Perlecan is a massive heparan sulfate proteoglycan (468 kDa, 4391 amino acids) that functions as a critical structural organizer and signaling hub of basement membranes throughout the body. The protein contains five structurally distinct domains that enable diverse functions through interactions with extracellular matrix components (laminin, type IV collagen, nidogens, fibrillin-1) and cell surface receptors. Heparan sulfate chains attached primarily to domain I (at serines 65, 71, 76) and domain V create high negative charge density essential for basement membrane hydration and charge-based filtration, particularly in the glomerular basement membrane. These heparan sulfate chains sequester and present growth factors (FGF-2, FGF-18, VEGF, BMP, PDGF) to their cognate receptors, forming ternary complexes that activate downstream signaling cascades regulating cell proliferation, differentiation, and angiogenesis. Domain III binds FGF-18 and PDGF through its core protein. Perlecan plays essential roles in growth plate development and endochondral ossification by modulating FGF receptor signaling and enabling vascular invasion required for bone formation. At neuromuscular junctions, perlecan localizes acetylcholinesterase and maintains synaptic stability. Proteolytic cleavage by cathepsin L and BMP1-tolloid metalloproteinases generates endorepellin (domain V fragment) and LG3 peptide, which exhibit anti-angiogenic activity opposing the pro-angiogenic function of full-length perlecan through dual antagonism of VEGFR2 and Ξ±2Ξ²1 integrin. Loss-of-function mutations cause dyssegmental dysplasia (Silverman-Handmaker type, typically perinatally lethal), while hypomorphic mutations cause Schwartz-Jampel syndrome characterized by chondrodysplasia and myotonia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043005 neuron projection | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation based on phylogenetic analysis. Perlecan localizes at neuromuscular junctions where it anchors acetylcholinesterase and maintains synaptic stability. The deep research document confirms perlecan's role at neuromuscular junctions and in neural tissues including blood-brain barrier basement membranes. UniProt features list "Interaction with PRPH" (peripherin) suggesting neuron projection localization. Reason: Well-supported by both phylogenetic inference and experimental evidence. Perlecan is present at neuromuscular junctions (a specialized neuron projection) and in neural basement membranes. This represents a core function of perlecan in neural tissues. Supporting Evidence: PMID:14702351 The collagen-tailed form of acetylcholinesterase (A(12)-AChE) appears to be localized at the neuromuscular junction in association with the transmembrane dystroglycan complex through binding of its collagenic tail (ColQ) to the proteoglycan perlecan. |
| GO:0001525 angiogenesis | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation from UniProtKB keyword mapping. Perlecan has dual pro- and anti-angiogenic roles. Full-length perlecan promotes angiogenesis through its heparan sulfate chains that bind and present VEGF and FGF-2 to their receptors. Proteolytically cleaved endorepellin (domain V) exhibits potent anti-angiogenic activity through dual antagonism of VEGFR2 and Ξ±2Ξ²1 integrin. Deep research extensively documents both activities. Reason: Core function of perlecan. Despite the dual nature (both pro- and anti-angiogenic depending on proteolytic state), perlecan is fundamentally involved in angiogenesis regulation. The term captures the biological process without specifying direction, which is appropriate given perlecan's context-dependent activities. Supporting Evidence: PMID:21596751 Endorepellin, the C-terminal module of perlecan, negatively regulates angiogenesis counter to its proangiogenic parental molecule. file:human/HSPG2/HSPG2-deep-research-perplexity.md Perlecan exerts pro-angiogenic activity principally through modulation of the FGF-2 pathway via its heparan sulfate side chains, which present this ligand to its receptor and induce complex downstream signaling cascades promoting cell proliferation, motility, and adhesion. Additionally, perlecan positively affects angiogenesis through modulation of the VEGFR2-Neuropilin-1 signaling axis. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: IEA annotation from InterPro domain IPR001881 (EGF-like calcium-binding domain). Perlecan domain V contains multiple EGF-like repeats that may have calcium-binding capacity. However, calcium binding is not a characterized or functionally important activity for perlecan. UniProt does not list calcium as a cofactor. Reason: While perlecan contains EGF-like domains that structurally may bind calcium, this is not a characterized molecular function of perlecan and does not contribute to its known biological activities. This represents computational over-annotation based on domain presence without functional validation. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from UniProtKB subcellular location. Perlecan is secreted and localized to extracellular spaces including basement membranes, extracellular matrix, and extracellular space. This is universally accepted. Reason: Core localization. Perlecan is a secreted protein that functions entirely in the extracellular space. The term is appropriately general for this widely distributed ECM protein. |
| GO:0005604 basement membrane | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation combining ARBA and UniProtKB subcellular location. Perlecan is the major heparan sulfate proteoglycan of basement membranes throughout the body. This is perlecan's canonical and most important localization, critical for basement membrane structural integrity, growth factor sequestration, and barrier function. Reason: Core localization representing perlecan's primary and most important site of action. Basement membrane is where perlecan carries out its essential structural and signaling functions. Supporting Evidence: file:human/HSPG2/HSPG2-deep-research-perplexity.md Perlecan functions as a critical cross-linking component of basement membranes, interacting with and stabilizing the major basement membrane proteins including laminin, type IV collagen, and nidogens. Through its multiple binding partners, perlecan bridges and stabilizes the laminin network with the type IV collagen network within basement membranes. |
| GO:0005796 Golgi lumen | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA annotation from ARBA machine learning. Perlecan transits through the Golgi during biosynthesis where heparan sulfate chains are added and modified. This is a transient biosynthetic localization, not a functional site. Reason: Accurate but non-core annotation. All secreted proteoglycans transit through the Golgi for glycosylation. This does not represent a functional localization where perlecan carries out its biological activities, merely a biosynthetic transit point. |
| GO:0007420 brain development | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation from ARBA machine learning. Perlecan plays roles in blood-brain barrier integrity, neural stem cell niches, and brain vascular development. Deep research documents perlecan's role in maintaining blood-brain barrier basement membrane and promoting angiogenic repair following stroke. Reason: Well-supported role. Perlecan is essential for brain vascular development and blood-brain barrier function. While not as central as its skeletal roles, this represents an important developmental function. |
