PSAP

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005576 extracellular region	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Prosaposin is secreted as a ~70 kDa glycoprotein and is well documented in extracellular fluids and the extracellular space; the extracellular pool includes the neurotrophic prosaposin ligand for GPR37/GPR37L1. This phylogenetic (IBA) localization is consistent with the UniProt Secreted annotation and with multiple proteomic detections. Reason: Well supported by UniProt subcellular location (Secreted) and by HDA proteomics annotations; a genuine, though non-core, localization for the secreted prosaposin form (the core compartment is the lysosome). Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005764 lysosome	IBA GO_REF:0000033	ACCEPT	Summary: The lysosome is the principal site of action of prosaposin and the saposins, where the precursor is proteolytically processed and the saposin cofactors activate acid hydrolases for sphingolipid degradation. This is a core cellular component for the gene. Reason: Strongly supported by UniProt (Lysosome subcellular location) and by experimental IDA annotations; represents the core site of saposin activator function. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: Lysosome
GO:0006629 lipid metabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Prosaposin/saposins participate in lysosomal lipid (sphingolipid) metabolism as non-enzymatic activator cofactors. This broad process term is correct but less informative than the specific glycosphingolipid catabolic role captured in core_functions. Reason: Correct but general; the specific and core process is glycosphingolipid/sphingolipid catabolism (see core_functions and the sphingolipid metabolic process IEA). Retained as a broader parent. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt act as activator proteins for lysosomal sphingolipid-degrading enzymes, facilitating the hydrolysis of sphingolipids
GO:0030882 lipid antigen binding	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Saposins (notably saposin C/D and the related GM2 activator family) bind and load lipid antigens onto CD1 molecules for antigen presentation, and structural work explicitly notes a role in lipid antigen presentation. This is a genuine but peripheral activity relative to the core sphingolipid-catabolic cofactor function. Reason: Lipid antigen binding/presentation is an established but non-core saposin function; keep as an accurate phylogenetic annotation, not a core function. Supporting Evidence: PMID:18462685 Human saposins are essential proteins required for degradation of sphingolipids and lipid antigen presentation.
GO:0060736 prostate gland growth	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Secreted prosaposin has trophic/growth-promoting effects reported in prostate biology, propagated here by phylogenetic inference. This is a tissue-specific developmental role of the secreted prosaposin form, well outside the core lysosomal cofactor function. Reason: Plausible tissue-specific trophic role of secreted prosaposin (IBA), but peripheral to the gene's core function; retained as non-core.
GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Secreted prosaposin is a ligand for the Gi-coupled receptors GPR37 and GPR37L1, consistent with an adenylate cyclase-inhibiting (Gi) GPCR signaling pathway. This reflects the neurotrophic prosaposin signalling role, not the intralysosomal cofactor function. Reason: Consistent with the GPR37/GPR37L1 neurotrophic-signalling role of secreted prosaposin; genuine but non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt these effects are mediated by its G protein-coupled receptors, GPR37 and GPR37L1
GO:0019216 regulation of lipid metabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: As an activator of lysosomal lipid-degrading hydrolases, prosaposin/saposins modulate the rate of sphingolipid catabolism, which can be framed as regulation of lipid metabolism. This is a general regulatory framing of the core cofactor activity. Reason: Regulatory framing of the activator role; correct but subsumed by the more specific activator MF and catabolic BP in core_functions. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt act as activator proteins for lysosomal sphingolipid-degrading enzymes
GO:0005576 extracellular region	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Extracellular region localization derived from the UniProt Secreted subcellular-location mapping. Consistent with prosaposin being secreted as a glycoprotein; a genuine non-core location. Reason: Correct SubCell-derived location for the secreted prosaposin form; non-core relative to the lysosome. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005764 lysosome	IEA GO_REF:0000120	ACCEPT	Summary: Lysosome localization from combined IEA methods (InterPro saposin domains + SubCell). This is the core site of prosaposin/saposin action and is strongly corroborated experimentally. Reason: Correct core localization, redundant with and confirmed by experimental IDA lysosome annotations. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: Lysosome
