asah2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: Plasma membrane is the site of action of neutral ceramidase; the PAINT node (PTN000292661) is seeded by human, mouse, rat and the zebrafish gene itself, whose overexpressed enzyme localized to the plasma membrane in CHOP/BRF41 cells. Reason: Zebrafish Asah2 is a type II single-pass membrane protein whose catalytic domain faces the lumen/extracellular side, and the zebrafish study directly placed the overexpressed enzyme at the plasma membrane; UniProt records cell membrane with experimental evidence. ZFIN:ZDB-GENE-041112-1 in WITH/FROM reflects that target-level IDA evidence and is expected, not circular. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Cell membrane {ECO:0000269\|PubMed:15271994}; Single-pass type II membrane protein PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes file:DANRE/asah2/asah2-uniprot.txt Signal-anchor for type II membrane protein
GO:0042759 long-chain fatty acid biosynthetic process	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Long-chain fatty acid biosynthetic process is propagated from a family node (PTN004377481) seeded by two Pseudomonas aeruginosa ceramidases; the free fatty acid released by Asah2 is a hydrolysis product of ceramide catabolism, not the output of a fatty acid biosynthetic pathway. Reason: The reaction is N-acylsphingosine + H2O -> sphingosine + fatty acid with a left-to-right physiological direction; describing the fatty acid leaving group as fatty acid biosynthesis conflates a catabolic amide hydrolysis with a biosynthetic pathway. The zebrafish enzyme is a plasma-membrane/extracellular-facing ceramidase, so this family-level term overstates its role in fatty acid biosynthesis; ceramide catabolic process (GO:0046514) and sphingosine biosynthetic process (GO:0046512) already capture the correct process context. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN004377481 SUPPORTS SOURCE BUT NOT TARGET Ancestral node placement covers the amidase reaction, but the biosynthetic framing of the fatty acid leaving group does not describe what the zebrafish ceramidase does physiologically. UniProtKB:O06769 SOURCE WEAK OR INFERRED Pseudomonas aeruginosa ceramidase donor; the term reflects fatty acid release during ceramide hydrolysis rather than a biosynthetic pathway. UniProtKB:Q9I596 SOURCE WEAK OR INFERRED Second Pseudomonas donor with the same reaction-derived term. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Reaction=an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid file:DANRE/asah2/asah2-uniprot.txt PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20857 file:DANRE/asah2/asah2-uniprot.txt Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH (PubMed:15271994)
GO:0046512 sphingosine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Sphingosine biosynthetic process: ceramide hydrolysis by Asah2 is the principal non-lysosomal source of free sphingosine; the node is seeded by human, mouse and rat neutral ceramidases and bacterial homologs. Reason: The reaction product sphing-4-enine is sphingosine, and the zebrafish enzyme was shown to have neutral ceramidase activity, so Asah2 directly performs the sphingosine-forming step of the salvage pathway. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Reaction=an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid file:DANRE/asah2/asah2-uniprot.txt Together with sphingomyelinase, participates in the production of sphingosine and sphingosine-1-phosphate from the degradation of sphingomyelin PMID:15271994 The enzyme activity at neutral pH increased markedly after transformation of Chinese hamster CHOP and zebrafish BRF41 cells with the cDNA
GO:0017040 N-acylsphingosine amidohydrolase activity	IBA GO_REF:0000033	ACCEPT	Summary: N-acylsphingosine amidohydrolase (ceramidase) activity is the defining activity of the family; the zebrafish cDNA conferred neutral-pH ceramidase activity on CHOP and BRF41 cells, and the zebrafish gene is itself among the IBD donors. Reason: Direct target-level evidence (IDA from PMID:15271994) plus conserved Zn-dependent amidase catalytic machinery (active-site nucleophile and four Zn ligands annotated by similarity to the human structure) support the core molecular function. Supporting Evidence: PMID:15271994 The enzyme activity at neutral pH increased markedly after transformation of Chinese hamster CHOP and zebrafish BRF41 cells with the cDNA file:DANRE/asah2/asah2-uniprot.txt Reaction=an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid PMID:26190575 Our results suggest that nCDase uses a new catalytic strategy for Zn(2+)-dependent amidases
GO:0046514 ceramide catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Ceramide catabolic process: Asah2 hydrolyzes ceramide to sphingosine and fatty acid, and knockdown in embryos raised ceramide levels, showing the zebrafish enzyme degrades ceramide in vivo. Reason: Both the in vitro activity and the in vivo ceramide accumulation in morphants show that Asah2 performs the ceramide-degrading step; this is the core process for the gene. Supporting Evidence: PMID:15271994 The ceramide level in AMO-injected embryos increased significantly compared with that in control embryos PMID:15271994 These results indicate that znCD is essential for the metabolism of ceramide and the early development of zebrafish file:DANRE/asah2/asah2-uniprot.txt Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH (PubMed:15271994)
