modification.
Reason: Correct annotation from Reactome dermatan sulfate biosynthesis pathway. Additional sulfation of position 2 of iduronate in decorin's DS chain occurs in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-2022061
Dermatan sulfate can be further sulfated on position 2 of iduronate
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-3595175
KEEP AS NON CORE
Summary: Reactome disease pathway for defective CHST3 (SEDCJD mutation - spondyloepiphyseal dysplasia with congenital joint dislocations). Decorin present in Golgi.
Reason: Correct annotation from Reactome disease pathway. In SEDCJD, defective CHST3 cannot transfer sulfate to chondroitin, but decorin substrates are present in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-3595175
Defective CHST3 does not transfer SO4(2-) to chondroitin
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-3595176
KEEP AS NON CORE
Summary: Reactome disease pathway for defective CHSY1 (TPBS mutation - Temtamy preaxial brachydactyly syndrome). Decorin present in Golgi.
Reason: Correct annotation from Reactome disease pathway. In TPBS, defective CHSY1 cannot transfer GalNAc to chondroitin, but decorin is present in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-3595176
Defective CHSY1 does not transfer GalNAc to chondroitin
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-3595178
KEEP AS NON CORE
Summary: Reactome disease pathway for defective CHSY1 (TPBS mutation). Decorin present in Golgi during defective CS biosynthesis.
Reason: Correct annotation from Reactome disease pathway. In TPBS, defective CHSY1 cannot transfer GlcA to chondroitin, but decorin is present in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-3595178
Defective CHSY1 does not transfer GlcA to chondroitin
GO:0005796 Golgi lumen
TAS
Reactome:R-HSA-9632033
KEEP AS NON CORE
Summary: Reactome pathway for GalNAc transfer to CS chain by CSGALNACTs. Decorin in Golgi during CS chain elongation.
Reason: Correct annotation from Reactome chondroitin sulfate biosynthesis pathway. CSGALNACTs add GalNAc residues to elongate CS chain on decorin in Golgi. Transient biosynthetic localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-9632033
CSGALNACTs transfer GalNAc to CS chain
GO:0043202 lysosomal lumen
TAS
Reactome:R-HSA-2022056
KEEP AS NON CORE
Summary: Reactome pathway for DSPG/CSPG translocation to lysosome for degradation. Decorin eventually degraded in lysosomal lumen.
Reason: Correct annotation from Reactome degradation pathway. Decorin (as dermatan/chondroitin sulfate proteoglycan) is internalized and translocated to lysosomes for degradation. Terminal degradation step, not functional localization. Marking as non-core.
Supporting Evidence:
Reactome:R-HSA-2022056
DSPG and CSPG translocate to the lysosome for degradation
GO:0009887 animal organ morphogenesis
TAS
PMID:7961765
The murine decorin. Complete cDNA cloning, genomic organizat...
KEEP AS NON CORE
Summary: Decorin expression during organogenesis and tissue differentiation in mouse. TAS (traceable author statement) from developmental study.
Reason: Correct annotation from PMID:7961765 studying murine decorin expression during development. Decorin is expressed during organ morphogenesis and tissue differentiation. However, this is a developmental/tissue-specific process rather than decorin's core molecular/cellular function. Decorin's core functions are collagen fibril organization and TGF-beta sequestration. Marking as non-core.
Supporting Evidence:
PMID:7961765
The murine decorin. Complete cDNA cloning, genomic organization, chromosomal assignment, and expression during organogenesis and tissue differentiation.

References

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Deep Research

Falcon

(DCN-deep-research-falcon.md)

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