Rv0247c Family assigned · medium auto-curated

H37Rv Rv0247c · MTBC0 mtbc0_000263 · 248 aa · 298498–299244 (-) · RefSeq NP_214761.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)succinate dehydrogenase iron-sulfur subunit
MTBC0 PGAP re-annotationsuccinate dehydrogenase/fumarate reductase iron-sulfur subunit
Revised (this work)Succinate dehydrogenase/fumarate reductase iron-sulfur subunit. Pfam: Fer2_3 (PF13085.12), Fer2 (PF00111.33), Fer4_8 (PF13183.12).

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

Curated reference (UniProt)

UniProt O53669 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable succinate dehydrogenase [iron-sulfur subunit]

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namesdhB_1
eggNOG descriptionfumarate reductase
Orthologous groupCOG0479
EC number EC 1.3.5.1, EC 1.3.5.4
KEGG orthology K00240
KEGG pathways map00020, map00190, map00650, map00720, map01100, map01110, map01120, map01130, map01200
KEGG modules M00009, M00011, M00149, M00173, M00374, M00376

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 0.144 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 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
Fer2_3PF13085.12 1.6e-248–105 2Fe-2S iron-sulfur cluster binding domain
Fer2PF00111.33 3.0e-0421–69 2Fe-2S iron-sulfur cluster binding domain
Fer4_8PF13183.12 1.1e-08141–216 4Fe-4S dicluster domain

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

Closest characterised functional partner: Rv0249c (succinate dehydrogenase membrane anchor subunit), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0249c succinate dehydrogenase membrane anchor subunit 999 1000 ctx neighborhood:839 cooccurence:774 experimental:997 textmining:870
Rv0248c succinate dehydrogenase flavoprotein subunit 999 1000 ctx neighborhood:881 cooccurence:774 coexpression:882 experimental:997 database:956 textmining:852
Rv3316 sdhC succinate dehydrogenase cytochrome B-556 subunit 999 998 coexpression:696 experimental:788 database:962 textmining:861
Rv3317 sdhD succinate dehydrogenase hydrophobic membrane anchor subunit 998 993 coexpression:670 experimental:784 database:900 textmining:822
Rv1552 frdA fumarate reductase flavoprotein subunit 995 991 coexpression:484 experimental:454 database:956 textmining:483
Rv3318 sdhA succinate dehydrogenase flavoprotein subunit 995 990 coexpression:491 experimental:454 database:956 textmining:569
Rv0952 sucD succinyl-CoA ligase subunit alpha 979 976 coexpression:668 database:900
Rv0951 sucC succinyl-CoA ligase subunit beta 981 975 coexpression:656 database:900
Rv1554 frdC fumarate reductase membrane anchor subunit 983 974 coexpression:452 experimental:549 database:900
Rv1555 frdD fumarate reductase membrane anchor subunit 981 972 coexpression:417 experimental:549 database:900
Rv1098c fum fumarate hydratase 956 951 coexpression:445 database:900
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 967 950 coexpression:931
Rv1553 frdB fumarate reductase iron-sulfur subunit 924 915 database:900
Rv0234c gabD1 succinate-semialdehyde dehydrogenase 915 912 database:900
Rv1731 gabD2 succinate-semialdehyde dehydrogenase 915 912 database:900

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: succinate dehydrogenase iron-sulfur subunit
  • MTBC0 PGAP product: succinate dehydrogenase/fumarate reductase iron-sulfur subunit
  • Pfam (hmmscan --cut_ga): Fer2_3 PF13085.12 (E=2e-24), Fer2 PF00111.33 (E=3e-04), Fer4_8 PF13183.12 (E=1e-08)
  • (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_214761.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Fer2_3 (PF13085.12), Fer2 (PF00111.33), Fer4_8 (PF13183.12)
  • 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 COG0479
  • Curated reference: UniProt O53669 (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 — 99 functional partner(s); context anchor Rv0249c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000263|Rv0247c|
MTYSASMRVWRGDESCGELREFTVEVNEGEVVLDVILRLQQTQTPDLAVRWNCKAGKCGSCSAEINGKPRLMCMTRMSTFDEDEIVTVTPMRTFPVIRDLVTDVSFNYQKAREIPSFAPPKELQPSEYRMAQVDVARSQEFRKCIECFLCQNVCHVVRDHEENKDAFAGPRFLMRIAELEMHPLDTRDRRSQAQEEHGLGYCNITKCCTEVCPENIKITDNALIPMKERVADRKYDPVVWLGSKLFRR