GO:0000139 Golgi membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Golgi membrane mapped from the UniProt subcellular-location line, which itself is inferred from human ASAH2; in zebrafish the overexpressed enzyme was seen in ER/Golgi compartments. Reason: Golgi presence is consistent with secretory-pathway transit of an overexpressed type II membrane glycoprotein, but the physiological site of ceramide hydrolysis is the plasma membrane; retain as a non-core location. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Golgi apparatus membrane {ECO:0000250\|UniProtKB:Q9NR71} PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes
GO:0005576 extracellular region	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Extracellular region mapped from the UniProt "Secreted, extracellular exosome" annotation, which is transferred from human ASAH2; no zebrafish data address release of the enzyme. Reason: Release of neutral ceramidase in exosomes or as a shed form is documented for mammalian orthologs and is plausible for a type II membrane protein with an O-glycosylated stalk, but it has not been observed in zebrafish; keep as a non-core location. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Secreted, extracellular exosome {ECO:0000250\|UniProtKB:Q9NR71}
GO:0005737 cytoplasm	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Cytoplasm is an ARBA machine-learning prediction; Asah2 is a single-pass type II membrane protein with a 14-residue cytoplasmic tail and a lumenal/extracellular catalytic domain. Reason: Only the short N-terminal tail is cytosolic and no cytoplasmic pool of the enzyme has been reported; the term is not strictly false (mitochondrion is a descendant) but is uninformative and misleading for a plasma-membrane ceramidase. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Signal-anchor for type II membrane protein PMID:15271994 A possible signal/anchor sequence near the N terminus and four potential O-glycosylation and eight potential N-glycosylation sites were found in the putative sequence file:DANRE/asah2/asah2-uniprot.txt Cell membrane {ECO:0000269\|PubMed:15271994}; Single-pass type II membrane protein
GO:0005739 mitochondrion	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: Mitochondrion is transferred from human ASAH2, where it rests on overexpression studies; the zebrafish overexpression study reported ER/Golgi and plasma membrane distribution and did not report mitochondria. Reason: UniProt lists mitochondrion only by similarity to human, the mammalian evidence comes from overexpressed protein that can confound steady-state localization, and the one zebrafish localization study found no mitochondrial signal. The claim exceeds the evidence for the zebrafish protein. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Mitochondrion {ECO:0000250\|UniProtKB:Q9NR71} PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes file:DANRE/asah2/asah2-deep-research-falcon.md reports of mitochondrial localization in overexpression studies (noting that overexpression can confound steady-state localization)
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: Plasma membrane (ARBA and UniProt subcellular-location mapping) matches the experimentally supported localization of zebrafish Asah2. Reason: UniProt records cell membrane with experimental evidence from the zebrafish study, in which the overexpressed enzyme localized to the plasma membrane. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Cell membrane {ECO:0000269\|PubMed:15271994}; Single-pass type II membrane protein PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes
GO:0005901 caveola	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Caveola is mapped from a UniProt location transferred from mouse Asah2 (Q9JHE3); no zebrafish data address membrane microdomain partitioning. Reason: Caveolar/raft partitioning is a mammalian refinement of the plasma-membrane localization; plausible for the ortholog but untested in zebrafish, so it is retained as non-core. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Membrane, caveola {ECO:0000250\|UniProtKB:Q9JHE3}
GO:0006672 ceramide metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: Ceramide metabolic process (ARBA) is the parent of the ceramide catabolic process that Asah2 performs. Reason: Correct though general; ceramide hydrolysis by Asah2 and ceramide accumulation in morphants place the enzyme squarely in ceramide metabolism. The more specific catabolic term is also annotated. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH (PubMed:15271994) PMID:15271994 The ceramide level in AMO-injected embryos increased significantly compared with that in control embryos
