Rv2575 Resolved · high auto-curated

H37Rv Rv2575 · MTBC0 mtbc0_002742 · 293 aa · 2922883–2923764 (+) · RefSeq NP_217091.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationneutral zinc metallopeptidase
Revised (this work)Neutral zinc metallopeptidase. Pfam: Zn_peptidase (PF04228.20).

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

Curated reference (UniProt)

UniProt P9WL85 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2575

UniProt still lists this protein as Uncharacterized protein Rv2575; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameypfJ
eggNOG descriptionPutative neutral zinc metallopeptidase
Orthologous groupCOG2321
KEGG orthology K07054
Gene Ontology (2) GO:0005575, GO:0005576

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 2.298 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 6 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.47% of strains (679) · clonal

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_peptidasePF04228.20 9.0e-7414–287 Putative neutral zinc metallopeptidase

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

Closest characterised functional partner: Rv2573 (2-dehydropantoate 2-reductase), high confidence from genomic context alone (score 812 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2573 2-dehydropantoate 2-reductase 811 812 ctx neighborhood:811
Rv2574 hyp hypothetical protein 697 697 ctx neighborhood:682
Rv2510c hyp hypothetical protein 658 659 ctx cooccurence:653
Rv2572c aspS aspartate--tRNA ligase 518 518 ctx neighborhood:515
Rv3092c integral membrane protein 408 409
Rv2571c transmembrane protein 407 407 ctx neighborhood:404
Rv2367c ybeY endoribonuclease 671 44 textmining:670

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: membrane protein
  • MTBC0 PGAP product: neutral zinc metallopeptidase
  • Pfam (hmmscan --cut_ga): Zn_peptidase PF04228.20 (E=9e-74)
  • (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_217091.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Zn_peptidase (PF04228.20)
  • 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 COG2321
  • Curated reference: UniProt P9WL85 (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); context anchor Rv2573
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002742|Rv2575|
MTFNEGVQIDTSTTSTSGSGGGRRLAIGGGLGGLLVVVVAMLLGVDPGGVLSQQPLDTRDHVAPGFDLSQCRTGADANRFVQCRVVATGNSVDAVWKPLLPGYTRPHMRLFSGQVGTGCGPASSEVGPFYCPVDKTAYFDTDFFQVLVTQFGSSGGPFAEEYVVAHEYGHHVQNLLGVLGRAQQGAQGAAGSGVRTELQADCYAGVWAYYASTVKQESTGVPYLEPLSDKDIQDALAAAAAVGDDRIQQQTTGRTNPETWTHGSAAQRQKWFTVGYQTGDPNICDTFSAADLG