GO:0006629 lipid metabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro-based mapping to lipid metabolic process. Correct at a broad level given the saposin role in lysosomal lipid catabolism, but superseded by more specific terms. Reason: Broadly correct parent term; the specific catabolic process is captured in core_functions. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt facilitating the hydrolysis of sphingolipids by extracting lipid substrates from membranes
GO:0006665 sphingolipid metabolic process	IEA GO_REF:0000002	MODIFY	Summary: InterPro saposin-domain mapping to sphingolipid metabolic process. This is the correct and central biological process for PSAP - the saposins are cofactors for lysosomal sphingolipid degradation. A more specific catabolic term (glycosphingolipid catabolic process) is provided in core_functions. Reason: Accurate but general; PSAP specifically drives sphingolipid/glycosphingolipid CATABOLISM. Modify toward the specific catabolic process while retaining the sphingolipid metabolism essence. Proposed replacements: glycosphingolipid catabolic process sphingolipid catabolic process Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt act as activator proteins for lysosomal sphingolipid-degrading enzymes
GO:0008289 lipid binding	IEA GO_REF:0000117	ACCEPT	Summary: ARBA-derived lipid binding. Saposins are bona fide lipid-binding/lipid-transfer proteins that extract glycosphingolipids and phospholipids from membranes; this molecular function is well supported experimentally (ganglioside and phospholipid binding IDAs). Reason: Correct molecular function, corroborated by experimental ganglioside- and phospholipid-binding annotations; broader parent of the specific activator MF in core_functions. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt extracting lipid substrates from membranes and presenting them to their respective enzymes
GO:0030290 sphingolipid activator protein activity	IDA file:human/PSAP/PSAP-uniprot.txt	NEW	Summary: Proposed core molecular function. The four saposins derived from prosaposin are the canonical non-enzymatic sphingolipid-activator proteins that stimulate lysosomal sphingolipid-degrading hydrolases (glucosylceramidase, galactosylceramidase, cerebroside-sulfatase, alpha- and beta-galactosidase, sphingomyelin phosphodiesterase). This term (GO:0030290) is the specific, informative MF for PSAP but is not currently present in the GOA TSV; it is added here as a NEW annotation to reflect the core function. Reason: The most informative molecular-function term for prosaposin/saposins is not in the current GOA (which spreads the MF across lipid/ganglioside/phospholipid binding). GO:0030290 directly captures the non-catalytic sphingolipid-activator cofactor activity that defines this gene; added as a NEW core annotation. Supported by decades of biochemistry (UniProt FUNCTION) and the term's own definition. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt act as activator proteins for lysosomal sphingolipid-degrading enzymes, facilitating the hydrolysis of sphingolipids
GO:0010467 gene expression	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ARBA electronic mapping to the very broad process gene expression. There is no evidence that prosaposin functions as a transcription/translation factor; the experimental link (PMID:27356620) is to post-translational regulation of progranulin protein levels, not gene expression per se. This IEA mapping is uninformative/over-broad. Reason: Vague, over-broad ARBA mapping not reflecting a real gene-expression role; the underlying biology is post-translational regulation of progranulin abundance (see the IDA/IMP entries).
GO:0042802 identical protein binding	IEA GO_REF:0000117	ACCEPT	Summary: ARBA-derived identical protein binding, consistent with prosaposin/saposin self-association (prosaposin oligomerization required for sorting; saposin homodimers). Supported experimentally by the protein homodimerization activity IDA (PMID:18462685). Reason: Consistent with documented prosaposin oligomerization and saposin homodimer formation. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt [Saposin-B]: Homodimer
GO:0005515 protein binding	IPI PMID:16713569 A protein-protein interaction network for human inherited at...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from an ataxia/Purkinje-cell protein-interaction network (interactor ZBED1/O96006). The generic term protein binding conveys no specific molecular function and the interaction is not clearly linked to prosaposin biology. Reason: Uninformative high-throughput protein binding annotation; per curation guidance the bare protein binding term should not be treated as a core function. Retained but flagged as over-annotated rather than removed (experimental IPI).
