MTBC Gene Atlas

cobO Resolved · high auto-curated

H37Rv Rv2849c · MTBC0 - · 207 aa · 3157521–3158144 (-) · RefSeq YP_177908.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cob(I)alamin adenosyltransferase
MTBC0 PGAP re-annotation—
Revised (this work)Cob(I)alamin adenosyltransferase. Pfam: CobA_CobO_BtuR (PF02572.22).

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 I6Y1V6 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable cob(I)alamin adenosyltransferase CobO

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namecobO
eggNOG descriptionATP corrinoid adenosyltransferase
Orthologous groupCOG2109
EC number EC 2.5.1.17
KEGG orthology K19221
KEGG pathways map00860, map01100
KEGG modules M00122

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 0.98 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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
CobA_CobO_BtuRPF02572.22 5.1e-5924–207 ATP:corrinoid adenosyltransferase BtuR/CobO/CobP

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

Closest characterised functional partner: cobB (cobyrinic acid A,C-diamide synthase), high confidence from genomic context alone (score 996 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2848c cobB cobyrinic acid A,C-diamide synthase 999 996 ctx neighborhood:881 cooccurence:611 database:900 textmining:850
Rv2208 cobS adenosylcobinamide-GDP ribazoletransferase 996 974 ctx cooccurence:676 database:900 textmining:888
Rv2236c cobD cobalamin biosynthesis transmembrane protein CobD 995 972 ctx cooccurence:684 database:900 textmining:842
Rv0255c cobQ1 cobyric acid synthase 989 971 ctx cooccurence:674 database:900 textmining:648
Rv2062c cobN cobalamin biosynthesis protein CobN 998 969 ctx cooccurence:651 database:900 textmining:965
Rv0254c cobU bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase 998 967 ctx cooccurence:636 database:900 textmining:965
Rv2850c magnesium chelatase 985 922 ctx neighborhood:857 cooccurence:458 textmining:818
Rv1314c cob(I)yrinic acid a,c-diamide adenosyltransferase 932 906 database:900
Rv2851c GCN5-like N-acetyltransferase 972 859 ctx neighborhood:857 textmining:810
Rv2847c cysG multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase 886 795 ctx neighborhood:721 textmining:471
Rv2852c mqo malate:quinone oxidoreductase 793 793 ctx neighborhood:787
Rv2846c efpA MFS-type transporter EfpA 708 708 ctx neighborhood:708
Rv2854 hyp hypothetical protein 686 679 ctx neighborhood:679
Rv2855 mtr mycothione reductase 677 677 ctx neighborhood:675
Rv2066 cobIJ bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase 866 663 ctx cooccurence:467 textmining:621

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): cob(I)alamin adenosyltransferase
  • Pfam (hmmscan --cut_ga): CobA_CobO_BtuR PF02572.22 (E=5e-59)
  • (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 YP_177908.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CobA_CobO_BtuR (PF02572.22)
  • 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 COG2109
  • Curated reference: UniProt I6Y1V6 (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 — 37 functional partner(s); context anchor cobB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2849c|cobO
MPQGNPLAVPNDGLTTRARRNMPILAVHTGEGKGKSTAAFGMALRAWNAGLDIAVFQFVKSAKWKVGEEAAFRQLGRLHDQHGIGGAVEWHKMGAGWSWTRTSRKAGTDVDRAAAAADGWAEIALRLATQRHDFYLLDEFTYPLKWGWLDVDEVVDVLRARPGHQHVVITGRDAPQRLVAAADLVTEMTKVKHPMDAGRKGQKGIEW