| GO:0030154 cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA annotation from ARBA machine learning. Perlecan influences chondrocyte differentiation and hypertrophic maturation in growth plates, and affects endothelial cell behavior. This is a very broad term that could apply to many pleiotropic effects. Reason: Too general. While perlecan does influence differentiation of multiple cell types (chondrocytes, endothelial cells, osteoprogenitors), this extremely broad term does not capture perlecan's specific functions. More specific terms for chondrocyte differentiation or endochondral ossification would be preferable. |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: IEA annotation from UniProtKB keyword mapping. This is an extremely generic molecular function term. While calcium ion binding annotation exists from EGF domains, metal ion binding is not a characterized activity of perlecan. Reason: Overly generic term providing no useful functional information. Not a characterized molecular function of perlecan. This represents computational over-annotation without functional significance. |
| GO:0072359 circulatory system development | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation from ARBA machine learning. Perlecan is essential for vascular development as demonstrated in knockout mice and zebrafish morphants showing severe vascular defects. Perlecan regulates angiogenesis through growth factor presentation and direct receptor interactions. Reason: Core developmental function. Perlecan is essential for normal vascular development, with knockout causing cardiovascular defects and embryonic lethality. Well-supported by genetic and developmental studies. Supporting Evidence: file:human/HSPG2/HSPG2-deep-research-falcon.md Perlecan modulates VEGFA/VEGFR2 signaling by localizing VEGF and stabilizing receptor-ligand complexes; supports FGF2-FGFR co-receptor functions via HS; engages integrins and dystroglycan to influence adhesion and downstream kinases. Hspg2-null mice exhibit embryonic lethality with severe cardiac and cartilaginous defects, emphasizing perlecan's nonredundant role in BM integrity and morphogenesis. |
| GO:0005515 protein binding | IPI PMID:12900424 A novel interaction between perlecan protein core and progra... | MODIFY | Summary: IPI annotation showing interaction with progranulin (P28799). This is uninformative as a molecular function term. Reason: Protein binding is uninformative. Perlecan interacts with numerous proteins (laminin, collagen IV, nidogens, fibrillin-1, growth factors, integrins, etc.). Better terms would be specific molecular functions like "extracellular matrix structural constituent" or "growth factor binding". Proposed replacements: extracellular matrix structural constituent growth factor binding Supporting Evidence: PMID:12900424 2003 Aug 4. A novel interaction between perlecan protein core and progranulin: potential effects on tumor growth. |
| GO:0005515 protein binding | IPI PMID:21596751 Endorepellin, the angiostatic module of perlecan, interacts ... | MODIFY | Summary: IPI annotation showing interaction with VEGFR2/KDR (P35968). This paper demonstrates endorepellin binds VEGFR2 and Ξ±2Ξ²1 integrin with dual receptor antagonism for anti-angiogenic activity. While the interaction is real, "protein binding" is uninformative. Reason: Protein binding is uninformative. The interaction with VEGFR2 represents a specific receptor-ligand interaction that antagonizes VEGF signaling. Better terms would capture the specific molecular function. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:21596751 perlecan and endorepellin bind directly and with high affinity to both vegf receptors |
| GO:0005515 protein binding | IPI PMID:23374253 Endorepellin laminin-like globular 1/2 domains bind Ig3-5 of... | MODIFY | Summary: IPI annotation showing interaction with VEGFR2/KDR (P35968). This paper demonstrates that endorepellin LG1/2 domains bind Ig3-5 of VEGFR2 and block VEGFA signaling. While technically correct, "protein binding" is uninformative. Reason: Protein binding is uninformative. The VEGFR2 interaction represents a specific antagonistic receptor binding activity. Better terms would capture this specific molecular function. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:23374253 LG1/2 did not bind Ig1-3, but did bind with high affinity to Ig3-5 |
| GO:0031594 neuromuscular junction | IC PMID:14702351 C-terminal and heparin-binding domains of collagenic tail su... | ACCEPT | Summary: IC annotation with experimental evidence. PMID:14702351 demonstrates that perlecan anchors acetylcholinesterase at the neuromuscular junction through interaction with ColQ. Perlecan-null mice lack AChE at the NMJ. This is a well-characterized and essential localization. Reason: Core localization supported by strong experimental evidence. Perlecan plays an essential structural role at the neuromuscular junction where it anchors acetylcholinesterase. Loss of perlecan causes myotonia in Schwartz-Jampel syndrome due to altered neuromuscular function. Supporting Evidence: PMID:14702351 The collagen-tailed form of acetylcholinesterase (A(12)-AChE) appears to be localized at the neuromuscular junction in association with the transmembrane dystroglycan complex through binding of its collagenic tail (ColQ) to the proteoglycan perlecan. file:human/HSPG2/HSPG2-deep-research-perplexity.md Perlecan plays a critical role at the neuromuscular junction. Perlecan localizes acetylcholinesterase in the neuromuscular junction and is of functional significance in neuromuscular control; in perlecan-null mice, acetylcholinesterase is absent at the neuromuscular junction. A reduced amount of functional perlecan at the neuromuscular junction likely alters the balance of other molecules that signal when muscles should contract and when they should relax. |
| GO:0032223 negative regulation of synaptic transmission, cholinergic | ISS GO_REF:0000024 | UNDECIDED | Summary: ISS annotation based on sequence similarity to mouse orthologs. This term suggests perlecan negatively regulates cholinergic transmission. Perlecan localizes acetylcholinesterase which terminates cholinergic signaling, but this is enabling proper termination rather than negative regulation of transmission itself. Reason: The relationship between perlecan and cholinergic transmission regulation is complex. Perlecan anchors AChE which breaks down acetylcholine, but whether this constitutes "negative regulation" of transmission or proper homeostatic control is unclear. Would need access to the mouse orthologue studies to evaluate this annotation properly. |
| GO:0035418 protein localization to synapse | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on mouse ortholog. Perlecan localizes acetylcholinesterase to the neuromuscular synapse. This is well-documented experimentally. Reason: Well-supported function. Perlecan serves as an anchor/scaffold that localizes acetylcholinesterase to the neuromuscular synapse, representing a core function at this site. Supporting Evidence: PMID:14702351 The collagen-tailed form of acetylcholinesterase (A(12)-AChE) appears to be localized at the neuromuscular junction in association with the transmembrane dystroglycan complex through binding of its collagenic tail (ColQ) to the proteoglycan perlecan. |
| GO:0060090 molecular adaptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on mouse ortholog. Perlecan functions as a molecular scaffold/adaptor that links multiple ECM components (laminin, collagen IV, nidogens) and localizes proteins like acetylcholinesterase. This is an appropriate molecular function term. Reason: Accurate molecular function. Perlecan serves as a molecular adaptor/scaffold in basement membranes, cross-linking laminin and collagen IV networks and localizing proteins like acetylcholinesterase. This is more informative than generic "protein binding". |
