Rv3471c Family assigned · medium auto-curated

H37Rv Rv3471c · MTBC0 - · 177 aa · 3888808–3889341 (-) · RefSeq NP_217988.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains Cupin_2 (PF07883.18) domain(s); putative function inferred from the domain architecture.

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O06336 TrEMBL · unreviewed · Predicted
UniProt nameCupin type-1 domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
eggNOG descriptionCupin 2, conserved barrel domain protein
Orthologous groupCOG0662
EC number EC 5.3.1.9
KEGG orthology K01810
KEGG pathways map00010, map00030, map00500, map00520, map01100, map01110, map01120, map01130, map01200
KEGG modules M00001, M00004, M00114

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 1 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.28% of strains (400) · 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
Cupin_2PF07883.18 1.0e-1386–154 Cupin domain

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

Closest characterised functional partner: ilvB2 (acetolactate synthase large subunit), high confidence from genomic context alone (score 883 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3470c ilvB2 acetolactate synthase large subunit 883 883 ctx neighborhood:881
Rv3472 hyp hypothetical protein 679 680 ctx neighborhood:618
Rv3468c dTDP-glucose 4,6-dehydratase 690 673 ctx neighborhood:616
Rv3469c mhpE 4-hydroxy-2-oxovalerate aldolase MhpE 649 649 ctx neighborhood:646
Rv1525 wbbL2 rhamnosyl transferase WbbL 604 585 ctx cooccurence:460
Rv3833 AraC family transcriptional regulator 575 514 experimental:408
Rv2949c chorismate pyruvate-lyase 494 495 ctx cooccurence:453
Rv1301 threonylcarbamoyl-AMP synthase 433 433 coexpression:415
Rv2839c infB translation initiation factor IF-2 422 397
Rv3465 rmlC dTDP-4-dehydrorhamnose 3,5-epimerase 452 372
Rv0334 rmlA glucose-1-phosphate thymidylyltransferase 450 368
Rv0322 udgA UDP-glucose 6-dehydrogenase UdgA 409 250

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Pfam (hmmscan --cut_ga): Cupin_2 PF07883.18 (E=1e-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_217988.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Cupin_2 (PF07883.18)
  • 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 COG0662
  • Curated reference: UniProt O06336 (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 — 12 functional partner(s); context anchor ilvB2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3471c|
MSTRPERERASTSTDAVLQATVALSAGHKPAFRGFVKDPPRARAHAAAMFVSNAREAEPFVAPDLSEIRVLVDRATVGVASVSLAHATVAAGAETVWHRLQATDEIYFVLSGRGLVSVGDESGEVGPGDAVWIPAGVPQKIRALGSVPLTFLCACGPAYLPERDQRMGEAAVIGAWP