plcA Resolved · high auto-curated
H37Rv Rv2351c · MTBC0 - ·
512 aa · 2630537–2632075 (-) ·
RefSeq NP_216867.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | membrane-associated phospholipase A |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Membrane-associated phospholipase A. Pfam: Phosphoesterase (PF04185.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WIB5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Phospholipase C A |
| EC (curated) |
EC 3.1.4.3
|
| Curated function | Involved in virulence. Induces cytotoxic effects on mouse macrophage cell lines, via direct or indirect enzymatic hydrolysis of cell membrane phospholipids. Hydrolyzes phosphatidylcholine and sphingomyelin. Does not have hemolytic activity. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | plc |
| eggNOG description | at the level of intracellular survival, by the alteration of cell signaling events or by direct cytotoxicity |
| Orthologous group | COG3511 |
| EC number |
EC 3.1.4.3
|
| KEGG orthology |
K01114
|
| KEGG pathways |
map00562, map00564, map00565, map01100, map01110, map02024, map04919
|
| Gene Ontology (31) |
GO:0003674, GO:0003824, GO:0004620, GO:0004629, GO:0005575, GO:0005623, GO:0005886, GO:0008081, GO:0008150, GO:0009405, GO:0016020, GO:0016298 +19 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) pseudogene candidate
| pN/pS | 0.411 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 10 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 3.02% of strains (4383) · 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 |
|---|---|---|---|---|
Phosphoesterase | PF04185.20 | 6.4e-137 | 43–423 | Phosphoesterase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: plcB (membrane-associated phospholipase B), high confidence from genomic context alone (score 952 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2350c plcB |
membrane-associated phospholipase B | 952 | 952 ctx | neighborhood:467 database:900 |
Rv2349c plcC |
phospholipase C | 936 | 936 | database:900 |
Rv3310 sapM |
acid phosphatase | 912 | 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 | 903 | 902 | database:900 |
Rv2252 dagK |
diacylglycerol kinase | 902 | 902 | database:900 |
Rv2701c suhB |
inositol-1-monophosphatase SuhB | 900 | 901 | database:900 |
Rv1604 impA |
inositol-monophosphatase ImpA | 900 | 900 | database:900 |
Rv0437c psd |
phosphatidylserine decarboxylase | 900 | 900 | database:900 |
Rv1822 pgsA2 |
CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase | 900 | 900 | database:900 |
Rv1279 |
GMC-type oxidoreductase | 802 | 803 | database:800 |
Rv0436c pssA |
CDP-diacylglycerol--serine O-phosphatidyltransferase | 801 | 801 | database:800 |
Rv2856 nicT |
nickel-transport integral membrane protein NicT | 466 | 467 ctx | cooccurence:465 |
Rv2348c hyp |
hypothetical protein | 475 | 258 | |
Rv2353c PPE39 |
PPE family protein PPE39 | 440 | 52 | textmining:434 |
Rv2352c PPE38 |
PPE family protein PPE38 | 656 | 49 | textmining:654 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): membrane-associated phospholipase A
- Pfam (hmmscan --cut_ga): Phosphoesterase PF04185.20 (E=6e-137)
- (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_216867.1)
- 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 P9WIB5 (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 —
18 functional partner(s); context anchor
plcB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2351c|plcA MSRREFLTKLTGAGAAAFLMDWAAPVIEKAYGAGPCPGHLTDIEHIVLLMQENRSFDHYFGTLSSTNGFNAASPAFQQMGWNPMTQALDPAGVTIPFRLDTTRGPFLDGECVNDPEHQWVGMHLAWNGGANDNWLPAQATTRAGPYVPLTMGYYTRQDIPIHYLLADTFTICDGYHCSLLTGTLPNRLYWLSANIDPAGTDGGPQLVEPGFLPLQQFSWRIMPENLEDAGVSWKVYQNKGLGRFINTPISNNGLVQAFRQAADPRSNLARYGIAPTYPGDFAADVRANRLPKVSWLVPNILQSEHPALPVALGAVSMVTALRILLSNPAVWEKTALIVSYDENGGFFDHVTPPTAPPGTPGEFVTVPNIDAVPGSGGIRGPLGLGFRVPCIVISPYSRGPLMVSDTFDHTSQLKLIRARFGVPVPNMTAWRDGVVGDMTSAFNFATPPNSTRPNLSHPLLGALPKLPQCIPNVVLGTTDGALPSIPYRVPYPQVMPTQETTPVRGTPSGLCS