| GO:0005515 protein binding | IPI PMID:14702351 C-terminal and heparin-binding domains of collagenic tail su... | MODIFY | Summary: IPI annotation showing interaction with ACHE/acetylcholinesterase (Q9Y215). While the interaction is real and important, "protein binding" is uninformative. Reason: Protein binding is uninformative. Better captured by "molecular adaptor activity" term which describes perlecan's role in localizing acetylcholinesterase to the synapse. Proposed replacements: molecular adaptor activity Supporting Evidence: PMID:14702351 2003 Dec 31. C-terminal and heparin-binding domains of collagenic tail subunit are both essential for anchoring acetylcholinesterase at the synapse. |
| GO:0031012 extracellular matrix | HDA PMID:23658023 Comparative proteomic analysis of supportive and unsupportiv... | ACCEPT | Summary: HDA annotation from proteomics study of extracellular matrix. Perlecan is a major structural component of extracellular matrix and basement membranes. This is a core localization. Reason: Core localization. Perlecan is one of the major heparan sulfate proteoglycans of extracellular matrix and basement membranes throughout the body. Supporting Evidence: PMID:23658023 2013 May 8. Comparative proteomic analysis of supportive and unsupportive extracellular matrix substrates for human embryonic stem cell maintenance. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-9940993 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway for heparan sulfate biosynthesis (PXYLP1 dephosphorylates Xyl moiety). Perlecan transits through the Golgi during biosynthesis where heparan sulfate chains undergo extensive modifications. This is a transient biosynthetic localization. Reason: Accurate but non-core. All heparan sulfate proteoglycans transit through the Golgi for glycosaminoglycan chain synthesis and modification. This is a biosynthetic compartment, not where perlecan carries out its biological functions. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-9941039 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway for heparan sulfate biosynthesis (FAM20B phosphorylates Xyl moiety). Perlecan transits through the Golgi during biosynthesis where heparan sulfate chains undergo enzymatic modifications. Transient biosynthetic localization. Reason: Accurate but non-core. Golgi transit is required for all secreted proteoglycans but does not represent functional localization. The numerous Reactome annotations document biosynthetic machinery but not core function. |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to mouse ortholog. Perlecan is a major structural constituent of basement membranes and cartilage ECM. Its high negative charge density from heparan sulfate chains attracts water and cations, providing compression resistance particularly important in cartilage and glomerular basement membrane. Reason: Core molecular function. Perlecan's proteoglycan structure with extended heparan sulfate chains provides hydration and compressive resilience to ECM, representing an essential biophysical function especially in cartilage where it enables load-bearing properties. |
| GO:0031012 extracellular matrix | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on mouse ortholog. Perlecan is a major heparan sulfate proteoglycan component of extracellular matrix and basement membranes throughout the body. Core localization. Reason: Core localization. Perlecan is one of the major structural and regulatory components of extracellular matrix, essential for ECM organization and function. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1592314 | ACCEPT | Summary: TAS annotation from Reactome pathway "HSPG2 (perlecan) degradation by MMP3, plasmin, (MMP12)". This documents perlecan degradation by matrix metalloproteinases and plasmin in the extracellular region, which is perlecan's native location. Reason: Core localization. Perlecan functions entirely in the extracellular region including basement membranes, extracellular matrix, and extracellular space. This annotation is accurate and supported by all evidence. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2534240 | ACCEPT | Summary: TAS annotation from Reactome pathway "HSPG2 (perlecan) degradation by MMP14, MMP15". This documents perlecan degradation by additional matrix metalloproteinases in the extracellular region. Reason: Core localization. Perlecan is secreted and functions entirely in the extracellular region, where it is subject to proteolytic processing by metalloproteinases. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4088220 | ACCEPT | Summary: TAS annotation from Reactome pathway "Endorepellin binds alpha2beta1 integrin". This documents the binding of endorepellin (perlecan domain V fragment) to integrin Ξ±2Ξ²1, which occurs in the extracellular region. Reason: Core localization. Endorepellin is generated by proteolytic cleavage in the extracellular space and exerts its anti-angiogenic effects through receptor binding in the extracellular region. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4088281 | ACCEPT | Summary: TAS annotation from Reactome pathway "Endorepellin binds KDR (VEGFR2)". This documents the binding of endorepellin to VEGFR2, a critical interaction for endorepellin's anti-angiogenic activity occurring in the extracellular region. Reason: Core localization. Endorepellin functions in the extracellular region where it binds VEGFR2 and Ξ±2Ξ²1 integrin to exert dual receptor antagonism and anti-angiogenic effects. |
| GO:0005576 extracellular region | TAS Reactome:R-NUL-2534170 | ACCEPT | Summary: TAS annotation from Reactome pathway "Degradation of HSPG2 by Mmp13 and Ctss". This documents perlecan degradation by MMP13 and cathepsin S in the extracellular region. Reason: Core localization. Perlecan is subject to proteolytic processing by multiple proteases including MMP13 and cathepsin S in its native extracellular location. |
| GO:0006629 lipid metabolic process | TAS PMID:21289173 Heparan sulphate proteoglycan and the low-density lipoprotei... | KEEP AS NON CORE | Summary: TAS annotation from PMID:21289173 describing perlecan's role in neuronal amyloid-beta uptake through cooperation with LRP1 (low-density lipoprotein receptor-related protein 1). The paper demonstrates that perlecan (as HSPG) cooperates with LRP1 in cellular uptake processes that include lipid metabolism. However, this is not a core function of perlecan. Reason: Peripheral function. While perlecan can cooperate with LRP1 in receptor-mediated endocytosis processes that involve lipid metabolism, this is not a primary or core function of perlecan. Perlecan's main functions are structural organization of basement membranes and growth factor sequestration/presentation, not lipid metabolism per se. Supporting Evidence: PMID:21289173 In addition, LRP1 and HSPG are part of an immunoprecipitable complex at the cell surface to mediate lipid metabolism ( Wilsie and Orlando, 2003 ) |
| GO:0050750 low-density lipoprotein particle receptor binding | TAS PMID:21289173 Heparan sulphate proteoglycan and the low-density lipoprotei... | ACCEPT | Summary: TAS annotation from PMID:21289173 demonstrating that HSPG (including perlecan) forms a complex with LRP1 and participates in receptor-mediated processes. Domain II of perlecan contains LDL receptor-like repeats, providing structural basis for potential interactions with LDL receptor pathway components. Reason: Well-supported molecular function. Perlecan domain II contains four LDL receptor-like repeats, and perlecan cooperates with LRP1 (LDL receptor-related protein 1) in cellular uptake processes. This represents a legitimate molecular function of perlecan's core protein domains. Supporting Evidence: PMID:21289173 Our findings demonstrate that LRP1 and HSPG function in a cooperative manner to mediate cellular AΞ² uptake and define a major pathway through which AΞ² gains entry to neuronal cells |
