Rv0374c Family assigned · medium auto-curated

H37Rv Rv0374c · MTBC0 mtbc0_000394 · 159 aa · 455162–455641 (-) · RefSeq NP_214888.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)carbon monoxyde dehydrogenase small subunit
MTBC0 PGAP re-annotation(2Fe-2S)-binding protein
Revised (this work)(2Fe-2S)-binding protein. Pfam: Fer2 (PF00111.33), Fer2_2 (PF01799.26).

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

Curated reference (UniProt)

UniProt O53709 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable carbon monoxyde dehydrogenase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namecoxS
eggNOG description2Fe-2S -binding domain
Orthologous groupCOG2080
EC number EC 1.2.5.3
KEGG orthology K03518

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 0.482 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.15% of strains (213) · 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
Fer2PF00111.33 5.7e-086–53 2Fe-2S iron-sulfur cluster binding domain
Fer2_2PF01799.26 5.6e-3173–147 [2Fe-2S] binding domain

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

Closest characterised functional partner: Rv0373c (carbon monoxyde dehydrogenase large subunit), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0373c carbon monoxyde dehydrogenase large subunit 999 1000 ctx neighborhood:882 fusion:900 cooccurence:773 coexpression:577 experimental:928 textmining:895
Rv0375c carbon monoxyde dehydrogenase medium subunit 999 999 ctx neighborhood:869 cooccurence:773 coexpression:440 experimental:928 textmining:895
Rv0372c hyp hypothetical protein 974 972 ctx neighborhood:861 cooccurence:752
Rv0371c hyp hypothetical protein 971 968 ctx neighborhood:861 cooccurence:756
Rv0376c hyp hypothetical protein 961 958 ctx neighborhood:782 cooccurence:767
Rv0370c oxidoreductase 896 891 ctx neighborhood:861
Rv0368c hyp hypothetical protein 870 870 ctx neighborhood:760 cooccurence:452
Rv0369c membrane oxidoreductase 841 841 ctx neighborhood:760
Rv0377 HTH-type transcriptional regulator 757 757 ctx neighborhood:719
Rv0365c hyp hypothetical protein 677 677 ctx neighborhood:676
Rv0367c hyp hypothetical protein 409 409 ctx neighborhood:409
Rv0408 pta phosphate acetyltransferase 413 171

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: carbon monoxyde dehydrogenase small subunit
  • MTBC0 PGAP product: (2Fe-2S)-binding protein
  • Pfam (hmmscan --cut_ga): Fer2 PF00111.33 (E=6e-08), Fer2_2 PF01799.26 (E=6e-31)
  • (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_214888.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Fer2 (PF00111.33), Fer2_2 (PF01799.26)
  • 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 COG2080
  • Curated reference: UniProt O53709 (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 — 12 functional partner(s); context anchor Rv0373c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000394|Rv0374c|
MQVNMTVNGEPVTAEVEPRMLLVHFLRDQLRLTGTHWGCDTSNCGTCVVEVDGVPVKSCTMLAVMASGHSIRTVEGLAGPDGQLDPVQEGFMRCHGLQCGFCTPGMLITARALLDRNPDPDEQTIREAISGQICRCTGYTTIVRSIQWAAAHQTVKAQS