GPC2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0015026 coreceptor activity	NAS UniProtKB:Q8N158	NEW	Summary: GPC2 functions as a signaling co-receptor at the cell surface, modulating ligand-receptor interactions through its heparan sulfate chains. It binds growth factors such as PTN and MDK to regulate neurite outgrowth signaling. This is the core molecular function of GPC2. Reason: This annotation captures the core molecular function of GPC2 as described in UniProt and the deep research literature. As a GPI-anchored HSPG, GPC2 serves as a cell-surface co-receptor that modulates ligand-receptor interactions. Supporting Evidence: UniProtKB:Q8N158 Interacts (via heparan sulfate) with PTN; this interaction promotes neurite outgrowth through binding of PTN with chondroitin sulfate of proteoglycans file:human/GPC2/GPC2-deep-research-falcon.md As a GPI-anchored HSPG, GPC2 serves as a cell-surface co-receptor that modulates ligand-receptor interactions
GO:0016477 cell migration	IBA GO_REF:0000033	ACCEPT	Summary: GPC2 is annotated to cell migration based on phylogenetic inference (IBA). Glypicans are known to modulate cell motility through their effects on growth factor signaling. UniProt states GPC2 may fulfill a function related to the motile behaviors of developing neurons. While the annotation is phylogenetically supported and consistent with glypican family function, direct experimental evidence for human GPC2 in cell migration is limited. Reason: The IBA annotation is well-supported by the known role of glypicans in modulating cell motility and the phylogenetic evidence from orthologs. UniProt independently notes the potential role in neuronal motile behaviors. Supporting Evidence: UniProtKB:Q8N158 May fulfill a function related to the motile behaviors of developing neurons
GO:0031012 extracellular matrix	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: GPC2 is annotated to extracellular matrix based on phylogenetic inference. As a GPI-anchored heparan sulfate proteoglycan, GPC2 is primarily localized to the cell surface, not as a structural component of the extracellular matrix. While glypicans can interact with ECM components and may transiently associate with the ECM, particularly after shedding, this annotation conflates the secreted form with typical ECM structural components. Reason: While GPC2 may interact with ECM components or be shed into the extracellular space, its primary localization is as a GPI-anchored cell surface protein. The ECM annotation is not incorrect but represents a secondary localization rather than the core function. Supporting Evidence: UniProtKB:Q8N158 Cell membrane {ECO:0000250}; Lipid-anchor, GPI- anchor {ECO:0000250}; Extracellular side {ECO:0000250}
GO:0009986 cell surface	IBA GO_REF:0000033	ACCEPT	Summary: GPC2 is annotated to cell surface based on phylogenetic inference. This is strongly supported by the known biology of glypicans as GPI-anchored proteins that localize to the external surface of the plasma membrane. UniProt confirms GPC2 has a GPI-anchor site and localizes to the cell membrane extracellular side. Recent cancer research confirms GPC2 as a cell-surface target for immunotherapy. Reason: The cell surface localization is a core feature of GPC2 function as a GPI-anchored signaling co-receptor. This is supported by UniProt, phylogenetic inference, and extensive cancer immunotherapy literature demonstrating cell surface expression. Supporting Evidence: UniProtKB:Q8N158 Cell membrane {ECO:0000250}; Lipid-anchor, GPI- anchor {ECO:0000250}; Extracellular side {ECO:0000250} file:human/GPC2/GPC2-deep-research-falcon.md GPC2 is cell-surface localized and GPI-anchored, consistent with glypican family features and its role as an extracellular signaling co-receptor
GO:0045202 synapse	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: GPC2 is annotated to synapse localization based on phylogenetic inference from orthologs. The related glypican GPC4 is known to be involved in synapse formation and function. GPC2 is expressed in developing neurons and promotes neurite outgrowth, which could involve synaptic localization. However, direct evidence for human GPC2 synaptic localization is limited. Reason: While the IBA annotation is phylogenetically supported and consistent with GPC2's role in neuronal development, synaptic localization is not the primary/core localization for GPC2. The core localization is general cell surface. Supporting Evidence: UniProtKB:Q8N158 May fulfill a function related to the motile behaviors of developing neurons
GO:1905475 regulation of protein localization to membrane	IBA GO_REF:0000033	ACCEPT	Summary: GPC2 is annotated to regulation of protein localization to membrane based on phylogenetic inference. As a cell-surface proteoglycan co-receptor, glypicans can influence the localization and clustering of signaling receptors at the membrane. The UniProt entry notes that MDK interaction with GPC2 induces GPC2 clustering through heparan sulfate chain. Reason: The annotation is consistent with the known function of glypicans as signaling co-receptors that can modulate receptor localization and clustering at the cell surface. The MDK-induced GPC2 clustering provides mechanistic support. Supporting Evidence: UniProtKB:Q8N158 this interaction induces GPC2 clustering through heparan sulfate chain
GO:0007224 smoothened signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: GPC2 is annotated to smoothened signaling pathway based on phylogenetic inference. Glypicans are well-established modulators of Hedgehog/smoothened signaling, with the Drosophila glypican Dally-like being essential for Hedgehog signaling. Mammalian glypicans including GPC2 are believed to function similarly in modulating Hedgehog pathway components. Reason: The role of glypicans in smoothened/Hedgehog signaling is well-established across species and the IBA inference from phylogenetic data is appropriate for this conserved function. Supporting Evidence: GO_REF:0000033 Phylogenetic inference from glypican orthologs known to modulate Hedgehog signaling
GO:0005576 extracellular region	IEA GO_REF:0000044	ACCEPT	Summary: GPC2 is annotated to extracellular region based on UniProt subcellular location mapping. The annotation is appropriate as GPC2 exists as a GPI-anchored protein on the extracellular face of the membrane, and can also be shed as Secreted glypican-2 into the extracellular space. Reason: The annotation is correct for both the GPI-anchored form (exposed to extracellular space) and the secreted/shed form. UniProt confirms both localizations. Supporting Evidence: UniProtKB:Q8N158 RecName: Full=Secreted glypican-2
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: GPC2 is annotated to plasma membrane based on automated annotation methods. This is correct for the mature GPI-anchored form of the protein, which is attached to the external leaflet of the plasma membrane. Reason: GPC2 is a GPI-anchored protein that localizes to the plasma membrane. UniProt confirms this localization. Supporting Evidence: UniProtKB:Q8N158 Cell membrane {ECO:0000250}; Lipid-anchor, GPI- anchor {ECO:0000250}; Extracellular side {ECO:0000250}
GO:0009966 regulation of signal transduction	IEA GO_REF:0000002	ACCEPT	Summary: GPC2 is annotated to regulation of signal transduction based on InterPro glypican domain mapping. This is appropriate as glypicans are established signaling co-receptors that modulate ligand-receptor interactions. GPC2 specifically interacts with PTN and MDK to regulate signaling pathways affecting neurite outgrowth. Reason: The annotation correctly captures the signaling co-receptor function of GPC2. This is a core function of all glypicans and is supported by specific interaction data for GPC2 with growth factors PTN and MDK. Supporting Evidence: UniProtKB:Q8N158 Interacts (via heparan sulfate) with PTN; this interaction promotes neurite outgrowth file:human/GPC2/GPC2-deep-research-falcon.md As a GPI-anchored HSPG, GPC2 serves as a cell-surface co-receptor that modulates ligand-receptor interactions
GO:0031012 extracellular matrix	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Duplicate annotation of extracellular matrix via InterPro mapping. Same assessment as the IBA annotation - GPC2 is primarily a cell-surface protein, though it may interact with ECM components. Reason: Same rationale as IBA annotation - ECM is a secondary/non-core localization for this GPI-anchored cell surface proteoglycan. Supporting Evidence: UniProtKB:Q8N158 Cell membrane {ECO:0000250}; Lipid-anchor, GPI- anchor {ECO:0000250}; Extracellular side {ECO:0000250}
GO:0043202 lysosomal lumen	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: GPC2 is annotated to lysosomal lumen based on ARBA machine learning. This likely reflects the degradation pathway for heparan sulfate proteoglycans, where they are internalized and degraded in lysosomes. This is part of the normal turnover of the protein rather than a functional localization. Reason: Lysosomal localization represents the degradation pathway for GPC2, not its functional site. The primary function occurs at the cell surface. Supporting Evidence: GO_REF:0000117 ARBA machine learning prediction for lysosomal localization based on proteoglycan turnover patterns
GO:0098552 side of membrane	IEA GO_REF:0000043	MODIFY	Summary: GPC2 is annotated to side of membrane based on UniProt keyword mapping. This is a very general term; the more specific annotation should be external side of plasma membrane given the GPI-anchor localization. Reason: While not incorrect, this annotation is too general. The protein is specifically on the external side of the plasma membrane via GPI anchor. Proposed replacements: external side of plasma membrane Supporting Evidence: UniProtKB:Q8N158 Extracellular side {ECO:0000250}
GO:0007224 smoothened signaling pathway	IEA GO_REF:0000107	ACCEPT	Summary: Duplicate annotation of smoothened signaling pathway via Ensembl Compara ortholog transfer from rat GPC2 (P51653). Same assessment as IBA annotation. Reason: Consistent with IBA annotation and supported by known glypican biology in Hedgehog/smoothened signaling modulation. Supporting Evidence: GO_REF:0000107 Automatic transfer from rat ortholog P51653 based on Ensembl Compara
GO:0010976 positive regulation of neuron projection development	IEA GO_REF:0000107	ACCEPT	Summary: GPC2 is annotated to positive regulation of neuron projection development based on ortholog transfer from rat. This is strongly supported by UniProt which describes GPC2 interactions with PTN and MDK that promote neurite outgrowth. Reason: The annotation is well-supported by the mechanistic data on GPC2-PTN and GPC2-MDK interactions promoting neurite outgrowth. UniProt explicitly states this function. Supporting Evidence: UniProtKB:Q8N158 this interaction promotes neurite outgrowth through binding of PTN with chondroitin sulfate of proteoglycans UniProtKB:Q8N158 this interaction induces neuronal cell adhesion and neurite outgrowth
GO:0030182 neuron differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: GPC2 is annotated to neuron differentiation based on Ensembl ortholog transfer. Given GPC2's role in neurite outgrowth and its expression in developing neurons, this annotation is reasonable though somewhat general. Reason: While GPC2 promotes neurite outgrowth which is part of neuron differentiation, the more specific annotation (positive regulation of neuron projection development) better captures its function. This broader term is kept as non-core. Supporting Evidence: UniProtKB:Q8N158 May fulfill a function related to the motile behaviors of developing neurons
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-9940993	KEEP AS NON CORE	Summary: GPC2 is annotated to Golgi lumen based on Reactome pathway annotations for heparan sulfate proteoglycan biosynthesis. As a proteoglycan, GPC2 transits through the Golgi where its heparan sulfate chains are synthesized and modified. This represents biosynthetic trafficking rather than the functional site. Reason: Golgi localization reflects the biosynthetic pathway for HS-GAG addition, not the functional localization of mature GPC2 at the cell surface. Supporting Evidence: Reactome:R-HSA-9940993 PXYLP1 dephosphorylates Xyl moiety
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-9941039	KEEP AS NON CORE	Summary: Duplicate Golgi lumen annotation from Reactome FAM20B phosphorylation pathway. Same assessment as above. Reason: Biosynthetic localization, not functional site. Supporting Evidence: Reactome:R-HSA-9941039 FAM20B phosphorylates Xyl moiety