GO:0017040 N-acylsphingosine amidohydrolase activity	IEA GO_REF:0000120	ACCEPT	Summary: N-acylsphingosine amidohydrolase activity from InterPro IPR006823/Rhea/EC 3.5.1.23 mapping; confirmed experimentally for the zebrafish enzyme. Reason: The zebrafish cDNA conferred neutral-pH ceramidase activity, matching the mapped EC 3.5.1.23 reaction. Supporting Evidence: PMID:15271994 The enzyme activity at neutral pH increased markedly after transformation of Chinese hamster CHOP and zebrafish BRF41 cells with the cDNA file:DANRE/asah2/asah2-uniprot.txt Reaction=an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid
GO:0045121 membrane raft	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Membrane raft is transferred from mouse Asah2 (Q9JHE3); raft partitioning has not been examined for the zebrafish protein. Reason: A sub-domain refinement of the supported plasma-membrane localization; plausible by orthology but not shown in zebrafish, so retained as non-core. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Membrane raft {ECO:0000250\|UniProtKB:Q9JHE3} file:DANRE/asah2/asah2-uniprot.txt Cell membrane {ECO:0000269\|PubMed:15271994}; Single-pass type II membrane protein
GO:0046514 ceramide catabolic process	IEA GO_REF:0000002	ACCEPT	Summary: Ceramide catabolic process mapped from the neutral ceramidase InterPro entry; supported by zebrafish in vivo data. Reason: Knockdown raised embryonic ceramide levels and the enzyme hydrolyzes ceramide in vitro, so the mapping is correct for this gene. Supporting Evidence: PMID:15271994 The ceramide level in AMO-injected embryos increased significantly compared with that in control embryos file:DANRE/asah2/asah2-uniprot.txt Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH (PubMed:15271994)
GO:0006665 sphingolipid metabolic process	IEA GO_REF:0000041	ACCEPT	Summary: Sphingolipid metabolic process from UniPathway UPA00222 (sphingolipid metabolism); a broad but correct parent of ceramide catabolism. Reason: Ceramide hydrolysis to sphingosine is a sphingolipid metabolic step that Asah2 catalyzes; the term is general but not wrong, and the specific child terms are also annotated. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Together with sphingomyelinase, participates in the production of sphingosine and sphingosine-1-phosphate from the degradation of sphingomyelin file:DANRE/asah2/asah2-uniprot.txt Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH (PubMed:15271994)
GO:0000139 Golgi membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Golgi membrane transferred from human ASAH2; the zebrafish overexpression study also saw ER/Golgi distribution. Reason: Golgi localization reflects secretory-pathway transit of a glycosylated type II membrane enzyme rather than its site of action, which is the plasma membrane; keep as non-core. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Golgi apparatus membrane {ECO:0000250\|UniProtKB:Q9NR71} PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes
GO:0005739 mitochondrion	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Mitochondrion is transferred from human ASAH2, where it rests on overexpression studies; the zebrafish overexpression study reported ER/Golgi and plasma membrane distribution and did not report mitochondria. Reason: UniProt lists mitochondrion only by similarity to human, the mammalian evidence comes from overexpressed protein that can confound steady-state localization, and the one zebrafish localization study found no mitochondrial signal. The claim exceeds the evidence for the zebrafish protein. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Mitochondrion {ECO:0000250\|UniProtKB:Q9NR71} PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes file:DANRE/asah2/asah2-deep-research-falcon.md reports of mitochondrial localization in overexpression studies (noting that overexpression can confound steady-state localization)
GO:0045121 membrane raft	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Membrane raft is transferred from mouse Asah2 (Q9JHE3); raft partitioning has not been examined for the zebrafish protein. Reason: A sub-domain refinement of the supported plasma-membrane localization; plausible by orthology but not shown in zebrafish, so retained as non-core. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Membrane raft {ECO:0000250\|UniProtKB:Q9JHE3} file:DANRE/asah2/asah2-uniprot.txt Cell membrane {ECO:0000269\|PubMed:15271994}; Single-pass type II membrane protein
GO:0005739 mitochondrion	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Mitochondrion is transferred from human ASAH2, where it rests on overexpression studies; the zebrafish overexpression study reported ER/Golgi and plasma membrane distribution and did not report mitochondria. Reason: UniProt lists mitochondrion only by similarity to human, the mammalian evidence comes from overexpressed protein that can confound steady-state localization, and the one zebrafish localization study found no mitochondrial signal. The claim exceeds the evidence for the zebrafish protein. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Mitochondrion {ECO:0000250\|UniProtKB:Q9NR71} PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes file:DANRE/asah2/asah2-deep-research-falcon.md reports of mitochondrial localization in overexpression studies (noting that overexpression can confound steady-state localization)
