Rv2765 Family assigned · medium auto-curated

H37Rv Rv2765 · MTBC0 mtbc0_002943 · 245 aa · 3097051–3097788 (+) · RefSeq NP_217281.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hydrolase
MTBC0 PGAP re-annotationdienelactone hydrolase family protein
Revised (this work)Dienelactone hydrolase family protein. Pfam: DLH (PF01738.25).

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

Curated reference (UniProt)

UniProt I6XF92 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable alanine rich hydrolase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptiondienelactone hydrolase
Orthologous groupCOG0412
EC number EC 3.1.1.45
KEGG orthology K01061
KEGG pathways map00361, map00364, map00623, map01100, map01110, map01120, map01130

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 0.577 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 7 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
DLHPF01738.25 9.1e-6917–243 Dienelactone hydrolase family

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

Closest characterised functional partner: dfrA (dihydrofolate reductase), high confidence from genomic context alone (score 713 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2054 hyp hypothetical protein 925 926 database:900
Rv2763c dfrA dihydrofolate reductase 713 713 ctx neighborhood:713
Rv2762c hyp hypothetical protein 673 673 ctx neighborhood:673
Rv3192 hyp hypothetical protein 582 582 ctx neighborhood:512
Rv2764c thyA thymidylate synthase ThyA 725 533 ctx neighborhood:532 textmining:435
Rv1832 gcvB glycine dehydrogenase 441 441 coexpression:422
Rv2761c hsdS type I restriction/modification system specificity determinant HsdS 533 371
Rv2755c hsdS.1 Rv2755c, (MTV002.20c), len: 91 aa. Possible hsdS.1,fragment of type I restriction/modification system specificity determinant (S protein), s 670 302 textmining:546
Rv2754c thyX thymidylate synthase ThyX 484 214
Rv3254 hyp hypothetical protein 719 198 textmining:664
Rv3366 spoU tRNA/rRNA methylase SpoU 662 73 textmining:651
Rv1781c malQ 4-alpha-glucanotransferase 517 55 textmining:510
Rv0724A Conserved hypothetical protein; Rv0724A, len: 111 aa. Similarity suggests that this CDS should be continuation of Rv0725c but we can find no 661 54 textmining:657
Rv3304 hyp hypothetical protein 444 49 textmining:440
Rv3253c cationic amino acid transport integral membrane protein 514 47 textmining:511

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: dienelactone hydrolase family protein
  • Pfam (hmmscan --cut_ga): DLH PF01738.25 (E=9e-69)
  • (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_217281.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DLH (PF01738.25)
  • 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 COG0412
  • Curated reference: UniProt I6XF92 (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 — 19 functional partner(s); context anchor dfrA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002943|Rv2765|
MPKTTDTAATPDGTCAVRLFTPDGPGRWPGVVMFPDAGGVRDTFDRMAAKLAGFGYVVLLPDVYYREGDWAPFDMKTAFGDPQERARIMFMIGTLTPDRVTRDADALLNYLASRPEVIGDRFGVCGYCMGGRMSVVVAGRLPDRVAAAAAFHPGGLVANSPDSPHLLADRISATVYIGGAENDPSFTADHAEKLDKAFSAAGVPHRIECYPAAHGFAVPDNPSYDAAADERHWAAMTETFGAALN