GO:0010976 positive regulation of neuron projection development	ISS GO_REF:0000024	ACCEPT	Summary: GPC2 is annotated to positive regulation of neuron projection development by sequence similarity (ISS) transfer. This is consistent with the IEA annotation and supported by mechanistic data on PTN and MDK interactions. Reason: Core function annotation consistent with known GPC2 biology. The ISS annotation provides additional support to the IEA annotation. Supporting Evidence: UniProtKB:Q8N158 this interaction induces neuronal cell adhesion and neurite outgrowth
GO:0005515 protein binding	IPI PMID:29162697 EB1-binding-myomegalin protein complex promotes centrosomal ...	REMOVE	Summary: GPC2 is annotated to protein binding based on high-throughput interactome analysis. The cited paper (PMID:29162697) is about EB1-binding-myomegalin complex and centrosomal microtubules - it does not appear to directly study GPC2 function. This appears to be from a large-scale protein-protein interaction screen. The annotation is too general to be informative. Reason: Per curation guidelines, protein binding does not provide informative functional annotation. The cited paper does not directly study GPC2, and the interactions detected in high-throughput screens lack specificity for GO annotation purposes. Supporting Evidence: PMID:29162697 EB1-binding-myomegalin protein complex promotes centrosomal microtubules functions
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-1878002	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome xylosyltransferase pathway for GAG linker biosynthesis. Non-core biosynthetic localization. Reason: Biosynthetic trafficking pathway, not functional localization. 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: Golgi lumen annotation from Reactome B3GAT pathway. Reason: Biosynthetic pathway localization. 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: Golgi lumen annotation from Reactome B3GALT6 pathway. Reason: Biosynthetic pathway localization. Supporting Evidence: Reactome:R-HSA-1889978 B3GALT6 transfers Gal to the tetrasaccharide linker
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2022851	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome EXT1:EXT2 heparan chain extension pathway. Reason: Biosynthetic pathway localization. Supporting Evidence: Reactome:R-HSA-2022851 EXT1:EXT2 transfers GlcNAc to the heparan chain
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2022856	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome heparan sulfate biosynthesis. Reason: Biosynthetic pathway localization. Supporting Evidence: Reactome:R-HSA-2022856 EXT1:EXT2 transfers GlcA to heparan
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2022860	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome NDST sulfation pathway. Reason: Biosynthetic pathway localization. Supporting Evidence: Reactome:R-HSA-2022860 NDST1-4 can sulfate a glucosamine residue in heparan
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2022887	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome NDST deacetylation pathway. Reason: Biosynthetic pathway localization. Supporting Evidence: Reactome:R-HSA-2022887 NDST1-4 N-deacetylates GlcNAc residues in heparan
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2024108	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome HSPG secretion pathway. Reason: Biosynthetic/secretory pathway localization. Supporting Evidence: Reactome:R-HSA-2024108 Some HSPGs are secreted to the plasma membrane
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2076383	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome HS3ST1 sulfation pathway. Reason: Biosynthetic pathway localization. Supporting Evidence: Reactome:R-HSA-2076383 HS3ST1 sulfates GlcN at C3 in heparan sulfate
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2076392	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome heparan biosynthesis. Reason: Biosynthetic pathway localization. Supporting Evidence: Reactome:R-HSA-2076392 EXT1:EXT2 transfers GlcA to heparan
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2076419	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome HS6ST sulfation pathway. Reason: Biosynthetic pathway localization. Supporting Evidence: Reactome:R-HSA-2076419 HS6STs sulfate GlcN at C6 in heparan sulfate/heparin
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2076508	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome HS2ST1 sulfation pathway. Reason: Biosynthetic pathway localization. Supporting Evidence: Reactome:R-HSA-2076508 HS2ST1 trimer sulfates IdoA at C2 in heparan sulfate
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-2076611	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome HS3ST2-6 sulfation pathway. Reason: Biosynthetic pathway localization. Supporting Evidence: Reactome:R-HSA-2076611 HS3ST2-6 sulfate GlcN at C3 in heparan sulfate
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3560802	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome defective B3GAT3 pathway. Reason: Biosynthetic pathway localization (disease context). Supporting Evidence: Reactome:R-HSA-3560802 Defective B3GAT3 does not transfer GlcA to tetrasaccharide linker
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3656254	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome defective EXT2 pathway. Reason: Biosynthetic pathway localization (disease context). Supporting Evidence: Reactome:R-HSA-3656254 Defective EXT2 (in EXT1:EXT2) does not transfer GlcNAc to the heparan chain
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3656257	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome defective EXT1 pathway. Reason: Biosynthetic pathway localization (disease context). Supporting Evidence: Reactome:R-HSA-3656257 Defective EXT1 (in EXT1:EXT2) does not transfer GlcA to heparan
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3656261	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome defective EXT1 pathway. Reason: Biosynthetic pathway localization (disease context). Supporting Evidence: Reactome:R-HSA-3656261 Defective EXT1 (in EXT1:EXT2) does not transfer GlcNAc to the heparan chain
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-3656267	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome defective EXT2 pathway. Reason: Biosynthetic pathway localization (disease context). Supporting Evidence: Reactome:R-HSA-3656267 Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparan
GO:0005886 plasma membrane	TAS Reactome:R-HSA-1678694	ACCEPT	Summary: Plasma membrane annotation from Reactome HPSE2 binding pathway. Reason: Plasma membrane is the core functional localization of GPC2 as a GPI-anchored signaling co-receptor. Supporting Evidence: Reactome:R-HSA-1678694 Heparanase 2 (HPSE2) binds heparan sulfate proteoglycans
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2024084	ACCEPT	Summary: Plasma membrane annotation from Reactome HS-GAG degradation pathway. Reason: Core localization annotation. Supporting Evidence: Reactome:R-HSA-2024084 HS-GAGs translocate to the lysosome for degradation
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2024108	ACCEPT	Summary: Plasma membrane annotation from Reactome HSPG secretion pathway. Reason: Core localization annotation. Supporting Evidence: Reactome:R-HSA-2024108 Some HSPGs are secreted to the plasma membrane
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2404131	ACCEPT	Summary: Plasma membrane annotation from Reactome retinoid transport pathway. Reason: Core localization annotation. Supporting Evidence: Reactome:R-HSA-2404131 LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2423785	ACCEPT	Summary: Plasma membrane annotation from Reactome retinoid metabolism pathway. Reason: Core localization annotation. Supporting Evidence: Reactome:R-HSA-2423785 CR:atREs binds apoE and HSPG
GO:0005886 plasma membrane	TAS Reactome:R-HSA-2429643	ACCEPT	Summary: Plasma membrane annotation from Reactome retinoid metabolism pathway. Reason: Core localization annotation. Supporting Evidence: Reactome:R-HSA-2429643 NREH hydrolyses atREs (HSPG:apoE) to atROL and FAs
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9694579	ACCEPT	Summary: Plasma membrane annotation from Reactome SARS-CoV-2 entry pathway. HSPGs including glypicans can serve as attachment factors for viral entry. Reason: The localization is correct and represents the core plasma membrane localization, even though this particular pathway involves viral exploitation. Supporting Evidence: Reactome:R-HSA-9694579 Spike glycoprotein of SARS-CoV-2 binds ACE2 on host cell
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9694661	ACCEPT	Summary: Plasma membrane annotation from Reactome SARS-CoV-2 entry pathway. Reason: Core localization annotation. Supporting Evidence: Reactome:R-HSA-9694661 TMPRSS2 Mediated SARS-CoV-2 Spike Protein Cleavage and Endocytosis
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9698988	ACCEPT	Summary: Plasma membrane annotation from Reactome SARS-CoV-2 entry pathway. Reason: Core localization annotation. Supporting Evidence: Reactome:R-HSA-9698988 Direct Host Cell Membrane Membrane Fusion and Release of SARS-CoV-2 Nucleocapsid
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9699007	ACCEPT	Summary: Plasma membrane annotation from Reactome SARS-CoV-2 entry pathway. Reason: Core localization annotation. Supporting Evidence: Reactome:R-HSA-9699007 FURIN Mediated SARS-CoV-2 Spike Protein Cleavage and Endocytosis
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9836899	ACCEPT	Summary: Plasma membrane annotation from Reactome RSV attachment pathway. sG binds to HSPGs. Reason: Core localization annotation. Supporting Evidence: Reactome:R-HSA-9836899 The secreted soluble isoform of hRSV G protein (sG) binds to proteoglycans on the surface of host cells
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1667005	KEEP AS NON CORE	Summary: Lysosomal lumen annotation from Reactome heparanase cleavage pathway. Reason: Degradation pathway localization, not functional site. Supporting Evidence: Reactome:R-HSA-1667005 Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-2024084	KEEP AS NON CORE	Summary: Lysosomal lumen annotation from Reactome HS-GAG degradation pathway. Reason: Degradation pathway localization. Supporting Evidence: Reactome:R-HSA-2024084 HS-GAGs translocate to the lysosome for degradation
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-1889981	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome B4GALT7 pathway. Reason: Biosynthetic pathway localization. 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-3560804	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome defective B4GALT7 pathway. Reason: Biosynthetic pathway localization (disease context). 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-9036285	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome defective EXT1 pathway. Reason: Biosynthetic pathway localization (disease context). Supporting Evidence: Reactome:R-HSA-9036285 Defective EXT1 (in EXT1:EXT2) does not transfer GlcA to heparan
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-9036289	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome defective EXT2 pathway. Reason: Biosynthetic pathway localization (disease context). Supporting Evidence: Reactome:R-HSA-9036289 Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparan
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-9953259	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome EXTL3 pathway. Reason: Biosynthetic pathway localization. Supporting Evidence: Reactome:R-HSA-9953259 EXTL3 dimer transfers GlcNAc to the GAG linker
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-1667005	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome heparanase pathway. Reason: This relates to the processing pathway for HSPGs. Supporting Evidence: Reactome:R-HSA-1667005 Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan
GO:0005796 Golgi lumen	TAS Reactome:R-HSA-4420365	KEEP AS NON CORE	Summary: Golgi lumen annotation from Reactome defective B3GALT6 pathway. Reason: Biosynthetic pathway localization (disease context). Supporting Evidence: Reactome:R-HSA-4420365 Defective B3GALT6 does not transfer Gal to the tetrasaccharide linker
GO:0005783 endoplasmic reticulum	IDA GO_REF:0000054	KEEP AS NON CORE	Summary: GPC2 is annotated to endoplasmic reticulum based on LIFEdb fusion protein localization data. As a secreted/membrane protein, GPC2 would transit through the ER during biosynthesis. This represents a biosynthetic localization. Reason: ER localization represents the biosynthetic pathway for GPC2. The functional localization is at the plasma membrane. Supporting Evidence: GO_REF:0000054 Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells

Core Functions

GPC2 functions as a signaling co-receptor at the cell surface, modulating ligand-receptor interactions through its heparan sulfate chains. It binds growth factors such as PTN and MDK to regulate neurite outgrowth signaling.

Molecular Function:

coreceptor activity

Directly Involved In:

positive regulation of neuron projection development smoothened signaling pathway

Cellular Locations:

cell surface

Supporting Evidence:

UniProtKB:Q8N158
Interacts (via heparan sulfate) with PTN; this interaction promotes neurite outgrowth
UniProtKB:Q8N158
this interaction induces neuronal cell adhesion and neurite outgrowth

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000054

Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:29162697

EB1-binding-myomegalin protein complex promotes centrosomal microtubules functions.

Paper focuses on EB1-binding complexes and centrosomal microtubules, not GPC2 function directly. GPC2 appears as part of high-throughput interactome data.

UniProtKB:Q8N158

UniProt entry for human Glypican-2

GPC2 is a GPI-anchored cell surface heparan sulfate proteoglycan
Interacts with PTN and MDK via heparan sulfate to promote neurite outgrowth
May function in developing neuron motility

file:human/GPC2/GPC2-deep-research-falcon.md

Falcon deep research on GPC2

GPC2 is a GPI-anchored HSPG functioning as a signaling co-receptor
Exhibits oncofetal expression pattern with re-expression in neuroblastoma
Expression is MYCN-regulated in neuroblastoma
Functions in WNT-associated signaling pathways

Reactome:R-HSA-1667005

Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome)

Reactome:R-HSA-1678694

Heparanase 2 (HPSE2) binds heparan sulfate proteoglycans

Reactome:R-HSA-1878002

XYLTs transfer Xyl to core protein

Reactome:R-HSA-1889955

B3GAT dimers transfer GlcA to tetrasaccharide linker

Reactome:R-HSA-1889978

B3GALT6 transfers Gal to the tetrasaccharide linker

Reactome:R-HSA-1889981

B4GALT7 transfers Gal group to xylosyl-unit of the tetrasaccharide linker

Reactome:R-HSA-2022851

EXT1:EXT2 transfers GlcNAc to the heparan chain

Reactome:R-HSA-2022856

EXT1:EXT2 transfers GlcA to heparan

Reactome:R-HSA-2022860

NDST1-4 can sulfate a glucosamine residue in heparan to form heparan sulfate (HS)

Reactome:R-HSA-2022887

NDST1-4 N-deacetylates GlcNAc residues in heparan

Reactome:R-HSA-2024084

HS-GAGs translocate to the lysosome for degradation

Reactome:R-HSA-2024108

Some HSPGs are secreted to the plasma membrane

Reactome:R-HSA-2076383

HS3ST1 sulfates GlcN at C3 in heparan sulfate

Reactome:R-HSA-2076392

EXT1:EXT2 transfers GlcA to heparan

Reactome:R-HSA-2076419

HS6STs sulfate GlcN at C6 in heparan sulfate/heparin

Reactome:R-HSA-2076508

HS2ST1 trimer sulfates IdoA at C2 in heparan sulfate

Reactome:R-HSA-2076611

HS3ST2-6 sulfate GlcN at C3 in heparan sulfate

Reactome:R-HSA-2404131

LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol

Reactome:R-HSA-2423785

CR:atREs binds apoE and HSPG

Reactome:R-HSA-2429643

NREH hydrolyses atREs (HSPG:apoE) to atROL and FAs

Reactome:R-HSA-3560802

Defective B3GAT3 does not transfer GlcA to tetrasaccharide linker

Reactome:R-HSA-3560804

Defective B4GALT7 does not transfer Gal to xylosyl-unit of the tetrasaccharide linker

Reactome:R-HSA-3656254

Defective EXT2 (in EXT1:EXT2) does not transfer GlcNAc to the heparan chain

Reactome:R-HSA-3656257

Defective EXT1 (in EXT1:EXT2) does not transfer GlcA to heparan

Reactome:R-HSA-3656261

Defective EXT1 (in EXT1:EXT2) does not transfer GlcNAc to the heparan chain

Reactome:R-HSA-3656267

Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparan

Reactome:R-HSA-4420365

Defective B3GALT6 does not transfer Gal to the tetrasaccharide linker

Reactome:R-HSA-9036285

Defective EXT1 (in EXT1:EXT2) does not transfer GlcA to heparan

Reactome:R-HSA-9036289

Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparan

Reactome:R-HSA-9694579

Spike glycoprotein of SARS-CoV-2 binds ACE2 on host cell

Reactome:R-HSA-9694661

TMPRSS2 Mediated SARS-CoV-2 Spike Protein Cleavage and Endocytosis

Reactome:R-HSA-9698988

Direct Host Cell Membrane Membrane Fusion and Release of SARS-CoV-2 Nucleocapsid

Reactome:R-HSA-9699007

FURIN Mediated SARS-CoV-2 Spike Protein Cleavage and Endocytosis

Reactome:R-HSA-9836899

sG binds to HSPGs

Reactome:R-HSA-9940993

PXYLP1 dephosphorylates Xyl moiety

Reactome:R-HSA-9941039

FAM20B phosphorylates Xyl moiety

Reactome:R-HSA-9953259

EXTL3 dimer transfers GlcNAc to the GAG linker

Deep Research

Falcon

(GPC2-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 11 citations 2025-12-27T23:46:23.971310

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan and verification
We verified the research target as human glypican-2 (GPC2), a member of the glypican family of heparan sulfate proteoglycans, consistent with the user-provided UniProt record (Q8N158) and with recent literature that describes GPC2 as a glycosylphosphatidylinositol (GPI)-anchored cell-surface signaling co-receptor (human context, glypican family) (day2025definingtheextracellular pages 3-4, giudice2025d3gpc2–directedcart pages 2-4).

1) Key concepts and definitions
- Molecular identity and family: GPC2 is a glypican-family heparan sulfate proteoglycan (HSPG) that localizes to the plasma membrane via a GPI anchor. Glypicans serve as signaling co-receptors by presenting heparan sulfate chains that modulate ligand-receptor interactions at the cell surface (day2025definingtheextracellular pages 3-4). In cancer biology, GPC2 is characterized as an oncofetal, cell-surface oncoprotein with differential expression between normal and tumor tissues (giudice2025d3gpc2–directedcart pages 2-4, giudice2025d3gpc2–directedcart pages 20-22).
- Cellular localization: GPC2 is cell-surface localized and GPI-anchored, consistent with glypican family features and its role as an extracellular signaling co-receptor (day2025definingtheextracellular pages 3-4). In preclinical models, it is readily detected on the surface of neuroblastoma cells by flow cytometry and immunohistochemistry (giudice2025d3gpc2–directedcart pages 1-2).
- Regulatory context: GPC2 expression is MYCN-regulated in neuroblastoma, supporting its linkage to aggressive disease biology (giudice2025d3gpc2–directedcart pages 1-2, giudice2025d3gpc2–directedcart pages 20-22).
- Pathway roles: As a GPI-anchored HSPG, GPC2 functions as a signaling co-receptor implicated in canonical oncogenic pathways (e.g., WNT signaling), aligning with its role in promoting proliferation and tumor growth in neuroblastoma (day2025definingtheextracellular pages 3-4, alkhazal2025emergingclinicaland pages 5-6).