GO:0005515 protein binding	IPI PMID:24872419 Mesotrypsin and caspase-14 participate in prosaposin process...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI capturing the prosaposin-CASP14 (caspase-14, P31944) interaction during epidermal prosaposin processing. The interaction is real and biologically meaningful (processing), but is more informatively captured by the protease binding annotation from the same paper. Reason: Redundant with, and less informative than, the GO:0002020 protease binding annotation from the same study; the generic protein binding term is uninformative. Supporting Evidence: PMID:24872419 mesotrypsin generated saposins A-D from prosaposin
GO:0005515 protein binding	IPI PMID:26370502 Prosaposin facilitates sortilin-independent lysosomal traffi...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI for the prosaposin-progranulin (GRN, P28799) interaction. This interaction underlies the physiologically important PSAP-mediated lysosomal trafficking of progranulin, better captured by the lysosomal transport annotations from the same study. Reason: The generic protein binding term is uninformative; the underlying PSAP-GRN interaction and its consequence are captured by GO:0007041 lysosomal transport (PMID:26370502). Supporting Evidence: PMID:26370502 prosaposin (PSAP) interacts with PGRN and facilitates its lysosomal
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from a large-scale binary interactome map (HuRI), reporting interactions with ZBED1 (O96006), PEX5 (P50542-3) and APPBP2 (Q92624). Generic and high-throughput. Reason: High-throughput binary-interactome protein binding, uninformative as a molecular function; flagged rather than removed.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from a neurodegenerative-disease interactome map (interactors include APP/P05067, LYN/P07948, CSNK1D/P48730-2). Generic high-throughput evidence. Reason: High-throughput interactome protein binding; uninformative bare term, flagged not removed.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI from a proteome-scale interaction network (BioPlex; interactor GRN/P28799). Recapitulates the PSAP-progranulin interaction in a high-throughput setting. Reason: Generic high-throughput protein binding; the PSAP-GRN interaction it reflects is better represented by the lysosomal-transport annotations. Flagged, not removed.
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-9840334	ACCEPT	Summary: Lysosomal lumen localization from the Reactome reaction in which prosaposin is cleaved. This is the core compartment where prosaposin is processed and the saposins act on glycosphingolipids. Reason: Correct core localization consistent with UniProt Lysosome and experimental lysosome IDAs. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt The lysosomal precursor is proteolytically processed to 4 small peptides
GO:0005576 extracellular region	HDA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin...	KEEP AS NON CORE	Summary: High-throughput (HDA) proteomic detection of prosaposin in the extracellular region. Consistent with the secreted prosaposin form; non-core localization. Reason: Valid proteomics-based extracellular detection of the secreted form; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005576 extracellular region	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Extracellular region by curator sequence-similarity transfer from the mouse ortholog (Q61207), which is documented as secreted. Consistent with the secreted prosaposin form. Reason: Correct ISS transfer of the Secreted location from a well-characterized ortholog; non-core relative to the lysosome. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt [Prosaposin]: Secreted {ECO:0000250\|UniProtKB:Q61207}
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1606312	ACCEPT	Summary: Lysosomal lumen localization from a Reactome glycosphingolipid-catabolism reaction (GLB1 hydrolyzes SapB/C:LacCer), where saposin B/C present lipid to the hydrolase. Core compartment. Reason: Correct core lysosomal-lumen localization consistent with UniProt and experimental IDAs. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt The lysosomal precursor is proteolytically processed to 4 small peptides
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1605624	ACCEPT	Summary: Lysosomal lumen localization from the Reactome reaction in which beta-galactosidase hydrolyses saposin-mobilized GM1 to GM2. Core compartment for the activator function. Reason: Correct core lysosomal-lumen localization, redundant with other lysosome annotations. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt The lysosomal precursor is proteolytically processed to 4 small peptides
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1605632	ACCEPT	Summary: Lysosomal lumen localization from a Reactome reaction (bHEXA/bHEXB hydrolyze PSAP(195-273):Gb4Cer:PE), reflecting saposin-B-mediated lipid presentation. Core compartment. Reason: Correct core lysosomal-lumen localization. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt The lysosomal precursor is proteolytically processed to 4 small peptides
