Rv2695 Resolved · medium auto-curated

H37Rv Rv2695 · MTBC0 mtbc0_002869 · 235 aa · 3034331–3035038 (+) · RefSeq NP_217211.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationalpha/beta fold hydrolase
Revised (this work)Alpha/beta fold hydrolase.

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

Curated reference (UniProt)

UniProt I6Y1I1 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved hypothetical alanine rich protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
eggNOG descriptionAldo Keto reductase
Orthologous groupCOG0667

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 0 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: Rv2693c (integral membrane protein), high confidence from genomic context alone (score 734 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2418c octT hyp hypothetical protein 779 771 ctx cooccurence:764
Rv3415c hyp hypothetical protein 771 771 ctx cooccurence:768
Rv2186c hyp hypothetical protein 748 749 ctx cooccurence:747
Rv2693c integral membrane protein 734 734 ctx neighborhood:694
Rv3031 1,4-alpha-glucan-branching protein 705 706 ctx cooccurence:704
Rv0419 lpqM lipoprotein peptidase LpqM 687 688 ctx cooccurence:687
Rv2694c hyp hypothetical protein 618 618 ctx neighborhood:616
Rv2091c membrane protein 609 609 ctx cooccurence:605
Rv3217c integral membrane protein 604 604 ctx cooccurence:604
Rv0556 transmembrane protein 599 599 ctx cooccurence:599
Rv2174 mptA alpha(1->6)-mannopyranosyltransferase A 591 591 ctx cooccurence:539
Rv0250c hyp hypothetical protein 588 589 ctx cooccurence:586
Rv3034c acetyltransferase 584 584 ctx cooccurence:578
Rv2468c hyp hypothetical protein 579 579 ctx cooccurence:577
Rv1411c lprG lipoprotein LprG 570 570 ctx cooccurence:570

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 fold hydrolase
  • (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_217211.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG0667
  • Curated reference: UniProt I6Y1I1 (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 — 76 functional partner(s); context anchor Rv2693c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002869|Rv2695|
MAVDLDGVTTVLLPGTGSDNDYVRRAFSAPLRRAGAVLVTPVPHPGRLIDGYRAALDDAARDGPVVVGGVSLGAAVAAAWALEHPDRAVAVLAALPAWTGEPELAPAAQAARYTAARLRCDGLAATTTRMRASSPVWLAEELTRSWRVQWPELPDAMEEAAAYVAPSRAELARLVAPLAVAAAVDDPIHPLQVAADWVSVAPHAALRTVTLDEIGADAAALGSACLAALAEVSGA