Rv0669c Resolved · high auto-curated
H37Rv Rv0669c · MTBC0 mtbc0_000708 ·
637 aa · 771770–773683 (-) ·
RefSeq NP_215183.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | neutral ceramidase |
|---|---|
| MTBC0 PGAP re-annotation | neutral ceramidase |
| Revised (this work) | Neutral ceramidase. Pfam: Ceramidase_alk (PF04734.19), Ceramidse_alk_C (PF17048.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O06769
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Neutral ceramidase |
| EC (curated) |
EC 3.5.1.23
|
| Curated function | Catalyzes the cleavage of the N-acyl linkage of the ceramides (Cers) to yield sphingosine (Sph) and free fatty acid. Also catalyzes the synthesis of Cers from Sph and fatty acid. Cers containning C6-C24 fatty acids are well hydrolyzed, and Cers with mono unsaturated fatty acids are much more hydrolyzed than those with saturated fatty acids. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Neutral/alkaline non-lysosomal ceramidase, C-terminal |
| Orthologous group | KOG2232 |
| EC number |
EC 3.5.1.23
|
| KEGG orthology |
K12349
|
| KEGG pathways |
map00600, map01100, map04071
|
| KEGG modules |
M00099
|
| Gene Ontology (70) |
GO:0001676, GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0006066, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0006643 +58 more
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.955 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 14 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (197) · clonal |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Ceramidase_alk | PF04734.19 | 2.6e-152 | 4–482 | Neutral/alkaline non-lysosomal ceramidase, N-terminal |
Ceramidse_alk_C | PF17048.12 | 1.4e-37 | 485–636 | Neutral/alkaline non-lysosomal ceramidase, C-terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: end (endonuclease IV), medium confidence from genomic context alone (score 576 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3332 nagA |
N-acetylglucosamine-6-phosphate deacetylase NagA | 845 | 824 | coexpression:687 experimental:431 |
Rv0670 end |
endonuclease IV | 577 | 576 ctx | neighborhood:558 |
Rv1447c zwf2 |
glucose-6-phosphate 1-dehydrogenase | 542 | 499 | coexpression:482 |
Rv1121 zwf1 |
glucose-6-phosphate 1-dehydrogenase | 539 | 496 | coexpression:479 |
Rv1547 dnaE1 |
DNA polymerase III subunit alpha | 486 | 486 | coexpression:482 |
Rv3370c dnaE2 |
error-prone DNA polymerase | 483 | 483 | coexpression:479 |
Rv0671 lpqP |
lipoprotein LpqP | 440 | 440 ctx | neighborhood:440 |
Rv2043c pncA |
pyrazinamidase/nicotinamidase PncA | 421 | 421 | coexpression:411 |
Rv1834 lipZ |
hydrolase | 413 | 412 ctx | cooccurence:412 |
Rv3068c pgmA |
phosphoglucomutase PgmA | 475 | 408 | |
Rv0957 purH |
bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase | 424 | 403 | |
Rv0189c ilvD |
dihydroxy-acid dehydratase | 457 | 396 | |
Rv1448c tal |
transaldolase | 464 | 393 | |
Rv0408 pta |
phosphate acetyltransferase | 406 | 154 | |
Rv3432c gadB |
glutamate decarboxylase GadB | 499 | 118 | textmining:456 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: neutral ceramidase
- MTBC0 PGAP product: neutral ceramidase
- Pfam (hmmscan --cut_ga): Ceramidase_alk PF04734.19 (E=3e-152), Ceramidse_alk_C PF17048.12 (E=1e-37)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215183.1)
- Domains: Pfam-A via hmmscan --cut_ga — Ceramidase_alk (PF04734.19), Ceramidse_alk_C (PF17048.12)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
KOG2232 - Curated reference: UniProt O06769 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
19 functional partner(s); context anchor
end - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000708|Rv0669c| MLSVGRGIADITGEAADCGMLGYGKSDQRTAGIHQRLRSRAFVFRDDSQDGDARLLLIVAELPLPMQNVNEEVLRRLADLYGDTYSEQNTLITATHTHAGPGGYCGYLLYNLTTSGFRPATFAAIVDGIVESVEHAHADVAPAEVSLSHGELYGASINRSPSAFDRNPPADKAFFPKRVDPHTTLVRIDRGEATVGVIHFFATHGTSMTNRNHLISGDNKGFAAYHWERTVGGADYLAGQPDFIAAFAQTNPGDMSPNVDGPLSPEAPPDREFDNTRRTGLCQFEDAFTQLSGATPIGAGIDARFTYVDLGSVLVRGEYTPDGEERRTGRPMFGAGAMAGTDEGPGFHGFRQGRNPFWDRLSRAMYRLARPTAAAQAPKGIVMPARLPNRIHPFVQEIVPVQLVRIGRLYLIGIPGEPTIVAGLRLRRMVASIVGADLADVLCVGYTNAYIHYVTTPEEYLEQRYEGGSTLFGRWELCALMQTVAELAEAMRDGRPVTLGRRPRPTRELSWVRGAPADAGSFGAVIAEPSATYRPGQAVEAVFVSALPNNDLRRGGTYLEVVRREGASWVRIADDGDWATSFRWQRQGRAGSHVSIRWDVPGDTTPGQYRIVHHGTARDRNGMLTAFSATTREFTVV