cobL Resolved · high auto-curated

H37Rv Rv2072c · MTBC0 mtbc0_002206 · 390 aa · 2357587–2358759 (-) · RefSeq NP_216588.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)precorrin-6Y C(5,15)-methyltransferase
MTBC0 PGAP re-annotationbifunctional cobalt-precorrin-7 (C(5))-methyltransferase/cobalt-precorrin-6B (C(15))-methyltransferase
Revised (this work)Bifunctional cobalt-precorrin-7 (C(5))-methyltransferase/cobalt-precorrin-6B (C(15))-methyltransferase. Pfam: TP_methylase (PF00590.26).

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

Curated reference (UniProt)

UniProt P9WGA9 SwissProt · reviewed · Evidence at protein level
UniProt namePrecorrin-6Y C(5,15)-methyltransferase [decarboxylating]
EC (curated) EC 2.1.1.132
Curated functionCatalyzes the methylation of both C-5 and C-15 in precorrin-6Y to form precorrin-8X.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namecobL
eggNOG descriptionPrecorrin-6Y C5,15-methyltransferase (Decarboxylating)
Orthologous groupCOG2241
EC number EC 2.1.1.132
KEGG orthology K00595
KEGG pathways map00860, map01100
Gene Ontology (6) GO:0005575, GO:0005618, GO:0005623, GO:0030312, GO:0044464, GO:0071944

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) pseudogene candidate

pN/pS 0.633 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 7 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 11.96% of strains (17361) · 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
TP_methylasePF00590.26 1.5e-161–183 Tetrapyrrole (Corrin/Porphyrin) Methylases

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

Closest characterised functional partner: cobIJ (bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2066 cobIJ bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase 999 1000 ctx neighborhood:544 cooccurence:774 coexpression:997 textmining:850
Rv2070c cobK precorrin-6A reductase 999 999 ctx neighborhood:881 cooccurence:774 coexpression:665 database:900 textmining:850
Rv2065 cobH precorrin-8X methylmutase 999 999 ctx cooccurence:774 coexpression:972 database:900 textmining:578
Rv2071c cobM precorrin-4 C(11)-methyltransferase 999 998 ctx neighborhood:881 cooccurence:735 coexpression:924 textmining:888
Rv2073c oxidoreductase 943 943 ctx neighborhood:796 coexpression:732
Rv2062c cobN cobalamin biosynthesis protein CobN 995 923 ctx cooccurence:723 coexpression:648 textmining:949
Rv2848c cobB cobyrinic acid A,C-diamide synthase 934 822 ctx cooccurence:699 textmining:647
Rv2236c cobD cobalamin biosynthesis transmembrane protein CobD 977 794 ctx cooccurence:564 coexpression:404 textmining:896
Rv2064 cobG precorrin-3B synthase 939 774 ctx cooccurence:737 textmining:745
Rv0255c cobQ1 cobyric acid synthase 885 754 coexpression:513 textmining:553
Rv2850c magnesium chelatase 834 733 ctx neighborhood:544 cooccurence:432 textmining:407
Rv2074 pyridoxamine 5'-phosphate oxidase 731 731 ctx neighborhood:731
Rv0511 hemD uroporphyrin-III C-methyltransferase 901 708 ctx neighborhood:544 textmining:676
Rv2847c cysG multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase 906 647 ctx neighborhood:544 textmining:745
Rv2208 cobS adenosylcobinamide-GDP ribazoletransferase 857 585 textmining:672

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: precorrin-6Y C(5,15)-methyltransferase
  • MTBC0 PGAP product: bifunctional cobalt-precorrin-7 (C(5))-methyltransferase/cobalt-precorrin-6B (C(15))-methyltransferase
  • Pfam (hmmscan --cut_ga): TP_methylase PF00590.26 (E=1e-16)
  • (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_216588.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TP_methylase (PF00590.26)
  • 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 COG2241
  • Curated reference: UniProt P9WGA9 (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 — 46 functional partner(s); context anchor cobIJ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002206|Rv2072c|cobL
MIIVVGIGADGMTGLSEHSRSELRRATVIYGSKRQLALLDDTVTAERWEWPTPMLPAVQGLSPDGADLHVVASGDPLLHGIGSTLIRLFGHDNVTVLPHVSAVTLACARMGWNVYDTEVISLVTAQPHTAVRRGGRAIVLSGDRSTPQALAVLLTEHGRGDSKFSVLEQLGGPAERRRDGTARAWACDPPLDVDELNVIAVRYLPDERTSWAPDEAFAHDGQITKHPIRVLTLAALAPRPGQRLWDVGAGSGAIAVQWCRSWPGCTAVAFERDERRRRNIGFNAAAFGVSVDVRGDAPDAFDDAARPSVIFLGGGVTQPGLLEACLDSLPAGGNLVANAVTVESEAALAHAYSRLGGELRRFQHYLGEPLGGFTGWRPQLPVTQWSVTKR