che1 Resolved · high auto-curated

H37Rv Rv2393 · MTBC0 - · 281 aa · 2687128–2687973 (+) · RefSeq NP_216909.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ferrochelatase
MTBC0 PGAP re-annotation
Revised (this work)Ferrochelatase. Pfam: CbiX (PF01903.23).

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 P71751 TrEMBL · unreviewed · Evidence at protein level
UniProt nameFerrochelatase Che1

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namecbiX
eggNOG descriptionCbiX
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 1.149 · 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
CbiXPF01903.23 2.0e-1953–151 CbiX

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

Closest characterised functional partner: cysH (phosphoadenosine phosphosulfate reductase), high confidence from genomic context alone (score 989 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2392 cysH phosphoadenosine phosphosulfate reductase 990 989 ctx neighborhood:881 coexpression:891
Rv2391 sirA sulfite reductase 989 987 ctx neighborhood:881 coexpression:871
Rv2394 ggtB gamma-glutamyltranspeptidase precursor GgtB 946 946 ctx neighborhood:662 coexpression:848
Rv2847c cysG multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase 955 935 coexpression:909
Rv2677c hemY protoporphyrinogen oxidase 559 509 database:500
Rv1286 cysC adenylyl-sulfate kinase 543 502 coexpression:404
Rv0511 hemD uroporphyrin-III C-methyltransferase 643 499 coexpression:429
Rv1162 narH nitrate reductase subunit beta 469 469 coexpression:451
Rv2395 integral membrane protein 460 460 ctx neighborhood:443
Rv2633c hyp hypothetical protein 450 429
Rv1163 narJ nitrate reductase subunit delta 424 424 coexpression:404
Rv1164 narI nitrate reductase subunit gamma 415 416
Rv1285 cysD sulfate adenylyltransferase subunit 2 480 398
Rv0255c cobQ1 cobyric acid synthase 455 391
Rv2072c cobL precorrin-6Y C(5,15)-methyltransferase 567 359

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): ferrochelatase
  • Pfam (hmmscan --cut_ga): CbiX PF01903.23 (E=2e-19)
  • (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_216909.1)
  • 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 P71751 (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 — 18 functional partner(s); context anchor cysH
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2393|che1
MTAPATMQSAAMLRSGAIEAPPATMQSAAMRWGHLPLAEESGTIAPQLVLTAHGSKDPRSAANARAIAGRLARMRPGLDVRVAFCELNSPNLVDVLNRCRGAAVVTPLLLADAYHARVDIPAQIASCRVGHRVRQASVLGEDIRLVSALHERLTELGVSPFDHTLGVVVLAIGSSHPAANARTSTVASRLAEGTQWAAVTTAFITRPEASLADATDRLRRHGARRMVIAPWLLAPGILSDRVRGYAREAGIAMAQPLGAHPMVAATMWDRYRQAVAGRIAA