2) Recent developments and latest research (emphasis 2023–2024)
- Translational immunotherapy targeting GPC2: Multiple groups have advanced GPC2-directed therapeutics, including fully human antibody–drug conjugates (ADCs) and chimeric antigen receptor (CAR) T cells. A comprehensive 2025 preclinical translation study (data generated 2021–2024) reported D3-GPC2 CAR T cells that were selective and potent against neuroblastoma and also active against GPC2-positive small cell lung cancer (SCLC) models; these data supported the first-in-human pediatric trial NCT05650749 (Clinical Cancer Research, Sep 2025; DOI: 10.1158/1078-0432.ccr-25-0089) (giudice2025d3gpc2–directedcart pages 1-2, giudice2025d3gpc2–directedcart pages 2-4, giudice2025d3gpc2–directedcart pages 20-22). URL: https://doi.org/10.1158/1078-0432.ccr-25-0089 (published Sep 2025).
- Brain tumor applications: In 2025, an NPJ Precision Oncology study profiled extracellular matrix and cell-surface landscapes in pediatric/adult gliomas and prioritized GPC2 among top immunotherapy targets; the authors validated GPC2-directed CAR activity in diffuse intrinsic pontine glioma (DIPG) models and summarized prior evidence of efficacy in neuroblastoma and medulloblastoma, including transient mRNA GPC2-CAR T approaches (NPJ Precision Oncology, Jun 2025; DOI: 10.1038/s41698-025-00956-z) (day2025definingtheextracellular pages 3-4). URL: https://doi.org/10.1038/s41698-025-00956-z (published Jun 2025).
- Cytokine augmentation of GPC2-CAR T: A 2024 JITC study reported that long-acting IL-7 (rhIL‑7‑hyFc, NT‑I7) enhances the efficacy of CAR T cells targeting multiple solid tumor antigens including GPC2, by increasing CD4+ CAR occupancy, expansion, and stem-like memory phenotypes while reducing exhaustion markers; this improved efficacy in low-antigen-density contexts across several solid tumor xenografts, including neuroblastoma (Journal for Immunotherapy of Cancer, Jul 2024; DOI: 10.1136/jitc-2024-008989) (giudice2025d3gpc2–directedcart pages 13-14). URL: https://doi.org/10.1136/jitc-2024-008989 (published Jul 2024).
- Field perspective/reviews (2025, reflecting 2023–2024 advances): Reviews summarize GPC2 as a GPI-anchored glypican oncoprotein, note its WNT-associated signaling role in neuroblastoma, correlations between high GPC2 and worse outcomes, and ongoing optimization of CAR constructs and combination strategies (Frontiers in Oncology, Mar 2025; DOI: 10.3389/fonc.2025.1553511) (alkhazal2025emergingclinicaland pages 5-6). URL: https://doi.org/10.3389/fonc.2025.1553511 (published Mar 2025).

3) Current applications and real-world implementations
- CAR T cells (neuroblastoma and beyond): D3-GPC2 CAR T cells (second-generation designs with CD28 or 4‑1BB costimulation) show potent, antigen-specific cytotoxicity in vitro and drive significant neuroblastoma xenograft regressions in vivo with no activation against multiple normal human primary cell types and no GPC2-CAR–related toxicities on necropsy in murine models; activity extends to GPC2-positive SCLC (Clinical Cancer Research, 2025) (giudice2025d3gpc2–directedcart pages 1-2, giudice2025d3gpc2–directedcart pages 13-14). URL: https://doi.org/10.1158/1078-0432.ccr-25-0089 (published Sep 2025).
- ADCs and other antibody-based approaches: D3-derived ADCs have shown preclinical efficacy in neuroblastoma and SCLC; the D3 binder recognizes a tumor-selective, conformational epitope and has been engineered into ADCs and CARs, enabling cross-species preclinical modeling due to conserved epitope structure (Clinical Cancer Research, 2025; synthesis of earlier work) (giudice2025d3gpc2–directedcart pages 16-18, giudice2025d3gpc2–directedcart pages 19-20). URL: https://doi.org/10.1158/1078-0432.ccr-25-0089 (published Sep 2025).
- CNS tumors: Cell-surface proteomic and orthogonal analyses identify GPC2 as a prioritized immunotherapy target in pediatric high-grade glioma and DIPG, with in vitro validation of GPC2-CAR T cell killing of DIPG models, supporting extension of GPC2 targeting beyond neuroblastoma (NPJ Precision Oncology, 2025) (day2025definingtheextracellular pages 3-4). URL: https://doi.org/10.1038/s41698-025-00956-z (published Jun 2025).

4) Expert opinions and analysis from authoritative sources
- Translational credentialing: Giudice et al. conclude that GPC2 is a bona fide CAR T target meeting optimal solid-tumor target criteria—differential tumor expression, limited normal tissue expression (oncofetal pattern), essentiality for tumor growth, and epitope suitable for selective targeting—supporting first-in-human evaluation (Clinical Cancer Research, 2025) (giudice2025d3gpc2–directedcart pages 2-4, giudice2025d3gpc2–directedcart pages 20-22).
- CNS tumor immunotherapy perspective: ECM-focused target discovery and prioritization nominate GPC2 highly for pediatric CNS tumors, with functional CAR validation; the authors advocate evaluation of low-affinity GPC2 CARs to balance efficacy with safety in the CNS (NPJ Precision Oncology, 2025) (day2025definingtheextracellular pages 3-4).
- Field review of neuroblastoma targeting: Reviews emphasize heterogeneity of GPC2 expression, enrichment in high-risk disease, WNT-associated growth signaling, and the need for biomarker-driven selection and persistence-enhancing strategies for GPC2 CAR T cells (Frontiers in Oncology, 2025) (alkhazal2025emergingclinicaland pages 5-6).

5) Relevant statistics and data from recent studies
- Selectivity and safety in vitro/in vivo: D3-GPC2 CAR T cells did not activate or kill across nine primary human normal cell lines in co-incubation assays and produced significant regression of GPC2-positive neuroblastoma xenografts in mice without observed treatment-related toxicities on necropsy (Clinical Cancer Research, 2025) (giudice2025d3gpc2–directedcart pages 1-2). URL: https://doi.org/10.1158/1078-0432.ccr-25-0089 (published Sep 2025).
- Xenograft regression kinetics: In multiple MYCN-amplified PDX models (e.g., NB‑1643, COG‑N‑421x), D3-GPC2 CAR constructs (4‑1BBζ or CD28ζ) induced rapid tumor regressions, with responses evident within approximately one week and improved progression-free survival; activity was comparable to GD2 CARs in an aggressive model (Clinical Cancer Research, 2025) (giudice2025d3gpc2–directedcart pages 13-14). URL: https://doi.org/10.1158/1078-0432.ccr-25-0089 (published Sep 2025).
- Breadth of tumor types: Preclinical activity extends to SCLC models in vivo, suggesting broader applicability beyond pediatric solid tumors (Clinical Cancer Research, 2025) (giudice2025d3gpc2–directedcart pages 1-2). URL: https://doi.org/10.1158/1078-0432.ccr-25-0089 (published Sep 2025).
- Cytokine augmentation (2024): rhIL‑7‑hyFc (NT‑I7) combined with GPC2 CAR T cells enhanced CAR T expansion, reduced exhaustion markers (PD‑1, LAG‑3), increased stem-like memory phenotypes, and improved efficacy against tumors with low antigen density across several solid tumor xenografts, including neuroblastoma (JITC, Jul 2024) (giudice2025d3gpc2–directedcart pages 13-14). URL: https://doi.org/10.1136/jitc-2024-008989 (published Jul 2024).

Biology and function synthesis
- Functional role: As a GPI-anchored HSPG, GPC2 serves as a cell-surface co-receptor that modulates ligand-receptor interactions, prominently in WNT signaling pertinent to neuroblastoma growth. Its expression is developmentally regulated (oncofetal), reactivated or amplified in tumors, and in neuroblastoma is transcriptionally driven by MYCN. These properties, together with restricted normal tissue expression, make it a compelling immunotherapy target (day2025definingtheextracellular pages 3-4, alkhazal2025emergingclinicaland pages 5-6, giudice2025d3gpc2–directedcart pages 1-2, giudice2025d3gpc2–directedcart pages 20-22).
- Epitope targeting: The D3 antibody recognizes a conformational, tumor-selective epitope conserved between mouse and human GPC2, enabling cross-species preclinical modeling and facilitating the engineering of selective ADCs and CARs (giudice2025d3gpc2–directedcart pages 16-18, giudice2025d3gpc2–directedcart pages 1-2).

Expression patterns in development and cancers
- Neuroblastoma: High and prevalent surface expression across neuroblastoma tumors and cell models, including MYCN-amplified PDXs; associated with aggressive biology and poorer outcomes per review synthesis (giudice2025d3gpc2–directedcart pages 1-2, giudice2025d3gpc2–directedcart pages 13-14, alkhazal2025emergingclinicaland pages 5-6).
- CNS tumors: Ranked among top cell-surface/ECM-associated targets in pediatric high-grade glioma/DIPG; validated GPC2-CAR activity against DIPG models in vitro (day2025definingtheextracellular pages 3-4).
- Small cell lung cancer: GPC2 CARs exhibited cytotoxicity against GPC2-positive SCLC models in vivo (giudice2025d3gpc2–directedcart pages 1-2).

Clinical trials (real-world implementations)
- NCT05650749 (GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma and Metastatic Retinoblastoma): Phase 1, single-institution (Children’s Hospital of Philadelphia; lead PI Stephan Grupp), open-label dose-escalation/expansion; status RECRUITING; estimated enrollment 45; evaluates autologous GPC2-directed CAR T cells in relapsed/refractory neuroblastoma and metastatic retinoblastoma; primary endpoints include MTD and safety, with secondary endpoints including manufacturing feasibility, persistence, and preliminary activity. URL: https://clinicaltrials.gov/study/NCT05650749 (recorded start May 23, 2023) (NCT05650749, giudice2025d3gpc2–directedcart pages 1-2).
- NCT07087002 (GPC2‑CAR T Cell Therapy for Relapsed or Refractory Medulloblastoma in Children and Young Adults): Phase 1, Stanford University; status RECRUITING; estimated enrollment 18; intracerebroventricular administration up to 8 doses q28 days with intrapatient dose escalation after lymphodepletion (fludarabine/cyclophosphamide); eligibility requires tumor GPC2 expression (IHC H‑score ≥100). URL: https://clinicaltrials.gov/study/NCT07087002 (actual start Aug 28, 2025; estimated primary/completion Aug 2027) (NCT07087002).

Conclusions and outlook
GPC2 (glypican‑2) is a human, GPI‑anchored HSPG with oncofetal expression and MYCN-linked regulation in neuroblastoma. Its cell-surface localization and role as a signaling co-receptor, including in WNT-associated tumor growth, make it amenable to targeted immunotherapies. Recent preclinical advances demonstrate selective, potent activity of D3‑GPC2 CAR T cells against neuroblastoma and SCLC with favorable preliminary safety, while CNS-focused analyses rank GPC2 among top targets in pediatric gliomas with supportive in vitro efficacy. Ongoing Phase 1 trials in neuroblastoma/retinoblastoma and medulloblastoma are evaluating feasibility, safety, and early activity, and combinatorial strategies such as long-acting IL‑7 are under exploration to improve efficacy and persistence in solid tumors (giudice2025d3gpc2–directedcart pages 1-2, giudice2025d3gpc2–directedcart pages 13-14, day2025definingtheextracellular pages 3-4, NCT05650749, NCT07087002, alkhazal2025emergingclinicaland pages 5-6).

