Rv2204c Resolved · high auto-curated

H37Rv Rv2204c · MTBC0 mtbc0_002340 · 118 aa · 2495088–2495444 (-) · RefSeq NP_216720.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationiron-sulfur cluster assembly accessory protein
Revised (this work)Iron-sulfur cluster assembly accessory protein. Pfam: Fe-S_biosyn (PF01521.27).

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

Curated reference (UniProt)

UniProt P9WMN5 SwissProt · reviewed · Evidence at protein level
UniProt nameProtein Rv2204c

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred nameiscA
eggNOG descriptionBelongs to the HesB IscA family
Orthologous groupCOG0316
KEGG orthology K13628
Gene Ontology (43) GO:0003674, GO:0005488, GO:0005506, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006790, GO:0006807, GO:0008150 +31 more

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 1 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
Fe-S_biosynPF01521.27 3.9e-1916–115 Iron-sulphur cluster biosynthesis

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

Closest characterised functional partner: Rv2206 (transmembrane protein), high confidence from genomic context alone (score 703 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1465 nitrogen fixation related protein 859 817 coexpression:802
Rv2205c hyp hypothetical protein 774 774 ctx neighborhood:773
Rv3025c iscS cysteine desulfurase 814 758 coexpression:691
Rv3053c nrdH glutaredoxin electron transport protein NrdH 757 737 coexpression:728
Rv2206 transmembrane protein 703 703 ctx neighborhood:701
Rv2207 cobT nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase 667 668 ctx neighborhood:663
Rv2208 cobS adenosylcobinamide-GDP ribazoletransferase 675 664 ctx neighborhood:663
Rv1463 sufC ABC transporter ATP-binding protein 689 652 coexpression:407
Rv1299 prfA peptide chain release factor PrfA 650 621 database:617
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 656 604 ctx cooccurence:598
Rv1462 sufD hyp hypothetical protein 649 603 coexpression:420
Rv1461 sufB hyp hypothetical protein 648 602 coexpression:419
Rv2373c dnaJ2 chaperone protein DnaJ 631 583 database:557
Rv0811c hyp hypothetical protein 679 581 experimental:412
Rv0352 dnaJ1 chaperone protein DnaJ 619 569 database:557

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: hypothetical protein
  • MTBC0 PGAP product: iron-sulfur cluster assembly accessory protein
  • Pfam (hmmscan --cut_ga): Fe-S_biosyn PF01521.27 (E=4e-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_216720.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Fe-S_biosyn (PF01521.27)
  • 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 COG0316
  • Curated reference: UniProt P9WMN5 (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 — 45 functional partner(s); context anchor Rv2206
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002340|Rv2204c|
MTVQNEPSAKTHGVILTEAAAAKAKSLLDQEGRDDLALRIAVQPGGCAGLRYNLFFDDRTLDGDQTAEFGGVRLIVDRMSAPYVEGASIDFVDTIEKQGFTIDNPNATGSCACGDSFN