Rv3786c Family assigned · medium auto-curated

H37Rv Rv3786c · MTBC0 mtbc0_004014 · 407 aa · 4256495–4257718 (-) · RefSeq NP_218303.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationpeptidoglycan DD-metalloendopeptidase family protein
Revised (this work)Peptidoglycan DD-metalloendopeptidase family protein. Pfam: Peptidase_M23 (PF01551.30).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WKW9 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv3786c

UniProt still lists this protein as Uncharacterized protein Rv3786c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
eggNOG descriptionGlycosyl transferase family 2
Orthologous groupCOG0739
Gene Ontology (8) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, GO:0044464, GO:0071944

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 1.051 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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
Peptidase_M23PF01551.30 2.7e-16275–369 Peptidase family M23

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

Closest characterised functional partner: Rv3787c (S-adenosyl-L-methionine-dependent methyltransferase), high confidence from genomic context alone (score 865 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3787c S-adenosyl-L-methionine-dependent methyltransferase 865 865 ctx neighborhood:864
Rv2812 transposase 738 739 ctx cooccurence:738
Rv3899c hyp hypothetical protein 719 702 ctx cooccurence:684
Rv3896c hyp hypothetical protein 699 688 ctx cooccurence:641
Rv1978 hyp hypothetical protein 677 677 ctx cooccurence:655
Rv1435c hyp hypothetical protein 672 672 ctx cooccurence:661
Rv0804 hyp hypothetical protein 665 665 ctx cooccurence:650
Rv1158c hyp hypothetical protein 655 633 ctx cooccurence:572
Rv3912 rsmA anti-sigma-M factor RsmA 642 622 ctx cooccurence:620
Rv3349c transposase 611 611 ctx cooccurence:608
Rv2687c antibiotic ABC transporter permease 600 600 ctx cooccurence:541
Rv1868 hyp hypothetical protein 594 571 ctx cooccurence:505
Rv1006 hyp hypothetical protein 563 563 ctx cooccurence:563
Rv3604c transmembrane protein 563 563 ctx cooccurence:562
Rv1181 pks4 polyketide beta-ketoacyl synthase 577 556

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: hypothetical protein
  • MTBC0 PGAP product: peptidoglycan DD-metalloendopeptidase family protein
  • Pfam (hmmscan --cut_ga): Peptidase_M23 PF01551.30 (E=3e-16)
  • (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_218303.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M23 (PF01551.30)
  • 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 COG0739
  • Curated reference: UniProt P9WKW9 (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 — 56 functional partner(s); context anchor Rv3787c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004014|Rv3786c|
MRILAMTRAHNAGRTLAATLDSLAVFSDDIYVIDDRSTDDTAEILANHPAVTNVVRARPDLPPTPWLIPESAGLELLYRMADFCRPDWVMMVDADWLVETDIDLRAVLARTPDDIVALMCPMVSRWDDPEYPDLIPVMGTAEALRGPLWRWYPGLRAGGKLMHNPHWPANITDHGRIGQLPGVRLVHSGWSTLAERILRVEHYLRLDPDYRFNFGVAYDRSLLFGYALDEVDLLKADYRRRIRGDFDPLEPGGRLPIDREPRAIGRGYGPHAGGFHPGVDFATDPGTPVYAVASGAVSAIDEVDGLVSLTIARCELDVVYVFRPGDEGRLVLGDRIAAGAQLGTIGAQGESADGYLHFEVRTQDGHVNPVRYLANMGLRPWPPPGRLRAVSGSYPPATPCTITAEDR