accE5 Family assigned · medium auto-curated

H37Rv Rv3281 · MTBC0 mtbc0_003489 · 156 aa · 3685832–3686302 (+) · RefSeq NP_217798.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)bifunctional protein acetyl-/propionyl-CoAcarboxylase subunit epsilon AccE
MTBC0 PGAP re-annotationacyl-CoA carboxylase subunit epsilon
Revised (this work)Acyl-CoA carboxylase subunit epsilon. Pfam: ACC_epsilon (PF13822.12).

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

Curated reference (UniProt)

UniProt P96886 SwissProt · reviewed · Evidence at protein level
UniProt nameBiotin-dependent acetyl-/propionyl-coenzyme A carboxylase epsilon subunit
Curated functionStimulates activity of the AccA3/AccD5 biotin-dependent acyl-CoA carboxylase complex. Interacts with AccD5 and modulates its carboxylase activity for acetyl-CoA and propionyl-CoA. Inhibits activity of the AccA3/AccD6 complex. Is also required for the activity of the long-chain acyl-CoA carboxylase (LCC) complex.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionAcyl-CoA carboxylase epsilon subunit
Orthologous group2B02F

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 0.152 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.75% of strains (1087) · clonal

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
ACC_epsilonPF13822.12 1.5e-1491–141 Acyl-CoA carboxylase epsilon subunit

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

Closest characterised functional partner: accD5 (propionyl-CoA carboxylase subunit beta), high confidence from genomic context alone (score 970 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3280 accD5 propionyl-CoA carboxylase subunit beta 996 970 ctx neighborhood:881 database:720 textmining:901
Rv3285 accA3 bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA 990 884 ctx neighborhood:597 database:720 textmining:922
Rv3282 hyp hypothetical protein 958 884 ctx neighborhood:882 textmining:653
Rv3284 hyp hypothetical protein 824 825 ctx neighborhood:822
Rv3283 sseA thiosulfate sulfurtransferase SseA 823 823 ctx neighborhood:822
Rv3279c birA bifunctional biotin operon repressor/biotin--[acetyl-CoA-carboxylase 864 767 ctx neighborhood:766 textmining:441
Rv3799c accD4 propionyl-CoA carboxylase subunit beta AccD 897 754 database:720 textmining:601
Rv3278c transmembrane protein 752 752 ctx neighborhood:748
Rv2247 accD6 acetyl-/propionyl-CoA carboxylase subunit beta 893 743 database:720 textmining:603
Rv0685 tuf elongation factor Tu 733 733 coexpression:733
Rv2501c accA1 acetyl/propionyl-CoA carboxylase subuit alpha 877 529 database:500 textmining:750
Rv0904c accD3 acetyl-CoAcarboxylase carboxyl transferase subunit beta 661 360 textmining:493
Rv0637 hadC (3R)-hydroxyacyl-ACP dehydratase subunit HadC 404 252
Rv2502c accD1 acetyl-/propionyl-CoA carboxylase subunit beta 716 93 textmining:700
Rv2524c fas fatty acid synthase 592 47 textmining:590

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: bifunctional protein acetyl-/propionyl-CoAcarboxylase subunit epsilon AccE
  • MTBC0 PGAP product: acyl-CoA carboxylase subunit epsilon
  • Pfam (hmmscan --cut_ga): ACC_epsilon PF13822.12 (E=1e-14)
  • (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_217798.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ACC_epsilon (PF13822.12)
  • 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 2B02F
  • Curated reference: UniProt P96886 (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 — 19 functional partner(s); context anchor accD5
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003489|Rv3281|accE5
MGTCPCESSERNEPVSRVSGTNEVSDGNETNNPAEVSDGNETNNPAEVSDGNETNNPAPVSRVSGTNEVSDGNETNNPAPVTEKPLHPHEPHIEILRGQPTDQELAALIAVLGSISGSTPPAQPEPTRWGLPVDQLRYPVFSWQRITLQEMTHMRR