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1605724	ACCEPT	Summary: Lysosomal lumen localization from a Reactome reaction (NEU1,4 hydrolyze PSAP(195-273):GM3:PE) reflecting saposin-B lipid presentation. Core compartment. Reason: Correct core lysosomal-lumen localization. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt The lysosomal precursor is proteolytically processed to 4 small peptides
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1605736	ACCEPT	Summary: Lysosomal lumen localization from a Reactome reaction (GLA hydrolyzes PSAP(195-273):Gb3Cer:PE) reflecting saposin-B lipid presentation. Core compartment. Reason: Correct core lysosomal-lumen localization. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt The lysosomal precursor is proteolytically processed to 4 small peptides
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-1606807	ACCEPT	Summary: Lysosomal lumen localization from a Reactome reaction (ARSA removes sulfate from PSAP(195-273):Sulfatide), the canonical saposin-B / arylsulfatase A activation step. Core compartment. Reason: Correct core lysosomal-lumen localization for the saposin-B sulfatide-desulfation reaction. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt The lysosomal precursor is proteolytically processed to 4 small peptides
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-351341	ACCEPT	Summary: Lysosomal lumen localization from the Reactome Exocytosis of Proactivator polypeptide reaction. Prosaposin transits the lysosomal lumen en route through the secretory/endolysosomal system. Reason: Correct core lysosomal-lumen localization consistent with prosaposin trafficking. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt The lysosomal precursor is proteolytically processed to 4 small peptides
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-9840470	ACCEPT	Summary: Lysosomal lumen localization from a Reactome reaction (PSAP(195-273) dimer:PE binds and mobilizes ligands), representing saposin-B lipid mobilization in the lumen. Core compartment. Reason: Correct core lysosomal-lumen localization. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt The lysosomal precursor is proteolytically processed to 4 small peptides
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-9840488	ACCEPT	Summary: Lysosomal lumen localization from a Reactome reaction (PSAP(195-273) forms a dimer), the saposin-B homodimerization step. Core compartment. Reason: Correct core lysosomal-lumen localization; consistent with saposin-B homodimer formation. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt The lysosomal precursor is proteolytically processed to 4 small peptides
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-9841189	ACCEPT	Summary: Lysosomal lumen localization from a Reactome reaction (GLA hydrolyzes PSAP(195-273):Gal2Cer:PE) reflecting saposin-B lipid presentation. Core compartment. Reason: Correct core lysosomal-lumen localization. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt The lysosomal precursor is proteolytically processed to 4 small peptides
GO:0043202 lysosomal lumen	TAS Reactome:R-HSA-9842115	ACCEPT	Summary: Lysosomal lumen localization from a Reactome reaction (PSAP(195-273) dimer binds PE), the saposin-B / phosphatidylethanolamine association step in the lumen. Core compartment. Reason: Correct core lysosomal-lumen localization; consistent with saposin-B co-purifying with PE. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt Saposin-B co-purifies with 1 molecule of phosphatidylethanolamine
GO:0097110 scaffold protein binding	IPI PMID:23555801 BANK1 and BLK act through phospholipase C gamma 2 in B-cell ...	MARK AS OVER ANNOTATED	Summary: Scaffold protein binding IPI (interactor Q8NDB2) assigned from a paper on BANK1/BLK/PLCg2 B-cell signalling. The cached publication does not mention prosaposin/PSAP or saposins anywhere in its text, so the supporting evidence for a PSAP scaffold-binding function cannot be verified, and the bare scaffold protein binding term is uninformative regardless. Reason: The cited reference (a BANK1/BLK B-cell signalling study) does not discuss PSAP; the annotation is a generic binding term that adds no specific molecular function for prosaposin. Flagged rather than removed. See reference_review for the likely citation mismatch.
