Rv0373c Family assigned · medium auto-curated

H37Rv Rv0373c · MTBC0 mtbc0_000393 · 799 aa · 452766–455165 (-) · RefSeq NP_214887.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)carbon monoxyde dehydrogenase large subunit
MTBC0 PGAP re-annotationaerobic carbon-monoxide dehydrogenase large subunit
Revised (this work)Aerobic carbon-monoxide dehydrogenase large subunit. Pfam: Ald_Xan_dh_C (PF01315.28), MoCoBD_1 (PF02738.24), MoCoBD_2 (PF20256.4).

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

Curated reference (UniProt)

UniProt O53708 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 namecoxL
eggNOG descriptionaldehyde oxidase and xanthine dehydrogenase, a b hammerhead
Orthologous groupCOG1529
EC number EC 1.2.5.3
KEGG orthology K03520

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 0.331 · purifying
Polymorphic sites (≥ 0.1% of strains) 17 synonymous, 17 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
Ald_Xan_dh_CPF01315.28 1.7e-3638–145 Aldehyde oxidase and xanthine dehydrogenase, a/b hammerhead domain
MoCoBD_1PF02738.24 1.7e-73169–415 Molybdopterin cofactor-binding domain
MoCoBD_2PF20256.4 2.3e-87442–729 Molybdopterin cofactor-binding domain

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

Closest characterised functional partner: Rv0374c (carbon monoxyde dehydrogenase small subunit), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0374c carbon monoxyde dehydrogenase small 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:860 cooccurence:774 coexpression:436 experimental:928 textmining:934
Rv0372c hyp hypothetical protein 980 978 ctx neighborhood:852 cooccurence:773
Rv0370c oxidoreductase 957 956 ctx neighborhood:861 cooccurence:690
Rv0371c hyp hypothetical protein 948 943 ctx neighborhood:798 cooccurence:714
Rv0368c hyp hypothetical protein 942 942 ctx neighborhood:748 cooccurence:770
Rv0369c membrane oxidoreductase 954 936 ctx neighborhood:760 cooccurence:735
Rv0376c hyp hypothetical protein 929 922 ctx neighborhood:619 cooccurence:752
Rv3621c PPE65 PPE family protein PPE65 730 730 coexpression:730
Rv0377 HTH-type transcriptional regulator 715 708 ctx neighborhood:442 cooccurence:471
Rv0345 hyp hypothetical protein 660 620 ctx neighborhood:544
Rv2426c hyp hypothetical protein 621 604 ctx cooccurence:553
Rv0887c hyp hypothetical protein 580 581 coexpression:580
Rv0344c lpqJ lipoprotein LpqJ 482 483 ctx neighborhood:480
Rv0367c hyp hypothetical protein 410 411 ctx neighborhood:409

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 large subunit
  • MTBC0 PGAP product: aerobic carbon-monoxide dehydrogenase large subunit
  • Pfam (hmmscan --cut_ga): Ald_Xan_dh_C PF01315.28 (E=2e-36), MoCoBD_1 PF02738.24 (E=2e-73), MoCoBD_2 PF20256.4 (E=2e-87)
  • (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_214887.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Ald_Xan_dh_C (PF01315.28), MoCoBD_1 (PF02738.24), MoCoBD_2 (PF20256.4)
  • 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 COG1529
  • Curated reference: UniProt O53708 (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 — 25 functional partner(s); context anchor Rv0374c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000393|Rv0373c|
MTTIESRPPSPEDLADNAQQPCGHGRMMRKEDPRFIRGRGTYVDDVALPGMLHLAILRSPYAHARIVRIDVTAAQAHPKVKAVVTGADLAAKGLAWMPTLANDVQAVLATDKTRFQGQEVAFVVAEDRYSARDACELVDVDYEPRDPVVDARTALDPSAPVIRTDLEGKSDNHIFDWETGDAAATEAVFAKADVVVQQEIVYPRVHPAPMETCGAVADLDPVTGKLTLWTTSQAPHAHRTLYALVAGLPEHKIRVISPDIGGGFGNKVPIYPGYVCAIVASLLLDKPVKWMEDRSENLTSTGFARDYIMVGEIAANRDGKILAIRSNVLADHGAFNAQAAPAKYPAGFFGVFTGSYDIEAAYCHMTAVYTNKAPGGVAYACSFRITEAVYFVERLVDCLAFELKMDPAELRLRNLLRPNQFPYQSKTGWVYDSGDYETTMRKAMNMIGYEALRAEQKQRRARGELMGIGMSFFTEAVGAGPRKDMDILGLGMADGCELRVHPTGKAVLRLSVQTQGQGHETTFAQIVAEELGIAPDDIEVVHGDTDQTPFGLGTYGSRSTPVSGGAAALVARKVRDKAKIIASGMLEVSVADLQWEKGKFHVKGDPSAAVTIADIAMRAHGAGDLPEGIEGGLDAEVCYNPSNLTYPYGAYFCVVDIDPGTAVVKVRRFLAVDDCGTRINPMIIEGQVHGGIVDGIGMALMEMIAFDEDGNCLGGSLMDYLIPTALEVPHLETGHTVTPSPHHPIGAKGIGESATVGSPPAVVNAVVDALAPFGVRHADMPLTPSRVWEAMQGRATPPI