frdA Family assigned · medium auto-curated
H37Rv Rv1552 · MTBC0 mtbc0_001659 ·
583 aa · 1767492–1769243 (+) ·
RefSeq NP_216068.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fumarate reductase flavoprotein subunit |
|---|---|
| MTBC0 PGAP re-annotation | fumarate reductase (quinol) flavoprotein subunit |
| Revised (this work) | Fumarate reductase (quinol) flavoprotein subunit. Pfam: FAD_binding_2 (PF00890.31), Succ_DH_flav_C (PF02910.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WN91
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Fumarate reductase flavoprotein subunit |
| EC (curated) |
EC 1.3.5.1
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | frdA |
| eggNOG description | Fumarate reductase flavoprotein C-term |
| Orthologous group | COG1053 |
| EC number |
EC 1.3.5.1, EC 1.3.5.4, EC 1.4.3.16
|
| KEGG orthology |
K00239, K00244, K00278
|
| KEGG pathways |
map00020, map00190, map00250, map00620, map00650, map00720, map00760, map01100, map01110, map01120, map01130, map01200, map02020, map05134
|
| KEGG modules |
M00009, M00011, M00115, M00149, M00150, M00173, M00374, M00376
|
| Gene Ontology (37) |
GO:0000104, GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005886, GO:0006091, GO:0006113, GO:0008150, GO:0008152, GO:0009055 +25 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 | 0.811 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 12 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
FAD_binding_2 | PF00890.31 | 2.1e-113 | 7–394 | FAD binding domain |
Succ_DH_flav_C | PF02910.26 | 6.5e-39 | 455–581 | Fumarate reductase flavoprotein C-term |
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).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1553 frdB |
fumarate reductase iron-sulfur subunit | 999 | 1000 ctx | neighborhood:881 cooccurence:774 coexpression:925 experimental:454 database:956 textmining:816 |
Rv1554 frdC |
fumarate reductase membrane anchor subunit | 999 | 1000 ctx | neighborhood:881 cooccurence:616 coexpression:879 experimental:469 database:900 textmining:799 |
Rv1555 frdD |
fumarate reductase membrane anchor subunit | 999 | 999 ctx | neighborhood:881 cooccurence:631 coexpression:542 experimental:455 database:900 textmining:887 |
Rv3316 sdhC |
succinate dehydrogenase cytochrome B-556 subunit | 998 | 997 | coexpression:650 experimental:707 database:960 textmining:614 |
Rv3319 sdhB |
succinate dehydrogenase iron-sulphur protein subunit | 997 | 997 ctx | cooccurence:766 coexpression:484 experimental:454 database:956 |
Rv3317 sdhD |
succinate dehydrogenase hydrophobic membrane anchor subunit | 997 | 994 | coexpression:646 experimental:784 database:900 textmining:597 |
Rv0247c |
succinate dehydrogenase iron-sulfur subunit | 995 | 991 | coexpression:484 experimental:454 database:956 textmining:483 |
Rv1098c fum |
fumarate hydratase | 971 | 968 | coexpression:510 database:900 |
Rv0951 sucC |
succinyl-CoA ligase subunit beta | 967 | 950 | coexpression:563 database:800 |
Rv0952 sucD |
succinyl-CoA ligase subunit alpha | 961 | 949 | coexpression:565 database:800 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 941 | 918 | coexpression:894 |
Rv0248c |
succinate dehydrogenase flavoprotein subunit | 921 | 918 | database:900 |
Rv3318 sdhA |
succinate dehydrogenase flavoprotein subunit | 911 | 909 | database:900 |
Rv0753c mmsA |
methylmalonate-semialdehyde dehydrogenase | 865 | 860 | database:800 |
Rv2501c accA1 |
acetyl/propionyl-CoA carboxylase subuit alpha | 816 | 808 | 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 flavoprotein subunit
- MTBC0 PGAP product: fumarate reductase (quinol) flavoprotein subunit
- Pfam (hmmscan --cut_ga): FAD_binding_2 PF00890.31 (E=2e-113), Succ_DH_flav_C PF02910.26 (E=7e-39)
- (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_216068.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_2 (PF00890.31), Succ_DH_flav_C (PF02910.26)
- 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
COG1053 - Curated reference: UniProt P9WN91 (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 —
98 functional partner(s); context anchor
frdB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001659|Rv1552|frdA MTAQHNIVVIGGGGAGLRAAIAIAETNPHLDVAIVSKVYPMRSHTVSAEGGAAAVTGDDDSLDEHAHDTVSGGDWLCDQDAVEAFVAEAPKELVQLEHWGCPWSRKPDGRVAVRPFGGMKKLRTWFAADKTGFHLLHTLFQRLLTYSDVMRYDEWFATTLLVDDGRVCGLVAIELATGRIETILADAVILCTGGCGRVFPFTTNANIKTGDGMALAFRAGAPLKDMEFVQYHPTGLPFTGILITEAARAEGGWLLNKDGYRYLQDYDLGKPTPEPRLRSMELGPRDRLSQAFVHEHNKGRTVDTPYGPVVYLDLRHLGADLIDAKLPFVRELCRDYQHIDPVVELVPVRPVVHYMMGGVHTDINGATTLPGLYAAGETACVSINGANRLGSNSLPELLVFGARAGRAAADYAARHQKSDRGPSSAVRAQARTEALRLERELSRHGQGGERIADIRADMQATLESAAGIYRDGPTLTKAVEEIRVLQERFATAGIDDHSRTFNTELTALLELSGMLDVALAIVESGLRREESRGAHQRTDFPNRDDEHFLAHTLVHRESDGTLRVGYLPVTITRWPPGERVYGR