sdhA Family assigned · medium auto-curated
H37Rv Rv3318 · MTBC0 mtbc0_003528 ·
590 aa · 3727138–3728910 (+) ·
RefSeq NP_217835.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | succinate dehydrogenase flavoprotein subunit |
|---|---|
| MTBC0 PGAP re-annotation | succinate dehydrogenase flavoprotein subunit |
| Revised (this work) | Succinate dehydrogenase 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 |
O53370
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Succinate dehydrogenase flavoprotein subunit |
| EC (curated) |
EC 1.3.5.1
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | sdhA |
| eggNOG description | Succinate dehydrogenase flavoprotein subunit |
| 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 (75) |
GO:0000104, GO:0000166, GO:0001539, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +63 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 | 0.391 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 6 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 | 1.3e-110 | 8–401 | FAD binding domain |
Succ_DH_flav_C | PF02910.26 | 3.3e-44 | 456–590 | Fumarate reductase flavoprotein C-term |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: sdhB (succinate dehydrogenase iron-sulphur protein subunit), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3319 sdhB |
succinate dehydrogenase iron-sulphur protein subunit | 999 | 1000 ctx | neighborhood:881 cooccurence:774 coexpression:570 experimental:997 database:956 textmining:901 |
Rv3316 sdhC |
succinate dehydrogenase cytochrome B-556 subunit | 999 | 1000 ctx | neighborhood:758 cooccurence:736 coexpression:664 experimental:870 database:960 textmining:967 |
Rv3317 sdhD |
succinate dehydrogenase hydrophobic membrane anchor subunit | 999 | 1000 ctx | neighborhood:758 cooccurence:718 coexpression:690 experimental:997 database:900 textmining:880 |
Rv1553 frdB |
fumarate reductase iron-sulfur subunit | 998 | 997 ctx | cooccurence:771 coexpression:486 experimental:454 database:956 textmining:626 |
Rv0247c |
succinate dehydrogenase iron-sulfur subunit | 995 | 990 | coexpression:491 experimental:454 database:956 textmining:569 |
Rv1098c fum |
fumarate hydratase | 985 | 984 ctx | fusion:639 coexpression:516 database:900 |
Rv0951 sucC |
succinyl-CoA ligase subunit beta | 984 | 974 | coexpression:566 database:900 textmining:405 |
Rv0952 sucD |
succinyl-CoA ligase subunit alpha | 981 | 973 | coexpression:570 database:900 |
Rv1554 frdC |
fumarate reductase membrane anchor subunit | 984 | 967 | coexpression:403 experimental:469 database:900 textmining:569 |
Rv1555 frdD |
fumarate reductase membrane anchor subunit | 981 | 961 | experimental:455 database:900 textmining:540 |
Rv1731 gabD2 |
succinate-semialdehyde dehydrogenase | 934 | 931 | database:900 |
Rv0234c gabD1 |
succinate-semialdehyde dehydrogenase | 933 | 931 | database:900 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 957 | 920 | coexpression:897 textmining:486 |
Rv0248c |
succinate dehydrogenase flavoprotein subunit | 925 | 917 | database:900 |
Rv1552 frdA |
fumarate reductase flavoprotein subunit | 911 | 909 | 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 flavoprotein subunit
- MTBC0 PGAP product: succinate dehydrogenase flavoprotein subunit
- Pfam (hmmscan --cut_ga): FAD_binding_2 PF00890.31 (E=1e-110), Succ_DH_flav_C PF02910.26 (E=3e-44)
- (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_217835.1)
- 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 O53370 (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 —
82 functional partner(s); context anchor
sdhB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003528|Rv3318|sdhA MICQHRYDVVIVGAGGAGMRAAVEAGPRVRTAVLTKLYPTRSHTGAAQGGMCAALANVEDDNWEWHTFDTVKGGDYLADQDAVEIMCKEAIDAVLDLEKMGMPFNRTPEGRIDQRRFGGHTRDHGKAPVRRACYAADRTGHMILQTLYQNCVKHDVEFFNEFYALDLALTQTPSGPVATGVIAYELATGDIHVFHAKAVVIATGGSGRMYKTTSNAHTLTGDGIGIVFRKGLPLEDMEFHQFHPTGLAGLGILISEAVRGEGGRLLNGEGERFMERYAPTIVDLAPRDIVARSMVLEVLEGRGAGPLKDYVYIDVRHLGEEVLEAKLPDITEFARTYLGVDPVTELVPVYPTCHYLMGGIPTTVTGQVLRDNTSVVPGLYAAGECACVSVHGANRLGTNSLLDINVFGRRAGIAAASYAQGHDFVDMPPNPEAMVVGWVSDILSEHGNERVADIRGALQQSMDNNAAVFRTEETLKQALTDIHALKERYSRITVHDKGKRFNTDLLEAIELGFLLELAEVTVVGALNRKESRGGHAREDYPNRDDVNYMRHTMAYKEIGADKEGPELRSDVRLDFKPVVQTRYEPKERKY