sucC Family assigned · medium auto-curated

H37Rv Rv0951 · MTBC0 mtbc0_001015 · 387 aa · 1069179–1070342 (+) · RefSeq NP_215466.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)succinyl-CoA ligase subunit beta
MTBC0 PGAP re-annotationADP-forming succinate--CoA ligase subunit beta
Revised (this work)ADP-forming succinate--CoA ligase subunit beta. Pfam: ATP-grasp_2 (PF08442.16), ATP-grasp_5 (PF13549.12), CPSase_L_D2 (PF02786.23), Ligase_CoA (PF00549.25).

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

Curated reference (UniProt)

UniProt P9WGC5 SwissProt · reviewed · Evidence at protein level
UniProt nameSuccinate--CoA ligase [ADP-forming] subunit beta
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 beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namesucC
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 beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit
Orthologous groupCOG0045
EC number EC 6.2.1.5
KEGG orthology K01903
KEGG pathways map00020, map00640, map00660, map00720, map01100, map01110, map01120, map01130, map01200
KEGG modules M00009, M00011, M00173, M00374, M00620
Gene Ontology (13) GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0008150, GO:0030312, GO:0040007, GO:0044424, GO:0044444, GO:0044464 +1 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 1.321 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 4 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
ATP-grasp_2PF08442.16 5.0e-703–194 ATP-grasp domain
ATP-grasp_5PF13549.12 1.2e-063–210 ATP-grasp domain
CPSase_L_D2PF02786.23 1.7e-057–55 Carbamoyl-phosphate synthase L chain, ATP binding domain
Ligase_CoAPF00549.25 1.9e-16256–378 CoA-ligase

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

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0952 sucD succinyl-CoA ligase subunit alpha 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 998 998 coexpression:988 database:540 textmining:430
Rv3316 sdhC succinate dehydrogenase cytochrome B-556 subunit 986 982 coexpression:811 database:900
Rv3319 sdhB succinate dehydrogenase iron-sulphur protein subunit 987 979 coexpression:646 database:900 textmining:428
Rv2215 dlaT pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase 989 978 coexpression:744 database:900 textmining:568
Rv3317 sdhD succinate dehydrogenase hydrophobic membrane anchor subunit 981 976 coexpression:756 database:900
Rv0247c succinate dehydrogenase iron-sulfur subunit 981 975 coexpression:656 database:900
Rv3318 sdhA succinate dehydrogenase flavoprotein subunit 984 974 coexpression:566 database:900 textmining:405
Rv0248c succinate dehydrogenase flavoprotein subunit 982 970 coexpression:584 database:900 textmining:452
Rv1553 frdB fumarate reductase iron-sulfur subunit 974 967 ctx cooccurence:496 coexpression:645 database:800
Rv1552 frdA fumarate reductase flavoprotein subunit 967 950 coexpression:563 database:800
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 979 946 database:900 textmining:631
Rv2495c bkdC branched-chain keto acid dehydrogenase E2 component 955 941 coexpression:662 database:800
Rv1493 mutB methylmalonyl-CoA mutase large subunit 941 923 database:900
Rv2454c korB 2-oxoglutarate oxidoreductase subunit KorB 944 912 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: succinyl-CoA ligase subunit beta
  • MTBC0 PGAP product: ADP-forming succinate--CoA ligase subunit beta
  • Pfam (hmmscan --cut_ga): ATP-grasp_2 PF08442.16 (E=5e-70), ATP-grasp_5 PF13549.12 (E=1e-06), CPSase_L_D2 PF02786.23 (E=2e-05), Ligase_CoA PF00549.25 (E=2e-16)
  • (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_215466.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ATP-grasp_2 (PF08442.16), ATP-grasp_5 (PF13549.12), CPSase_L_D2 (PF02786.23), 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 COG0045
  • Curated reference: UniProt P9WGC5 (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 sucD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001015|Rv0951|sucC
MDLFEYQAKELFAKHNVPSTPGRVTDTAEGAKAIATEIGRPVMVKAQVKIGGRGKAGGVKYAATPQDAYEHAKNILGLDIKGHIVKKLLVAEASDIAEEYYLSFLLDRANRTYLAMCSVEGGMEIEEVAATKPERLAKVPVNAVKGVDLDFARSIAEQGHLPAEVLDTAAVTIAKLWELFVAEDATLVEVNPLVRTPDHKILALDAKITLDGNADFRQPGHAEFEDRAATDPLELKAKEHDLNYVKLDGQVGIIGNGAGLVMSTLDVVAYAGEKHGGVKPANFLDIGGGASAEVMAAGLDVVLGDQQVKSVFVNVFGGITSCDAVATGIVKALGMLGDEANKPLVVRLDGNNVEEGRRILTEANHPLVTLVATMDEAADKAAELASA