Rv2854 Family assigned · medium auto-curated

H37Rv Rv2854 · MTBC0 mtbc0_003033 · 346 aa · 3184818–3185858 (+) · RefSeq NP_217370.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationalpha/beta hydrolase
Revised (this work)Alpha/beta hydrolase. Pfam: Hydrolase_4 (PF12146.16), Abhydrolase_1 (PF00561.27), Abhydrolase_6 (PF12697.14).

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

Curated reference (UniProt)

UniProt O05805 TrEMBL · unreviewed · Evidence at protein level
UniProt nameSerine aminopeptidase S33 domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
eggNOG descriptionSerine aminopeptidase, S33
Orthologous groupCOG2267

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 0.41 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 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
Hydrolase_4PF12146.16 1.7e-1651–194 Serine aminopeptidase, S33
Abhydrolase_1PF00561.27 1.7e-1053–165 alpha/beta hydrolase fold
Abhydrolase_6PF12697.14 4.4e-1354–315 Alpha/beta hydrolase family

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

Closest characterised functional partner: mtr (mycothione reductase), high confidence from genomic context alone (score 877 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3150 nuoF NADH-quinone oxidoreductase subunit F 902 897 coexpression:454 experimental:817
Rv3151 nuoG NADH-quinone oxidoreductase subunit G 897 888 coexpression:413 experimental:817
Rv3148 nuoD NADH-quinone oxidoreductase subunit D 885 880 experimental:817
Rv2855 mtr mycothione reductase 883 877 ctx neighborhood:869
Rv3149 nuoE NADH-quinone oxidoreductase subunit E 876 876 coexpression:443 experimental:787
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 855 855 experimental:817
Rv3146 nuoB NADH-quinone oxidoreductase subunit B 829 829 experimental:787
Rv3147 nuoC NADH-quinone oxidoreductase subunit C 837 828 experimental:817
Rv3152 nuoH NADH-quinone oxidoreductase subunit H 803 803 experimental:803
Rv0310c hyp hypothetical protein 803 800 experimental:787
Rv3145 nuoA NADH-quinone oxidoreductase subunit A 788 788 experimental:787
Rv3157 nuoM NADH-quinone oxidoreductase subunit M 787 788 experimental:787
Rv3158 nuoN NADH-quinone oxidoreductase subunit N 730 730 experimental:729
Rv2852c mqo malate:quinone oxidoreductase 726 727 ctx neighborhood:725
Rv2851c GCN5-like N-acetyltransferase 689 690 ctx neighborhood:688

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: alpha/beta hydrolase
  • Pfam (hmmscan --cut_ga): Hydrolase_4 PF12146.16 (E=2e-16), Abhydrolase_1 PF00561.27 (E=2e-10), Abhydrolase_6 PF12697.14 (E=4e-13)
  • (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_217370.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Hydrolase_4 (PF12146.16), Abhydrolase_1 (PF00561.27), Abhydrolase_6 (PF12697.14)
  • 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 COG2267
  • Curated reference: UniProt O05805 (TrEMBL, unreviewed; 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 — 52 functional partner(s); context anchor mtr
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003033|Rv2854|
MTGWVPDVLPGYWQCTIPLGPDPDDEGDIVATLVGRGPQTGKARGDTTGAHHTVLAVHGYTDYFFHTELADHFANRGFAFYALDLRKCGRSRAPGQTPHFITDLARYDTELEHSLSIINEQNRSAKVLVYGHSAGGLIVSLWLDRLRQRGEITRAGVTGLVLNSPFLDLQGPAILRLPLTSAFFAAMARMRPKWVARPPKEGGYGCTLHRDYDGEFDYNLQWKPVGGFPVTFGWIHASRRGHARLHRGIDVGVPNLILCSDHTVREKADPATLHRGDAVLDVTHITRWAGCIGNRSTVIAVADAKHDVFLSLPQPRQMAYRRLDLWLDDYLGTHNDTDASASSGKG