Rv0045c Family assigned · medium auto-curated

H37Rv Rv0045c · MTBC0 mtbc0_000050 · 298 aa · 49142–50038 (-) · RefSeq NP_214559.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hydrolase
MTBC0 PGAP re-annotationalpha/beta hydrolase
Revised (this work)Alpha/beta hydrolase. Pfam: 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 I6XU97 SwissProt · reviewed · Evidence at protein level
UniProt nameEsterase Rv0045c
EC (curated) EC 3.1.1.1
Curated functionEsterase likely involved in ester/lipid metabolism. Shows strong substrate selectivity toward short, straight chain alkyl esters with the highest activity toward four atom chains. The physiological substrate is unknown. Is able to hydrolyze ester bonds within a wide range of p-nitrophenyl derivatives (C2-C14) in vitro.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
eggNOG descriptionAlpha beta hydrolase
Orthologous groupCOG0596

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 0.83 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 6 missense, 1 nonsense, 5 frameshift
Disruption 6 distinct premature-stop/frameshift site(s); most common in 32.31% of strains (46923) · convergent

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
Abhydrolase_1PF00561.27 2.9e-1350–282 alpha/beta hydrolase fold
Abhydrolase_6PF12697.14 2.0e-1852–289 Alpha/beta hydrolase family

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

Closest characterised functional partner: Rv0044c (oxidoreductase), high confidence from genomic context alone (score 819 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0044c oxidoreductase 819 819 ctx neighborhood:813
Rv0043c HTH-type transcriptional regulator 731 732 ctx neighborhood:696
Rv0046c ino1 inositol-3-phosphate synthase 709 710 ctx neighborhood:671
Rv0047c hyp hypothetical protein 680 680 ctx neighborhood:675
Rv0042c transcriptional regulator 608 608 ctx neighborhood:608
Rv0048c membrane protein 592 592
Rv2940c mas multifunctional mycocerosic acid synthase 530 503 experimental:441
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 530 503 experimental:441
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 529 501 experimental:441
Rv2048c pks12 polyketide synthase 526 498 experimental:441
Rv1527c pks5 polyketide synthase 526 498 experimental:441
Rv2946c pks1 polyketide synthase 489 459
Rv2407 rnz ribonuclease Z 429 429 ctx cooccurence:428
Rv1181 pks4 polyketide beta-ketoacyl synthase 452 428
Rv1661 pks7 polyketide synthase 449 424

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: alpha/beta hydrolase
  • Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=3e-13), Abhydrolase_6 PF12697.14 (E=2e-18)
  • (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_214559.1)
  • Domains: Pfam-A via hmmscan --cut_ga — 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 COG0596
  • Curated reference: UniProt I6XU97 (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 — 22 functional partner(s); context anchor Rv0044c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000050|Rv0045c|
MLSDDELTGLDEFALLAENAEQAGVNGPLPEVERVQAGAISALRWGGSAPRVIFLHGGGQNAHTWDTVIVGLGEPALAVDLPGHGHSAWREDGNYSPQLNSETLAPVLRELAPGAEFVVGMSLGGLTAIRLAAMAPDLVGELVLVDVTPSALQRHAELTAEQRGTVALMHGEREFPSFQAMLDLTIAAAPHRDVKSLRRGVFHNSRRLDNGNWVWRYDAIRTFGDFAGLWDDVDALSAPITLVRGGSSGFVTDQDTAELHRRATHFRGVHIVEKSGHSVQSDQPRALIEIVRGVLDTR