plcC Resolved · high auto-curated

H37Rv Rv2349c · MTBC0 mtbc0_002501 · 508 aa · 2651922–2653448 (-) · RefSeq NP_216865.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phospholipase C
MTBC0 PGAP re-annotationphospholipase C
Revised (this work)Phospholipase C. 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 P9WIB1 SwissProt · reviewed · Evidence at protein level
UniProt namePhospholipase C C
EC (curated) EC 3.1.4.3
Curated functionInvolved in virulence. Induces cytotoxic effects on mouse macrophage cell lines, via direct or indirect enzymatic hydrolysis of cell membrane phospholipids. Hydrolyzes phosphatidylcholine. Does not have hemolytic activity.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred nameplcC
eggNOG descriptionPhosphoesterase family
Orthologous groupCOG3511
EC number EC 3.1.4.3
KEGG orthology K01114
KEGG pathways map00562, map00564, map00565, map01100, map01110, map02024, map04919
Gene Ontology (25) GO:0003674, GO:0003824, GO:0004620, GO:0004629, GO:0008081, GO:0008150, GO:0009405, GO:0016298, GO:0016787, GO:0016788, GO:0034480, GO:0035821 +13 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 0.591 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 10 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.44% of strains (635) · 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)

PfamAccessioni-EvalueResiduesDescription
PhosphoesterasePF04185.20 4.2e-13643–424 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 991 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2350c plcB membrane-associated phospholipase B 991 991 ctx neighborhood:578 coexpression:799 database:900
Rv2351c plcA membrane-associated phospholipase A 936 936 database:900
Rv3310 sapM acid phosphatase 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 904 903 database:900
Rv1604 impA inositol-monophosphatase ImpA 900 901 database:900
Rv2252 dagK diacylglycerol kinase 900 901 database:900
Rv1822 pgsA2 CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 900 900 database:900
Rv0437c psd phosphatidylserine decarboxylase 900 900 database:900
Rv2701c suhB inositol-1-monophosphatase SuhB 900 900 database:900
Rv1279 GMC-type oxidoreductase 803 803 database:800
Rv0436c pssA CDP-diacylglycerol--serine O-phosphatidyltransferase 801 801 database:800
Rv2856 nicT nickel-transport integral membrane protein NicT 474 475 ctx cooccurence:467
Rv2348c hyp hypothetical protein 495 469 ctx neighborhood:467
Rv3096 hyp hypothetical protein 474 296
Rv0798c cfp29 hyp hypothetical protein 420 226

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: phospholipase C
  • MTBC0 PGAP product: phospholipase C
  • Pfam (hmmscan --cut_ga): Phosphoesterase PF04185.20 (E=4e-136)
  • (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_216865.1)
  • 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 P9WIB1 (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

>mtbc0_002501|Rv2349c|plcC
MSRRAFLAKAAGAGAAAVLTDWAAPVIEKAYGAGPCSGHLTDIEHIVLCLQENRSFDHYFGTLSAVDGFDTPTPLFQQKGWNPETQALDPTGITLPYRINTTGGPNGVGECVNDPDHQWIAAHLSWNGGANDGWLPAQARTRSVANTPVVMGYYARPDIPIHYLLADTFTICDQYFSSLLGGTMPNRLYWISATVNPDGDQGGPQIVEPAIQPKLTFTWRIMPQNLSDAGISWKVYNSKLLGGLNDTSLSRNGYVGSFKQAADPRSDLARYGIAPAYPWDFIRDVINNTLPQVSWVVPLTVESEHPSFPVAVGAVTIVNLIRVLLRNPAVWEKTALIIAYDEHGGFFDHVTPLTAPEGTPGEWIPNSVDIDKVDGSGGIRGPIGLGFRVPCFVISPYSRGGLMVHDRFDHTSQLQLIGKRFGVPVPNLTPWRASVTGDMTSAFNFAAPPDPSPPNLDHPVRQLPKVAKCVPNVVLGFLNEGLPYRVPYPQTTPVQESGPARPIPSGIC