ASAH2B

UniProt ID: P0C7U1
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

ASAH2B (ASAH2L) is a partial paralog of the neutral ceramidase ASAH2, arising from a segmental duplication on chromosome 10. Its 165-residue product corresponds only to the C-terminal region of ASAH2 and lacks the catalytic nucleophile and zinc-binding residues, so it is predicted to be catalytically inactive. It is supported only at the transcript level. Its transcript is broadly expressed and decreases with age and further in late-onset Alzheimer disease. No function has been established.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005737 cytoplasm
IEA
GO_REF:0000117 		UNDECIDED
Summary: Cytoplasm (IEA, ARBA). The rule transfers neutral-ceramidase family locations. ASAH2B has only transcript-level evidence, lacks the N-terminal signal anchor that targets ASAH2, and has never been localized. Left undecided.
Reason: [file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md "Aligned ASAH2 region: 636-780 (145 aligned positions, 137 identical)"] [file:human/ASAH2B/ASAH2B-uniprot.txt "PE 2: Evidence at transcript level;"]
Supporting Evidence:
file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md
Aligned ASAH2 region: 636-780 (145 aligned positions, 137 identical)
file:human/ASAH2B/ASAH2B-uniprot.txt
PE 2: Evidence at transcript level;
GO:0005886 plasma membrane
IEA
GO_REF:0000117 		UNDECIDED
Summary: Plasma membrane (IEA, ARBA). The rule transfers neutral-ceramidase family locations. ASAH2B has only transcript-level evidence, lacks the N-terminal signal anchor that targets ASAH2, and has never been localized. Left undecided.
Reason: [file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md "Aligned ASAH2 region: 636-780 (145 aligned positions, 137 identical)"] [file:human/ASAH2B/ASAH2B-uniprot.txt "PE 2: Evidence at transcript level;"]
Supporting Evidence:
file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md
Aligned ASAH2 region: 636-780 (145 aligned positions, 137 identical)
file:human/ASAH2B/ASAH2B-uniprot.txt
PE 2: Evidence at transcript level;
GO:0017040 N-acylsphingosine amidohydrolase activity
IEA
GO_REF:0000120 		REMOVE
Summary: N-acylsphingosine amidohydrolase activity (IEA, ARBA/InterPro). ASAH2B matches only the C-terminal ~145 residues (636-780) of the neutral ceramidase ASAH2. It lacks the catalytic nucleophile S354 and all zinc-binding residues, and UniProt names it a putative inactive ceramidase. The domain-based mapping does not hold for this fragment; removed.
Reason: [file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md "Aligned ASAH2 region: 636-780 (145 aligned positions, 137 identical)"] [file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md "Active site ASAH2 S354 (Nucleophile): outside aligned region"] [file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md "Binding site ASAH2 H194 (Zn(2+)): outside aligned region"] [file:human/ASAH2B/ASAH2B-uniprot.txt "DE RecName: Full=Putative inactive neutral ceramidase B {ECO:0000305};"]
Supporting Evidence:
file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md
Aligned ASAH2 region: 636-780 (145 aligned positions, 137 identical)
file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md
Active site ASAH2 S354 (Nucleophile): outside aligned region
file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md
Binding site ASAH2 H194 (Zn(2+)): outside aligned region
file:human/ASAH2B/ASAH2B-uniprot.txt
DE RecName: Full=Putative inactive neutral ceramidase B {ECO:0000305};
GO:0046512 sphingosine biosynthetic process
IEA
GO_REF:0000117 		REMOVE
Summary: Sphingosine biosynthetic process (IEA, ARBA/InterPro). This process term depends on ceramidase activity, which ASAH2B cannot have: it lacks the ASAH2 catalytic nucleophile and zinc site. Removed.
Reason: [file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md "Active site ASAH2 S354 (Nucleophile): outside aligned region"] [file:human/ASAH2B/ASAH2B-uniprot.txt "DE RecName: Full=Putative inactive neutral ceramidase B {ECO:0000305};"]
Supporting Evidence:
file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md
Active site ASAH2 S354 (Nucleophile): outside aligned region
file:human/ASAH2B/ASAH2B-uniprot.txt
DE RecName: Full=Putative inactive neutral ceramidase B {ECO:0000305};
GO:0046513 ceramide biosynthetic process
IEA
GO_REF:0000117 		REMOVE
Summary: Ceramide biosynthetic process (IEA, ARBA/InterPro). This process term depends on ceramidase activity, which ASAH2B cannot have: it lacks the ASAH2 catalytic nucleophile and zinc site. Removed.
Reason: [file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md "Active site ASAH2 S354 (Nucleophile): outside aligned region"] [file:human/ASAH2B/ASAH2B-uniprot.txt "DE RecName: Full=Putative inactive neutral ceramidase B {ECO:0000305};"]
Supporting Evidence:
file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md
Active site ASAH2 S354 (Nucleophile): outside aligned region
file:human/ASAH2B/ASAH2B-uniprot.txt
DE RecName: Full=Putative inactive neutral ceramidase B {ECO:0000305};
GO:0046514 ceramide catabolic process
IEA
GO_REF:0000120 		REMOVE
Summary: Ceramide catabolic process (IEA, ARBA/InterPro). This process term depends on ceramidase activity, which ASAH2B cannot have: it lacks the ASAH2 catalytic nucleophile and zinc site. Removed.
Reason: [file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md "Active site ASAH2 S354 (Nucleophile): outside aligned region"] [file:human/ASAH2B/ASAH2B-uniprot.txt "DE RecName: Full=Putative inactive neutral ceramidase B {ECO:0000305};"]
Supporting Evidence:
file:human/ASAH2B/ASAH2B-bioinformatics/RESULTS.md
Active site ASAH2 S354 (Nucleophile): outside aligned region
file:human/ASAH2B/ASAH2B-uniprot.txt
DE RecName: Full=Putative inactive neutral ceramidase B {ECO:0000305};

