accA3 Family assigned · medium auto-curated
H37Rv Rv3285 · MTBC0 mtbc0_003493 ·
600 aa · 3688437–3690239 (+) ·
RefSeq NP_217802.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA |
|---|---|
| MTBC0 PGAP re-annotation | acetyl/propionyl/methylcrotonyl-CoA carboxylase subunit alpha |
| Revised (this work) | Acetyl/propionyl/methylcrotonyl-CoA carboxylase subunit alpha. Pfam: Biotin_carb_N (PF00289.29), CPSase_L_D2 (PF02786.23), ATP-grasp (PF02222.28), Dala_Dala_lig_C (PF07478.19), Biotin_carb_C (PF02785.26), Biotin_lipoyl (PF00364.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P96890
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Biotin-dependent acyl-coenzyme A carboxylase alpha3 subunit [Includes: Biotin carboxylase |
| EC (curated) |
EC 6.3.4.14
|
| Curated function | Component of a biotin-dependent acyl-CoA carboxylase complex. This subunit catalyzes the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain, resulting in the formation of carboxyl biotin. When associated with the beta5 subunit AccD5, is involved in the carboxylation of acetyl-CoA and propionyl-CoA, with a preference for propionyl-CoA. When associated with the beta6 subunit AccD6, is involved in the carboxylation of acetyl-CoA and propionyl-CoA, with a preference for acetyl-CoA. When associated with the beta4 subunit AccD4, the beta5 subunit AccD5 and . |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | accBC |
| eggNOG description | carboxylase |
| Orthologous group | COG4770 |
| EC number |
EC 6.3.4.14, EC 6.4.1.2, EC 6.4.1.3
|
| KEGG orthology |
K11263
|
| KEGG pathways |
map00061, map00280, map00620, map00630, map00640, map01100, map01110, map01120, map01130, map01200, map01212
|
| KEGG modules |
M00082, M00741
|
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 | 0.038 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 1 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Biotin_carb_N | PF00289.29 | 1.3e-43 | 12–120 | Biotin carboxylase, N-terminal domain |
CPSase_L_D2 | PF02786.23 | 1.7e-77 | 125–333 | Carbamoyl-phosphate synthase L chain, ATP binding domain |
ATP-grasp | PF02222.28 | 1.1e-07 | 149–302 | ATP-grasp domain |
Dala_Dala_lig_C | PF07478.19 | 1.6e-05 | 155–301 | D-ala D-ala ligase C-terminus |
Biotin_carb_C | PF02785.26 | 7.3e-35 | 345–455 | Biotin carboxylase C-terminal domain |
Biotin_lipoyl | PF00364.29 | 1.2e-17 | 534–599 | Biotin-requiring enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: accD3 (acetyl-CoAcarboxylase carboxyl transferase subunit beta), high confidence from genomic context alone (score 996 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0904c accD3 |
acetyl-CoAcarboxylase carboxyl transferase subunit beta | 998 | 996 ctx | cooccurence:461 coexpression:483 experimental:975 textmining:605 |
Rv3280 accD5 |
propionyl-CoA carboxylase subunit beta | 999 | 995 ctx | neighborhood:591 coexpression:449 experimental:454 database:956 textmining:993 |
Rv2247 accD6 |
acetyl-/propionyl-CoA carboxylase subunit beta | 998 | 991 | coexpression:464 experimental:454 database:956 textmining:868 |
Rv2524c fas |
fatty acid synthase | 995 | 988 ctx | neighborhood:544 coexpression:759 database:900 textmining:612 |
Rv3799c accD4 |
propionyl-CoA carboxylase subunit beta AccD | 998 | 974 | coexpression:466 experimental:454 database:877 textmining:945 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 972 | 965 | coexpression:459 database:900 |
Rv3221c TB7.3 |
acetyl-CoA carboxylase biotin carboxyl carrier protein subunit | 964 | 964 | database:958 |
Rv3710 leuA |
2-isopropylmalate synthase | 945 | 943 | coexpression:431 database:900 |
Rv3279c birA |
bifunctional biotin operon repressor/biotin--[acetyl-CoA-carboxylase | 956 | 928 ctx | neighborhood:406 cooccurence:685 database:644 textmining:421 |
Rv2790c ltp1 |
lipid-transfer protein | 928 | 925 | database:900 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 923 | 920 | database:900 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 940 | 919 | database:900 |
Rv3667 acs |
acetyl-CoAsynthetase | 924 | 917 | database:900 |
Rv0973c accA2 |
acetyl/propionyl-CoA carboxylase subuit alpha | 942 | 916 | database:900 |
Rv1837c glcB |
malate synthase | 923 | 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
- Legacy H37Rv annotation: bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA
- MTBC0 PGAP product: acetyl/propionyl/methylcrotonyl-CoA carboxylase subunit alpha
- Pfam (hmmscan --cut_ga): Biotin_carb_N PF00289.29 (E=1e-43), CPSase_L_D2 PF02786.23 (E=2e-77), ATP-grasp PF02222.28 (E=1e-07), Dala_Dala_lig_C PF07478.19 (E=2e-05), Biotin_carb_C PF02785.26 (E=7e-35), Biotin_lipoyl PF00364.29 (E=1e-17)
- (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_217802.1)
- Domains: Pfam-A via hmmscan --cut_ga — Biotin_carb_N (PF00289.29), CPSase_L_D2 (PF02786.23), ATP-grasp (PF02222.28), Dala_Dala_lig_C (PF07478.19), Biotin_carb_C (PF02785.26), Biotin_lipoyl (PF00364.29)
- 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
COG4770 - Curated reference: UniProt P96890 (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 —
88 functional partner(s); context anchor
accD3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003493|Rv3285|accA3 MASHAGSRIARISKVLVANRGEIAVRVIRAARDAGLPSVAVYAEPDAESPHVRLADEAFALGGQTSAESYLDFAKILDAAAKSGANAIHPGYGFLAENADFAQAVIDAGLIWIGPSPQSIRDLGDKVTARHIAARAQAPLVPGTPDPVKGADEVVAFAEEYGLPIAIKAAHGGGGKGMKVARTIDEIPELYESAVREATAAFGRGECYVERYLDKPRHVEAQVIADQHGNVVVAGTRDCSLQRRYQKLVEEAPAPFLTDFQRKEIHDSAKRICKEAHYHGAGTVEYLVGQDGLISFLEVNTRLQVEHPVTEETAGIDLVLQQFRIANGEKLDITEDPTPRGHAIEFRINGEDAGRNFLPAPGPVTKFHPPSGPGVRVDSGVETGSVIGGQFDSMLAKLIVHGADRAEALARARRALNEFGVEGLATVIPFHRAVVSDPAFIGDANGFSVHTRWIETEWNNTIEPFTDGEPLDEDARPRQKVVVEIDGRRVEVSLPADLALSNGGGCDPVGVIRRKPKPRKRGAHTGAAASGDAVTAPMQGTVVKFAVEEGQEVVAGDLVVVLEAMKMENPVTAHKDGTITGLAVEAGAAITQGTVLAEIK