References

(day2025definingtheextracellular pages 3-4): Zoe I. Day, Samuel Roberts-Thomson, Yasmin J. Nouri, Nathan S. Dalton, Stacie S. Wang, Alexander Davenport, Louise E. Ludlow, Mark D. Hulett, Ryan S. Cross, and Misty R. Jenkins. Defining the extracellular matrix for targeted immunotherapy in adult and pediatric brain cancer. NPJ Precision Oncology, Jun 2025. URL: https://doi.org/10.1038/s41698-025-00956-z, doi:10.1038/s41698-025-00956-z. This article has 3 citations and is from a peer-reviewed journal.
(giudice2025d3gpc2–directedcart pages 2-4): Anna Maria Giudice, Stephanie Matlaga, Sydney L. Roth, Whitney Gladney, David Groff, Ted J. Hofmann, Kendra S. McDaid, Guillem Pascual-Pasto, Brendan McIntyre, Vincent Zecchino, Dan Martinez, Timothy T. Spear, Adam J. Wolpaw, Charles-Antoine Assenmacher, Enrico Radaelli, Jenny Pogoriler, Bruce Pawel, David Barrett, Stephan A. Grupp, John M. Maris, and Kristopher R. Bosse. D3-gpc2–directed car t cells are safe and efficacious in preclinical models of neuroblastoma and small cell lung cancer. Clinical Cancer Research, 31:5276-5293, Sep 2025. URL: https://doi.org/10.1158/1078-0432.ccr-25-0089, doi:10.1158/1078-0432.ccr-25-0089. This article has 1 citations and is from a highest quality peer-reviewed journal.
(giudice2025d3gpc2–directedcart pages 20-22): Anna Maria Giudice, Stephanie Matlaga, Sydney L. Roth, Whitney Gladney, David Groff, Ted J. Hofmann, Kendra S. McDaid, Guillem Pascual-Pasto, Brendan McIntyre, Vincent Zecchino, Dan Martinez, Timothy T. Spear, Adam J. Wolpaw, Charles-Antoine Assenmacher, Enrico Radaelli, Jenny Pogoriler, Bruce Pawel, David Barrett, Stephan A. Grupp, John M. Maris, and Kristopher R. Bosse. D3-gpc2–directed car t cells are safe and efficacious in preclinical models of neuroblastoma and small cell lung cancer. Clinical Cancer Research, 31:5276-5293, Sep 2025. URL: https://doi.org/10.1158/1078-0432.ccr-25-0089, doi:10.1158/1078-0432.ccr-25-0089. This article has 1 citations and is from a highest quality peer-reviewed journal.
(giudice2025d3gpc2–directedcart pages 1-2): Anna Maria Giudice, Stephanie Matlaga, Sydney L. Roth, Whitney Gladney, David Groff, Ted J. Hofmann, Kendra S. McDaid, Guillem Pascual-Pasto, Brendan McIntyre, Vincent Zecchino, Dan Martinez, Timothy T. Spear, Adam J. Wolpaw, Charles-Antoine Assenmacher, Enrico Radaelli, Jenny Pogoriler, Bruce Pawel, David Barrett, Stephan A. Grupp, John M. Maris, and Kristopher R. Bosse. D3-gpc2–directed car t cells are safe and efficacious in preclinical models of neuroblastoma and small cell lung cancer. Clinical Cancer Research, 31:5276-5293, Sep 2025. URL: https://doi.org/10.1158/1078-0432.ccr-25-0089, doi:10.1158/1078-0432.ccr-25-0089. This article has 1 citations and is from a highest quality peer-reviewed journal.
(alkhazal2025emergingclinicaland pages 5-6): Albatool AlKhazal, Samiha Chohan, Destani J. Ross, Jinhwan Kim, and Erin G. Brown. Emerging clinical and research approaches in targeted therapies for high-risk neuroblastoma. Frontiers in Oncology, Mar 2025. URL: https://doi.org/10.3389/fonc.2025.1553511, doi:10.3389/fonc.2025.1553511. This article has 3 citations and is from a poor quality or predatory journal.
(giudice2025d3gpc2–directedcart pages 13-14): Anna Maria Giudice, Stephanie Matlaga, Sydney L. Roth, Whitney Gladney, David Groff, Ted J. Hofmann, Kendra S. McDaid, Guillem Pascual-Pasto, Brendan McIntyre, Vincent Zecchino, Dan Martinez, Timothy T. Spear, Adam J. Wolpaw, Charles-Antoine Assenmacher, Enrico Radaelli, Jenny Pogoriler, Bruce Pawel, David Barrett, Stephan A. Grupp, John M. Maris, and Kristopher R. Bosse. D3-gpc2–directed car t cells are safe and efficacious in preclinical models of neuroblastoma and small cell lung cancer. Clinical Cancer Research, 31:5276-5293, Sep 2025. URL: https://doi.org/10.1158/1078-0432.ccr-25-0089, doi:10.1158/1078-0432.ccr-25-0089. This article has 1 citations and is from a highest quality peer-reviewed journal.
(giudice2025d3gpc2–directedcart pages 16-18): Anna Maria Giudice, Stephanie Matlaga, Sydney L. Roth, Whitney Gladney, David Groff, Ted J. Hofmann, Kendra S. McDaid, Guillem Pascual-Pasto, Brendan McIntyre, Vincent Zecchino, Dan Martinez, Timothy T. Spear, Adam J. Wolpaw, Charles-Antoine Assenmacher, Enrico Radaelli, Jenny Pogoriler, Bruce Pawel, David Barrett, Stephan A. Grupp, John M. Maris, and Kristopher R. Bosse. D3-gpc2–directed car t cells are safe and efficacious in preclinical models of neuroblastoma and small cell lung cancer. Clinical Cancer Research, 31:5276-5293, Sep 2025. URL: https://doi.org/10.1158/1078-0432.ccr-25-0089, doi:10.1158/1078-0432.ccr-25-0089. This article has 1 citations and is from a highest quality peer-reviewed journal.
(giudice2025d3gpc2–directedcart pages 19-20): Anna Maria Giudice, Stephanie Matlaga, Sydney L. Roth, Whitney Gladney, David Groff, Ted J. Hofmann, Kendra S. McDaid, Guillem Pascual-Pasto, Brendan McIntyre, Vincent Zecchino, Dan Martinez, Timothy T. Spear, Adam J. Wolpaw, Charles-Antoine Assenmacher, Enrico Radaelli, Jenny Pogoriler, Bruce Pawel, David Barrett, Stephan A. Grupp, John M. Maris, and Kristopher R. Bosse. D3-gpc2–directed car t cells are safe and efficacious in preclinical models of neuroblastoma and small cell lung cancer. Clinical Cancer Research, 31:5276-5293, Sep 2025. URL: https://doi.org/10.1158/1078-0432.ccr-25-0089, doi:10.1158/1078-0432.ccr-25-0089. This article has 1 citations and is from a highest quality peer-reviewed journal.
(NCT05650749): Stephan Grupp MD PhD. GPC2 CAR T Cells for Relapsed or Refractory Neuroblastoma and Metastatic Retinoblastoma. Stephan Grupp MD PhD. 2023. ClinicalTrials.gov Identifier: NCT05650749
(NCT07087002): GPC2-CAR T Cell Therapy for Relapsed or Refractory Medulloblastoma in Children and Young Adults. Stanford University. 2025. ClinicalTrials.gov Identifier: NCT07087002

Citations

day2025definingtheextracellular pages 3-4
alkhazal2025emergingclinicaland pages 5-6
https://doi.org/10.1158/1078-0432.ccr-25-0089
https://doi.org/10.1038/s41698-025-00956-z
https://doi.org/10.1136/jitc-2024-008989
https://doi.org/10.3389/fonc.2025.1553511
https://clinicaltrials.gov/study/NCT05650749
https://clinicaltrials.gov/study/NCT07087002
https://doi.org/10.1038/s41698-025-00956-z,
https://doi.org/10.1158/1078-0432.ccr-25-0089,
https://doi.org/10.3389/fonc.2025.1553511,

