accD1 Family assigned · medium auto-curated

H37Rv Rv2502c · MTBC0 mtbc0_002664 · 529 aa · 2839775–2841364 (-) · RefSeq NP_217018.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)acetyl-/propionyl-CoA carboxylase subunit beta
MTBC0 PGAP re-annotationacetyl-/propionyl-CoA carboxylase subunit beta
Revised (this work)Acetyl-/propionyl-CoA carboxylase subunit beta. Pfam: Carboxyl_trans (PF01039.28), ACCA (PF03255.20).

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

Curated reference (UniProt)

UniProt I6YDK7 SwissProt · reviewed · Evidence at protein level
UniProt nameBiotin-dependent 3-methylcrotonyl-coenzyme A carboxylase beta1 subunit
EC (curated) EC 2.1.3.-
Curated functionComponent of a biotin-dependent acyl-CoA carboxylase complex. This subunit transfers the CO2 from carboxybiotin to the CoA ester substrate. When associated with the alpha1 subunit AccA1, is involved in branched amino-acid catabolism with methylcrotonyl coenzyme A as the substrate. Shows residual with propionyl-CoA and acetyl-CoA.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred nameaccD1
eggNOG descriptionAcetyl-CoA carboxylase, carboxyltransferase component (subunits alpha and beta)
Orthologous groupCOG4799
EC number EC 6.4.1.4
KEGG orthology K01969
KEGG pathways map00280, map01100
KEGG modules M00036

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 0.846 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 10 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
Carboxyl_transPF01039.28 1.1e-15642–519 Carboxyl transferase domain
ACCAPF03255.20 1.0e-0583–199 Acetyl co-enzyme A carboxylase carboxyltransferase-like

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

Closest characterised functional partner: accA1 (acetyl/propionyl-CoA carboxylase subuit alpha), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2501c accA1 acetyl/propionyl-CoA carboxylase subuit alpha 999 1000 ctx neighborhood:882 coexpression:842 experimental:454 database:956 textmining:909
Rv2503c scoB succinyl-CoA:3-ketoacid-CoA transferase subunit B 977 969 ctx neighborhood:881 coexpression:750
Rv2499c oxidase regulatory-like protein 950 933 ctx neighborhood:881
Rv2500c fadE19 acyl-CoA dehydrogenase FadE19 982 930 ctx neighborhood:881 coexpression:433 textmining:764
Rv2504c scoA succinyl-CoA:3-ketoacid-CoA transferase subunit A 971 923 ctx neighborhood:882 textmining:647
Rv0975c fadE13 acyl-CoA dehydrogenase FadE13 925 922 database:900
Rv0131c fadE1 acyl-CoA dehydrogenase FadE1 925 922 database:900
Rv0154c fadE2 acyl-CoA dehydrogenase FadE2 925 921 database:900
Rv3140 fadE23 acyl-CoA dehydrogenase FadE23 924 921 database:900
Rv0231 fadE4 acyl-CoA dehydrogenase FadE4 924 921 database:900
Rv2498c citE citrate (pro-3S)-lyase subunit beta 991 907 ctx neighborhood:881 textmining:916
Rv3285 accA3 bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA 982 883 coexpression:437 experimental:454 database:578 textmining:861
Rv0973c accA2 acetyl/propionyl-CoA carboxylase subuit alpha 977 874 coexpression:443 experimental:454 database:578 textmining:829
Rv2497c bkdA 3-methyl-2-oxobutanoate dehydrogenase subunit alpha 877 817 ctx neighborhood:724
Rv0971c echA7 enoyl-CoA hydratase EchA7 805 799 database:650

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: acetyl-/propionyl-CoA carboxylase subunit beta
  • MTBC0 PGAP product: acetyl-/propionyl-CoA carboxylase subunit beta
  • Pfam (hmmscan --cut_ga): Carboxyl_trans PF01039.28 (E=1e-156), ACCA PF03255.20 (E=1e-05)
  • (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_217018.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Carboxyl_trans (PF01039.28), ACCA (PF03255.20)
  • 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 COG4799
  • Curated reference: UniProt I6YDK7 (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 — 69 functional partner(s); context anchor accA1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002664|Rv2502c|accD1
MTTPSIAIAPSFADEHRRLVAELNNKLAAAALGGNERARKRHVSRGKLLPRERVDRLLDPGSPFLELAPLAAGGMYGDESPGAGIITGIGRVSGRQCVIVANDATVKGGTYYPMTVKKHLRAQEVALQNMLPCIYLVDSGGAFLPRQDEVFPDREHFGRIFYNQATMSAKGIPQVAAVLGSCTAGGAYVPAMSDEAVIVREQGTIFLGGPPLVKAATGEIVSAEELGGGDLHSRTSGVTDHLADDDEDALRIVRAIADTFGPCEPAQWDVRRSVEPKYPQAELYDVVPPDPRVPYDVHEVVVRIVDGSEFSEFKAKYGKTLVTAFARVHGHPVGIVANNGVLFSESALKGAHFIELCDKRKIPLLFLQNIAGFMVGRDYEAGGIAKHGAKMVTAVACARVPKLTVVIGGSYGAGNYSMCGRAYSPRFLWMWPNARISVMGGEQAASVLATVRGEQLSAAGTPWSPDEEEAFKAPIRAQYEDQGNPYYSTARLWDDGIIDPADTRTVVGLALSLCAHAPLDQVGYGVFRM