GO:0010467 gene expression	IDA PMID:27356620 Prosaposin is a regulator of progranulin levels and oligomer...	KEEP AS NON CORE	Summary: Experimental finding that PSAP modulates progranulin (PGRN) protein abundance - both PSAP reduction and overexpression raise extracellular PGRN. The annotation is captured here under the very broad gene expression term with a negative-effect qualifier, but the actual mechanism is post-translational regulation of PGRN levels/oligomerization, not transcriptional gene expression. Reason: Real experimental effect on progranulin protein levels, but the gene expression term is a coarse/imperfect fit (the mechanism is post-translational) and the role is peripheral to PSAP core lysosomal cofactor function. Keep as non-core; do not treat as core. Supporting Evidence: PMID:27356620 both PSAP reduction and overexpression lead to significantly elevated extracellular PGRN levels
GO:0010467 gene expression	IMP PMID:27356620 Prosaposin is a regulator of progranulin levels and oligomer...	KEEP AS NON CORE	Summary: IMP counterpart of the same PSAP-to-progranulin-level effect (PSAP knockdown/overexpression alters extracellular PGRN and its oligomerization state). Same caveat regarding the coarse gene expression term applies. Reason: Duplicate evidence (IMP) for the post-translational regulation of progranulin abundance; non-core, and the gene expression term is a loose fit for the actual mechanism. Supporting Evidence: PMID:27356620 PSAP knockdown increases PGRN monomers, whereas PSAP overexpression increases PGRN oligomers
GO:0005764 lysosome	IDA PMID:28541286 Impaired prosaposin lysosomal trafficking in frontotemporal ...	ACCEPT	Summary: Direct experimental (IDA) demonstration of prosaposin in the lysosome, in the context of PGRN-dependent PSAP lysosomal trafficking in neurons. Confirms the core lysosomal localization. Reason: Experimental confirmation of core lysosomal localization. Supporting Evidence: PMID:28541286 PGRN facilitates neuronal uptake and lysosomal delivery of prosaposin (PSAP)
GO:0007041 lysosomal transport	IMP PMID:28541286 Impaired prosaposin lysosomal trafficking in frontotemporal ...	KEEP AS NON CORE	Summary: Reciprocal to the PSAP-progranulin trafficking axis - progranulin promotes lysosomal delivery of prosaposin, and impaired PSAP lysosomal trafficking is implicated in FTLD/NCL. PSAP participates in a lysosomal-transport process as both cargo and chaperone. Moonlighting role of secreted prosaposin. Reason: Genuine experimental role in lysosomal transport (PSAP-PGRN co-trafficking), but a moonlighting chaperone/cargo function distinct from the core sphingolipid-activator activity. Supporting Evidence: PMID:28541286 a role of PGRN in PSAP lysosomal trafficking
GO:0007041 lysosomal transport	IMP PMID:28835281 Lysosomal processing of progranulin.	KEEP AS NON CORE	Summary: Study of lysosomal processing of progranulin in which the PSAP-PGRN lysosomal-delivery relationship is examined; PSAP is annotated to lysosomal transport (progranulin co-trafficking). Non-core moonlighting role. Reason: Supports the lysosomal-transport (progranulin co-trafficking) role; non-core relative to the saposin activator function. Supporting Evidence: PMID:28835281 PGRN endocytosed from the extracellular space is also processed in a similar manner
GO:0005764 lysosome	IDA PMID:26370502 Prosaposin facilitates sortilin-independent lysosomal traffi...	ACCEPT	Summary: Direct experimental localization of prosaposin to the lysosome in the study establishing the PSAP-progranulin lysosomal-trafficking pathway. Confirms the core lysosomal localization. Reason: Experimental confirmation of core lysosomal localization. Supporting Evidence: PMID:26370502 prosaposin (PSAP) interacts with PGRN and facilitates its lysosomal
GO:0005770 late endosome	IDA PMID:26370502 Prosaposin facilitates sortilin-independent lysosomal traffi...	KEEP AS NON CORE	Summary: Direct experimental detection of prosaposin in late endosomes, consistent with its transit through the endolysosomal system during trafficking of itself and progranulin. Non-core compartment on the route to the lysosome. Reason: Valid endolysosomal-pathway localization (transit compartment); non-core relative to the lysosome. Supporting Evidence: PMID:26370502 late endosomes
GO:0007041 lysosomal transport	IDA PMID:26370502 Prosaposin facilitates sortilin-independent lysosomal traffi...	KEEP AS NON CORE	Summary: Direct experimental demonstration that prosaposin facilitates lysosomal targeting/delivery of progranulin via CI-M6PR and LRP1 in biosynthetic and endocytic pathways. Establishes PSAP as a trafficking chaperone for progranulin - a moonlighting function. Reason: Well-supported experimental lysosomal-transport role for progranulin cargo, but a moonlighting chaperone function distinct from the core sphingolipid-activator activity. Supporting Evidence: PMID:26370502 facilitates its lysosomal targeting in both biosynthetic and endocytic pathways via the cation-independent mannose 6-phosphate receptor and low density lipoprotein receptor-related protein 1