| GO:0001540 amyloid-beta binding | IC PMID:21289173 Heparan sulphate proteoglycan and the low-density lipoprotei... | ACCEPT | Summary: IC annotation from PMID:21289173 demonstrating that perlecan (as HSPG) binds amyloid-beta peptide. The paper shows that heparan sulfate chains of perlecan mediate AΞ² binding to cell surfaces, with HSPG being more important for AΞ² binding than LRP1. Heparan sulfate binds the HHQK (amino acids 13-16) region of AΞ². Reason: Well-characterized molecular function relevant to Alzheimer's disease pathology. Perlecan's heparan sulfate chains bind amyloid-beta with functional consequences for AΞ² aggregation, plaque formation, and neuronal uptake. This is a specific and important molecular function, though not a core developmental/structural function. Supporting Evidence: PMID:21289173 HSPG is more important for the binding of AΞ² to the cell surface than LRP1. |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | RCA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Summary: RCA annotation from proteomics study of stem cell-derived extracellular matrices. Perlecan's heparan sulfate chains create high negative charge density that attracts water and cations, providing hydration and compression resistance essential for ECM mechanical properties. Reason: Core molecular function. Perlecan's proteoglycan structure with extended heparan sulfate chains provides hydration and compressive resilience to ECM, representing an essential biophysical function especially important in cartilage and glomerular basement membrane. Supporting Evidence: PMID:28327460 Epub 2017 Mar 7. Comprehensive proteomic characterization of stem cell-derived extracellular matrices. |
| GO:0031012 extracellular matrix | HDA PMID:28327460 Comprehensive proteomic characterization of stem cell-derive... | ACCEPT | Summary: HDA annotation from proteomics analysis of stem cell-derived extracellular matrices. Perlecan identified as a component of ECM by mass spectrometry. Reason: Core localization. Perlecan is a major structural component of extracellular matrix identified in multiple proteomics studies across diverse tissue types. Supporting Evidence: PMID:28327460 Epub 2017 Mar 7. 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... | ACCEPT | Summary: RCA annotation from proteomics characterization of ECM from normal and diseased tissues. Perlecan provides compression resistance through its hydrated heparan sulfate chains. Reason: Core molecular function. Perlecan's high negative charge density from heparan sulfate provides essential compression resistance in tissues including cartilage, basement membranes, and vascular ECM. Supporting Evidence: PMID:28675934 Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics. |
| GO:0031012 extracellular matrix | HDA PMID:28675934 Characterization of the Extracellular Matrix of Normal and D... | ACCEPT | Summary: HDA annotation from proteomics study characterizing ECM of normal and diseased tissues. Perlecan detected as ECM component by mass spectrometry. Reason: Core localization confirmed by proteomics. Perlecan is consistently identified as a major ECM component across multiple tissue types and disease states. 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 | RCA PMID:23979707 SILAC-based proteomics of human primary endothelial cell mor... | ACCEPT | Summary: RCA annotation from SILAC-based proteomics of human endothelial cell morphogenesis. Perlecan identified as structural ECM component conferring compression resistance. Reason: Core molecular function. Perlecan's structural properties provide compression resistance essential for ECM mechanical function in vascular and other tissues. Supporting Evidence: PMID:23979707 Epub 2013 Aug 26. SILAC-based proteomics of human primary endothelial cell morphogenesis unveils tumor angiogenic markers. |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | RCA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: RCA annotation from proteomics characterization of human aorta extracellular space components. Perlecan provides structural support and compression resistance in vascular ECM. Reason: Core molecular function. Perlecan's compression resistance properties are essential for vascular ECM integrity and function in large vessels like the aorta. Supporting Evidence: PMID:20551380 2010 Jun 15. Proteomics characterization of extracellular space components in the human aorta. |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | RCA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: RCA annotation from proteomics of primary metastatic colon cancers. Perlecan identified as ECM structural component even in tumor microenvironments. Reason: Core molecular function maintained even in pathological contexts. Perlecan provides compression resistance in both normal and tumor ECM. Supporting Evidence: PMID:25037231 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. |
| GO:0030021 extracellular matrix structural constituent conferring compression resistance | RCA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: RCA annotation from glycoproteomics study in human atrial fibrillation. Perlecan provides structural ECM function including compression resistance in cardiac tissues. Reason: Core molecular function. Perlecan's compression resistance properties are important in cardiac ECM and basement membranes. Supporting Evidence: PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity in Human Atrial Fibrillation. |
| GO:0031012 extracellular matrix | HDA PMID:25037231 Extracellular matrix signatures of human primary metastatic ... | ACCEPT | Summary: HDA annotation from proteomics of colon cancer and liver metastases ECM. Perlecan detected in tumor-associated ECM. Reason: Core localization. Perlecan is present in ECM even in pathological tumor microenvironments, confirming its fundamental ECM localization. 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: HDA annotation from proteomics of extracellular matrix remodeling in venous hypertension and varicose veins. Perlecan detected in remodeling vascular ECM. Reason: Core localization. Perlecan functions in the extracellular region including vascular basement membranes and ECM. Supporting Evidence: PMID:27068509 Apr 11. 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: HDA annotation from glycoproteomics in atrial fibrillation. Perlecan detected in cardiac ECM. Reason: Core localization. Perlecan is present in cardiac extracellular matrix and basement membranes. 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: HDA annotation from proteomics of human aorta extracellular space. Perlecan identified as a component of extracellular space in vascular tissues. Reason: Core localization. Perlecan is secreted into the extracellular space where it functions in basement membranes and ECM. Supporting Evidence: PMID:20551380 2010 Jun 15. 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: HDA annotation from proteomics characterization of aorta extracellular matrix. Perlecan is a major ECM component in vascular tissues. Reason: Core localization. Perlecan is essential for vascular ECM organization and function. Supporting Evidence: PMID:20551380 2010 Jun 15. Proteomics characterization of extracellular space components in the human aorta. |
