sapM Resolved · high auto-curated
H37Rv Rv3310 · MTBC0 mtbc0_003518 ·
299 aa · 3719336–3720235 (+) ·
RefSeq NP_217827.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acid phosphatase |
|---|---|
| MTBC0 PGAP re-annotation | phosphatidylinositol-3-phosphatase |
| Revised (this work) | Phosphatidylinositol-3-phosphatase. Pfam: Phosphoesterase (PF04185.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53361
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phosphatidylinositol-3-phosphatase |
| EC (curated) |
EC 3.1.3.2, EC 3.1.3.64
|
| Curated function | Virulence factor that plays an important role in blocking phagosome-lysosome fusion and thus participates in the intracellular survival of the pathogen. Acts as a phosphatase that dephosphorylates phosphatidylinositol 3-phosphate (PI3P), a membrane trafficking regulatory lipid essential for phagosomal acquisition of lysosomal constituents. Therefore, SapM eliminates PI3P from the phagosomal membrane by catalyzing its hydrolysis, and thus contributes to inhibition of phagosome maturation. Also interferes with autophagy: SapM blocks autophagosome-lysosome fusion in macrophages by binding to the . |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | sapM |
| eggNOG description | Phosphoesterase family |
| Orthologous group | COG3511 |
| EC number |
EC 3.1.3.64
|
| KEGG orthology |
K21302
|
| KEGG pathways |
map00562, map01100, map05152
|
| Gene Ontology (86) |
GO:0003674, GO:0003824, GO:0003993, GO:0004438, GO:0004805, GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0006139, GO:0006629, GO:0006644 +74 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 | 0.986 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 missense, 0 nonsense, 0 frameshift |
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 |
|---|---|---|---|---|
Phosphoesterase | PF04185.20 | 4.0e-52 | 70–282 | Phosphoesterase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: upp (uracil phosphoribosyltransferase), high confidence from genomic context alone (score 780 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2351c plcA |
membrane-associated phospholipase A | 912 | 903 | database:900 |
Rv2349c plcC |
phospholipase C | 908 | 903 | database:900 |
Rv1755c plcD |
Rv1755c, (MT1799, MTCY28.21c), len: 280 aa. Probable plcD, phospholipase C 4 (fragment) (see citations below),highly similar to C-terminus o | 902 | 903 | database:900 |
Rv2350c plcB |
membrane-associated phospholipase B | 902 | 903 | database:900 |
Rv3309c upp |
uracil phosphoribosyltransferase | 780 | 780 ctx | neighborhood:780 |
Rv3311 hyp |
hypothetical protein | 817 | 779 ctx | neighborhood:779 |
Rv0090 |
membrane protein | 649 | 649 ctx | cooccurence:649 |
Rv2963 |
integral membrane protein | 645 | 645 ctx | cooccurence:645 |
Rv0180c |
transmembrane protein | 598 | 598 ctx | cooccurence:591 |
Rv2638 hyp |
hypothetical protein | 520 | 520 ctx | cooccurence:520 |
Rv2612c pgsA1 |
CDP-diacylglycerol--inositol 3-phosphatidyltransferase | 499 | 500 | database:500 |
Rv3199c nudC |
NADH pyrophosphatase | 499 | 500 | database:500 |
Rv1695 ppnK |
inorganic polyphosphate/ATP-NAD kinase | 499 | 500 | database:500 |
Rv1871c hyp |
hypothetical protein | 488 | 488 ctx | cooccurence:488 |
Rv3434c |
transmembrane protein | 481 | 481 ctx | cooccurence:481 |
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: acid phosphatase
- MTBC0 PGAP product: phosphatidylinositol-3-phosphatase
- Pfam (hmmscan --cut_ga): Phosphoesterase PF04185.20 (E=4e-52)
- (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_217827.1)
- Domains: Pfam-A via hmmscan --cut_ga — Phosphoesterase (PF04185.20)
- 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
COG3511 - Curated reference: UniProt O53361 (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 —
24 functional partner(s); context anchor
upp - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003518|Rv3310|sapM MLRGIQALSRPLTRVYRALAVIGVLAASLLASWVGAVPQVGLAASALPTFAHVVIVVEENRSQAAIIGNKSAPFINSLAANGAMMAQAFAETHPSEPNYLALFAGNTFGLTKNTCPVNGGALPNLGSELLSAGYTFMGFAEDLPAVGSTVCSAGKYARKHVPWVNFSNVPATLSVPFSAFPKPQNYPGLPTVSFVIPNADNDMHDGSIAQGDAWLNRHLSAYANWAKTNNSLLVVTWDEDDGSSRNQIPTVFYGAHVRPGTYNETISHYNVLSTLEQIYGLPKTGYATNAPPITDIWGD