📄 View Raw YAML

id: Q8N158
gene_symbol: GPC2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  Glypican-2 (GPC2) is a GPI-anchored heparan sulfate proteoglycan (HSPG) belonging to the
  glypican family. The protein functions as a cell-surface signaling co-receptor that modulates
  ligand-receptor interactions through its heparan sulfate chains. GPC2 binds growth factors
  such as pleiotrophin (PTN) and midkine (MDK) via its heparan sulfate moieties, promoting
  neuronal cell adhesion and neurite outgrowth during development. The protein is involved
  in multiple signaling pathways including Wnt/smoothened signaling. GPC2 exhibits an
  oncofetal expression pattern, being expressed during neural development and re-expressed
  in certain tumors (particularly neuroblastoma, where it is MYCN-regulated), making it a
  target for immunotherapy approaches. The mature protein is located on the external side
  of the plasma membrane attached via a GPI anchor, though it can also be secreted after
  cleavage.
existing_annotations:
- term:
    id: GO:0015026
    label: coreceptor activity
  evidence_type: NAS
  original_reference_id: UniProtKB:Q8N158
  review:
    summary: >-
      GPC2 functions as a signaling co-receptor at the cell surface, modulating ligand-receptor
      interactions through its heparan sulfate chains. It binds growth factors such as PTN
      and MDK to regulate neurite outgrowth signaling. This is the core molecular function
      of GPC2.
    action: NEW
    reason: >-
      This annotation captures the core molecular function of GPC2 as described in UniProt
      and the deep research literature. As a GPI-anchored HSPG, GPC2 serves as a cell-surface
      co-receptor that modulates ligand-receptor interactions.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "Interacts (via heparan sulfate) with PTN; this interaction promotes neurite outgrowth through binding of PTN with chondroitin sulfate of proteoglycans"
      - reference_id: file:human/GPC2/GPC2-deep-research-falcon.md
        supporting_text: "As a GPI-anchored HSPG, GPC2 serves as a cell-surface co-receptor that modulates ligand-receptor interactions"
- term:
    id: GO:0016477
    label: cell migration
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GPC2 is annotated to cell migration based on phylogenetic inference (IBA). Glypicans
      are known to modulate cell motility through their effects on growth factor signaling.
      UniProt states GPC2 may fulfill a function related to the motile behaviors of
      developing neurons. While the annotation is phylogenetically supported and consistent
      with glypican family function, direct experimental evidence for human GPC2 in cell
      migration is limited.
    action: ACCEPT
    reason: >-
      The IBA annotation is well-supported by the known role of glypicans in modulating
      cell motility and the phylogenetic evidence from orthologs. UniProt independently
      notes the potential role in neuronal motile behaviors.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "May fulfill a function related to the motile behaviors of developing neurons"
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GPC2 is annotated to extracellular matrix based on phylogenetic inference. As a
      GPI-anchored heparan sulfate proteoglycan, GPC2 is primarily localized to the cell
      surface, not as a structural component of the extracellular matrix. While glypicans
      can interact with ECM components and may transiently associate with the ECM,
      particularly after shedding, this annotation conflates the secreted form with
      typical ECM structural components.
    action: KEEP_AS_NON_CORE
    reason: >-
      While GPC2 may interact with ECM components or be shed into the extracellular space,
      its primary localization is as a GPI-anchored cell surface protein. The ECM annotation
      is not incorrect but represents a secondary localization rather than the core function.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "Cell membrane {ECO:0000250}; Lipid-anchor, GPI- anchor {ECO:0000250}; Extracellular side {ECO:0000250}"
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GPC2 is annotated to cell surface based on phylogenetic inference. This is strongly
      supported by the known biology of glypicans as GPI-anchored proteins that localize
      to the external surface of the plasma membrane. UniProt confirms GPC2 has a GPI-anchor
      site and localizes to the cell membrane extracellular side. Recent cancer research
      confirms GPC2 as a cell-surface target for immunotherapy.
    action: ACCEPT
    reason: >-
      The cell surface localization is a core feature of GPC2 function as a GPI-anchored
      signaling co-receptor. This is supported by UniProt, phylogenetic inference, and
      extensive cancer immunotherapy literature demonstrating cell surface expression.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "Cell membrane {ECO:0000250}; Lipid-anchor, GPI- anchor {ECO:0000250}; Extracellular side {ECO:0000250}"
      - reference_id: file:human/GPC2/GPC2-deep-research-falcon.md
        supporting_text: "GPC2 is cell-surface localized and GPI-anchored, consistent with glypican family features and its role as an extracellular signaling co-receptor"
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GPC2 is annotated to synapse localization based on phylogenetic inference from
      orthologs. The related glypican GPC4 is known to be involved in synapse formation
      and function. GPC2 is expressed in developing neurons and promotes neurite outgrowth,
      which could involve synaptic localization. However, direct evidence for human
      GPC2 synaptic localization is limited.
    action: KEEP_AS_NON_CORE
    reason: >-
      While the IBA annotation is phylogenetically supported and consistent with GPC2's
      role in neuronal development, synaptic localization is not the primary/core
      localization for GPC2. The core localization is general cell surface.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "May fulfill a function related to the motile behaviors of developing neurons"
- term:
    id: GO:1905475
    label: regulation of protein localization to membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GPC2 is annotated to regulation of protein localization to membrane based on
      phylogenetic inference. As a cell-surface proteoglycan co-receptor, glypicans
      can influence the localization and clustering of signaling receptors at the membrane.
      The UniProt entry notes that MDK interaction with GPC2 induces GPC2 clustering
      through heparan sulfate chain.
    action: ACCEPT
    reason: >-
      The annotation is consistent with the known function of glypicans as signaling
      co-receptors that can modulate receptor localization and clustering at the cell
      surface. The MDK-induced GPC2 clustering provides mechanistic support.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "this interaction induces GPC2 clustering through heparan sulfate chain"
- term:
    id: GO:0007224
    label: smoothened signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GPC2 is annotated to smoothened signaling pathway based on phylogenetic inference.
      Glypicans are well-established modulators of Hedgehog/smoothened signaling, with
      the Drosophila glypican Dally-like being essential for Hedgehog signaling. Mammalian
      glypicans including GPC2 are believed to function similarly in modulating Hedgehog
      pathway components.
    action: ACCEPT
    reason: >-
      The role of glypicans in smoothened/Hedgehog signaling is well-established across
      species and the IBA inference from phylogenetic data is appropriate for this
      conserved function.
    supported_by:
      - reference_id: GO_REF:0000033
        supporting_text: "Phylogenetic inference from glypican orthologs known to modulate Hedgehog signaling"
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      GPC2 is annotated to extracellular region based on UniProt subcellular location
      mapping. The annotation is appropriate as GPC2 exists as a GPI-anchored protein
      on the extracellular face of the membrane, and can also be shed as Secreted
      glypican-2 into the extracellular space.
    action: ACCEPT
    reason: >-
      The annotation is correct for both the GPI-anchored form (exposed to extracellular
      space) and the secreted/shed form. UniProt confirms both localizations.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "RecName: Full=Secreted glypican-2"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      GPC2 is annotated to plasma membrane based on automated annotation methods.
      This is correct for the mature GPI-anchored form of the protein, which is
      attached to the external leaflet of the plasma membrane.
    action: ACCEPT
    reason: >-
      GPC2 is a GPI-anchored protein that localizes to the plasma membrane. UniProt
      confirms this localization.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "Cell membrane {ECO:0000250}; Lipid-anchor, GPI- anchor {ECO:0000250}; Extracellular side {ECO:0000250}"
- term:
    id: GO:0009966
    label: regulation of signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      GPC2 is annotated to regulation of signal transduction based on InterPro glypican
      domain mapping. This is appropriate as glypicans are established signaling
      co-receptors that modulate ligand-receptor interactions. GPC2 specifically interacts
      with PTN and MDK to regulate signaling pathways affecting neurite outgrowth.
    action: ACCEPT
    reason: >-
      The annotation correctly captures the signaling co-receptor function of GPC2.
      This is a core function of all glypicans and is supported by specific interaction
      data for GPC2 with growth factors PTN and MDK.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "Interacts (via heparan sulfate) with PTN; this interaction promotes neurite outgrowth"
      - reference_id: file:human/GPC2/GPC2-deep-research-falcon.md
        supporting_text: "As a GPI-anchored HSPG, GPC2 serves as a cell-surface co-receptor that modulates ligand-receptor interactions"
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      Duplicate annotation of extracellular matrix via InterPro mapping. Same assessment
      as the IBA annotation - GPC2 is primarily a cell-surface protein, though it may
      interact with ECM components.
    action: KEEP_AS_NON_CORE
    reason: >-
      Same rationale as IBA annotation - ECM is a secondary/non-core localization for
      this GPI-anchored cell surface proteoglycan.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "Cell membrane {ECO:0000250}; Lipid-anchor, GPI- anchor {ECO:0000250}; Extracellular side {ECO:0000250}"
- term:
    id: GO:0043202
    label: lysosomal lumen
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      GPC2 is annotated to lysosomal lumen based on ARBA machine learning. This likely
      reflects the degradation pathway for heparan sulfate proteoglycans, where they
      are internalized and degraded in lysosomes. This is part of the normal turnover
      of the protein rather than a functional localization.
    action: KEEP_AS_NON_CORE
    reason: >-
      Lysosomal localization represents the degradation pathway for GPC2, not its
      functional site. The primary function occurs at the cell surface.
    supported_by:
      - reference_id: GO_REF:0000117
        supporting_text: "ARBA machine learning prediction for lysosomal localization based on proteoglycan turnover patterns"
- term:
    id: GO:0098552
    label: side of membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      GPC2 is annotated to side of membrane based on UniProt keyword mapping. This is
      a very general term; the more specific annotation should be external side of
      plasma membrane given the GPI-anchor localization.
    action: MODIFY
    reason: >-
      While not incorrect, this annotation is too general. The protein is specifically
      on the external side of the plasma membrane via GPI anchor.
    proposed_replacement_terms:
      - id: GO:0009897
        label: external side of plasma membrane
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "Extracellular side {ECO:0000250}"
- term:
    id: GO:0007224
    label: smoothened signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      Duplicate annotation of smoothened signaling pathway via Ensembl Compara ortholog
      transfer from rat GPC2 (P51653). Same assessment as IBA annotation.
    action: ACCEPT
    reason: >-
      Consistent with IBA annotation and supported by known glypican biology in