| GO:0031012 extracellular matrix | HDA PMID:23979707 SILAC-based proteomics of human primary endothelial cell mor... | ACCEPT | Summary: HDA annotation from SILAC proteomics of endothelial cell morphogenesis. Perlecan detected as ECM component during endothelial tube formation. Reason: Core localization. Perlecan is a key ECM component in angiogenesis and vascular development. Supporting Evidence: PMID:23979707 Epub 2013 Aug 26. SILAC-based proteomics of human primary endothelial cell morphogenesis unveils tumor angiogenic markers. |
| GO:0005604 basement membrane | TAS PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² ne... | ACCEPT | Summary: TAS annotation from PMID:21126803 on endorepellin (perlecan domain V) and Ξ±2 integrin-mediated amyloid-beta neurotoxicity. While the study focuses on endorepellin function, it acknowledges perlecan's primary basement membrane localization. Reason: Core localization. Basement membrane is perlecan's primary and canonical localization where it performs essential structural and signaling functions. Supporting Evidence: PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² neurotoxicity. |
| GO:0006954 inflammatory response | TAS PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² ne... | KEEP AS NON CORE | Summary: TAS annotation from PMID:21126803. The study examines endorepellin's protective effects against AΞ² neurotoxicity, which has inflammatory components. However, inflammatory response is not a core function of perlecan. Reason: Peripheral function. While perlecan and endorepellin may modulate inflammatory processes indirectly through AΞ² binding and effects on integrin signaling, inflammatory response is not a primary or core function of perlecan. The main functions are structural ECM organization and growth factor signaling. Supporting Evidence: PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² neurotoxicity. |
| GO:0007420 brain development | TAS PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² ne... | ACCEPT | Summary: TAS annotation from PMID:21126803 on endorepellin and amyloid-beta. While this study focuses on Alzheimer's disease pathology rather than development, perlecan does play roles in blood-brain barrier formation and neural tissue development as documented in the deep research. Reason: Well-supported developmental function. Perlecan is essential for blood-brain barrier integrity, neural stem cell niches, and brain vascular development. Though not as central as skeletal functions, brain development represents an important role for perlecan. Supporting Evidence: PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² neurotoxicity. |
| GO:0016525 negative regulation of angiogenesis | TAS PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² ne... | ACCEPT | Summary: TAS annotation from PMID:21126803 on endorepellin. Endorepellin (perlecan domain V) exhibits potent anti-angiogenic activity through dual antagonism of VEGFR2 and Ξ±2Ξ²1 integrin, opposing the pro-angiogenic function of full-length perlecan. Reason: Well-characterized function of endorepellin. While full-length perlecan promotes angiogenesis, proteolytic cleavage generates endorepellin which negatively regulates angiogenesis. This represents an important biological switch in perlecan function and is a core activity of the endorepellin fragment. Supporting Evidence: file:human/HSPG2/HSPG2-deep-research-perplexity.md Endorepellin functions as a potent mediator of angiogenesis repression both in vitro and in vivo, exerting this effect through dual receptor antagonism by simultaneously engaging VEGFR2 and alpha2beta1 integrin at sites independent of the VEGFA binding site. Signaling through the alpha2beta1 integrin leads to actin disassembly and blockade of endothelial cell migration, which is necessary for capillary morphogenesis. PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² neurotoxicity. |
| GO:0030154 cell differentiation | TAS PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² ne... | KEEP AS NON CORE | Summary: TAS annotation from PMID:21126803. This study does not directly address cell differentiation. While perlecan influences chondrocyte differentiation in growth plates, this very broad term does not capture specific functions. Reason: Too general. While perlecan influences differentiation of multiple cell types (chondrocytes, endothelial cells, osteoprogenitors), this extremely broad term does not usefully describe perlecan's specific functions. More specific terms for chondrocyte differentiation or endochondral ossification would be preferable. Supporting Evidence: PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² neurotoxicity. |
| GO:0072359 circulatory system development | TAS PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² ne... | ACCEPT | Summary: TAS annotation from PMID:21126803. While this paper focuses on Alzheimer's pathology, perlecan is essential for vascular development as extensively documented in the deep research, with knockout mice showing cardiovascular defects. Reason: Core developmental function. Perlecan is essential for normal circulatory system development, with genetic ablation causing severe vascular defects and embryonic lethality. Well-supported by developmental studies in multiple model organisms. Supporting Evidence: PMID:21126803 Perlecan domain V inhibits Ξ±2 integrin-mediated amyloid-Ξ² neurotoxicity. |
| GO:0006898 receptor-mediated endocytosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation based on sequence similarity to mouse ortholog. PMID:21289173 demonstrates that perlecan cooperates with LRP1 in receptor-mediated endocytosis of amyloid-beta, with HSPG acting as a coreceptor for LRP1-mediated uptake. Reason: Non-core function. While perlecan participates in receptor-mediated endocytosis as a coreceptor for LRP1, particularly for amyloid-beta uptake, this is not a primary structural or signaling function. This represents a specialized role in Alzheimer's disease pathology rather than a core developmental or ECM function. Supporting Evidence: PMID:21289173 First, HSPG may function as a coreceptor for LRP1 |
| GO:0098797 plasma membrane protein complex | TAS PMID:21289173 Heparan sulphate proteoglycan and the low-density lipoprotei... | KEEP AS NON CORE | Summary: TAS annotation from PMID:21289173 describing perlecan as part of an HSPG-LRP1 complex at the plasma membrane. The study shows that "LRP1 and HSPG are part of an immunoprecipitable complex at the cell surface." Reason: Non-core localization. While perlecan can be part of a plasma membrane protein complex with LRP1 for receptor-mediated endocytosis, this is not perlecan's primary localization. Perlecan's core locations are basement membranes and extracellular matrix, not plasma membrane complexes. This represents a specialized interaction in specific contexts (e.g., AΞ² uptake). Supporting Evidence: PMID:21289173 In addition, LRP1 and HSPG are part of an immunoprecipitable complex at the cell surface to mediate lipid metabolism ( Wilsie and Orlando, 2003 ) |