GO:0002020 protease binding	IPI PMID:24872419 Mesotrypsin and caspase-14 participate in prosaposin process...	ACCEPT	Summary: Prosaposin was identified as an interactor of the proteases caspase-14 and epidermal mesotrypsin, which process prosaposin into saposins A-D; mesotrypsin directly generates the saposins from prosaposin. This protease binding reflects the physiological maturation of prosaposin. Reason: Experimentally supported protease-binding interaction underlying prosaposin processing; informative (unlike bare protein binding) though peripheral to the mature-saposin cofactor activity. Supporting Evidence: PMID:24872419 mesotrypsin generated saposins A-D from prosaposin
GO:0005576 extracellular region	HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper...	KEEP AS NON CORE	Summary: High-throughput proteomic detection of prosaposin in extracellular matrix/space (varicose vein proteomics). Consistent with the secreted prosaposin form; non-core location. Reason: Valid proteomics-based extracellular detection; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005576 extracellular region	HDA PMID:20551380 Proteomics characterization of extracellular space component...	KEEP AS NON CORE	Summary: High-throughput proteomic detection of prosaposin in the extracellular space of human aorta. Consistent with the secreted prosaposin form; non-core location. Reason: Valid proteomics-based extracellular detection; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005576 extracellular region	ISS PMID:22261194 Proteomics analysis of cardiac extracellular matrix remodeli...	KEEP AS NON CORE	Summary: Extracellular region assigned by sequence-similarity from a porcine cardiac ECM proteomics dataset (ortholog F1SU97). Consistent with secreted prosaposin; non-core. Reason: Ortholog-based extracellular localization consistent with the secreted form; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005576 extracellular region	IDA PMID:1454804 Binding and transport of gangliosides by prosaposin.	KEEP AS NON CORE	Summary: Prosaposin is described as existing as a secretory protein (and as an integral membrane protein), directly supporting its extracellular localization. Non-core relative to the lysosome. Reason: Direct evidence for the secreted prosaposin form; non-core localization. Supporting Evidence: PMID:1454804 Prosaposin exists as a secretory protein and as an integral membrane protein
GO:1905572 ganglioside GM1 transport to membrane	IDA PMID:1454804 Binding and transport of gangliosides by prosaposin.	ACCEPT	Summary: Prosaposin and saposins transferred gangliosides (including GM1) from donor liposomes to acceptor membranes, directly demonstrating ganglioside transport activity. This lipid-transfer function underlies the activator role (presenting glycosphingolipids to hydrolases). Reason: Direct experimental evidence for ganglioside transport between membranes, a specific manifestation of the saposin lipid-transfer/presentation function. Supporting Evidence: PMID:1454804 Prosaposin and saposins transferred gangliosides from donor liposomes to erythrocyte ghost membranes
GO:1905573 ganglioside GM1 binding	IDA PMID:1454804 Binding and transport of gangliosides by prosaposin.	ACCEPT	Summary: Prosaposin and saposins formed stable complexes with multiple gangliosides, including the gangliotetraose (a-series) gangliosides such as GM1, demonstrating direct ganglioside binding. Reason: Direct experimental binding of GM1-type gangliosides, consistent with the lipid-binding activator function. Supporting Evidence: PMID:1454804 formed stable complexes with 13 different gangliosides
GO:1905574 ganglioside GM2 binding	IDA PMID:1454804 Binding and transport of gangliosides by prosaposin.	ACCEPT	Summary: Ganglioside binding assay showing stable complex formation with a panel of 13 gangliosides, supporting direct binding of GM2-type gangliosides. Reason: Direct experimental ganglioside binding; consistent with lipid-binding function. Supporting Evidence: PMID:1454804 formed stable complexes with 13 different gangliosides
GO:1905575 ganglioside GM3 binding	IDA PMID:1454804 Binding and transport of gangliosides by prosaposin.	ACCEPT	Summary: Ganglioside binding assay showing stable complex formation with a panel of 13 gangliosides, supporting direct binding of GM3-type gangliosides. Reason: Direct experimental ganglioside binding; consistent with lipid-binding function. Supporting Evidence: PMID:1454804 formed stable complexes with 13 different gangliosides
GO:1905576 ganglioside GT1b binding	IDA PMID:1454804 Binding and transport of gangliosides by prosaposin.	ACCEPT	Summary: Ganglioside binding assay showing stable complex formation with a panel of 13 gangliosides, spanning a- and b-series; supports direct binding of GT1b (a b-series ganglioside), reported to bind with lower affinity. Reason: Direct experimental ganglioside binding; b-series gangliosides bound with lower affinity. Supporting Evidence: PMID:1454804 b series gangliosides, O-acetylated gangliosides, and gangliosides with shorter carbohydrate chains, were bound with lower affinity