      Hedgehog/smoothened signaling modulation.
    supported_by:
      - reference_id: GO_REF:0000107
        supporting_text: "Automatic transfer from rat ortholog P51653 based on Ensembl Compara"
- term:
    id: GO:0010976
    label: positive regulation of neuron projection development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      GPC2 is annotated to positive regulation of neuron projection development based
      on ortholog transfer from rat. This is strongly supported by UniProt which describes
      GPC2 interactions with PTN and MDK that promote neurite outgrowth.
    action: ACCEPT
    reason: >-
      The annotation is well-supported by the mechanistic data on GPC2-PTN and GPC2-MDK
      interactions promoting neurite outgrowth. UniProt explicitly states this function.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "this interaction promotes neurite outgrowth through binding of PTN with chondroitin sulfate of proteoglycans"
      - reference_id: UniProtKB:Q8N158
        supporting_text: "this interaction induces neuronal cell adhesion and neurite outgrowth"
- term:
    id: GO:0030182
    label: neuron differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      GPC2 is annotated to neuron differentiation based on Ensembl ortholog transfer.
      Given GPC2's role in neurite outgrowth and its expression in developing neurons,
      this annotation is reasonable though somewhat general.
    action: KEEP_AS_NON_CORE
    reason: >-
      While GPC2 promotes neurite outgrowth which is part of neuron differentiation,
      the more specific annotation (positive regulation of neuron projection development)
      better captures its function. This broader term is kept as non-core.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "May fulfill a function related to the motile behaviors of developing neurons"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9940993
  review:
    summary: >-
      GPC2 is annotated to Golgi lumen based on Reactome pathway annotations for
      heparan sulfate proteoglycan biosynthesis. As a proteoglycan, GPC2 transits
      through the Golgi where its heparan sulfate chains are synthesized and modified.
      This represents biosynthetic trafficking rather than the functional site.
    action: KEEP_AS_NON_CORE
    reason: >-
      Golgi localization reflects the biosynthetic pathway for HS-GAG addition, not
      the functional localization of mature GPC2 at the cell surface.
    supported_by:
      - reference_id: Reactome:R-HSA-9940993
        supporting_text: "PXYLP1 dephosphorylates Xyl moiety"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9941039
  review:
    summary: >-
      Duplicate Golgi lumen annotation from Reactome FAM20B phosphorylation pathway.
      Same assessment as above.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic localization, not functional site.
    supported_by:
      - reference_id: Reactome:R-HSA-9941039
        supporting_text: "FAM20B phosphorylates Xyl moiety"
- term:
    id: GO:0010976
    label: positive regulation of neuron projection development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      GPC2 is annotated to positive regulation of neuron projection development by
      sequence similarity (ISS) transfer. This is consistent with the IEA annotation
      and supported by mechanistic data on PTN and MDK interactions.
    action: ACCEPT
    reason: >-
      Core function annotation consistent with known GPC2 biology. The ISS annotation
      provides additional support to the IEA annotation.
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "this interaction induces neuronal cell adhesion and neurite outgrowth"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29162697
  review:
    summary: >-
      GPC2 is annotated to protein binding based on high-throughput interactome analysis.
      The cited paper (PMID:29162697) is about EB1-binding-myomegalin complex and
      centrosomal microtubules - it does not appear to directly study GPC2 function.
      This appears to be from a large-scale protein-protein interaction screen. The
      annotation is too general to be informative.
    action: REMOVE
    reason: >-
      Per curation guidelines, protein binding does not provide informative functional
      annotation. The cited paper does not directly study GPC2, and the interactions
      detected in high-throughput screens lack specificity for GO annotation purposes.
    supported_by:
      - reference_id: PMID:29162697
        supporting_text: "EB1-binding-myomegalin protein complex promotes centrosomal microtubules functions"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1878002
  review:
    summary: >-
      Golgi lumen annotation from Reactome xylosyltransferase pathway for GAG linker
      biosynthesis. Non-core biosynthetic localization.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic trafficking pathway, not functional localization.
    supported_by:
      - reference_id: Reactome:R-HSA-1878002
        supporting_text: "XYLTs transfer Xyl to core protein"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1889955
  review:
    summary: >-
      Golgi lumen annotation from Reactome B3GAT pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-1889955
        supporting_text: "B3GAT dimers transfer GlcA to tetrasaccharide linker"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1889978
  review:
    summary: >-
      Golgi lumen annotation from Reactome B3GALT6 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-1889978
        supporting_text: "B3GALT6 transfers Gal to the tetrasaccharide linker"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2022851
  review:
    summary: >-
      Golgi lumen annotation from Reactome EXT1:EXT2 heparan chain extension pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-2022851
        supporting_text: "EXT1:EXT2 transfers GlcNAc to the heparan chain"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2022856
  review:
    summary: >-
      Golgi lumen annotation from Reactome heparan sulfate biosynthesis.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-2022856
        supporting_text: "EXT1:EXT2 transfers GlcA to heparan"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2022860
  review:
    summary: >-
      Golgi lumen annotation from Reactome NDST sulfation pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-2022860
        supporting_text: "NDST1-4 can sulfate a glucosamine residue in heparan"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2022887
  review:
    summary: >-
      Golgi lumen annotation from Reactome NDST deacetylation pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-2022887
        supporting_text: "NDST1-4 N-deacetylates GlcNAc residues in heparan"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2024108
  review:
    summary: >-
      Golgi lumen annotation from Reactome HSPG secretion pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic/secretory pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-2024108
        supporting_text: "Some HSPGs are secreted to the plasma membrane"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2076383
  review:
    summary: >-
      Golgi lumen annotation from Reactome HS3ST1 sulfation pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-2076383
        supporting_text: "HS3ST1 sulfates GlcN at C3 in heparan sulfate"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2076392
  review:
    summary: >-
      Golgi lumen annotation from Reactome heparan biosynthesis.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-2076392
        supporting_text: "EXT1:EXT2 transfers GlcA to heparan"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2076419
  review:
    summary: >-
      Golgi lumen annotation from Reactome HS6ST sulfation pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-2076419
        supporting_text: "HS6STs sulfate GlcN at C6 in heparan sulfate/heparin"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2076508
  review:
    summary: >-
      Golgi lumen annotation from Reactome HS2ST1 sulfation pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-2076508
        supporting_text: "HS2ST1 trimer sulfates IdoA at C2 in heparan sulfate"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2076611
  review:
    summary: >-
      Golgi lumen annotation from Reactome HS3ST2-6 sulfation pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-2076611
        supporting_text: "HS3ST2-6 sulfate GlcN at C3 in heparan sulfate"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3560802
  review:
    summary: >-
      Golgi lumen annotation from Reactome defective B3GAT3 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization (disease context).
    supported_by:
      - reference_id: Reactome:R-HSA-3560802
        supporting_text: "Defective B3GAT3 does not transfer GlcA to tetrasaccharide linker"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3656254
  review:
    summary: >-
      Golgi lumen annotation from Reactome defective EXT2 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization (disease context).
    supported_by:
      - reference_id: Reactome:R-HSA-3656254
        supporting_text: "Defective EXT2 (in EXT1:EXT2) does not transfer GlcNAc to the heparan chain"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3656257
  review:
    summary: >-
      Golgi lumen annotation from Reactome defective EXT1 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization (disease context).
    supported_by:
      - reference_id: Reactome:R-HSA-3656257
        supporting_text: "Defective EXT1 (in EXT1:EXT2) does not transfer GlcA to heparan"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3656261
  review:
    summary: >-
      Golgi lumen annotation from Reactome defective EXT1 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization (disease context).
    supported_by:
      - reference_id: Reactome:R-HSA-3656261
        supporting_text: "Defective EXT1 (in EXT1:EXT2) does not transfer GlcNAc to the heparan chain"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3656267
  review:
    summary: >-
      Golgi lumen annotation from Reactome defective EXT2 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization (disease context).
    supported_by:
      - reference_id: Reactome:R-HSA-3656267
        supporting_text: "Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparan"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1678694
  review:
    summary: >-
      Plasma membrane annotation from Reactome HPSE2 binding pathway.
    action: ACCEPT
    reason: >-
      Plasma membrane is the core functional localization of GPC2 as a GPI-anchored
      signaling co-receptor.
    supported_by:
      - reference_id: Reactome:R-HSA-1678694
        supporting_text: "Heparanase 2 (HPSE2) binds heparan sulfate proteoglycans"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2024084
  review:
    summary: >-
      Plasma membrane annotation from Reactome HS-GAG degradation pathway.
    action: ACCEPT
    reason: >-
      Core localization annotation.
    supported_by:
      - reference_id: Reactome:R-HSA-2024084
        supporting_text: "HS-GAGs translocate to the lysosome for degradation"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2024108
  review:
    summary: >-
      Plasma membrane annotation from Reactome HSPG secretion pathway.
    action: ACCEPT
    reason: >-
      Core localization annotation.
    supported_by:
      - reference_id: Reactome:R-HSA-2024108
        supporting_text: "Some HSPGs are secreted to the plasma membrane"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2404131
  review:
    summary: >-
      Plasma membrane annotation from Reactome retinoid transport pathway.
    action: ACCEPT
    reason: >-
      Core localization annotation.
    supported_by:
      - reference_id: Reactome:R-HSA-2404131
        supporting_text: "LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2423785
  review:
    summary: >-
      Plasma membrane annotation from Reactome retinoid metabolism pathway.
    action: ACCEPT
    reason: >-
      Core localization annotation.
    supported_by:
      - reference_id: Reactome:R-HSA-2423785
        supporting_text: "CR:atREs binds apoE and HSPG"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2429643
  review:
    summary: >-
      Plasma membrane annotation from Reactome retinoid metabolism pathway.
    action: ACCEPT
    reason: >-
      Core localization annotation.
    supported_by:
      - reference_id: Reactome:R-HSA-2429643
        supporting_text: "NREH hydrolyses atREs (HSPG:apoE) to atROL and FAs"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9694579
