fum Resolved · high auto-curated
H37Rv Rv1098c · MTBC0 mtbc0_001181 ·
474 aa · 1234581–1236005 (-) ·
RefSeq NP_215614.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | fumarate hydratase |
|---|---|
| MTBC0 PGAP re-annotation | class II fumarate hydratase |
| Revised (this work) | Class II fumarate hydratase. Pfam: Lyase_1 (PF00206.26), FumaraseC_C (PF10415.15). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WN93
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Fumarate hydratase class II |
| EC (curated) |
EC 4.2.1.2
|
| Curated function | Involved in the TCA cycle. Catalyzes the stereospecific interconversion of fumarate to L-malate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | fumC |
| eggNOG description | Involved in the TCA cycle. Catalyzes the stereospecific interconversion of fumarate to L-malate |
| Orthologous group | COG0114 |
| EC number |
EC 4.2.1.2
|
| KEGG orthology |
K01679
|
| KEGG pathways |
map00020, map00620, map00720, map01100, map01110, map01120, map01130, map01200, map04934, map05200, map05211
|
| KEGG modules |
M00009, M00011, M00173, M00376
|
| Gene Ontology (44) |
GO:0003674, GO:0003824, GO:0004333, GO:0005575, GO:0005576, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006082 +32 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 | 0.864 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 5 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 |
|---|---|---|---|---|
Lyase_1 | PF00206.26 | 5.5e-101 | 18–342 | Lyase |
FumaraseC_C | PF10415.15 | 3.6e-15 | 408–464 | Fumarase C C-terminus |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: sdhA (succinate dehydrogenase flavoprotein subunit), high confidence from genomic context alone (score 984 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3318 sdhA |
succinate dehydrogenase flavoprotein subunit | 985 | 984 ctx | fusion:639 coexpression:516 database:900 |
Rv1552 frdA |
fumarate reductase flavoprotein subunit | 971 | 968 | coexpression:510 database:900 |
Rv0248c |
succinate dehydrogenase flavoprotein subunit | 970 | 963 | coexpression:531 database:900 |
Rv1240 mdh |
malate dehydrogenase | 982 | 957 | coexpression:491 database:900 textmining:617 |
Rv0247c |
succinate dehydrogenase iron-sulfur subunit | 956 | 951 | coexpression:445 database:900 |
Rv3319 sdhB |
succinate dehydrogenase iron-sulphur protein subunit | 954 | 949 | coexpression:423 database:900 |
Rv1553 frdB |
fumarate reductase iron-sulfur subunit | 953 | 949 | coexpression:419 database:900 |
Rv3316 sdhC |
succinate dehydrogenase cytochrome B-556 subunit | 959 | 947 | coexpression:490 database:900 |
Rv2332 mez |
malate oxidoreductase | 975 | 945 | coexpression:418 database:900 textmining:567 |
Rv3317 sdhD |
succinate dehydrogenase hydrophobic membrane anchor subunit | 922 | 911 | database:900 |
Rv1837c glcB |
malate synthase | 986 | 908 | database:900 textmining:857 |
Rv2852c mqo |
malate:quinone oxidoreductase | 970 | 905 | database:900 textmining:707 |
Rv1555 frdD |
fumarate reductase membrane anchor subunit | 900 | 900 | database:900 |
Rv1554 frdC |
fumarate reductase membrane anchor subunit | 900 | 900 | database:900 |
Rv0896 gltA2 |
citrate synthase 1 | 973 | 896 | coexpression:426 database:800 textmining:751 |
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 hydratase
- MTBC0 PGAP product: class II fumarate hydratase
- Pfam (hmmscan --cut_ga): Lyase_1 PF00206.26 (E=5e-101), FumaraseC_C PF10415.15 (E=4e-15)
- (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_215614.1)
- Domains: Pfam-A via hmmscan --cut_ga — Lyase_1 (PF00206.26), FumaraseC_C (PF10415.15)
- 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
COG0114 - Curated reference: UniProt P9WN93 (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 —
103 functional partner(s); context anchor
sdhA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001181|Rv1098c|fum MAVDADSANYRIEHDTMGEVRVPAKALWRAQTQRAVENFPISGRGLERTQIRALGLLKGACAQVNSDLGLLAPEKADAIIAAAAEIADGQHDDQFPIDVFQTGSGTSSNMNTNEVIASIAAKGGVTLHPNDDVNMSQSSNDTFPTATHIAATEAAVAHLIPALQQLHDALAAKALDWHTVVKSGRTHLMDAVPVTLGQEFSGYARQIEAGIERVRACLPRLGELAIGGTAVGTGLNAPDDFGVRVVAVLVAQTGLSELRTAANSFEAQAARDGLVEASGALRTIAVSLTKIANDIRWMGSGPLTGLAEIQLPDLQPGSSIMPGKVNPVLPEAVTQVAAQVIGNDAAIAWGGANGAFELNVYIPMMARNILESFKLLTNVSRLFAQRCIAGLTANVEHLRRLAESSPSIVTPLNSAIGYEEAAAVAKQALKERKTIRQTVIDRGLIGDRLSIEDLDRRLDVLAMAKAEQLDSDRL