dacB Resolved · high auto-curated
H37Rv Rv3627c · MTBC0 mtbc0_003844 ·
461 aa · 4089604–4090989 (-) ·
RefSeq NP_218144.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | D-alanyl-D-alanine carboxypeptidase/D-alanyl-D-alanine-endopeptidase |
| Revised (this work) | D-alanyl-D-alanine carboxypeptidase/D-alanyl-D-alanine-endopeptidase. Pfam: Rv3627c_N (PF23714.2), Peptidase_S13 (PF02113.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O06380
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Carboxypeptidase Rv3627c |
| EC (curated) |
EC 3.4.16.-
|
| Curated function | Carboxypeptidase that cleaves terminal D-alanine from peptidoglycan in the mycobacterial cell wall. May cleave L-Lys-D-Ala and/or D-Ala-D-Ala peptide bonds. Exerts important effects on mycobacterial cell morphology and cell division. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | dacB |
| eggNOG description | D-alanyl-D-alanine carboxypeptidase |
| Orthologous group | COG2027 |
| EC number |
EC 3.4.16.4
|
| KEGG orthology |
K07259
|
| KEGG pathways |
map00550
|
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 | 0.308 · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Rv3627c_N | PF23714.2 | 4.5e-20 | 1–59 | Carboxypeptidase Rv3627c-like, N-terminal domain |
Peptidase_S13 | PF02113.21 | 1.2e-75 | 238–453 | D-Ala-D-Ala carboxypeptidase 3 (S13) family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mesJ (tRNA(Ile)-lysidine synthase), high confidence from genomic context alone (score 906 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3626c hyp |
hypothetical protein | 991 | 922 ctx | neighborhood:882 textmining:896 |
Rv3625c mesJ |
tRNA(Ile)-lysidine synthase | 981 | 906 ctx | neighborhood:881 textmining:808 |
Rv3330 dacB1 |
penicillin-binding protein DacB | 995 | 900 | database:900 textmining:954 |
Rv2911 dacB2 |
penicillin-binding protein DacB2 | 991 | 900 | database:900 textmining:920 |
Rv3624c hpt |
hypoxanthine-guanine phosphoribosyltransferase | 969 | 882 ctx | neighborhood:881 textmining:754 |
Rv3628 ppa |
inorganic pyrophosphatase | 774 | 775 ctx | neighborhood:774 |
Rv0200 |
transmembrane protein | 433 | 426 | experimental:404 |
Rv0178 |
Mce associated membrane protein | 432 | 425 | experimental:404 |
Rv0199 |
membrane protein | 432 | 425 | experimental:404 |
Rv1972 |
Mce associated membrane protein | 432 | 425 | experimental:404 |
Rv1973 |
Mce associated membrane protein | 431 | 424 | experimental:404 |
Rv1363c |
membrane protein | 431 | 424 | experimental:404 |
Rv0177 |
Mce associated protein | 429 | 422 | experimental:404 |
Rv3492c |
Mce associated protein | 429 | 422 | experimental:404 |
Rv2390c hyp |
hypothetical protein | 429 | 422 | experimental:404 |
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: hypothetical protein
- MTBC0 PGAP product: D-alanyl-D-alanine carboxypeptidase/D-alanyl-D-alanine-endopeptidase
- Pfam (hmmscan --cut_ga): Rv3627c_N PF23714.2 (E=5e-20), Peptidase_S13 PF02113.21 (E=1e-75)
- (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_218144.1)
- Domains: Pfam-A via hmmscan --cut_ga — Rv3627c_N (PF23714.2), Peptidase_S13 (PF02113.21)
- 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
COG2027 - Curated reference: UniProt O06380 (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
mesJ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003844|Rv3627c|dacB MGPTRWRKSTHVVVGAAVLAFVAVVVAAAALVTTGGHRAGVRAPVPPPRPPTVKAGVVPVADTAATPSAAGVTAALAVVAADPDLGKLAGRITDALTGQELWQRLDDVPLVPASTNKILTAAAALLTLDRQARISTRVVAGGQNPQGPVVLVGAGDPTLSAAPPGQDTWYHGAARIGDLVEQIRRSGVTPTAVQVDASAFSGPTMAPGWDPADIDNGDIAPIEAAMIDAGRIQPTTVNSRRSRTPALDAGRELAKALGLDPAAVTIASAPAGARQLAVVQSAPLIQRLSQMMNASDNVMAECIGREVAVAINRPQSFSGAVDAVTSRLNTAHIDTAGAALVDSSGLSLDNRLTARTLDATMQAAAGPDQPALRPLLDLLPIAGGSGTLGERFLDAATDQGPAGWLRAKTGSLTAINSLVGVLTDRSGRVLTFAFISNEAGPNGRNAMDALATKLWFCGCTT