spmT Resolved · high auto-curated
H37Rv Rv0888 · MTBC0 mtbc0_000943 ·
490 aa · 990447–991919 (+) ·
RefSeq NP_215403.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | sphingomyelinase |
| Revised (this work) | Sphingomyelinase. Pfam: Big_9 (PF17963.8), Exo_endo_phos (PF03372.30). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKQ1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sphingomyelinase |
| EC (curated) |
EC 3.1.4.12
|
| Curated function | Catalyzes the cleavage of sphingomyelin, a major lipid in eukaryotic cells, into ceramide and phosphocholine, which are then utilized by M.tuberculosis as carbon, nitrogen and phosphorus sources, respectively. Thus, enables M.tuberculosis to utilize sphingomyelin as a source of several essential nutrients for intracellular growth during infection. Furthermore, lyses erythrocytes and constitutes the main hemolytic factor of M.tuberculosis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Endonuclease/Exonuclease/phosphatase family |
| Orthologous group | COG3021 |
| Gene Ontology (75) |
GO:0001906, GO:0003674, GO:0003824, GO:0004620, GO:0004767, GO:0005215, GO:0005575, GO:0005623, GO:0006629, GO:0006643, GO:0006644, GO:0006665 +63 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 | 0.813 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 10 missense, 0 nonsense, 6 frameshift |
| Disruption | 6 distinct premature-stop/frameshift site(s); most common in 21.21% of strains (30806) · convergent |
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 |
|---|---|---|---|---|
Big_9 | PF17963.8 | 1.5e-11 | 104–187 | Bacterial Ig domain |
Exo_endo_phos | PF03372.30 | 9.0e-10 | 335–473 | Endonuclease/Exonuclease/phosphatase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: celA2b (Rv1090, (MTV017.43), len: 151 aa. Probable celA2b,second part of cellulase (endoglucanase), similar to C-terminus of others e.g. O08468 cell), medium confidence from genomic context alone (score 687 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1469 ctpD |
cobalt/nickel-exporting P-type ATPase | 799 | 800 | coexpression:799 |
Rv0312 hyp |
hypothetical protein | 792 | 788 | coexpression:734 |
Rv3700c egtE |
pyridoxal-phosphate-dependent protein EgtE | 783 | 784 | experimental:780 |
Rv3778c |
aminotransferase | 783 | 783 | experimental:780 |
Rv1464 csd |
cysteine desulfurase | 781 | 781 | experimental:780 |
Rv3403c hyp |
hypothetical protein | 764 | 765 ctx | cooccurence:599 coexpression:438 |
Rv1754c hyp |
hypothetical protein | 764 | 733 | coexpression:732 |
Rv0040c mtc28 hyp |
hypothetical protein | 703 | 703 | coexpression:703 |
Rv3903c cpnT hyp |
hypothetical protein | 823 | 692 | database:540 textmining:450 |
Rv1090 celA2b |
Rv1090, (MTV017.43), len: 151 aa. Probable celA2b,second part of cellulase (endoglucanase), similar to C-terminus of others e.g. O08468 cell | 687 | 687 ctx | cooccurence:685 |
Rv1690 lprJ |
lipoprotein LprJ | 687 | 687 | coexpression:687 |
Rv1004c |
membrane protein | 679 | 680 ctx | cooccurence:660 |
Rv1651c PE_PGRS30 |
PE-PGRS family protein PE_PGRS30 | 659 | 650 ctx | cooccurence:650 |
Rv0330c hyp |
hypothetical protein | 648 | 648 ctx | cooccurence:645 |
Rv3347c PPE55 |
PPE family protein PPE55 | 641 | 641 ctx | cooccurence:639 |
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: hypothetical protein
- MTBC0 PGAP product: sphingomyelinase
- Pfam (hmmscan --cut_ga): Big_9 PF17963.8 (E=1e-11), Exo_endo_phos PF03372.30 (E=9e-10)
- (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_215403.1)
- Domains: Pfam-A via hmmscan --cut_ga — Big_9 (PF17963.8), Exo_endo_phos (PF03372.30)
- 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
COG3021 - Curated reference: UniProt P9WKQ1 (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 —
80 functional partner(s); context anchor
celA2b - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000943|Rv0888|spmT MDYAKRIGQVGALAVVLGVGAAVTTHAIGSAAPTDPSSSSTDSPVDACSPLGGSASSLAAIPGASVPQVGVRQVDPGSIPDDLLNALIDFLAAVRNGLVPIIENRTPVANPQQVSVPEGGTVGPVRFDACDPDGNRMTFAVRERGAPGGPQHGIVTVDQRTASFIYTADPGFVGTDTFSVNVSDDTSLHVHGLAGYLGPFHGHDDVATVTVFVGNTPTDTISGDFSMLTYNIAGLPFPLSSAILPRFFYTKEIGKRLNAYYVANVQEDFAYHQFLIKKSKMPSQTPPEPPTLLWPIGVPFSDGLNTLSEFKVQRLDRQTWYECTSDNCLTLKGFTYSQMRLPGGDTVDVYNLHTNTGGGPTTNANLAQVANYIQQNSAGRAVIVTGDFNARYSDDQSALLQFAQVNGLTDAWVQVEHGPTTPPFAPTCMVGNECELLDKIFYRSGQGVTLQAVSYGNEAPKFFNSKGEPLSDHSPAVVGFHYVADNVAVR