cobN Family assigned · medium auto-curated

H37Rv Rv2062c · MTBC0 mtbc0_002195 · 1194 aa · 2345782–2349366 (-) · RefSeq NP_216578.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cobalamin biosynthesis protein CobN
MTBC0 PGAP re-annotationcobaltochelatase subunit CobN
Revised (this work)Cobaltochelatase subunit CobN. Pfam: CobN-Mg_chel (PF02514.22).

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

Curated reference (UniProt)

UniProt O53498 TrEMBL · unreviewed · Evidence at protein level
UniProt nameCobalamin biosynthesis protein CobN

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namecobN
eggNOG descriptioncobaltochelatase, CobN subunit
Orthologous groupCOG1429
EC number EC 6.6.1.2
KEGG orthology K02230
KEGG pathways map00860, map01100

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 0.814 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 10 synonymous, 23 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
CobN-Mg_chelPF02514.22 0.0e+00104–1175 CobN/Magnesium Chelatase

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

Closest characterised functional partner: cobO (cob(I)alamin adenosyltransferase), high confidence from genomic context alone (score 969 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2849c cobO cob(I)alamin adenosyltransferase 998 969 ctx cooccurence:651 database:900 textmining:965
Rv2848c cobB cobyrinic acid A,C-diamide synthase 982 965 ctx cooccurence:507 database:900 textmining:519
Rv2066 cobIJ bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase 969 926 ctx neighborhood:672 cooccurence:759 textmining:608
Rv2072c cobL precorrin-6Y C(5,15)-methyltransferase 995 923 ctx cooccurence:723 coexpression:648 textmining:949
Rv2850c magnesium chelatase 965 915 ctx cooccurence:774 coexpression:480 textmining:610
Rv1314c cob(I)yrinic acid a,c-diamide adenosyltransferase 933 907 database:900
Rv2065 cobH precorrin-8X methylmutase 935 897 ctx neighborhood:633 cooccurence:696 textmining:400
Rv2064 cobG precorrin-3B synthase 952 853 ctx neighborhood:639 cooccurence:604 textmining:690
Rv2070c cobK precorrin-6A reductase 960 749 ctx cooccurence:704 textmining:851
Rv2061c hyp hypothetical protein 612 612 ctx neighborhood:607
Rv2063 mazE7 antitoxin MazE7 554 553 ctx neighborhood:552
Rv2063A mazF7 mRNA interferase MazF7 600 552 ctx neighborhood:552
Rv0958 magnesium chelatase 542 481 coexpression:451
Rv1234 transmembrane protein 529 461 coexpression:417
Rv1138c oxidoreductase 517 454 coexpression:436

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: cobalamin biosynthesis protein CobN
  • MTBC0 PGAP product: cobaltochelatase subunit CobN
  • Pfam (hmmscan --cut_ga): CobN-Mg_chel PF02514.22 (E=0e+00)
  • (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_216578.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CobN-Mg_chel (PF02514.22)
  • 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 COG1429
  • Curated reference: UniProt O53498 (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 — 62 functional partner(s); context anchor cobO
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002195|Rv2062c|cobN
MPEPTVLLLSTSDTDLISARSSGKNYRWANPSRLSDLELTDLLAEASIVVIRILGGYRAWQSGIDTVIAGGVPAVLVSGEQAADAELTDRSTVAAGTALQAHIYLAHGGVDNLRELHAFLCDTVLMTGFGFTPPVATPTWGVLERPDAGKTGPTIAVLYYRAQHLAGNTGYVEALCRAIEDAGGRPLPLYCASLRTAEPRLLERLGGADAMVVTVLAAGGVKPAAASAGGDDDSWNVEHLAALDIPILQGLCLTSPRDQWCANDDGLSPLDVASQVAVPEFDGRIITVPFSFKEIDDDGLISYVADPERCARVAGLAVRHARLRQVAPADKRVALVFSAYPTKHARIGNAVGLDTPASAVALLQAMRQRGYRVGDLPGVESNDGDALIHALIECGGHDPDWLTEGQLAGNPIRVSAKEYRDWFATLPAELTDVVTAYWGPPPGELFVDRSHDPDGEIVIAALRAGNLVLMVQPPRGFGENPVAIYHDPDLPPSHHYLAAYRWLDTGFSNGFGAHAVVHLGKHGNLEWLPGKTLGMSASCGPDAALGDLPLIYPFLVNDPGEGTQAKRRAHAVLVDHLIPPMARAETYGDIARLEQLLDEHASVAALDPGKLPAIRQQIWTLIRAAKMDHDLGLTERPEEDSFDDMLLHVDGWLCEIKDVQIRDGLHILGQNPTGEQELDLVLAILRARQLFGGAHAIPGLRQALGLAEDGTDERATVDQTEAKARELVAALQATGWDPSAADRLTGNADAAAVLRFAATEVIPRLAGTATEIEQVLRALDGRFIPAGPSGSPLRGLVNVLPTGRNFYSVDPKAVPSRLAWEAGVALADSLLARYRDEHGRWPRSVGLSVWGTSAMRTAGDDIAEVLALLGVRPVWDDASRRVIDLAPMQPAELGRPRIDVTVRISGFFRDAFPHVVTMLDDAVRLVADLDEAAEDNYVRAHAQADLAHHGDQRRATTRIFGSKPGTYGAGLLQLIDSRSWRDDADLAQVYTAWGGFAYGRDLDGREAIDDMNRQYRRIAVAAKNTDTREHDIADSDDYFQYHGGMVATVRALTGQAPAAYIGDNTRPDAIRTRTLSEETTRVFRARVVNPRWMAAMRRHGYKGAFEMAATVDYLFGYDATAGVMADWMYEQLTQRYVLDAQNRTFMTESNPWALHGMAERLLEAAGRGLWAQPAPETLDGLRQVLLETEGDLEA