frdB Family assigned · medium auto-curated

H37Rv Rv1553 · MTBC0 mtbc0_001660 · 247 aa · 1769246–1769989 (+) · RefSeq NP_216069.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)fumarate reductase iron-sulfur subunit
MTBC0 PGAP re-annotationsuccinate dehydrogenase iron-sulfur subunit
Revised (this work)Succinate dehydrogenase iron-sulfur subunit. Pfam: Fer2_3 (PF13085.12), Fer4_8 (PF13183.12), Fer4_10 (PF13237.12), Fer4 (PF00037.33), Fer4_7 (PF12838.13), Fer4_17 (PF13534.12).

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

Curated reference (UniProt)

UniProt P9WN89 SwissProt · reviewed · Evidence at protein level
UniProt nameFumarate reductase iron-sulfur subunit
EC (curated) EC 1.3.5.1

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namesdhB
eggNOG description2Fe-2S iron-sulfur cluster binding domain
Orthologous groupCOG0479
EC number EC 1.3.5.1, EC 1.3.5.4
KEGG orthology K00240, K00245
KEGG pathways map00020, map00190, map00620, map00650, map00720, map01100, map01110, map01120, map01130, map01200, map02020
KEGG modules M00009, M00011, M00149, M00150, 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 0.105 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 1 missense, 0 nonsense, 4 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 2.73% of strains (3970) · convergent

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 1.5e-327–110 2Fe-2S iron-sulfur cluster binding domain
Fer4_8PF13183.12 4.4e-13146–219 4Fe-4S dicluster domain
Fer4_10PF13237.12 1.1e-08146–216 4Fe-4S dicluster domain
Fer4PF00037.33 1.6e-05147–164 4Fe-4S binding domain
Fer4_7PF12838.13 2.9e-08149–219 4Fe-4S dicluster domain
Fer4_17PF13534.12 3.5e-08149–220 4Fe-4S dicluster domain

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

Closest characterised functional partner: frdA (fumarate reductase flavoprotein subunit), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1552 frdA fumarate reductase flavoprotein subunit 999 1000 ctx neighborhood:881 cooccurence:774 coexpression:925 experimental:454 database:956 textmining:816
Rv1555 frdD fumarate reductase membrane anchor subunit 999 1000 ctx neighborhood:881 cooccurence:674 coexpression:878 experimental:549 database:900 textmining:822
Rv1554 frdC fumarate reductase membrane anchor subunit 999 1000 ctx neighborhood:881 cooccurence:662 coexpression:912 experimental:549 database:900 textmining:824
Rv3316 sdhC succinate dehydrogenase cytochrome B-556 subunit 999 998 coexpression:694 experimental:788 database:962 textmining:653
Rv3318 sdhA succinate dehydrogenase flavoprotein subunit 998 997 ctx cooccurence:771 coexpression:486 experimental:454 database:956 textmining:626
Rv3317 sdhD succinate dehydrogenase hydrophobic membrane anchor subunit 997 994 coexpression:666 experimental:784 database:900 textmining:661
Rv0248c succinate dehydrogenase flavoprotein subunit 996 994 ctx cooccurence:585 coexpression:484 experimental:454 database:956 textmining:426
Rv0951 sucC succinyl-CoA ligase subunit beta 974 967 ctx cooccurence:496 coexpression:645 database:800
Rv0952 sucD succinyl-CoA ligase subunit alpha 971 967 ctx cooccurence:467 coexpression:649 database:800
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 969 949 coexpression:930 textmining:420
Rv1098c fum fumarate hydratase 953 949 coexpression:419 database:900
Rv0247c succinate dehydrogenase iron-sulfur subunit 924 915 database:900
Rv3319 sdhB succinate dehydrogenase iron-sulphur protein subunit 915 912 database:900
Rv1817 flavoprotein 881 875 coexpression:487 experimental:454 database:578
Rv3537 kstD 3-oxosteroid 1-dehydrogenase 881 875 coexpression:487 experimental:454 database:578

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: fumarate reductase iron-sulfur subunit
  • MTBC0 PGAP product: succinate dehydrogenase iron-sulfur subunit
  • Pfam (hmmscan --cut_ga): Fer2_3 PF13085.12 (E=2e-32), Fer4_8 PF13183.12 (E=4e-13), Fer4_10 PF13237.12 (E=1e-08), Fer4 PF00037.33 (E=2e-05), Fer4_7 PF12838.13 (E=3e-08), Fer4_17 PF13534.12 (E=4e-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_216069.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Fer2_3 (PF13085.12), Fer4_8 (PF13183.12), Fer4_10 (PF13237.12), Fer4 (PF00037.33), Fer4_7 (PF12838.13), Fer4_17 (PF13534.12)
  • 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 P9WN89 (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 — 118 functional partner(s); context anchor frdA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001660|Rv1553|frdB
MMDRIVMEVSRYRPEIESAPTFQAYEVPLTREWAVLDGLTYIKDHLDGTLSFRWSCRMGICGSSGMTINGDPKLACATFLADYLPGPVRVEPMRNFPVIRDLVVDISDFMAKLPSVKPWLVRHDEPPVEDGEYRQTPAELDAFKQFSMCINCMLCYSACPVYALDPDFLGPAAIALGQRYNLDSRDQGAADRRDVLAAADGAWACTLVGECSTACPKGVDPAGAIQRYKLTAATHALKKLLFPWGGG