dacB2 Family assigned · medium auto-curated

H37Rv Rv2911 · MTBC0 - · 291 aa · 3218339–3219214 (+) · RefSeq YP_177914.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)penicillin-binding protein DacB2
MTBC0 PGAP re-annotation
Revised (this work)Penicillin-binding protein DacB2. Pfam: Peptidase_S11 (PF00768.26), Beta-lactamase2 (PF13354.13).

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 I6Y204 SwissProt · reviewed · Evidence at protein level
UniProt nameD-alanyl-D-alanine carboxypeptidase DacB2
EC (curated) EC 3.4.16.-
Curated functionProbably cleaves the terminal D-Ala-D-Ala dipeptide of the peptidoglycan stem peptide (Probable). Shows significant D,D-carboxypeptidase activity in vitro. Acts on the synthetic penta-peptide substrate Penta-DAP (L-Ala-gamma-D-Gln-DAP-D-Ala-D-Ala). Also shows weak activity on Penta-Lys (L-Ala-gamma-Glu-L-Lys-D-Ala-D-Ala). The catalytic domain binds weakly to peptidoglycan in vitro. Plays an important role in the maintenance of colony morphology and cell wall permeability and integrity.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namedac
eggNOG descriptionBelongs to the peptidase S11 family
Orthologous groupCOG1686
EC number EC 3.4.16.4
KEGG orthology K07258
KEGG pathways map00550, map01100

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (161) · 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
Peptidase_S11PF00768.26 2.8e-3539–257 D-alanyl-D-alanine carboxypeptidase
Beta-lactamase2PF13354.13 1.3e-1145–186 Beta-lactamase enzyme family

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

Closest characterised functional partner: trmD (tRNA (guanine-N1)-methyltransferase), medium confidence from genomic context alone (score 441 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3330 dacB1 penicillin-binding protein DacB 921 911 database:900
Rv3627c dacB hyp hypothetical protein 991 900 database:900 textmining:920
Rv0017c rodA cell division protein RodA 680 650 database:500
Rv0050 ponA1 bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase 872 595 database:500 textmining:697
Rv2518c ldtB L,D-transpeptidase LdtB 655 580 database:500
Rv2910c hyp hypothetical protein 580 579 ctx neighborhood:579
Rv0192 hyp hypothetical protein 546 521 database:500
Rv2906c trmD tRNA (guanine-N1)-methyltransferase 440 441 ctx neighborhood:406
Rv2908c hyp hypothetical protein 436 436 ctx neighborhood:428
Rv2909c rpsP 30S ribosomal protein S16 435 435 ctx neighborhood:428
Rv2907c rimM 16S rRNA processing protein RimM 429 429 ctx neighborhood:407
Rv2154c ftsW lipid II flippase FtsW 429 376
Rv2163c pbpB penicillin-binding membrane protein PbpB 640 352 textmining:468
Rv0016c pbpA penicillin-binding protein PbpA 697 333 textmining:565
Rv3915 cwlM peptidoglycan hydrolase 469 290

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): penicillin-binding protein DacB2
  • Pfam (hmmscan --cut_ga): Peptidase_S11 PF00768.26 (E=3e-35), Beta-lactamase2 PF13354.13 (E=1e-11)
  • (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 YP_177914.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_S11 (PF00768.26), Beta-lactamase2 (PF13354.13)
  • 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 COG1686
  • Curated reference: UniProt I6Y204 (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 — 31 functional partner(s); context anchor trmD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2911|dacB2
MRKLMTATAALCACAVTVSAGAAWADADVQPAGSVPIPDGPAQTWIVADLDSGQVLAGRDQNVAHPPASTIKVLLALVALDELDLNSTVVADVADTQAECNCVGVKPGRSYTARQLLDGLLLVSGNDAANTLAHMLGGQDVTVAKMNAKAATLGATSTHATTPSGLDGPGGSGASTAHDLVVIFRAAMANPVFAQITAEPSAMFPSDNGEQLIVNQDELLQRYPGAIGGKTGYTNAARKTFVGAAARGGRRLVIAMMYGLVKEGGPTYWDQAATLFDWGFALNPQASVGSL