GO:1905577 ganglioside GP1c binding	IDA PMID:1454804 Binding and transport of gangliosides by prosaposin.	ACCEPT	Summary: Ganglioside binding assay showing stable complex formation with a panel of 13 gangliosides, supporting direct binding of GP1c-type gangliosides. Reason: Direct experimental ganglioside binding; consistent with lipid-binding function. Supporting Evidence: PMID:1454804 formed stable complexes with 13 different gangliosides
GO:0005543 phospholipid binding	IDA PMID:14674747 Solution structure of human saposin C: pH-dependent interact...	ACCEPT	Summary: Saposin C binds phospholipid vesicles/membranes in a pH-dependent, reversible manner (NMR study), directly demonstrating phospholipid binding. Membrane binding is essential for saposin C to activate lysosomal lipid degradation. Reason: Direct experimental evidence for saposin C phospholipid/membrane binding, integral to the activator/lipid-transfer function. Supporting Evidence: PMID:14674747 the binding of saposin C to phospholipid vesicles is a pH-controlled reversible process
GO:0042803 protein homodimerization activity	IDA PMID:18462685 Crystal structures of human saposins C andD: implications fo...	ACCEPT	Summary: Crystal structures show saposin C forming domain-swapped homodimers and saposin D forming a defined homodimer (confirmed in solution), directly supporting protein homodimerization activity. Saposin B likewise functions as a homodimer. Reason: Direct structural evidence for saposin homodimerization; consistent with the functional dimeric lipid-binding shells of the saposins. Supporting Evidence: PMID:18462685 two crystal structures of human saposin C in an "open" configuration with unusual domain swapped homodimers
GO:0005515 protein binding	IPI PMID:22431521 The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) ...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI reflecting the prosaposin-sortilin (SORT1) interaction examined in the CLN5/endosomal-sorting study; unlike prosaposin, CLN5 does not require sortilin for lysosomal localization. The generic term is uninformative, though the underlying PSAP-sortilin interaction is real and relevant to lysosomal targeting. Reason: Uninformative bare protein binding term; the biologically meaningful PSAP-SORT1 interaction (lysosomal targeting) is documented in UniProt SUBUNIT and better captured functionally elsewhere. Supporting Evidence: PMID:22431521 CLN5, unlike prosaposin, does not require sortilin to localize to the lysosomal compartment
GO:0005764 lysosome	IDA PMID:22431521 The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) ...	ACCEPT	Summary: Prosaposin is used as a sortilin-dependent lysosomal cargo in this study; its lysosomal localization is directly observed. Confirms the core lysosomal localization. Reason: Experimental confirmation of core lysosomal localization. Supporting Evidence: PMID:22431521 CLN5, unlike prosaposin, does not require sortilin to localize to the lysosomal compartment
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6798739	KEEP AS NON CORE	Summary: Plasma membrane localization from a Reactome neutrophil-degranulation (azurophil granule exocytosis) reaction. Reflects transient association during secretion of granule contents rather than a stable functional plasma-membrane pool. Reason: Reactome degranulation pathway localization; peripheral/transient, non-core.
GO:0035577 azurophil granule membrane	TAS Reactome:R-HSA-6798739	KEEP AS NON CORE	Summary: Azurophil granule membrane localization from a Reactome neutrophil-degranulation reaction, reflecting prosaposin cargo in neutrophil secretory granules. Non-core. Reason: Neutrophil granule localization from the degranulation pathway; non-core.
GO:0010506 regulation of autophagy	TAS PMID:22949512 Reduced cathepsins B and D cause impaired autophagic degrada...	KEEP AS NON CORE	Summary: In saposin C-deficient fibroblasts, autophagic degradation is impaired (delayed autolysosome degradation, reduced cathepsins B/D). This links PSAP/saposin C to autophagy, but as a downstream consequence of impaired lysosomal function rather than a direct autophagy-regulatory role. Reason: Autophagy phenotype is a secondary consequence of saposin C deficiency and lysosomal dysfunction; genuine but indirect and non-core. Supporting Evidence: PMID:22949512 Reduced cathepsins B and D cause impaired autophagic degradation
