Rv3915 Resolved · high auto-curated

H37Rv Rv3915 · MTBC0 - · 406 aa · 4403192–4404412 (+) · RefSeq YP_178027.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)peptidoglycan hydrolase
MTBC0 PGAP re-annotation
Revised (this work)Peptidoglycan hydrolase. Pfam: PG_binding_1 (PF01471.24), Amidase_3 (PF01520.24).

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 L7N653 SwissProt · reviewed · Evidence at protein level
UniProt nameN-acetylmuramoyl-L-alanine amidase CwlM
EC (curated) EC 3.5.1.28
Curated functionCell-wall hydrolase that hydrolyzes the amide bond between N-acetylmuramic acid and L-alanine in cell-wall glycopeptides. Is able to lyse whole mycobacteria, release peptidoglycan from the cell wall of M.luteus and M.smegmatis, and cleave N-acetylmuramoyl-L-alanyl-D-isoglutamine, releasing free N-acetylmuramic acid and dipeptide.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namecwlM
eggNOG descriptionN-acetylmuramoyl-L-alanine amidase
Orthologous groupCOG0860
EC number EC 3.5.1.28
KEGG orthology K01448
KEGG pathways map01503
KEGG modules M00727
Gene Ontology (7) GO:0005575, GO:0005623, GO:0030288, GO:0030313, GO:0031975, GO:0042597, GO:0044464

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 0.26 · purifying
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 6 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
PG_binding_1PF01471.24 9.4e-18105–160 Putative peptidoglycan binding domain
Amidase_3PF01520.24 3.1e-33193–370 N-acetylmuramoyl-L-alanine amidase

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

Closest characterised functional partner: trxC (thioredoxin TrxC), high confidence from genomic context alone (score 754 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3717 hyp hypothetical protein 989 905 database:900 textmining:896
Rv3914 trxC thioredoxin TrxC 794 754 ctx neighborhood:719
Rv0948c chorismate mutase 719 720 ctx cooccurence:712
Rv1315 murA UDP-N-acetylglucosamine 1-carboxyvinyltransferase 908 719 ctx cooccurence:701 textmining:686
Rv2179c 3'-5' exoribonuclease 670 670 ctx cooccurence:670
Rv3913 trxB2 thioredoxin reductase 708 653 ctx neighborhood:632
Rv1209 hyp hypothetical protein 615 591 ctx cooccurence:576
Rv3311 hyp hypothetical protein 550 551 ctx cooccurence:548
Rv3908 mutT4 mutator protein MutT 534 534 ctx neighborhood:449
Rv2744c 35kd_ag hyp hypothetical protein 520 521 ctx cooccurence:516
Rv3911 sigM ECF RNA polymerase sigma factor SigM 522 500 ctx neighborhood:482
Rv1337 integral membrane protein 648 498 experimental:465
Rv3433c nnr bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase 585 496 ctx neighborhood:427
Rv1343c lprD lipoprotein LprD 495 496 ctx cooccurence:494
Rv3912 rsmA anti-sigma-M factor RsmA 514 495 ctx neighborhood:489

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): peptidoglycan hydrolase
  • Pfam (hmmscan --cut_ga): PG_binding_1 PF01471.24 (E=9e-18), Amidase_3 PF01520.24 (E=3e-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 YP_178027.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PG_binding_1 (PF01471.24), Amidase_3 (PF01520.24)
  • 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 COG0860
  • Curated reference: UniProt L7N653 (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 — 72 functional partner(s); context anchor trxC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3915|
MPSPRREDGDALRCGDRSAAVTEIRAALTALGMLDHQEEDLTTGRNVALELFDAQLDQAVRAFQQHRGLLVDGIVGEATYRALKEASYRLGARTLYHQFGAPLYGDDVATLQARLQDLGFYTGLVDGHFGLQTHNALMSYQREYGLAADGICGPETLRSLYFLSSRVSGGSPHAIREEELVRSSGPKLSGKRIIIDPGRGGVDHGLIAQGPAGPISEADLLWDLASRLEGRMAAIGMETHLSRPTNRSPSDAERAATANAVGADLMISLRCETQTSLAANGVASFHFGNSHGSVSTIGRNLADFIQREVVARTGLRDCRVHGRTWDLLRLTRMPTVQVDIGYITNPHDRGMLVSTQTRDAIAEGILAAVKRLYLLGKNDRPTGTFTFAELLAHELSVERAGRLGGS