Rv2568c Family assigned · medium auto-curated

H37Rv Rv2568c · MTBC0 mtbc0_002735 · 341 aa · 2915990–2917015 (-) · RefSeq NP_217084.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationputative zinc-binding metallopeptidase
Revised (this work)Putative zinc-binding metallopeptidase. Pfam: Zn_ribbon_DZR_6 (PF10005.15), Peptidase_Mx (PF15887.12).

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

Curated reference (UniProt)

UniProt P9WL95 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2568c

UniProt still lists this protein as Uncharacterized protein Rv2568c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionprotein conserved in bacteria
Orthologous groupCOG4307

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 0.127 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 2 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
Zn_ribbon_DZR_6PF10005.15 3.5e-174–81 zinc-ribbon domain
Peptidase_MxPF15887.12 1.5e-10188–324 Putative zinc-binding metallo-peptidase

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv2569c hyp hypothetical protein 952 952 ctx neighborhood:882 cooccurence:569
Rv2566 hyp hypothetical protein 846 846 ctx neighborhood:544 cooccurence:675
Rv2567 hyp hypothetical protein 815 816 ctx neighborhood:544 cooccurence:613
Rv2570 hyp hypothetical protein 655 655 ctx neighborhood:655
Rv2411c hyp hypothetical protein 430 430
Rv2410c hyp hypothetical protein 413 414
Rv2409c hyp hypothetical protein 411 411

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: putative zinc-binding metallopeptidase
  • Pfam (hmmscan --cut_ga): Zn_ribbon_DZR_6 PF10005.15 (E=4e-17), Peptidase_Mx PF15887.12 (E=2e-101)
  • (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_217084.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Zn_ribbon_DZR_6 (PF10005.15), Peptidase_Mx (PF15887.12)
  • 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 COG4307
  • Curated reference: UniProt P9WL95 (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 — 7 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002735|Rv2568c|
MRDFHCPNCGQRLAFENSACLSCGSALGFSLGRMALLVIADDADVQLCANLHLAQCNWLVPSDQLGGLCSSCVLTIERPSDTNTAGLAEFARAEGAKRRLIAELHELKLPIVGRDQDPDHGLAFRLLSSAHENVTTGHQNGVITLDLAEGDDVHREQLRVEMDEPYRTLLGHFRHEIGHYYFYRLIASSSDYLSRFNELFGDPDADYSQALDRHYRGGPPEGWQDSFVSSYATMHASEDWAETFAHYLHIRDALDTAAWCGLAPASATFDRPALGPSAFNTIIDKWLPLSWSLNMVNRSMGHDDLYPFVLPAAVLEKMRFIHTVVDEVAPDFEPAHSRRTV