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: High-throughput proteomic detection of prosaposin in exosomes (prostatic secretions). Consistent with the secreted prosaposin form; non-core localization. Reason: Proteomics-based exosome detection of the secreted form; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005576 extracellular region	HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu...	KEEP AS NON CORE	Summary: High-throughput proteomic detection of prosaposin in human colostrum/milk aqueous phase, consistent with the secreted prosaposin form (prosaposin is abundant in milk). Non-core. Reason: Proteomics-based extracellular detection of the secreted form; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005576 extracellular region	TAS Reactome:R-HSA-380073	KEEP AS NON CORE	Summary: Extracellular region from a Reactome Gi-GPCR signalling reaction, reflecting secreted prosaposin acting as an extracellular GPCR ligand (GPR37/GPR37L1). Non-core. Reason: Extracellular localization tied to the secreted prosaposin GPCR-ligand role; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005576 extracellular region	TAS Reactome:R-HSA-5336182	KEEP AS NON CORE	Summary: Extracellular region from the Reactome reaction GPR37 binds prosaptide, i.e. secreted prosaposin/prosaptide engaging its GPCR. Non-core. Reason: Extracellular localization for the secreted prosaposin GPCR-ligand role; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005576 extracellular region	TAS Reactome:R-HSA-5336184	KEEP AS NON CORE	Summary: Extracellular region from the Reactome reaction GPR37L binds prosaposin, reflecting secreted prosaposin engaging GPR37L1. Non-core. Reason: Extracellular localization for the secreted prosaposin GPCR-ligand role; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005576 extracellular region	TAS Reactome:R-HSA-749454	KEEP AS NON CORE	Summary: Extracellular region from a Reactome Gi-GPCR complex-dissociation reaction, part of the secreted-prosaposin GPCR signalling pathway. Non-core. Reason: Extracellular localization for the secreted prosaposin GPCR-ligand role; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005576 extracellular region	TAS Reactome:R-HSA-749456	KEEP AS NON CORE	Summary: Extracellular region from a Reactome ligand-GPCR-Gi binding reaction, part of the secreted prosaposin GPCR signalling pathway. Non-core. Reason: Extracellular localization for the secreted prosaposin GPCR-ligand role; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: High-throughput proteomic detection of prosaposin in urinary exosomes. Consistent with the secreted prosaposin form; non-core localization. Reason: Proteomics-based exosome detection of the secreted form; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005515 protein binding	IPI PMID:20709014 Regulation of cell proliferation and apoptosis through fibro...	MARK AS OVER ANNOTATED	Summary: Bare protein binding IPI capturing the prosaposin-fibrocystin/polyductin (FPC, PKHD1 product; P08F94) interaction identified by yeast two-hybrid and confirmed by GST pull-down/co-IP. The interaction is real and proposed to modulate cell proliferation/apoptosis, but the generic term is uninformative. Reason: Uninformative bare protein binding term; the specific PSAP-fibrocystin interaction is documented but its molecular function for prosaposin is not captured by this generic term. Flagged, not removed (experimental IPI). Supporting Evidence: PMID:20709014 we confirmed the interaction between FPC and prosaposin
GO:0005576 extracellular region	TAS Reactome:R-HSA-351341	KEEP AS NON CORE	Summary: Extracellular region from the Reactome Exocytosis of Proactivator polypeptide reaction, reflecting secretion of prosaposin. Consistent with the secreted form; non-core. Reason: Extracellular localization from the prosaposin-exocytosis reaction; non-core. Supporting Evidence: file:human/PSAP/PSAP-uniprot.txt SUBCELLULAR LOCATION: [Prosaposin]: Secreted
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-1605591	ACCEPT	Summary: Lysosomal membrane localization from the Reactome reaction GBA1:SAPC hydrolyzes GlcCer, where saposin C acts at the lysosomal membrane to present glucosylceramide to glucocerebrosidase. Consistent with saposin C membrane association during the core activator reaction. Reason: Correct - saposin C associates with the lysosomal (intralysosomal) membrane to present substrate to GBA1; consistent with the pH-dependent membrane-binding of saposin C. Supporting Evidence: PMID:14674747 Saposin C binds to membranes to activate lipid degradation in lysosomes
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-9840334	ACCEPT	Summary: Lysosomal membrane localization from the Reactome reaction PSAP is cleaved, reflecting the membrane-associated processing/action of prosaposin and saposins in the lysosome. Consistent with the lysosomal site of function. Reason: Correct lysosomal-membrane localization consistent with the intralysosomal membrane-associated saposin function. Supporting Evidence: PMID:14674747 Saposin C binds to membranes to activate lipid degradation in lysosomes

Gene Description

Existing Annotations Review

Core Functions

The saposins act as lipid-binding/lipid-transfer proteins that extract or solubilise membrane glycosphingolipids (including gangliosides and sulfatide) and phospholipids and present them to their cognate acid hydrolases, enabling sphingolipid catabolism in the lysosome.

References

📚 Additional Documentation

Notes

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