Rv2864c Family assigned · medium auto-curated

H37Rv Rv2864c · MTBC0 mtbc0_003046 · 603 aa · 3196120–3197931 (-) · RefSeq NP_217380.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)penicillin-binding lipoprotein
MTBC0 PGAP re-annotationpenicillin-binding protein
Revised (this work)Penicillin-binding protein. Pfam: MecA_N (PF05223.18), 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 O33346 TrEMBL · unreviewed · Predicted
UniProt namePossible penicillin-binding lipoprotein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namepbp2B
eggNOG descriptionpenicillin-binding protein
Orthologous groupCOG0768
EC number EC 3.4.16.4
KEGG orthology K01286

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 0.152 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 3 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
MecA_NPF05223.18 1.3e-2732–139 NTF2-like N-terminal transpeptidase domain
TranspeptidasePF00905.28 7.2e-33326–581 Penicillin binding protein transpeptidase domain

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

Closest characterised functional partner: ponA2 (bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase), high confidence from genomic context alone (score 785 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2151c ftsQ cell division protein FtsQ 872 858 experimental:781
Rv2154c ftsW lipid II flippase FtsW 800 787 experimental:589
Rv3682 ponA2 bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase 941 785 ctx cooccurence:599 experimental:419 textmining:738
Rv0017c rodA cell division protein RodA 782 768 experimental:589
Rv2091c membrane protein 680 670 ctx cooccurence:670
Rv2867c GCN5-like N-acetyltransferase 614 614 ctx neighborhood:544
Rv0185 hyp hypothetical protein 562 562 ctx cooccurence:561
Rv2868c gcpE 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (flavodoxin) 556 556 ctx neighborhood:544
Rv2869c rip zinc metalloprotease 579 554 ctx neighborhood:528
Rv2870c dxr 1-deoxy-D-xylulose 5-phosphate reductoisomerase 550 551 ctx neighborhood:539
Rv2446c integral membrane protein 547 548 ctx cooccurence:540
Rv2158c murE UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase 551 522 coexpression:443
Rv0863 hyp hypothetical protein 518 519 ctx cooccurence:517
Rv0050 ponA1 bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase 880 515 experimental:419 textmining:762
Rv0556 transmembrane protein 493 494 ctx cooccurence:491

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 lipoprotein
  • MTBC0 PGAP product: penicillin-binding protein
  • Pfam (hmmscan --cut_ga): MecA_N PF05223.18 (E=1e-27), Transpeptidase PF00905.28 (E=7e-33)
  • (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_217380.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MecA_N (PF05223.18), 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 O33346 (TrEMBL, unreviewed; Predicted)
  • 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 — 63 functional partner(s); context anchor ponA2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003046|Rv2864c|
MVTKTTLASATSGLLLLAVVAMSGCTPRPQGPGPAAEKFFAALAIGDTASAAQLSDNPNEAREALNAAWAGLQAAHLDAQVLSAKYAEDTGTVAYRFSWHLPKDRIWTYDGQLKMARDEGRWHVRWTTSGLHPKLGEHQTFALRADPPRRASVNEVGGTDVLVPGYLYHYSLDAGQAGRELFGTAHAVVGALHPFDDTLNDPQLLAEQASSSTQPLDLVTLHADDSNRVAAAIGQLPGVVITPQAELLPTDKHFAPAVLNDVKKAVVDELDGKAGWRVVSVNQNGVDVSVLHEVAPSPASSVSITLDRVVQNAAQHAVNTRGGKAMIVVIKPSTGEILAIAQNAGADADGPVATTGLYPPGSTFKMITAGAAVERDLATPETLLGCPGEIDIGHRTIPNYGGFDLGVVPMSRAFASSCNTTFAELSSRLPPRGLTQAARRYGIGLDYQVDGITTVTGSVPPTVDLAERTEDGFGQGKVLASPFGMALVAATVAAGKTPVPQLIAGRPTAVEGDATPISQKMIDALRPMMRLVVTNGTAKEIAGCGEVFGKTGEAEFPGGSHSWFAGYRGDLAFASLIVGGGSSEYAVRMTKVMFESLPPGYLA