MTBC Gene Atlas

Rv0259c Family assigned · medium

H37Rv Rv0259c · MTBC0 mtbc0_000275 · 247 aa · 311156–311899 (-) · RefSeq NP_214773.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationsirohydrochlorin chelatase
Revised (this work)Sirohydrochlorin chelatase (CbiX family, Pfam CbiX PF01903): inserts cobalt or ferrous iron into sirohydrochlorin during siroheme / cobalamin (vitamin B12) cofactor biosynthesis.

Curated reference (UniProt)

UniProt P95216 TrEMBL · unreviewed · Predicted
UniProt nameSirohydrochlorin chelatase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namecbiX
eggNOG descriptioncobalamin (vitamin B12) biosynthesis CbiX
Orthologous groupCOG2138

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 0.387 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 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
CbiXPF01903.23 6.1e-198–104 CbiX

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

Closest characterised functional partner: Rv0260c (transcriptional regulator), high confidence from genomic context alone (score 966 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0260c transcriptional regulator 969 966 ctx neighborhood:882 cooccurence:630
Rv2847c cysG multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase 976 965 ctx fusion:466 coexpression:908
Rv0261c narK3 nitrate/nitrite transporter 775 775 ctx neighborhood:567
Rv0258c hyp hypothetical protein 761 762 ctx neighborhood:760
Rv1372 pks18 alpha-pyrone synthesis polyketide synthase-like protein 732 732 coexpression:732
Rv0253 nirD nitrite reductase small subunit NirD 608 592
Rv3909 hyp hypothetical protein 544 544 ctx cooccurence:544
Rv0252 nirB nitrite reductase large subunit NirB 538 514
Rv0262c aac aminoglycoside 2'-N-acetyltransferase 514 514
Rv1024 membrane protein 505 506 ctx cooccurence:504
Rv1286 cysC adenylyl-sulfate kinase 545 503 coexpression:406
Rv2391 sirA sulfite reductase 523 493
Rv0511 hemD uroporphyrin-III C-methyltransferase 638 492 coexpression:421
Rv2392 cysH phosphoadenosine phosphosulfate reductase 513 488
Rv0267 narU nitrite extrusion protein NarU 487 487

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

  • MTBC0 PGAP product: 'sirohydrochlorin chelatase'
  • Pfam: CbiX PF01903 (E=6.1e-19)

ESM Atlas signal (exploratory)

Ancestral protein hash 8e2efc84b116f708d5dba0a91afa1b17 · 10 ESM-space neighbours (max similarity 0.901). SAE features are orienting indices, not validated domains.

#IndexActivationInterpretation
14337 1.29 Active site buttress helix
2397 1.15 Amphipathic tunnels, pores, cofactor sites
31403 0.94 Histidine/acidic cofactor-binding surfaces
47536 0.86 N-terminal hydrophobic helices CN hydrolase
57520 0.56 Noncatalytic enzyme core scaffold
67957 0.54 Flexible domain-edge lid loops
715809 0.50 Active-site rim beta-loop-alpha module
82241 0.50 N-terminal glycine-rich anion-binding loop

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_214773.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CbiX (PF01903.23)
  • 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 COG2138
  • Curated reference: UniProt P95216 (TrEMBL, unreviewed; Predicted)
  • 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 Rv0260c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000275|Rv0259c|
MNLILTAHGTRRPSGVAMIADIAAQVSALVDRTVQVAFVDVLGPSPSEVLSALSCRPAIVVPAFLSRGYHVRTDLPAHVAASAHPHVTVTPALGPCREIAQIVTQQLVESGWRPGDSVILAAAGASDRRARADLHTTRTLVSELTGSWVDMGFAGTGGPDVRTAVQRARDRAEANRGARRVVVASFLLAEGLFQERLRASGADVVTRPLGTHPGLAQLVANRFRSAVARQQRLHRWHGTPTPVTLDL