GO:0007346 regulation of mitotic cell cycle	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Regulation of mitotic cell cycle is transferred from human ASAH2, where it derives from cell-culture effects of altering the ceramide/sphingosine-1-phosphate balance. Reason: Asah2 does no work in cell-cycle control; any effect is a downstream consequence of changing bioactive sphingolipid levels. No zebrafish data address proliferation, and UniProt itself frames proliferation only as a downstream signaling outcome of ceramide/S1P. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation
GO:0046512 sphingosine biosynthetic process	ISS GO_REF:0000024	ACCEPT	Summary: Sphingosine biosynthetic process transferred from human ASAH2; the zebrafish enzyme produces sphingosine by ceramide hydrolysis. Reason: Same reaction demonstrated directly for the zebrafish protein; the transfer is sound. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Reaction=an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid PMID:15271994 The enzyme activity at neutral pH increased markedly after transformation of Chinese hamster CHOP and zebrafish BRF41 cells with the cDNA
GO:0046513 ceramide biosynthetic process	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Ceramide biosynthetic process is transferred from human ASAH2 on the basis of the in vitro reverse (condensation) reaction; the physiological direction of the zebrafish enzyme is hydrolysis. Reason: UniProt records the reverse reaction only by similarity and annotates the physiological direction as left-to-right (hydrolysis); in vivo, loss of Asah2 raised, not lowered, ceramide, so a ceramide-biosynthetic role over-interprets an in vitro reversibility. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine file:DANRE/asah2/asah2-uniprot.txt PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20857 PMID:15271994 The ceramide level in AMO-injected embryos increased significantly compared with that in control embryos
GO:0046514 ceramide catabolic process	ISS GO_REF:0000024	ACCEPT	Summary: Ceramide catabolic process transferred from human ASAH2; directly supported in zebrafish. Reason: Zebrafish Asah2 hydrolyzes ceramide in vitro and its knockdown raises embryonic ceramide, so the transferred term is correct. Supporting Evidence: PMID:15271994 The ceramide level in AMO-injected embryos increased significantly compared with that in control embryos file:DANRE/asah2/asah2-uniprot.txt Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH (PubMed:15271994)
GO:0005509 calcium ion binding	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Calcium ion binding transferred from human ASAH2, whose crystal structure contains a structural Ca2+ site; UniProt annotates the equivalent zebrafish ligands (residues 672, 674 and 677) by similarity. Reason: The Ca2+ site is a conserved structural feature, not the catalytic metal (Zn2+ is the cofactor), and it has not been tested in the zebrafish protein; retain as a non-core molecular feature rather than a defining activity. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt /ligand="Ca(2+)" file:DANRE/asah2/asah2-uniprot.txt /ligand_id="ChEBI:CHEBI:29108" file:DANRE/asah2/asah2-uniprot.txt Note=Binds 1 zinc ion per subunit.
GO:0006670 sphingosine metabolic process	ISS GO_REF:0000024	ACCEPT	Summary: Sphingosine metabolic process transferred from human ASAH2; a parent of sphingosine biosynthesis, which the zebrafish enzyme performs. Reason: Asah2 generates sphingosine from ceramide; the general term is correct and the specific biosynthetic child is also annotated. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Reaction=an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid file:DANRE/asah2/asah2-uniprot.txt Together with sphingomyelinase, participates in the production of sphingosine and sphingosine-1-phosphate from the degradation of sphingomyelin
GO:0008270 zinc ion binding	ISS GO_REF:0000024	ACCEPT	Summary: Zinc ion binding transferred from human ASAH2, a Zn2+-dependent amidase; UniProt annotates one catalytic zinc with four ligands (151, 260, 498, 538) in the zebrafish protein by similarity. Reason: Zinc is the catalytic cofactor of the neutral ceramidase fold, so zinc binding is integral to the core amidohydrolase activity of the zebrafish enzyme. Supporting Evidence: file:DANRE/asah2/asah2-uniprot.txt Note=Binds 1 zinc ion per subunit. file:DANRE/asah2/asah2-uniprot.txt /ligand="Zn(2+)" PMID:26190575 Our results suggest that nCDase uses a new catalytic strategy for Zn(2+)-dependent amidases