| GO:0005604 basement membrane | TAS PMID:8621634 Perlecan and basement membrane-chondroitin sulfate proteogly... | ACCEPT | Summary: TAS annotation from PMID:8621634 identifying perlecan as a basement membrane component in the Engelbreth-Holm-Swarm tumor matrix, which is a classical source of basement membrane proteins. Reason: Core localization. This paper characterizes perlecan as "basement membrane-specific heparan sulfate proteoglycan" and demonstrates its basement membrane localization by immunohistochemistry. Basement membrane is perlecan's primary and defining localization. Supporting Evidence: PMID:8621634 Both are, however, basement membrane components, although there are tissue-specific differences in their distribution |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | KEEP AS NON CORE | Summary: HDA annotation from proteomics analysis of focal adhesion complexes during myosin-II-responsive adhesion maturation. Perlecan detected in focal adhesion proteome. Reason: Non-core localization. While perlecan may be present in or near focal adhesions where ECM interacts with integrin-based cell adhesion complexes, this is not a primary or characteristic localization for perlecan. Perlecan's core localizations are basement membranes and extracellular matrix. Focal adhesion presence likely reflects ECM-integrin interactions rather than a specific functional role at focal adhesions. Supporting Evidence: PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for Ξ²-Pix in negative regulation of focal adhesion maturation. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: HDA annotation from proteomics of extracellular exosomes isolated from expressed prostatic secretions in urine. Perlecan detected in exosome preparations. Reason: Non-core localization. Detection of perlecan in exosome preparations likely reflects extracellular contamination or non-specific association rather than a functional role in exosome biology. Perlecan is a massive secreted ECM protein not expected to be packaged into exosomes. This annotation does not represent a core function or localization. Supporting Evidence: PMID:23533145 2013 Apr 23. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. |
| GO:0005615 extracellular space | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | ACCEPT | Summary: HDA annotation from proteomics identification of proteins in human colostrum aqueous phase. Perlecan detected in extracellular fluids. Reason: Core localization. Perlecan is secreted into the extracellular space where it functions in basement membranes and ECM. Detection in biological fluids like colostrum confirms its extracellular localization. Supporting Evidence: PMID:16502470 Human colostrum: identification of minor proteins in the aqueous phase by proteomics. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: HDA annotation from proteomics of human parotid gland exosomes. Perlecan detected in exosome preparations. Reason: Non-core localization. Similar to other exosome annotations, detection of this massive ECM protein in exosome preparations likely reflects contamination or non-specific association rather than true exosomal packaging. Not a functional or core localization for perlecan. Supporting Evidence: PMID:19199708 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: HDA annotation from large-scale proteomics of urinary exosomes. Perlecan detected in exosome preparations. Reason: Non-core localization. Detection in exosome preparations does not represent a core function. Given perlecan's size (468 kDa) and role as an ECM structural protein, presence in exosomes likely reflects extracellular contamination rather than functional exosomal packaging. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-3814820 | ACCEPT | Summary: TAS annotation from Reactome pathway "HSPG2 (perlecan) is cleaved by BMP1, TLL1, TLL2, Cathepsin L1". Documents proteolytic processing of perlecan in the extracellular region by BMP1-tolloid metalloproteinases and cathepsin L to generate endorepellin. Reason: Core localization and function. Proteolytic cleavage of perlecan to generate endorepellin is a key regulatory mechanism occurring in the extracellular region. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2396337 | ACCEPT | Summary: TAS annotation from Reactome pathway "HSPG2 binds FGF2(10-155), Fibronectin matrix, Transthyretin tetramer, PDGFA homodimer, PDGFB homodimer". Documents perlecan's binding interactions with growth factors and ECM proteins occurring in the extracellular region. Reason: Core localization and function. Perlecan's binding of growth factors (FGF-2, PDGF) and ECM proteins (fibronectin) in the extracellular region represents core functions. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2396395 | ACCEPT | Summary: TAS annotation from Reactome pathway "HSPG2 (perlecan) binds alpha-dystroglycan". Documents perlecan's interaction with dystroglycan, which occurs in the extracellular region at sites like the neuromuscular junction. Reason: Core localization. Perlecan interacts with dystroglycan in basement membranes, particularly at the neuromuscular junction, representing a key structural interaction in the extracellular region. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-4084505 | ACCEPT | Summary: TAS annotation from Reactome pathway "Laminins bind HSPG2". Documents perlecan's binding to laminins, critical basement membrane proteins, occurring in the extracellular region. Reason: Core localization and function. Perlecan-laminin interactions are essential for basement membrane assembly and function in the extracellular region. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-976734 | ACCEPT | Summary: TAS annotation from Reactome pathway "Amyloid fibrils have additional components". Documents perlecan as a component of amyloid plaques in Alzheimer's disease, which form in the extracellular region. Reason: Valid localization. While not a core function, perlecan's presence in amyloid plaques in the extracellular region is well-documented and relevant to Alzheimer's disease pathology. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9914537 | ACCEPT | Summary: TAS annotation from Reactome pathway "DGC complex binds AGRN and HSPG2". Documents perlecan's binding to the dystroglycan complex (DGC) and agrin in the extracellular region at the neuromuscular junction. Reason: Core localization. Perlecan functions in the extracellular region at the neuromuscular junction where it interacts with the dystroglycan complex. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-1878002 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "XYLTs transfer Xyl to core protein". This documents the first step of heparan sulfate tetrasaccharide linker synthesis in the Golgi, where perlecan transits during biosynthesis. Reason: Non-core biosynthetic localization. All heparan sulfate proteoglycans transit through the Golgi for glycosaminoglycan chain synthesis and modification. This is a required biosynthetic compartment but not where perlecan carries out its biological functions. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-1889981 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "B4GALT7 transfers Gal group to xylosyl-unit of the tetrasaccharide linker". Documents heparan sulfate linker biosynthesis in Golgi during perlecan glycosylation. Reason: Non-core biosynthetic localization. Golgi transit is required for all secreted proteoglycans but represents a transient biosynthetic step, not functional localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-3560804 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Defective B4GALT7 does not transfer Gal to xylosyl-unit of the tetrasaccharide linker". Documents disease pathway affecting perlecan glycosylation in Golgi. Reason: Non-core biosynthetic localization. This documents biosynthetic machinery defects, not core perlecan function. Golgi is a transient biosynthetic compartment. |
| GO:0070062 extracellular exosome | HDA PMID:21362503 Protein profile of exosomes from trabecular meshwork cells. | KEEP AS NON CORE | Summary: HDA annotation from proteomics of exosomes from trabecular meshwork cells. Perlecan detected in exosome preparations. Reason: Non-core localization. Similar to other exosome annotations, detection of this large ECM structural protein in exosome preparations likely reflects contamination. Not a functional localization. Supporting Evidence: PMID:21362503 Epub 2011 Mar 8. Protein profile of exosomes from trabecular meshwork cells. |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-1667005 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome)". Documents degradation of perlecan's heparan sulfate chains by heparanase in lysosomes during turnover. Reason: Non-core degradation localization. While perlecan can be taken up and degraded in lysosomes, this represents a catabolic endpoint rather than a functional localization. Perlecan's functions occur in the extracellular space, not in lysosomes. |