References

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Suggested Questions for Experts

Q: Is ASAH2B translated into a stable protein, and if so does its retained C-terminal calcium-binding segment interfere with ASAH2?

Suggested Experiments

Experiment: Detect endogenous ASAH2B peptides by targeted proteomics in human brain, and test ASAH2B co-expression effects on ASAH2 ceramidase activity.

Knowledge Gaps

What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).

Gap: ASAH2B has no established function, and it is unclear whether a stable protein is made at all.

OPEN BIOLOGY WHOLLY_DARK

What is known: Established: partial ASAH2 duplicate with transcript-level evidence; the predicted product covers only ASAH2 residues 636-780 and lacks the catalytic site. Reported: age- and Alzheimer-associated decrease in transcript levels. Not established: protein detection, location or any activity.

Significance: The age- and LOAD-related expression change has no functional explanation; ASAH2B may act as an RNA or a non-catalytic fragment, or have no function.

What would resolve it: Test for endogenous ASAH2B protein by targeted mass spectrometry, and measure whether ASAH2B expression affects ASAH2 activity or ceramide levels.

Provenance (the field's own admissions):

Deep Research

Affinage

(ASAH2B-deep-research-affinage.md)

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📚 Additional Documentation

Notes

(ASAH2B-notes.md)

ASAH2B review notes

Sources

  • UniProt: "Putative inactive neutral ceramidase B"; PE2 (transcript level); a partial paralog of ASAH2 from segmental duplication.
  • Affinage: no mechanistic findings.
  • PMID:17334805 (abstract): ASAH2L expression falls with age and in LOAD.
  • Bioinformatics (ASAH2B-bioinformatics/asah2_coverage.py): ASAH2B aligns only to ASAH2 residues 636-780 (137/145 identical). It lacks the S354 nucleophile and all four Zn-binding residues, keeping one C-terminal Ca-binding site.

Decisions

  • REMOVE: N-acylsphingosine amidohydrolase activity and the three ceramide/sphingosine process rows (all IEA). The fragment cannot form the catalytic site.
  • UNDECIDED: cytoplasm and plasma membrane (IEA ARBA family-location transfers; there is no localization data, and the ASAH2 signal anchor is absent).
  • Knowledge gap: wholly dark; even protein existence is uncertain.

Bioinformatics Results

(RESULTS.md)

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📄 View Raw YAML

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