accD2 Family assigned · medium auto-curated

H37Rv Rv0974c · MTBC0 mtbc0_001040 · 529 aa · 1092971–1094560 (-) · RefSeq NP_215489.1

Annotation: from legacy to revised

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

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

Curated reference (UniProt)

UniProt O86318 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable biotin-dependent acyl-coenzyme A carboxylase beta2 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.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred nameaccD2
eggNOG descriptionAcetyl-CoA carboxylase, carboxyltransferase component (subunits alpha and beta)
Orthologous groupCOG4799

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 0.479 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 7 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
ACCAPF03255.20 4.5e-0920–199 Acetyl co-enzyme A carboxylase carboxyltransferase-like
Carboxyl_transPF01039.28 9.0e-15446–519 Carboxyl transferase domain

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

Closest characterised functional partner: accA2 (acetyl/propionyl-CoA carboxylase subuit alpha), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0973c accA2 acetyl/propionyl-CoA carboxylase subuit alpha 999 1000 ctx neighborhood:881 coexpression:918 experimental:454 database:956 textmining:898
Rv0976c hyp hypothetical protein 992 992 ctx neighborhood:881 coexpression:907
Rv0975c fadE13 acyl-CoA dehydrogenase FadE13 989 988 ctx neighborhood:881 coexpression:888
Rv0972c fadE12 acyl-CoA dehydrogenase fadE12 992 986 ctx neighborhood:881 coexpression:876 textmining:491
Rv0971c echA7 enoyl-CoA hydratase EchA7 976 934 ctx neighborhood:881 textmining:656
Rv3285 accA3 bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA 943 878 coexpression:437 experimental:454 database:578 textmining:556
Rv2501c accA1 acetyl/propionyl-CoA carboxylase subuit alpha 956 875 coexpression:442 experimental:454 database:578 textmining:663
Rv2967c pca pyruvate carboxylase 702 685 database:576
Rv3221c TB7.3 acetyl-CoA carboxylase biotin carboxyl carrier protein subunit 701 684 database:576
Rv3279c birA bifunctional biotin operon repressor/biotin--[acetyl-CoA-carboxylase 713 657 database:622
Rv2524c fas fatty acid synthase 797 618 ctx neighborhood:544 textmining:493
Rv2502c accD1 acetyl-/propionyl-CoA carboxylase subunit beta 586 570 database:540
Rv0979A rpmF 50S ribosomal protein L32 549 550 ctx neighborhood:531
Rv0977 PE_PGRS16 PE-PGRS family protein PE_PGRS16 495 495 ctx neighborhood:495
Rv0860 fadB fatty oxidation protein FadB 519 468 coexpression:450

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: acyl-CoA carboxylase subunit beta
  • Pfam (hmmscan --cut_ga): ACCA PF03255.20 (E=4e-09), Carboxyl_trans PF01039.28 (E=9e-154)
  • (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_215489.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ACCA (PF03255.20), Carboxyl_trans (PF01039.28)
  • 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 O86318 (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 — 38 functional partner(s); context anchor accA2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001040|Rv0974c|accD2
MLQSTLDPNASAYDEAAATMSGKLDEINAELAKALAGGGPKYVDRHHARGKLTPRERIELLVDPDSPFLELSPLAAYGSNFQIGASLVTGIGAVCGVECMIVANDPTVKGGTSNPWTLRKILRANQIAFENRLPVISLVESGGADLPTQKEIFIPGGQMFRDLTRLSAAGIPTIALVFGNSTAGGAYVPGMSDHVVMIKERSKVFLAGPPLVKMATGEESDDESLGGAEMHARISGLADYFALDELDAIRIGRRIVARLNWIKQGPAPAPVTEPLFDAEELIGIVPPDLRIPFDPREVIARIVDGSEFDEFKPLYGSSLVTGWARLHGYPLGILANARGVLFSEESQKATQFIQLANRADTPLLFLHNTTGYMVGKDYEEGGMIKHGSMMINAVSNSTVPHISLLIGASYGAGHYGMCGRAYDPRFLFAWPSAKSAVMGGAQLSGVLSIVARAAAEARGQQVDEAADAAMRAAVEGQIEAESLPLVLSGMLYDDGVIDPRDTRTVLGMCLSAIANGPIKGTSNFGVFRM