Rv0492c Family assigned · medium auto-curated

H37Rv Rv0492c · MTBC0 mtbc0_000517 · 629 aa · 584830–586719 (-) · RefSeq NP_215006.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)GMC-type oxidoreductase
MTBC0 PGAP re-annotationGMC family oxidoreductase
Revised (this work)GMC family oxidoreductase. Pfam: FAD_binding_3 (PF01494.26), FAD_binding_2 (PF00890.31), NAD_binding_8 (PF13450.13), GMC_oxred_N (PF00732.26), GMC_oxred_C (PF05199.20).

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

Curated reference (UniProt)

UniProt P9WMV7 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized GMC-type oxidoreductase Rv0492c
EC (curated) EC 1.1.-.-

UniProt still lists this protein as Uncharacterized GMC-type oxidoreductase Rv0492c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
eggNOG descriptionoxidoreductase
Orthologous groupCOG2303
Gene Ontology (8) GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0044424, GO:0044444, GO:0044464

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 1.952 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 10 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
FAD_binding_3PF01494.26 1.1e-05147–216 FAD binding domain
FAD_binding_2PF00890.31 1.5e-04148–179 FAD binding domain
NAD_binding_8PF13450.13 1.1e-04151–180 NAD(P)-binding Rossmann-like domain
GMC_oxred_NPF00732.26 1.6e-62196–408 GMC oxidoreductase
GMC_oxred_CPF05199.20 9.2e-18496–614 GMC oxidoreductase

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

Closest characterised functional partner: Rv0494 (HTH-type transcriptional regulator), high confidence from genomic context alone (score 741 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0493c hyp hypothetical protein 976 976 ctx neighborhood:881 cooccurence:770
Rv0492A hyp hypothetical protein 932 933 ctx neighborhood:881 coexpression:458
Rv1691 hyp hypothetical protein 799 791 experimental:411 database:583
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 784 773 experimental:762
Rv1973 Mce associated membrane protein 770 761 database:536
Rv1972 Mce associated membrane protein 765 756 database:536
Rv3529c hyp hypothetical protein 756 745 experimental:411 database:583
Rv2267c stf3 hyp hypothetical protein 755 745 experimental:411 database:583
Rv0494 HTH-type transcriptional regulator 741 741 ctx neighborhood:622
Rv2328 PE23 PE family protein PE23 739 729 database:573
Rv3812 PE_PGRS62 PE-PGRS family protein PE_PGRS62 739 729 database:573
Rv3036c TB22.2 hyp hypothetical protein 739 729 database:573
Rv0832 PE_PGRS12 PE-PGRS family protein PE_PGRS12 739 729 database:573
Rv3492c Mce associated protein 692 680 database:536
Rv0200 transmembrane protein 692 680 database:536

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: GMC-type oxidoreductase
  • MTBC0 PGAP product: GMC family oxidoreductase
  • Pfam (hmmscan --cut_ga): FAD_binding_3 PF01494.26 (E=1e-05), FAD_binding_2 PF00890.31 (E=1e-04), NAD_binding_8 PF13450.13 (E=1e-04), GMC_oxred_N PF00732.26 (E=2e-62), GMC_oxred_C PF05199.20 (E=9e-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_215006.2)
  • Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_3 (PF01494.26), FAD_binding_2 (PF00890.31), NAD_binding_8 (PF13450.13), GMC_oxred_N (PF00732.26), GMC_oxred_C (PF05199.20)
  • 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 COG2303
  • Curated reference: UniProt P9WMV7 (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 — 31 functional partner(s); context anchor Rv0494
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000517|Rv0492c|
MSRLADRAKSYPLASFGAALLPPELGGPLPAQFVQRVDRYVTRLPATSRFAVRAGLASLAAASYLTTGRSLPRLHPDERARVLHRIAALSPEVAAAVEGLKAIVLLANGADTYAHELLARAQEHDAARPDAELTVILSADSPSVTRADAVVVGSGAGGAMVARTLARAGLDVVVLEEGRRWTVEEFRSTHPVDRYAGLYRGAGATVALGRPAVVLPMGRAVGGTTVVNSGTCFRPSLAVQRRWRDEFGLGLADPDQLGRRLDDAEQTLRVAPVPLEIMGRNGRLLLQAAKSLGWRAAPIPRNAPGCRGCCQCAIGCPSNAKFGVHLNALPQACAAGARIISWARVERILHRAGRAYGVRARRPDGTTLDVLADAVVVAAGATETPGLLRRSGLGGHPRLGHNLALHPATMLAGLFDDDVFAWRGVLQSAAVHEFHESDGVLIEATSTPPGMGSMVFPGYGAELLRWLDRAPQIATFGAMVADRGVGTVRSVRGETVVRYDIAPGEIAKLRVALQAIGRLLFAAGAVEVLTGIPGAPPMRSLPELQDVLRRANPRSLHLAAFHPTGTAAAGADEQLCPVDATGRLRGVEGVWVADASILPSCPEVNPQLSIMAMALAVADQTVAKVVGVR