| GO:0043202 lysosomal lumen | TAS Reactome:R-HSA-2024084 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "HS-GAGs translocate to the lysosome for degradation". Documents transport of heparan sulfate proteoglycans including perlecan to lysosomes for degradation. Reason: Non-core degradation localization. Lysosomal degradation is a catabolic process, not a site where perlecan performs its biological functions. This is a terminal degradation pathway. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-2022851 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "EXT1:EXT2 transfers GlcNAc to the heparan chain". Documents heparan sulfate chain elongation in Golgi during perlecan biosynthesis. Reason: Non-core biosynthetic localization. Golgi transit for heparan sulfate synthesis is required but represents transient biosynthetic processing, not functional localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-2022856 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "EXT1:EXT2 transfers GlcA to heparan". Documents heparan sulfate chain elongation in Golgi. Reason: Non-core biosynthetic localization. Golgi transit for HS synthesis is required but represents transient biosynthetic processing, not functional localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-2022860 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "NDST1-4 can sulfate a glucosamine residue in heparan to form heparan sulfate". Documents HS sulfation in Golgi. Reason: Non-core biosynthetic localization. HS modifications occur in Golgi during biosynthesis but not where perlecan functions biologically. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-2022887 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "NDST1-4 N-deacetylates GlcNAc residues in heparan". Documents HS modification in Golgi. Reason: Non-core biosynthetic localization. Golgi modifications of HS are biosynthetic steps, not functional localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-2024108 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Some HSPGs are secreted to the plasma membrane". Documents trafficking of perlecan through Golgi to secretion. Reason: Non-core biosynthetic localization. Golgi is a transient biosynthetic and trafficking compartment, not functional localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-2076383 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "HS3ST1 sulfates GlcN at C3 in heparan sulfate". Documents HS sulfation in Golgi. Reason: Non-core biosynthetic localization. HS sulfation is a biosynthetic modification step in Golgi, not functional localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-2076392 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "EXT1:EXT2 transfers GlcA to heparan". Documents HS chain elongation in Golgi. Reason: Non-core biosynthetic localization. Golgi HS biosynthesis is transient, not where perlecan functions. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-2076419 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "HS6STs sulfate GlcN at C6 in heparan sulfate/heparin". Documents HS sulfation in Golgi. Reason: Non-core biosynthetic localization. HS sulfation in Golgi is biosynthetic processing, not functional localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-2076508 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "HS2ST1 trimer sulfates IdoA at C2 in heparan sulfate". Documents HS sulfation in Golgi. Reason: Non-core biosynthetic localization. Golgi HS modifications are biosynthetic steps, not functional localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-2076611 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "HS3ST2-6 sulfate GlcN at C3 in heparan sulfate". Documents HS sulfation in Golgi. Reason: Non-core biosynthetic localization. HS sulfation is biosynthetic processing in Golgi, not functional localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-3656254 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Defective EXT2 does not transfer GlcNAc to heparan chain". Documents disease mutations affecting HS biosynthesis. Reason: Non-core biosynthetic localization. Documents disease mutations in HS biosynthesis enzymes, not core perlecan function. Golgi is transient biosynthetic compartment. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-3656257 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Defective EXT1 does not transfer GlcA to heparan". Documents disease mutations affecting HS biosynthesis. Reason: Non-core biosynthetic localization. Documents disease mutations in HS biosynthesis, not core perlecan function. Golgi is transient biosynthetic compartment. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-3656261 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Defective EXT1 does not transfer GlcNAc to heparan chain". Documents disease mutations affecting HS biosynthesis. Reason: Non-core biosynthetic localization. Documents disease mutations in HS biosynthesis enzymes, not core perlecan function. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-3656267 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Defective EXT2 does not transfer GlcA to heparan". Documents disease mutations affecting HS biosynthesis. Reason: Non-core biosynthetic localization. Documents disease mutations in HS biosynthesis, not core perlecan function. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-9036285 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Defective EXT1 does not transfer GlcA to heparan". Documents disease mutations affecting HS biosynthesis. Reason: Non-core biosynthetic localization. Documents disease mutations in HS biosynthesis, not core perlecan function. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-9036289 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Defective EXT2 does not transfer GlcA to heparan". Documents disease mutations affecting HS biosynthesis. Reason: Non-core biosynthetic localization. Documents disease mutations in HS biosynthesis, not core perlecan function. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-9953259 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "EXTL3 dimer transfers GlcNAc to the GAG linker". Documents HS linker synthesis in Golgi. Reason: Non-core biosynthetic localization. Golgi HS linker synthesis is biosynthetic processing, not functional localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1678694 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Heparanase 2 (HPSE2) binds heparan sulfate proteoglycans". Documents HPSE2 binding to HSPGs including perlecan. Reason: Non-core localization. While heparanase 2 binds perlecan's heparan sulfate chains, this interaction occurs wherever perlecan is localized (primarily ECM/basement membranes). The pathway annotation implies plasma membrane localization, but this is not a characteristic or primary localization for perlecan. