ponA1 Resolved · high auto-curated
H37Rv Rv0050 · MTBC0 - ·
678 aa · 53663–55699 (+) ·
RefSeq YP_177687.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase. Pfam: Transgly (PF00912.29), Transpeptidase (PF00905.28). |
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 |
P71707
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Penicillin-binding protein A1 |
| EC (curated) |
EC 2.4.99.28, EC 3.4.16.4
|
| Curated function | Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits) (By similarity). Has little peptidoglycan hydrolytic activity; however it inhibits the synergistic peptidoglycan hydrolysis of RipA plus RpfB. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | pbp1A |
| eggNOG description | penicillin-binding protein |
| Orthologous group | COG0744 |
| Gene Ontology (36) |
GO:0001666, GO:0003674, GO:0005488, GO:0005575, GO:0005623, GO:0006950, GO:0008144, GO:0008150, GO:0008658, GO:0009628, GO:0009987, GO:0030288 +24 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 | 0.55 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 13 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 |
|---|---|---|---|---|
Transgly | PF00912.29 | 4.7e-57 | 39–217 | Transglycosylase |
Transpeptidase | PF00905.28 | 3.0e-25 | 311–578 | Penicillin binding protein transpeptidase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0051 (transmembrane protein), high confidence from genomic context alone (score 908 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0051 |
transmembrane protein | 908 | 908 ctx | neighborhood:882 |
Rv0016c pbpA |
penicillin-binding protein PbpA | 875 | 764 | experimental:419 database:500 textmining:496 |
Rv0017c rodA |
cell division protein RodA | 778 | 758 ctx | cooccurence:449 database:500 |
Rv0053 rpsF |
30S ribosomal protein S6 | 745 | 745 ctx | neighborhood:708 |
Rv0052 hyp |
hypothetical protein | 734 | 735 ctx | neighborhood:722 |
Rv2145c wag31 |
cell wall synthesis protein Wag31 | 920 | 720 | experimental:708 textmining:729 |
Rv2927c sepIVA hyp |
hypothetical protein | 740 | 720 | experimental:708 |
Rv2154c ftsW |
lipid II flippase FtsW | 758 | 677 ctx | cooccurence:623 |
Rv2163c pbpB |
penicillin-binding membrane protein PbpB | 813 | 670 ctx | cooccurence:431 experimental:419 textmining:457 |
Rv3682 ponA2 |
bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase | 835 | 660 | database:500 textmining:536 |
Rv3330 dacB1 |
penicillin-binding protein DacB | 886 | 643 | database:500 textmining:695 |
Rv2553c mltG |
membrane protein | 659 | 614 ctx | cooccurence:587 |
Rv2911 dacB2 |
penicillin-binding protein DacB2 | 872 | 595 | database:500 textmining:697 |
Rv0054 ssb |
single-strand DNA-binding protein | 571 | 572 ctx | neighborhood:569 |
Rv1209 hyp |
hypothetical protein | 583 | 558 | experimental:538 |
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): bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase
- Pfam (hmmscan --cut_ga): Transgly PF00912.29 (E=5e-57), Transpeptidase PF00905.28 (E=3e-25)
- (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_177687.1)
- Domains: Pfam-A via hmmscan --cut_ga — Transgly (PF00912.29), 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
COG0744 - Curated reference: UniProt P71707 (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 —
71 functional partner(s); context anchor
Rv0051 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0050|ponA1 MVILLPMVTFTMAYLIVDVPKPGDIRTNQVSTILASDGSEIAKIVPPEGNRVDVNLSQVPMHVRQAVIAAEDRNFYSNPGFSFTGFARAVKNNLFGGDLQGGSTITQQYVKNALVGSAQHGWSGLMRKAKELVIATKMSGEWSKDDVLQAYLNIIYFGRGAYGISAASKAYFDKPVEQLTVAEGALLAALIRRPSTLDPAVDPEGAHARWNWVLDGMVETKALSPNDRAAQVFPETVPPDLARAENQTKGPNGLIERQVTRELLELFNIDEQTLNTQGLVVTTTIDPQAQRAAEKAVAKYLDGQDPDMRAAVVSIDPHNGAVRAYYGGDNANGFDFAQAGLQTGSSFKVFALVAALEQGIGLGYQVDSSPLTVDGIKITNVEGEGCGTCNIAEALKMSLNTSYYRLMLKLNGGPQAVADAAHQAGIASSFPGVAHTLSEDGKGGPPNNGIVLGQYQTRVIDMASAYATLAASGIYHPPHFVQKVVSANGQVLFDASTADNTGDQRIPKAVADNVTAAMEPIAGYSRGHNLAGGRDSAAKTGTTQFGDTTANKDAWMVGYTPSLSTAVWVGTVKGDEPLVTASGAAIYGSGLPSDIWKATMDGALKGTSNETFPKPTEVGGYAGVPPPPPPPEVPPSETVIQPTVEIAPGITIPIGPPTTITLAPPPPAPPAATPTPPP