ponA2 Resolved · high auto-curated
H37Rv Rv3682 · MTBC0 - ·
810 aa · 4121916–4124348 (+) ·
RefSeq YP_178005.1
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), PASTA (PF03793.25). |
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 |
I6YGX2
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Penicillin-binding protein A2 |
| 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). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | pon1 |
| eggNOG description | penicillin-binding protein |
| Orthologous group | COG0744 |
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 | 0.344 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 15 synonymous, 15 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 | 2.3e-53 | 70–256 | Transglycosylase |
Transpeptidase | PF00905.28 | 1.7e-17 | 364–619 | Penicillin binding protein transpeptidase domain |
PASTA | PF03793.25 | 7.9e-12 | 702–762 | PASTA 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 817 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2927c sepIVA hyp |
hypothetical protein | 944 | 922 | experimental:848 |
Rv2145c wag31 |
cell wall synthesis protein Wag31 | 937 | 913 | experimental:848 |
Rv1209 hyp |
hypothetical protein | 930 | 906 | experimental:807 |
Rv0017c rodA |
cell division protein RodA | 869 | 817 ctx | cooccurence:551 database:500 |
Rv0016c pbpA |
penicillin-binding protein PbpA | 927 | 805 ctx | cooccurence:634 experimental:419 textmining:644 |
Rv2163c pbpB |
penicillin-binding membrane protein PbpB | 889 | 787 ctx | cooccurence:601 experimental:419 textmining:504 |
Rv2864c |
penicillin-binding lipoprotein | 941 | 785 ctx | cooccurence:599 experimental:419 textmining:738 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 745 | 745 ctx | neighborhood:525 coexpression:403 |
Rv2154c ftsW |
lipid II flippase FtsW | 792 | 709 ctx | cooccurence:629 |
Rv0358 hyp |
hypothetical protein | 685 | 686 ctx | cooccurence:685 |
Rv1638A hyp |
hypothetical protein | 687 | 667 ctx | cooccurence:485 |
Rv0050 ponA1 |
bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase | 835 | 660 | database:500 textmining:536 |
Rv3205c hyp |
hypothetical protein | 647 | 648 ctx | cooccurence:632 |
Rv2446c |
integral membrane protein | 647 | 647 ctx | cooccurence:643 |
Rv0556 |
transmembrane protein | 645 | 645 ctx | cooccurence:630 |
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=2e-53), Transpeptidase PF00905.28 (E=2e-17), PASTA PF03793.25 (E=8e-12)
- (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_178005.1)
- Domains: Pfam-A via hmmscan --cut_ga — Transgly (PF00912.29), Transpeptidase (PF00905.28), PASTA (PF03793.25)
- 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 I6YGX2 (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 —
114 functional partner(s); context anchor
rodA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3682|ponA2 MPERLPAAITVLKLAGCCLLASVVATALTFPFAGGLGLMSNRASEVVANGSAQLLEGQVPAVSTMVDAKGNTIAWLYSQRRFEVPSDKIANTMKLAIVSIEDKRFADHSGVDWKGTLTGLAGYASGDLDTRGGSTLEQQYVKNYQLLVTAQTDAEKRAAVETTPARKLREIRMALTLDKTFTKSEILTRYLNLVSFGNNSFGVQDAAQTYFGINASDLNWQQAALLAGMVQSTSTLNPYTNPDGALARRNVVLDTMIENLPGEAEALRAAKAEPLGVLPQPNELPRGCIAAGDRAFFCDYVQEYLSRAGISKEQVATGGYLIRTTLDPEVQAPVKAAIDKYASPNLAGISSVMSVIKPGKDAHKVLAMASNRKYGLDLEAGETMRPQPFSLVGDGAGSIFKIFTTAAALDMGMGINAQLDVPPRFQAKGLGSGGAKGCPKETWCVVNAGNYRGSMNVTDALATSPNTAFAKLISQVGVGRAVDMAIKLGLRSYANPGTARDYNPDSNESLADFVKRQNLGSFTLGPIELNALELSNVAATLASGGVWCPPNPIDQLIDRNGNEVAVTTETCDQVVPAGLANTLANAMSKDAVGSGTAAGSAGAAGWDLPMSGKTGTTEAHRSAGFVGFTNRYAAANYIYDDSSSPTDLCSGPLRHCGSGDLYGGNEPSRTWFAAMKPIANNFGEVQLPPTDPRYVDGAPGSRVPSVAGLDVDAARQRLKDAGFQVADQTNSVNSSAKYGEVVGTSPSGQTIPGSIVTIQISNGIPPAPPPPPLPEDGGPPPPVGSQVVEIPGLPPITIPLLAPPPPAPPP