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2024084 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "HS-GAGs translocate to the lysosome for degradation". Documents trafficking of HSPGs from plasma membrane to lysosomes. Reason: Non-core localization. This documents a degradative trafficking pathway. While perlecan may transit through or near the plasma membrane during internalization, this is not a primary functional localization. Perlecan's core functions occur in basement membranes and ECM, not at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2024108 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Some HSPGs are secreted to the plasma membrane". Documents secretion of HSPGs. Reason: Non-core localization. While perlecan is secreted and some HSPGs associate with plasma membranes, perlecan's primary destination is the extracellular matrix and basement membranes, not the plasma membrane. This annotation likely reflects general HSPG secretion pathways rather than perlecan-specific localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2404131 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol". Documents lipoprotein uptake involving HSPGs and LRP receptors at the plasma membrane. Reason: Non-core localization. While perlecan can participate in LRP-mediated endocytosis processes at the cell surface, this is not a primary localization. Perlecan's core functions occur in basement membranes and ECM, not at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2423785 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "CR:atREs binds apoE and HSPG". Documents carotenoid-retinoid complexes binding apoE and HSPGs. Reason: Non-core localization and function. This documents a specialized lipoprotein metabolism interaction at the cell surface. While perlecan can interact with apoE-containing complexes, this is not a core function and plasma membrane is not a primary perlecan localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2429643 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "NREH hydrolyses atREs (HSPG:apoE) to atROL and FAs". Documents metabolism of internalized lipids involving HSPGs. Reason: Non-core localization and function. This documents a metabolic pathway involving HSPGs as coreceptors. Plasma membrane is not a primary perlecan localization, and this represents a peripheral function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9694579 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Spike glycoprotein of SARS-CoV-2 binds ACE2 on host cell". Documents SARS-CoV-2 interaction with cell surface HSPGs during viral entry. Reason: Non-core and non-physiological. While HSPGs including perlecan may facilitate SARS-CoV-2 attachment to cells, this is pathogen exploitation of cell surface glycans, not a physiological function. This does not represent a core function or characteristic localization of perlecan. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9694661 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "TMPRSS2 Mediated SARS-CoV-2 Spike Protein Cleavage and Endocytosis". Documents SARS-CoV-2 viral entry involving HSPGs. Reason: Non-core and non-physiological. SARS-CoV-2 exploitation of HSPGs is not a physiological perlecan function. Plasma membrane is not a characteristic perlecan localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9698988 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Direct Host Cell Membrane Fusion and Release of SARS-CoV-2 Nucleocapsid". Documents SARS-CoV-2 viral entry. Reason: Non-core and non-physiological. Viral exploitation of HSPGs is not a physiological perlecan function. Plasma membrane is not a characteristic perlecan localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9699007 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "FURIN Mediated SARS-CoV-2 Spike Protein Cleavage and Endocytosis". Documents SARS-CoV-2 viral entry involving HSPGs. Reason: Non-core and non-physiological. SARS-CoV-2 exploitation of HSPGs is not a physiological perlecan function. Plasma membrane is not a characteristic perlecan localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9836899 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "sG binds to HSPGs". Documents viral glycoprotein (sG) binding to heparan sulfate proteoglycans. Reason: Non-core and likely non-physiological. Viral protein exploitation of HSPGs is not a physiological perlecan function. Plasma membrane is not a characteristic perlecan localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-1667005 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome)". Actually documents lysosomal degradation, not Golgi localization. Reason: Non-core degradation localization. Despite Golgi annotation, this pathway actually describes lysosomal heparanase activity. Both Golgi biosynthesis and lysosomal degradation are non-core localizations representing biosynthetic/catabolic endpoints rather than functional sites. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-1889955 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "B3GAT dimers transfer GlcA to tetrasaccharide linker". Documents HS linker biosynthesis in Golgi. Reason: Non-core biosynthetic localization. Golgi HS linker synthesis is transient biosynthetic processing, not functional localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-1889978 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "B3GALT6 transfers Gal to the tetrasaccharide linker". Documents HS linker biosynthesis in Golgi. Reason: Non-core biosynthetic localization. Golgi HS linker synthesis is transient biosynthetic processing, not functional localization. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-3560802 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Defective B3GAT3 does not transfer GlcA to tetrasaccharide linker". Documents disease mutations affecting HS biosynthesis. Reason: Non-core biosynthetic localization. Documents disease mutations in HS biosynthesis enzymes, not core perlecan function. Golgi is transient biosynthetic compartment. |
| GO:0005796 Golgi lumen | TAS Reactome:R-HSA-4420365 | KEEP AS NON CORE | Summary: TAS annotation from Reactome pathway "Defective B3GALT6 does not transfer Gal to the tetrasaccharide linker". Documents disease mutations affecting HS biosynthesis. Reason: Non-core biosynthetic localization. Documents disease mutations in HS biosynthesis enzymes, not core perlecan function. Golgi is transient biosynthetic compartment. |
| GO:0005515 protein binding | IPI PMID:12604605 Perlecan protein core interacts with extracellular matrix pr... | MODIFY | Summary: IPI annotation showing interaction with ECM1 (Q16610). PMID:12604605 demonstrates perlecan C-terminus interacts with ECM1 C-terminus, a glycoprotein involved in bone formation and angiogenesis. Reason: Protein binding is uninformative. Better terms would capture perlecan's specific molecular functions such as "extracellular matrix structural constituent" or molecular adaptor activity for organizing ECM components. Proposed replacements: extracellular matrix structural constituent molecular adaptor activity Supporting Evidence: PMID:12604605 Perlecan protein core interacts with extracellular matrix protein 1 (ECM1), a glycoprotein involved in bone formation and angiogenesis. |
| GO:0005515 protein binding | IPI PMID:11956183 The type XIII collagen ectodomain is a 150-nm rod and capabl... | MODIFY | Summary: IPI annotation showing interaction with COL13A1 (Q5TAT6). PMID:11956183 demonstrates type XIII collagen ectodomain binds perlecan along with fibronectin, nidogen-2, and heparin. Reason: Protein binding is uninformative. Better terms would capture perlecan's specific role in extracellular matrix organization through binding multiple ECM components including collagens. Proposed replacements: extracellular matrix structural constituent molecular adaptor activity Supporting Evidence: PMID:11956183 The type XIII collagen ectodomain is a 150-nm rod and capable of binding to fibronectin, nidogen-2, perlecan, and heparin. |
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