Rv2800 Family assigned · medium auto-curated

H37Rv Rv2800 · MTBC0 mtbc0_002979 · 549 aa · 3130831–3132480 (+) · RefSeq NP_217316.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hydrolase
MTBC0 PGAP re-annotationCocE/NonD family hydrolase
Revised (this work)CocE/NonD family hydrolase. Pfam: Peptidase_S15 (PF02129.25), PepX_C (PF08530.17).

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

Curated reference (UniProt)

UniProt I6YEE6 TrEMBL · unreviewed · Predicted
UniProt namePossible hydrolase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionHydrolase
Orthologous groupCOG2936
KEGG orthology K06978

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) pseudogene candidate

pN/pS 0.349 · purifying
Polymorphic sites (≥ 0.1% of strains) 12 synonymous, 10 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 2.84% of strains (4131) · 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
Peptidase_S15PF02129.25 8.1e-7049–310 X-Pro dipeptidyl-peptidase (S15 family)
PepX_CPF08530.17 1.5e-25339–541 X-Pro dipeptidyl-peptidase C-terminal non-catalytic domain

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

Closest characterised functional partner: Rv2799 (membrane protein), high confidence from genomic context alone (score 793 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2799 membrane protein 793 793 ctx neighborhood:787
Rv1215c hyp hypothetical protein 690 691 ctx cooccurence:686
Rv3433c nnr bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase 615 615 coexpression:615
Rv2797c hyp hypothetical protein 568 567 ctx neighborhood:562
Rv2798c hyp hypothetical protein 565 565 ctx neighborhood:562
Rv2796c lppV lipoprotein LppV 529 529 ctx neighborhood:529
Rv2794c pptT 4'-phosphopantetheinyl transferase 458 458 ctx neighborhood:455
Rv2793c truB tRNA pseudouridine synthase B 458 458 ctx neighborhood:455
Rv2795c hyp hypothetical protein 475 456 ctx neighborhood:456
Rv2790c ltp1 lipid-transfer protein 449 450 ctx neighborhood:430

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: hydrolase
  • MTBC0 PGAP product: CocE/NonD family hydrolase
  • Pfam (hmmscan --cut_ga): Peptidase_S15 PF02129.25 (E=8e-70), PepX_C PF08530.17 (E=1e-25)
  • (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_217316.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_S15 (PF02129.25), PepX_C (PF08530.17)
  • 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 COG2936
  • Curated reference: UniProt I6YEE6 (TrEMBL, unreviewed; Predicted)
  • 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 — 10 functional partner(s); context anchor Rv2799
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002979|Rv2800|
MSTTSARPERPKLRALTGRVGGQALGGLLGLPRATTRYTVGHVRVPMRDGVQLVADHYAPATSQPVGTLLVRGPYGRRFPFSLVFARIYAARGYHVVLQSVRGTFGSGGVFEPMVNEAADGADTVAWLREQPWFTGRFGTIGLPYLGFTQWALLHDPPPELAAAVITVGPHDFRASVWGTGSFTVNDFLGWSDLVSHQEDPGRIRAGIRQLTAPRRVARTAATLPLGESARTLLGTGAPWFESWVEHTDRDDPFWDRLRFPAALDRVQVPVLLVGGWQDIFLRQTLQQYRHLRDRGVHVALTVGPWTHTQMLTKGLATGARESLDWLDAHLGRAPALRPSPVRVFVTGQGWRHLPDWPPATTERAWYLQPGGRLGESAPASGTPPATFRYHPADPTPTTGGPLLSSNGGYRDDSRLATRADVLCFTGAPLTHDLCVHGNPVVELVHSSDNPYVDVFVRVSEVDAKGRSRNVSDGYRRLGDAPELVRVELDAIAHRFRADSRIRVLIAGSWFPRYARNLGTPEPILTGRQLKPATHAVHFGRSRLLLPVG