pbpA Resolved · high auto-curated
H37Rv Rv0016c · MTBC0 mtbc0_000020 ·
491 aa · 18759–20234 (-) ·
RefSeq NP_214530.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | penicillin-binding protein PbpA |
|---|---|
| MTBC0 PGAP re-annotation | D%2CD-transpeptidase PbpA |
| Revised (this work) | D%2CD-transpeptidase PbpA. Pfam: PBP_dimer_2 (PF21922.2), Transpeptidase (PF00905.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKD1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Peptidoglycan D,D-transpeptidase PbpA |
| EC (curated) |
EC 3.4.16.4
|
| Curated function | Transpeptidase that catalyzes cross-linking of the peptidoglycan cell wall (Probable). Required for the regulation of cell length. Plays critical roles for the survival of the pathogen inside the host. Required for both bacterial survival and formation of granuloma structures in a guinea pig infection model. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | pbpA |
| eggNOG description | penicillin-binding protein |
| Orthologous group | COG0768 |
| KEGG orthology |
K05364
|
| KEGG pathways |
map00550
|
| Gene Ontology (8) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0044424, GO:0044444, GO:0044464
|
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 | 0.487 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
PBP_dimer_2 | PF21922.2 | 1.3e-28 | 52–134 | Penicillin binding protein A dimerisation domain |
Transpeptidase | PF00905.28 | 6.6e-67 | 160–484 | Penicillin binding protein transpeptidase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rodA (cell division protein RodA), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0017c rodA |
cell division protein RodA | 999 | 1000 ctx | neighborhood:882 fusion:894 cooccurence:749 coexpression:418 experimental:589 database:500 textmining:869 |
Rv2163c pbpB |
penicillin-binding membrane protein PbpB | 948 | 921 | database:900 |
Rv2154c ftsW |
lipid II flippase FtsW | 944 | 907 ctx | cooccurence:649 experimental:589 textmining:431 |
Rv0018c pstP |
phosphoserine/threonine phosphatase PstP | 992 | 901 ctx | neighborhood:882 textmining:931 |
Rv0014c pknB |
serine/threonine-protein kinase PknB | 993 | 888 ctx | neighborhood:881 textmining:945 |
Rv0015c pknA |
serine/threonine-protein kinase PknA | 993 | 887 ctx | neighborhood:882 textmining:941 |
Rv2151c ftsQ |
cell division protein FtsQ | 968 | 840 | experimental:781 textmining:814 |
Rv0019c fhaB |
FHA domain-containing protein FhaB | 967 | 835 ctx | neighborhood:780 textmining:810 |
Rv3682 ponA2 |
bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase | 927 | 805 ctx | cooccurence:634 experimental:419 textmining:644 |
Rv0020c fhaA |
FHA domain-containing protein FhaA | 916 | 773 ctx | neighborhood:700 textmining:650 |
Rv0050 ponA1 |
bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase | 875 | 764 | experimental:419 database:500 textmining:496 |
Rv2157c murF |
UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase | 683 | 649 ctx | cooccurence:448 |
Rv2152c murC |
UDP-N-acetylmuramate--alanine ligase | 679 | 602 ctx | cooccurence:497 |
Rv2156c murX |
phospho-N-acetylmuramoyl-pentappeptidetransferase | 624 | 601 ctx | cooccurence:522 |
Rv2155c murD |
UDP-N-acetylmuramoylalanine--D-glutamate ligase | 632 | 545 |
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 PbpA
- MTBC0 PGAP product: D%2CD-transpeptidase PbpA
- Pfam (hmmscan --cut_ga): PBP_dimer_2 PF21922.2 (E=1e-28), Transpeptidase PF00905.28 (E=7e-67)
- (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_214530.1)
- Domains: Pfam-A via hmmscan --cut_ga — PBP_dimer_2 (PF21922.2), Transpeptidase (PF00905.28)
- 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
COG0768 - Curated reference: UniProt P9WKD1 (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 —
51 functional partner(s); context anchor
rodA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000020|Rv0016c|pbpA MNASLRRISVTVMALIVLLLLNATMTQVFTADGLRADPRNQRVLLDEYSRQRGQITAGGQLLAYSVATDGRFRFLRVYPNPEVYAPVTGFYSLRYSSTALERAEDPILNGSDRRLFGRRLADFFTGRDPRGGNVDTTINPRIQQAGWDAMQQGCYGPCKGAVVALEPSTGKILALVSSPSYDPNLLASHNPEVQAQAWQRLGDNPASPLTNRAISETYPPGSTFKVITTAAALAAGATETEQLTAAPTIPLPGSTAQLENYGGAPCGDEPTVSLREAFVKSCNTAFVQLGIRTGADALRSMARAFGLDSPPRPTPLQVAESTVGPIPDSAALGMTSIGQKDVALTPLANAEIAATIANGGITMRPYLVGSLKGPDLANISTTVGYQQRRAVSPQVAAKLTELMVGAEKVAQQKGAIPGVQIASKTGTAEHGTDPRHTPPHAWYIAFAPAQAPKVAVAVLVENGADRLSATGGALAAPIGRAVIEAALQGEP