sucD Family assigned · medium auto-curated

H37Rv Rv0952 · MTBC0 - · 303 aa · 1063140–1064051 (+) · RefSeq NP_215467.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)succinyl-CoA ligase subunit alpha
MTBC0 PGAP re-annotation
Revised (this work)Succinyl-CoA ligase subunit alpha. Pfam: CoA_binding (PF02629.26), Succ_CoA_lig (PF13607.12), Ligase_CoA (PF00549.25).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WGC7 SwissProt · reviewed · Evidence at protein level
UniProt nameSuccinate--CoA ligase [ADP-forming] subunit alpha
EC (curated) EC 6.2.1.5
Curated functionSuccinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of either ATP or GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The alpha subunit of the enzyme binds the substrates coenzyme A and phosphate, while succinate binding and nucleotide specificity is provided by the beta subunit.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namesucD
eggNOG descriptionSuccinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of either ATP or GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The alpha subunit of the enzyme binds the substrates coenzyme A and phosphate, while succinate binding and nucleotide specificity is provided by the beta subunit
Orthologous groupCOG0074
EC number EC 6.2.1.5
KEGG orthology K01902
KEGG pathways map00020, map00640, map00660, map00720, map01100, map01110, map01120, map01130, map01200
KEGG modules M00009, M00011, M00173, M00374, M00620
Gene Ontology (15) GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0040007, GO:0044424 +3 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 0.341 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 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)

PfamAccessioni-EvalueResiduesDescription
CoA_bindingPF02629.26 1.4e-2410–111 CoA binding domain
Succ_CoA_ligPF13607.12 6.3e-11159–288 Succinyl-CoA ligase like flavodoxin domain
Ligase_CoAPF00549.25 3.6e-19165–283 CoA-ligase

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

Closest characterised functional partner: sucC (succinyl-CoA ligase subunit beta), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0951 sucC succinyl-CoA ligase subunit beta 999 1000 ctx neighborhood:869 fusion:899 cooccurence:774 coexpression:968 experimental:928 database:984 textmining:854
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 998 996 coexpression:982 database:540 textmining:479
Rv3319 sdhB succinate dehydrogenase iron-sulphur protein subunit 985 979 coexpression:651 database:900
Rv0247c succinate dehydrogenase iron-sulfur subunit 979 976 coexpression:668 database:900
Rv3316 sdhC succinate dehydrogenase cytochrome B-556 subunit 980 974 coexpression:726 database:900
Rv3318 sdhA succinate dehydrogenase flavoprotein subunit 981 973 coexpression:570 database:900
Rv2215 dlaT pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase 980 970 coexpression:662 database:900
Rv0248c succinate dehydrogenase flavoprotein subunit 979 969 coexpression:588 database:900
Rv1553 frdB fumarate reductase iron-sulfur subunit 971 967 ctx cooccurence:467 coexpression:649 database:800
Rv1552 frdA fumarate reductase flavoprotein subunit 961 949 coexpression:565 database:800
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 979 948 database:900 textmining:628
Rv2495c bkdC branched-chain keto acid dehydrogenase E2 component 950 937 coexpression:648 database:800
Rv3317 sdhD succinate dehydrogenase hydrophobic membrane anchor subunit 954 936 database:900
Rv1493 mutB methylmalonyl-CoA mutase large subunit 944 919 database:900
Rv2454c korB 2-oxoglutarate oxidoreductase subunit KorB 945 916 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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): succinyl-CoA ligase subunit alpha
  • Pfam (hmmscan --cut_ga): CoA_binding PF02629.26 (E=1e-24), Succ_CoA_lig PF13607.12 (E=6e-11), Ligase_CoA PF00549.25 (E=4e-19)
  • (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_215467.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CoA_binding (PF02629.26), Succ_CoA_lig (PF13607.12), Ligase_CoA (PF00549.25)
  • 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 COG0074
  • Curated reference: UniProt P9WGC7 (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 — 154 functional partner(s); context anchor sucC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0952|sucD
MTHMSIFLSRDNKVIVQGITGSEATVHTARMLRAGTQIVGGVNARKAGTTVTHEDKGGRLIKLPVFGSVAEAMEKTGADVSIIFVPPTFAKDAIIEAIDAEIPLLVVITEGIPVQDTAYAWAYNLEAGHKTRIIGPNCPGIISPGQSLAGITPANITGPGPIGLVSKSGTLTYQMMFELRDLGFSTAIGIGGDPVIGTTHIDAIEAFERDPDTKLIVMIGEIGGDAEERAADFIKTNVSKPVVGYVAGFTAPEGKTMGHAGAIVSGSSGTAAAKQEALEAAGVKVGKTPSATAALAREILLSL