Rv0008c Resolved · high auto-curated

H37Rv Rv0008c · MTBC0 - · 145 aa · 11874–12311 (-) · RefSeq NP_214522.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cell wall synthesis protein CwsA
MTBC0 PGAP re-annotation
Revised (this work)Cell wall synthesis protein CwsA. Pfam: CwsA (PF10814.15).

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 P9WJF3 SwissProt · reviewed · Evidence at protein level
UniProt nameCell wall synthesis protein CwsA
Curated functionRequired for regulated cell division, cell wall synthesis and the maintenance of cell shape.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category D Cell cycle control, cell division, chromosome partitioning
Preferred namecwsA
eggNOG descriptionRequired for regulated cell division, cell wall synthesis and the maintenance of cell shape
Orthologous group29YDV
Gene Ontology (16) GO:0005575, GO:0005623, GO:0005886, GO:0005887, GO:0008104, GO:0008150, GO:0016020, GO:0016021, GO:0031224, GO:0031226, GO:0033036, GO:0044425 +4 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 0.395 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 3 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)

PfamAccessioni-EvalueResiduesDescription
CwsAPF10814.15 6.4e-619–144 Cell wall synthesis protein CwsA

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: ppiA (iron-regulated peptidyl-prolyl cis-trans isomerase PpiA), high confidence from genomic context alone (score 770 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0009 ppiA iron-regulated peptidyl-prolyl cis-trans isomerase PpiA 770 770 ctx neighborhood:770
Rv0011c crgA cell division protein CrgA 937 501 experimental:500 textmining:879
Rv2145c wag31 cell wall synthesis protein Wag31 980 399 textmining:968
Rv3330 dacB1 penicillin-binding protein DacB 520 50 textmining:516
Rv2518c ldtB L,D-transpeptidase LdtB 480 45 textmining:479
Rv2150c ftsZ cell division protein FtsZ 694 44 textmining:693
Rv0016c pbpA penicillin-binding protein PbpA 658 44 textmining:657
Rv2748c ftsK DNA translocase FtsK 435 44 textmining:434
Rv0015c pknA serine/threonine-protein kinase PknA 406 44 textmining:405
Rv2151c ftsQ cell division protein FtsQ 670 42 textmining:670
Rv3061c fadE22 acyl-CoA dehydrogenase FadE22 517 42 textmining:517
Rv2921c ftsY signal recognition particle receptor FtsY 432 42 textmining:432
Rv0215c fadE3 Rv0215c, (MTCY08D5.10c), len: 357 aa. Probable fadE3, acyl- dehydrogenase, similar to many e.g. ACDB_BACSU|P45857 acyl-CoA dehydrogenase fro 665 41 textmining:665
Rv2163c pbpB penicillin-binding membrane protein PbpB 650 41 textmining:650
Rv3564 fadE33 acyl-CoA dehydrogenase FadE33 647 41 textmining:647

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): cell wall synthesis protein CwsA
  • Pfam (hmmscan --cut_ga): CwsA PF10814.15 (E=6e-61)
  • (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_214522.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CwsA (PF10814.15)
  • 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 29YDV
  • Curated reference: UniProt P9WJF3 (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 ppiA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0008c|
MSEQVETRLTPRERLTRGLAYSAVGPVDVTRGLLELGVGLGLQSARSTAAGLRRRYREGRLAREVAAAQETLAQELTAAQDVVANLPQALQDARTQRRSKHHLWIFAGIAAAILAGGAVAFSIVRRSSRPEPSPRPPSVEVQPRS