dacB1 Resolved · high auto-curated

H37Rv Rv3330 · MTBC0 mtbc0_003543 · 405 aa · 3741762–3742979 (+) · RefSeq NP_217847.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)penicillin-binding protein DacB
MTBC0 PGAP re-annotationD-alanyl-D-alanine carboxypeptidase DacB1
Revised (this work)D-alanyl-D-alanine carboxypeptidase DacB1. 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.

Curated reference (UniProt)

UniProt O53380 SwissProt · reviewed · Evidence at protein level
UniProt nameD-alanyl-D-alanine carboxypeptidase DacB1
EC (curated) EC 3.4.16.-
Curated functionProbably cleaves the terminal D-Ala-D-Ala dipeptide of the peptidoglycan stem peptide (Probable). Shows weak 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). The catalytic domain binds weakly to peptidoglycan in vitro.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namedacC
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 0.299 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 4 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
Peptidase_S11PF00768.26 4.0e-3688–310 D-alanyl-D-alanine carboxypeptidase
Beta-lactamase2PF13354.13 1.2e-0897–216 Beta-lactamase enzyme family

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

Closest characterised functional partner: nagA (N-acetylglucosamine-6-phosphate deacetylase NagA), high confidence from genomic context alone (score 705 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2911 dacB2 penicillin-binding protein DacB2 921 911 database:900
Rv3627c dacB hyp hypothetical protein 995 900 database:900 textmining:954
Rv3332 nagA N-acetylglucosamine-6-phosphate deacetylase NagA 938 705 ctx neighborhood:659 textmining:801
Rv3331 sugI sugar-transport integral membrane protein SugI 840 656 ctx neighborhood:654 textmining:556
Rv3329 aminotransferase 909 654 ctx neighborhood:628 textmining:750
Rv0050 ponA1 bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase 886 643 database:500 textmining:695
Rv0017c rodA cell division protein RodA 661 630 database:500
Rv2518c ldtB L,D-transpeptidase LdtB 699 587 database:500
Rv0192 hyp hypothetical protein 598 576 database:500
Rv3328c sigJ ECF RNA polymerase sigma factor SigJ 459 459 ctx neighborhood:457
Rv2864c penicillin-binding lipoprotein 820 450 coexpression:432 textmining:687
Rv2163c pbpB penicillin-binding membrane protein PbpB 708 391 textmining:542
Rv2154c ftsW lipid II flippase FtsW 442 389
Rv0016c pbpA penicillin-binding protein PbpA 607 328 textmining:439
Rv2157c murF UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase 402 327

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: penicillin-binding protein DacB
  • MTBC0 PGAP product: D-alanyl-D-alanine carboxypeptidase DacB1
  • Pfam (hmmscan --cut_ga): Peptidase_S11 PF00768.26 (E=4e-36), Beta-lactamase2 PF13354.13 (E=1e-08)
  • (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_217847.1)
  • 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 O53380 (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 — 33 functional partner(s); context anchor nagA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003543|Rv3330|dacB1
MAFLRSVSCLAAAVFAVGTGIGLPTAAGEPNAAPAACPYKVSTPPAVDSSEVPAAGEPPLPLVVPPTPVGGNALGGCGIITAPGSAPAPGDVSAEAWLVADLDSGAVIAARDPHGRHRPASVIKVLVAMASINTLTLNKSVAGTADDAAVEGTKVGVNTGGTYTVNQLLHGLLMHSGNDAAYALARQLGGMPAALEKINLLAAKLGGRDTRVATPSGLDGPGMSTSAYDIGLFYRYAWQNPVFADIVATRTFDFPGHGDHPGYELENDNQLLYNYPGALGGKTGYTDDAGQTFVGAANRDGRRLMTVLLHGTRQPIPPWEQAAHLLDYGFNTPAGTQIGTLIEPDPSLMSTDRNPADRQRVDPQAAARISAADALPVRVGVAVIGALIVFGLIMVARAMNRRPQH