GO:0000139 Golgi membrane	IDA PMID:15271994 Molecular cloning and functional analysis of zebrafish neutr...	KEEP AS NON CORE	Summary: Golgi membrane: overexpressed zebrafish neutral ceramidase distributed to ER/Golgi compartments as well as the plasma membrane (abstract-only cache). Reason: The observation is direct, but it is of overexpressed enzyme in transit through the secretory pathway; the site of ceramide hydrolysis is the plasma membrane, so Golgi is retained as a non-core location. Supporting Evidence: PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes
GO:0005789 endoplasmic reticulum membrane	IDA PMID:15271994 Molecular cloning and functional analysis of zebrafish neutr...	KEEP AS NON CORE	Summary: Endoplasmic reticulum membrane: overexpressed zebrafish neutral ceramidase was distributed to ER/Golgi compartments (abstract-only cache). Reason: Direct but overexpression-derived ER signal consistent with biosynthetic transit of a glycosylated type II membrane protein; not the site of action, so non-core. Supporting Evidence: PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes
GO:0005886 plasma membrane	ISS PMID:15271994 Molecular cloning and functional analysis of zebrafish neutr...	ACCEPT	Summary: Plasma membrane by similarity to mouse Asah2, cited to the zebrafish cloning paper, which itself observed plasma-membrane distribution. Reason: Consistent with the direct zebrafish observation and with the type II membrane topology; the plasma membrane is where ceramide hydrolysis occurs. Supporting Evidence: PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes file:DANRE/asah2/asah2-uniprot.txt Cell membrane {ECO:0000269\|PubMed:15271994}; Single-pass type II membrane protein
GO:0005886 plasma membrane	IDA PMID:15271994 Molecular cloning and functional analysis of zebrafish neutr...	ACCEPT	Summary: Plasma membrane: the overexpressed zebrafish enzyme localized to the plasma membranes of transfected cells. Reason: Direct observation of the zebrafish protein at its expected site of action; UniProt records this as the experimentally supported location. Supporting Evidence: PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes file:DANRE/asah2/asah2-uniprot.txt Cell membrane {ECO:0000269\|PubMed:15271994}; Single-pass type II membrane protein
GO:0006672 ceramide metabolic process	IDA PMID:15271994 Molecular cloning and functional analysis of zebrafish neutr...	ACCEPT	Summary: Ceramide metabolic process (acts_upstream_of_or_within): morpholino knockdown of znCD significantly increased embryonic ceramide, and co-injected mRNA rescued activity. Reason: In vivo evidence that the zebrafish enzyme controls ceramide levels; the curator chose the general metabolic term, which is correct, and the catabolic child is annotated from other evidence. Supporting Evidence: PMID:15271994 The ceramide level in AMO-injected embryos increased significantly compared with that in control embryos PMID:15271994 Simultaneous injection of both AMO and synthetic znCD mRNA into one-cell-stage embryos rescued znCD activity and blood cell circulation PMID:15271994 These results indicate that znCD is essential for the metabolism of ceramide and the early development of zebrafish
GO:0016324 apical plasma membrane	IDA PMID:15271994 Molecular cloning and functional analysis of zebrafish neutr...	ACCEPT	Summary: Apical plasma membrane: ZFIN annotation from the zebrafish cloning paper; the cached abstract reports plasma-membrane distribution and UniProt records intestinal protein expression from the same study, consistent with brush-border localization. Reason: The abstract does not itself state apical localization, but the ZFIN curator read the full text (immunolocalization in intestine is the likely basis) and apical brush-border localization is the known pattern for neutral ceramidase in epithelia; accepted, deferring to the curator on the full-text detail. Supporting Evidence: PMID:15271994 The overexpressed enzyme was found to be distributed in endoplasmic reticulum/Golgi compartments as well as the plasma membranes file:DANRE/asah2/asah2-uniprot.txt Detected in intestine (at protein level)
GO:0017040 N-acylsphingosine amidohydrolase activity	IDA PMID:15271994 Molecular cloning and functional analysis of zebrafish neutr...	ACCEPT	Summary: N-acylsphingosine amidohydrolase activity: transfection of the zebrafish cDNA markedly increased neutral-pH ceramidase activity in CHOP and BRF41 cells, and synthetic mRNA rescued activity in morphants. Reason: Direct demonstration of the core catalytic activity of the zebrafish enzyme. Supporting Evidence: PMID:15271994 The enzyme activity at neutral pH increased markedly after transformation of Chinese hamster CHOP and zebrafish BRF41 cells with the cDNA PMID:15271994 Simultaneous injection of both AMO and synthetic znCD mRNA into one-cell-stage embryos rescued znCD activity and blood cell circulation file:DANRE/asah2/asah2-uniprot.txt Reaction=an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid

Gene Description

Existing Annotations Review

Core Functions

Neutral ceramidase: hydrolyzes ceramide to sphingosine and a free fatty acid at the plasma membrane, driving ceramide catabolism and supplying sphingosine for sphingosine-1-phosphate synthesis.

References

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