Rv2525c Family assigned · medium auto-curated

H37Rv Rv2525c · MTBC0 mtbc0_002689 · 240 aa · 2872742–2873464 (-) · RefSeq NP_217041.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF1906 domain-containing protein
Revised (this work)DUF1906 domain-containing protein. Pfam: Rv2525c_GlyHyd-like (PF08924.18).

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

Curated reference (UniProt)

UniProt I6XEI5 SwissProt · reviewed · Evidence at protein level
UniProt namePutative peptidoglycan hydrolase Rv2525c
EC (curated) EC 3.2.1.17
Curated functionMay function as a peptidoglycan hydrolase with glycosidase activity. In vitro, displays esterase activity toward p-nitrophenyl esters of various acyl chain length (C4 to C16), with a preference for p-nitrophenyl butyrate (C4).

UniProt still lists this protein as Putative peptidoglycan hydrolase Rv2525c; 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 descriptionDomain of unknown function (DUF1906)
Orthologous groupCOG3757

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 0.506 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 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
Rv2525c_GlyHyd-likePF08924.18 1.9e-4953–230 Rv2525c-like, glycoside hydrolase-like domain

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

Closest characterised functional partner: Rv3668c (protease), high confidence from genomic context alone (score 755 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3668c protease 769 755 ctx cooccurence:752
Rv1566c ripD hyp hypothetical protein 761 750 coexpression:745
Rv3810 pirG cell surface protein 744 744 coexpression:744
Rv1158c hyp hypothetical protein 732 732 coexpression:732
Rv3847 hyp hypothetical protein 729 730 ctx cooccurence:728
Rv2673 aftC alpha-(1->3)-arabinofuranosyltransferase 720 720 ctx cooccurence:719
Rv2524c fas fatty acid synthase 719 720 ctx neighborhood:510 cooccurence:435
Rv0531 membrane protein 707 708 ctx cooccurence:706
Rv0048c membrane protein 704 703 ctx cooccurence:697
Rv3805c aftB terminal beta-(1->2)-arabinofuranosyltransferase 694 694 ctx cooccurence:691
Rv3802c membrane protein 727 687 ctx cooccurence:678
Rv1275 lprC lipoprotein LprC 665 665 ctx cooccurence:663
Rv0479c membrane protein 633 633 ctx cooccurence:631
Rv0227c membrane protein 631 631 ctx cooccurence:629
Rv3244c lpqB lipoprotein LpqB 622 622 ctx cooccurence:618

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: DUF1906 domain-containing protein
  • Pfam (hmmscan --cut_ga): Rv2525c_GlyHyd-like PF08924.18 (E=2e-49)
  • (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_217041.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Rv2525c_GlyHyd-like (PF08924.18)
  • 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 COG3757
  • Curated reference: UniProt I6XEI5 (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 — 62 functional partner(s); context anchor Rv3668c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002689|Rv2525c|
MSVSRRDVLKFAAATPGVLGLGVVASSLRAAPASAGSLGTLLDYAAGVIPASQIRAAGAVGAIRYVSDRRPGGAWMLGKPIQLSEARDLSGNGLKIVSCYQYGKGSTADWLGGASAGVQHARRGSELHAAAGGPTSAPIYASIDDNPSYEQYKNQIVPYLRSWESVIGHQRTGVYANSKTIDWAVNDGLGSYFWQHNWGSPKGYTHPAAHLHQVEIDKRKVGGVGVDVNQILKPQFGQWA