  review:
    summary: >-
      Plasma membrane annotation from Reactome SARS-CoV-2 entry pathway. HSPGs including
      glypicans can serve as attachment factors for viral entry.
    action: ACCEPT
    reason: >-
      The localization is correct and represents the core plasma membrane localization,
      even though this particular pathway involves viral exploitation.
    supported_by:
      - reference_id: Reactome:R-HSA-9694579
        supporting_text: "Spike glycoprotein of SARS-CoV-2 binds ACE2 on host cell"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9694661
  review:
    summary: >-
      Plasma membrane annotation from Reactome SARS-CoV-2 entry pathway.
    action: ACCEPT
    reason: >-
      Core localization annotation.
    supported_by:
      - reference_id: Reactome:R-HSA-9694661
        supporting_text: "TMPRSS2 Mediated SARS-CoV-2 Spike Protein Cleavage and Endocytosis"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9698988
  review:
    summary: >-
      Plasma membrane annotation from Reactome SARS-CoV-2 entry pathway.
    action: ACCEPT
    reason: >-
      Core localization annotation.
    supported_by:
      - reference_id: Reactome:R-HSA-9698988
        supporting_text: "Direct Host Cell Membrane Membrane Fusion and Release of SARS-CoV-2 Nucleocapsid"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9699007
  review:
    summary: >-
      Plasma membrane annotation from Reactome SARS-CoV-2 entry pathway.
    action: ACCEPT
    reason: >-
      Core localization annotation.
    supported_by:
      - reference_id: Reactome:R-HSA-9699007
        supporting_text: "FURIN Mediated SARS-CoV-2 Spike Protein Cleavage and Endocytosis"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9836899
  review:
    summary: >-
      Plasma membrane annotation from Reactome RSV attachment pathway. sG binds to HSPGs.
    action: ACCEPT
    reason: >-
      Core localization annotation.
    supported_by:
      - reference_id: Reactome:R-HSA-9836899
        supporting_text: "The secreted soluble isoform of hRSV G protein (sG) binds to proteoglycans on the surface of host cells"
- term:
    id: GO:0043202
    label: lysosomal lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1667005
  review:
    summary: >-
      Lysosomal lumen annotation from Reactome heparanase cleavage pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Degradation pathway localization, not functional site.
    supported_by:
      - reference_id: Reactome:R-HSA-1667005
        supporting_text: "Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan"
- term:
    id: GO:0043202
    label: lysosomal lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2024084
  review:
    summary: >-
      Lysosomal lumen annotation from Reactome HS-GAG degradation pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Degradation pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-2024084
        supporting_text: "HS-GAGs translocate to the lysosome for degradation"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1889981
  review:
    summary: >-
      Golgi lumen annotation from Reactome B4GALT7 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-1889981
        supporting_text: "B4GALT7 transfers Gal group to xylosyl-unit of the tetrasaccharide linker"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3560804
  review:
    summary: >-
      Golgi lumen annotation from Reactome defective B4GALT7 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization (disease context).
    supported_by:
      - reference_id: Reactome:R-HSA-3560804
        supporting_text: "Defective B4GALT7 does not transfer Gal to xylosyl-unit of the tetrasaccharide linker"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9036285
  review:
    summary: >-
      Golgi lumen annotation from Reactome defective EXT1 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization (disease context).
    supported_by:
      - reference_id: Reactome:R-HSA-9036285
        supporting_text: "Defective EXT1 (in EXT1:EXT2) does not transfer GlcA to heparan"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9036289
  review:
    summary: >-
      Golgi lumen annotation from Reactome defective EXT2 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization (disease context).
    supported_by:
      - reference_id: Reactome:R-HSA-9036289
        supporting_text: "Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparan"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9953259
  review:
    summary: >-
      Golgi lumen annotation from Reactome EXTL3 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization.
    supported_by:
      - reference_id: Reactome:R-HSA-9953259
        supporting_text: "EXTL3 dimer transfers GlcNAc to the GAG linker"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1667005
  review:
    summary: >-
      Golgi lumen annotation from Reactome heparanase pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      This relates to the processing pathway for HSPGs.
    supported_by:
      - reference_id: Reactome:R-HSA-1667005
        supporting_text: "Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan"
- term:
    id: GO:0005796
    label: Golgi lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4420365
  review:
    summary: >-
      Golgi lumen annotation from Reactome defective B3GALT6 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Biosynthetic pathway localization (disease context).
    supported_by:
      - reference_id: Reactome:R-HSA-4420365
        supporting_text: "Defective B3GALT6 does not transfer Gal to the tetrasaccharide linker"
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: GO_REF:0000054
  review:
    summary: >-
      GPC2 is annotated to endoplasmic reticulum based on LIFEdb fusion protein
      localization data. As a secreted/membrane protein, GPC2 would transit through
      the ER during biosynthesis. This represents a biosynthetic localization.
    action: KEEP_AS_NON_CORE
    reason: >-
      ER localization represents the biosynthetic pathway for GPC2. The functional
      localization is at the plasma membrane.
    supported_by:
      - reference_id: GO_REF:0000054
        supporting_text: "Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells"
core_functions:
  - molecular_function:
      id: GO:0015026
      label: coreceptor activity
    description: >-
      GPC2 functions as a signaling co-receptor at the cell surface, modulating ligand-receptor
      interactions through its heparan sulfate chains. It binds growth factors such as PTN
      and MDK to regulate neurite outgrowth signaling.
    locations:
      - id: GO:0009986
        label: cell surface
    directly_involved_in:
      - id: GO:0010976
        label: positive regulation of neuron projection development
      - id: GO:0007224
        label: smoothened signaling pathway
    supported_by:
      - reference_id: UniProtKB:Q8N158
        supporting_text: "Interacts (via heparan sulfate) with PTN; this interaction promotes neurite outgrowth"
      - reference_id: UniProtKB:Q8N158
        supporting_text: "this interaction induces neuronal cell adhesion and neurite outgrowth"
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000054
  title: Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:29162697
  title: EB1-binding-myomegalin protein complex promotes centrosomal microtubules functions.
  findings:
    - statement: Paper focuses on EB1-binding complexes and centrosomal microtubules, not GPC2 function directly. GPC2 appears as part of high-throughput interactome data.
- id: UniProtKB:Q8N158
  title: UniProt entry for human Glypican-2
  findings:
    - statement: GPC2 is a GPI-anchored cell surface heparan sulfate proteoglycan
    - statement: Interacts with PTN and MDK via heparan sulfate to promote neurite outgrowth
    - statement: May function in developing neuron motility
- id: file:human/GPC2/GPC2-deep-research-falcon.md
  title: Falcon deep research on GPC2
  findings:
    - statement: GPC2 is a GPI-anchored HSPG functioning as a signaling co-receptor
    - statement: Exhibits oncofetal expression pattern with re-expression in neuroblastoma
    - statement: Expression is MYCN-regulated in neuroblastoma
    - statement: Functions in WNT-associated signaling pathways
- id: Reactome:R-HSA-1667005
  title: Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome)
  findings: []
- id: Reactome:R-HSA-1678694
  title: Heparanase 2 (HPSE2) binds heparan sulfate proteoglycans
  findings: []
- id: Reactome:R-HSA-1878002
  title: XYLTs transfer Xyl to core protein
  findings: []
- id: Reactome:R-HSA-1889955
  title: B3GAT dimers transfer GlcA to tetrasaccharide linker
  findings: []
- id: Reactome:R-HSA-1889978
  title: B3GALT6 transfers Gal to the tetrasaccharide linker
  findings: []
- id: Reactome:R-HSA-1889981
  title: B4GALT7 transfers Gal group to xylosyl-unit of the tetrasaccharide linker
  findings: []
- id: Reactome:R-HSA-2022851
  title: EXT1:EXT2 transfers GlcNAc to the heparan chain
  findings: []
- id: Reactome:R-HSA-2022856
  title: EXT1:EXT2 transfers GlcA to heparan
  findings: []
- id: Reactome:R-HSA-2022860
  title: NDST1-4 can sulfate a glucosamine residue in heparan to form heparan sulfate (HS)
  findings: []
- id: Reactome:R-HSA-2022887
  title: NDST1-4 N-deacetylates GlcNAc residues in heparan
  findings: []
- id: Reactome:R-HSA-2024084
  title: HS-GAGs translocate to the lysosome for degradation
  findings: []
- id: Reactome:R-HSA-2024108
  title: Some HSPGs are secreted to the plasma membrane
  findings: []
- id: Reactome:R-HSA-2076383
  title: HS3ST1 sulfates GlcN at C3 in heparan sulfate
  findings: []
- id: Reactome:R-HSA-2076392
  title: EXT1:EXT2 transfers GlcA to heparan
  findings: []
- id: Reactome:R-HSA-2076419
  title: HS6STs sulfate GlcN at C6 in heparan sulfate/heparin
  findings: []
- id: Reactome:R-HSA-2076508
  title: HS2ST1 trimer sulfates IdoA at C2 in heparan sulfate
  findings: []
- id: Reactome:R-HSA-2076611
  title: HS3ST2-6 sulfate GlcN at C3 in heparan sulfate
  findings: []
- id: Reactome:R-HSA-2404131
  title: LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol
  findings: []
- id: Reactome:R-HSA-2423785
  title: CR:atREs binds apoE and HSPG
  findings: []
- id: Reactome:R-HSA-2429643
  title: NREH hydrolyses atREs (HSPG:apoE) to atROL and FAs
  findings: []
- id: Reactome:R-HSA-3560802
  title: Defective B3GAT3 does not transfer GlcA to tetrasaccharide linker
  findings: []
- id: Reactome:R-HSA-3560804
  title: Defective B4GALT7 does not transfer Gal to xylosyl-unit of the tetrasaccharide linker
  findings: []
- id: Reactome:R-HSA-3656254
  title: Defective EXT2 (in EXT1:EXT2) does not transfer GlcNAc to the heparan chain
  findings: []
- id: Reactome:R-HSA-3656257
  title: Defective EXT1 (in EXT1:EXT2) does not transfer GlcA to heparan
  findings: []
- id: Reactome:R-HSA-3656261
  title: Defective EXT1 (in EXT1:EXT2) does not transfer GlcNAc to the heparan chain
  findings: []
- id: Reactome:R-HSA-3656267
  title: Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparan
  findings: []
- id: Reactome:R-HSA-4420365
  title: Defective B3GALT6 does not transfer Gal to the tetrasaccharide linker
  findings: []
- id: Reactome:R-HSA-9036285
  title: Defective EXT1 (in EXT1:EXT2) does not transfer GlcA to heparan
  findings: []
- id: Reactome:R-HSA-9036289
  title: Defective EXT2 (in EXT1:EXT2) does not transfer GlcA to heparan
  findings: []
- id: Reactome:R-HSA-9694579
  title: Spike glycoprotein of SARS-CoV-2 binds ACE2 on host cell
  findings: []
- id: Reactome:R-HSA-9694661
  title: TMPRSS2 Mediated SARS-CoV-2 Spike Protein Cleavage and Endocytosis
  findings: []
- id: Reactome:R-HSA-9698988
  title: Direct Host Cell Membrane Membrane Fusion and Release of SARS-CoV-2 Nucleocapsid
  findings: []
- id: Reactome:R-HSA-9699007
  title: FURIN Mediated SARS-CoV-2 Spike Protein Cleavage and Endocytosis
  findings: []
- id: Reactome:R-HSA-9836899
  title: sG binds to HSPGs
  findings: []
- id: Reactome:R-HSA-9940993
  title: PXYLP1 dephosphorylates Xyl moiety
  findings: []
- id: Reactome:R-HSA-9941039
  title: FAM20B phosphorylates Xyl moiety
  findings: []
- id: Reactome:R-HSA-9953259
  title: EXTL3 dimer transfers GlcNAc to the GAG linker
  findings: []

Gene Description

Existing Annotations Review

Core Functions

GPC2 functions as a signaling co-receptor at the cell surface, modulating ligand-receptor interactions through its heparan sulfate chains. It binds growth factors such as PTN and MDK to regulate neurite outgrowth signaling.

References

Deep Research

Falcon

Citations

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