Rv0498 Resolved · high auto-curated

H37Rv Rv0498 · MTBC0 mtbc0_000524 · 280 aa · 591666–592508 (+) · RefSeq NP_215012.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationsugar phosphate isomerase/epimerase
Revised (this work)Sugar phosphate isomerase/epimerase. Pfam: AP_endonuc_2 (PF01261.31).

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

Curated reference (UniProt)

UniProt P9WKU1 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0498

UniProt still lists this protein as Uncharacterized protein Rv0498; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
eggNOG descriptionTIM barrel
Orthologous groupCOG1082

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 0.468 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 4 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
AP_endonuc_2PF01261.31 4.5e-2223–276 Xylose isomerase-like TIM barrel

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

Closest characterised functional partner: proC (pyrroline-5-carboxylate reductase), high confidence from genomic context alone (score 831 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0499 hyp hypothetical protein 964 965 ctx neighborhood:863 coexpression:754
Rv1752 hyp hypothetical protein 902 873 coexpression:863
Rv0496 ppx1 hyp hypothetical protein 864 864 ctx neighborhood:863
Rv0500 proC pyrroline-5-carboxylate reductase 831 831 ctx neighborhood:830
Rv0497 transmembrane protein 786 786 ctx neighborhood:783
Rv0500A DNA-binding protein 740 740 ctx neighborhood:724
Rv0495c hyp hypothetical protein 618 619 ctx neighborhood:617
Rv2436 rbsK ribokinase RbsK 614 562 coexpression:537
Rv2202c adoK adenosine kinase 612 560 coexpression:535
Rv1457c antibiotic ABC transporter permease 552 553 ctx cooccurence:540
Rv3015c hyp hypothetical protein 529 529 ctx cooccurence:526
Rv3597c lsr2 iron-regulated H-NS-like protein 523 523 ctx cooccurence:520
Rv0360c hyp hypothetical protein 516 516 ctx cooccurence:516
Rv2867c GCN5-like N-acetyltransferase 513 513 ctx cooccurence:510
Rv3197A whiB7 transcriptional regulator WhiB7 510 511 ctx cooccurence:508

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: sugar phosphate isomerase/epimerase
  • Pfam (hmmscan --cut_ga): AP_endonuc_2 PF01261.31 (E=4e-22)
  • (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_215012.1)
  • Domains: Pfam-A via hmmscan --cut_ga — AP_endonuc_2 (PF01261.31)
  • 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 COG1082
  • Curated reference: UniProt P9WKU1 (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 proC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000524|Rv0498|
MRPAIKVGLSTASVYPLRAEAAFEYADRLGYDGVELMVWGESVSQDIDAVRKLSRRYRVPVLSVHAPCLLISQRVWGANPILKLDRSVRAAEQLGAQTVVVHPPFRWQRRYAEGFSDQVAALEAASTVMVAVENMFPFRADRFFGAGQSRERMRKRGGGPGPAISAFAPSYDPLDGNHAHYTLDLSHTATAGTDSLDMARRMGPGLVHLHLCDGSGLPADEHLVPGRGTQPTAEVCQMLAGSGFVGHVVLEVSTSSARSANERESMLAESLQFARTHLLR