frdC Family assigned · medium auto-curated

H37Rv Rv1554 · MTBC0 mtbc0_001661 · 126 aa · 1769986–1770366 (+) · RefSeq NP_216070.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)fumarate reductase membrane anchor subunit
MTBC0 PGAP re-annotationfumarate reductase subunit C
Revised (this work)Fumarate reductase subunit C. Pfam: Fumarate_red_C (PF02300.23).

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

Curated reference (UniProt)

UniProt P9WNB7 SwissProt · reviewed · Inferred from homology
UniProt nameFumarate reductase subunit C
Curated functionAnchors the catalytic components of the fumarate reductase complex to the cell membrane, binds quinones.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namefrdC
eggNOG descriptionSeems to be involved in the anchoring of the catalytic components of the fumarate reductase complex to the cytoplasmic membrane
Orthologous groupCOG3029
KEGG orthology K00246
KEGG pathways map00020, map00190, map00620, map00650, map00720, map01100, map01110, map01120, map01130, map01200, map02020
KEGG modules M00009, M00011, M00150, M00173

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 0.48 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 6 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.49% of strains (705) · clonal

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
Fumarate_red_CPF02300.23 1.2e-423–125 Fumarate reductase subunit C

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

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv1553 frdB fumarate reductase iron-sulfur subunit 999 1000 ctx neighborhood:881 cooccurence:662 coexpression:912 experimental:549 database:900 textmining:824
Rv1552 frdA fumarate reductase flavoprotein subunit 999 1000 ctx neighborhood:881 cooccurence:616 coexpression:879 experimental:469 database:900 textmining:799
Rv1555 frdD fumarate reductase membrane anchor subunit 999 1000 ctx neighborhood:881 cooccurence:774 coexpression:939 experimental:895 database:900 textmining:850
Rv0247c succinate dehydrogenase iron-sulfur subunit 983 974 coexpression:452 experimental:549 database:900
Rv3319 sdhB succinate dehydrogenase iron-sulphur protein subunit 981 974 coexpression:452 experimental:549 database:900
Rv3318 sdhA succinate dehydrogenase flavoprotein subunit 984 967 coexpression:403 experimental:469 database:900 textmining:569
Rv0248c succinate dehydrogenase flavoprotein subunit 975 967 coexpression:401 experimental:469 database:900
Rv3317 sdhD succinate dehydrogenase hydrophobic membrane anchor subunit 966 901 database:900 textmining:680
Rv3316 sdhC succinate dehydrogenase cytochrome B-556 subunit 954 900 database:900 textmining:565
Rv1098c fum fumarate hydratase 900 900 database:900
Rv1659 argH argininosuccinate lyase 801 801 database:800
Rv3221c TB7.3 acetyl-CoA carboxylase biotin carboxyl carrier protein subunit 801 801 database:800
Rv2501c accA1 acetyl/propionyl-CoA carboxylase subuit alpha 800 801 database:800
Rv0337c aspC aspartate aminotransferase 800 800 database:800
Rv0951 sucC succinyl-CoA ligase subunit beta 800 800 database:800

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 membrane anchor subunit
  • MTBC0 PGAP product: fumarate reductase subunit C
  • Pfam (hmmscan --cut_ga): Fumarate_red_C PF02300.23 (E=1e-42)
  • (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_216070.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Fumarate_red_C (PF02300.23)
  • 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 COG3029
  • Curated reference: UniProt P9WNB7 (SwissProt, reviewed; Inferred from homology)
  • 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 — 43 functional partner(s); context anchor frdB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001661|Rv1554|frdC
MSAYRQPVERYWWARRRSYLRFMLREISCIFVAWFVLYLVLVLRAVGAGGNSYQRFLDFSANPVVVVLNVVALSFLLLHAVTWFGSAPRAMVIQVRGRRVPARAVLAGHYAAWLVVSVIVAWMVLS