pbpB Resolved · high auto-curated

H37Rv Rv2163c · MTBC0 mtbc0_002299 · 679 aa · 2452413–2454452 (-) · RefSeq NP_216679.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)penicillin-binding membrane protein PbpB
MTBC0 PGAP re-annotationD%2CD-transpeptidase PbpB
Revised (this work)D%2CD-transpeptidase PbpB. Pfam: PBP_dimer (PF03717.21), 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 L0T911 SwissProt · reviewed · Evidence at protein level
UniProt namePenicillin-binding protein PbpB
Curated functionSynthesis of cross-linked peptidoglycan from the lipid intermediates.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred nameftsI
eggNOG descriptionCell division protein FtsI
Orthologous groupCOG0768
EC number EC 3.4.16.4
KEGG orthology K03587
KEGG pathways map00550, map01501

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 0.428 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 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
PBP_dimerPF03717.21 9.8e-10131–295 Penicillin-binding Protein dimerisation domain
TranspeptidasePF00905.28 1.3e-84339–654 Penicillin binding protein transpeptidase domain

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

Closest characterised functional partner: ftsW (lipid II flippase FtsW), high confidence from genomic context alone (score 961 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2164c hyp hypothetical protein 988 979 ctx neighborhood:881 coexpression:806 textmining:475
Rv2154c ftsW lipid II flippase FtsW 998 961 ctx neighborhood:544 cooccurence:753 experimental:589 textmining:964
Rv2165c rsmH rRNA small subunit methyltransferase H 972 945 ctx neighborhood:881 coexpression:500 textmining:520
Rv0016c pbpA penicillin-binding protein PbpA 948 921 database:900
Rv2151c ftsQ cell division protein FtsQ 994 916 ctx neighborhood:544 experimental:781 textmining:940
Rv2152c murC UDP-N-acetylmuramate--alanine ligase 953 889 ctx neighborhood:544 cooccurence:711 textmining:603
Rv2166c mraZ transcriptional regulator MraZ 951 886 ctx neighborhood:816 textmining:594
Rv2158c murE UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase 943 875 ctx neighborhood:544 cooccurence:532 coexpression:445 textmining:565
Rv2156c murX phospho-N-acetylmuramoyl-pentappeptidetransferase 882 875 ctx neighborhood:544 cooccurence:697
Rv2157c murF UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase 927 859 ctx neighborhood:544 cooccurence:547 textmining:507
Rv0017c rodA cell division protein RodA 984 857 ctx cooccurence:562 experimental:589 textmining:899
Rv2155c murD UDP-N-acetylmuramoylalanine--D-glutamate ligase 937 854 ctx neighborhood:544 cooccurence:535 textmining:588
Rv2153c murG UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol-N-acetylglucosamine transferase 964 787 ctx neighborhood:544 cooccurence:499 textmining:839
Rv3682 ponA2 bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase 889 787 ctx cooccurence:601 experimental:419 textmining:504
Rv1315 murA UDP-N-acetylglucosamine 1-carboxyvinyltransferase 837 693 ctx cooccurence:680 textmining:494

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 membrane protein PbpB
  • MTBC0 PGAP product: D%2CD-transpeptidase PbpB
  • Pfam (hmmscan --cut_ga): PBP_dimer PF03717.21 (E=1e-09), Transpeptidase PF00905.28 (E=1e-84)
  • (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_216679.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PBP_dimer (PF03717.21), 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 L0T911 (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 — 74 functional partner(s); context anchor ftsW
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002299|Rv2163c|pbpB
MSRAAPRRASQSQSTRPARGLRRPPGAQEVGQRKRPGKTQKARQAQEATKSRPATRSDVAPAGRSTRARRTRQVVDVGTRGASFVFRHRTGNAVILVLMLVAATQLFFLQVSHAAGLRAQAAGQLKVTDVQPAARGSIVDRNNDRLAFTIEARALTFQPKRIRRQLEEARKKTSAAPDPQQRLRDIAQEVAGKLNNKPDAAAVLKKLQSDETFVYLARAVDPAVASAICAKYPEVGAERQDLRQYPGGSLAANVVGGIDWDGHGLLGLEDSLDAVLAGTDGSVTYDRGSDGVVIPGSYRNRHKAVHGSTVVLTLDNDIQFYVQQQVQQAKNLSGAHNVSAVVLDAKTGEVLAMANDNTFDPSQDIGRQGDKQLGNPAVSSPFEPGSVNKIVAASAVIEHGLSSPDEVLQVPGSIQMGGVTVHDAWEHGVMPYTTTGVFGKSSNVGTLMLSQRVGPERYYDMLRKFGLGQRTGVGLPGESAGLVPPIDQWSGSTFANLPIGQGLSMTLLQMTGMYQAIANDGVRVPPRIIKATVAPDGSRTEEPRPDDIRVVSAQTAQTVRQMLRAVVQRDPMGYQQGTGPTAGVPGYQMAGKTGTAQQINPGCGCYFDDVYWITFAGIATADNPRYVIGIMLDNPARNSDGAPGHSAAPLFHNIAGWLMQRENVPLSPDPGPPLVLQAT