cobT Resolved · high auto-curated

H37Rv Rv2207 · MTBC0 mtbc0_002343 · 361 aa · 2497568–2498653 (+) · RefSeq NP_216723.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase
MTBC0 PGAP re-annotationnicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase
Revised (this work)Nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase. Pfam: DBI_PRT (PF02277.23).

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

Curated reference (UniProt)

UniProt P9WP85 SwissProt · reviewed · Evidence at protein level
UniProt nameNicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase
EC (curated) EC 2.4.2.21
Curated functionCatalyzes the synthesis of alpha-ribazole-5'-phosphate from nicotinate mononucleotide (NAMN) and 5,6-dimethylbenzimidazole (DMB).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namecobT
eggNOG descriptionCatalyzes the synthesis of alpha-ribazole-5'-phosphate from nicotinate mononucleotide (NAMN) and 5,6- dimethylbenzimidazole (DMB)
Orthologous groupCOG2038
EC number EC 2.4.2.21
KEGG orthology K00768
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 0.673 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 7 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
DBI_PRTPF02277.23 2.9e-1298–343 Phosphoribosyltransferase

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

Closest characterised functional partner: cobU (bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase), high confidence from genomic context alone (score 994 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0254c cobU bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase 996 994 ctx neighborhood:461 fusion:899 cooccurence:768 coexpression:557 textmining:421
Rv2208 cobS adenosylcobinamide-GDP ribazoletransferase 995 992 ctx neighborhood:882 cooccurence:772 coexpression:467 database:500 textmining:500
Rv0306 bluB oxidoreductase 989 989 ctx fusion:900 cooccurence:447 database:800
Rv2228c multifunctional RNASE H/alpha-ribazole phosphatase/acid phosphatase 938 935 database:900
Rv2848c cobB cobyrinic acid A,C-diamide synthase 922 899 ctx fusion:497 cooccurence:623 coexpression:440
Rv0255c cobQ1 cobyric acid synthase 906 878 ctx cooccurence:767 coexpression:426
Rv2236c cobD cobalamin biosynthesis transmembrane protein CobD 852 806 ctx cooccurence:761
Rv2206 transmembrane protein 788 789 ctx neighborhood:786
Rv2205c hyp hypothetical protein 710 710 ctx neighborhood:709
Rv2066 cobIJ bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase 847 676 coexpression:412 textmining:550
Rv2071c cobM precorrin-4 C(11)-methyltransferase 747 669 ctx cooccurence:568
Rv2204c hyp hypothetical protein 667 668 ctx neighborhood:663
Rv2209 integral membrane protein 535 535 ctx neighborhood:532
Rv2231c cobC aminotransferase 554 507 coexpression:424
Rv2065 cobH precorrin-8X methylmutase 609 490

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: nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase
  • MTBC0 PGAP product: nicotinate-nucleotide--dimethylbenzimidazole phosphoribosyltransferase
  • Pfam (hmmscan --cut_ga): DBI_PRT PF02277.23 (E=3e-129)
  • (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_216723.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DBI_PRT (PF02277.23)
  • 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 COG2038
  • Curated reference: UniProt P9WP85 (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 — 30 functional partner(s); context anchor cobU
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002343|Rv2207|cobT
MIGFAPVSTPDAAAEAAARARQDSLTKPRGALGSLEDLSVWVASCQQRCPPRQFERARVVVFAGDHGVARSGVSAYPPEVTAQMVANIDAGGAAINALADVAGATVRVADLAVDADPLSERIGAHKVRRGSGNIATEDALTNDETAAAITAGQQIADEEVDAGADLLIAGDMGIGNTTAAAVLVAALTDAEPVAVVGFGTGIDDAGWARKTAAVRDALFRVRPVLPDPVGLLRCAGGADLAAIAGFCAQAAVRRTPLLLDGVAVTAAALVAERLAPGAHRWWQAGHRSSEPGHGLALAALGLDPIVDLHMRLGEGTGAAVALMVLRAAVAALSSMATFTEAGVSTRSVDGVDRTAPPAVSP