accA1 Family assigned · medium auto-curated
H37Rv Rv2501c · MTBC0 mtbc0_002663 ·
654 aa · 2837806–2839770 (-) ·
RefSeq NP_217017.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acetyl/propionyl-CoA carboxylase subuit alpha |
|---|---|
| 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), Dala_Dala_lig_C (PF07478.19), Biotin_carb_C (PF02785.26), BT_MCC_alpha (PF21139.4), 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 |
P9WPQ3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Biotin-dependent 3-methylcrotonyl-coenzyme A carboxylase alpha1 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 beta1 subunit AccD1, is involved in branched amino-acid catabolism with methylcrotonyl coenzyme A as the substrate. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | accA1 |
| 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
|
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 0.642 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 9 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 | 1.6e-42 | 1–110 | Biotin carboxylase, N-terminal domain |
CPSase_L_D2 | PF02786.23 | 9.0e-81 | 115–323 | Carbamoyl-phosphate synthase L chain, ATP binding domain |
Dala_Dala_lig_C | PF07478.19 | 3.8e-08 | 143–293 | D-ala D-ala ligase C-terminus |
Biotin_carb_C | PF02785.26 | 6.9e-32 | 338–444 | Biotin carboxylase C-terminal domain |
BT_MCC_alpha | PF21139.4 | 1.3e-22 | 456–573 | Methylcrotonyl-CoA carboxylase, alpha-subunit, BT domain |
Biotin_lipoyl | PF00364.29 | 4.1e-15 | 587–652 | Biotin-requiring enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: accD1 (acetyl-/propionyl-CoA carboxylase subunit beta), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2502c accD1 |
acetyl-/propionyl-CoA carboxylase subunit beta | 999 | 1000 ctx | neighborhood:882 coexpression:842 experimental:454 database:956 textmining:909 |
Rv0904c accD3 |
acetyl-CoAcarboxylase carboxyl transferase subunit beta | 999 | 997 ctx | cooccurence:508 coexpression:486 experimental:975 database:500 textmining:759 |
Rv3280 accD5 |
propionyl-CoA carboxylase subunit beta | 997 | 988 | coexpression:435 experimental:454 database:956 textmining:826 |
Rv2247 accD6 |
acetyl-/propionyl-CoA carboxylase subunit beta | 996 | 988 | coexpression:436 experimental:454 database:956 textmining:706 |
Rv2524c fas |
fatty acid synthase | 994 | 987 ctx | neighborhood:544 coexpression:746 database:900 textmining:612 |
Rv2498c citE |
citrate (pro-3S)-lyase subunit beta | 990 | 981 ctx | neighborhood:881 coexpression:826 textmining:528 |
Rv2495c bkdC |
branched-chain keto acid dehydrogenase E2 component | 983 | 977 ctx | neighborhood:723 database:900 |
Rv2500c fadE19 |
acyl-CoA dehydrogenase FadE19 | 974 | 973 ctx | neighborhood:881 coexpression:767 |
Rv3221c TB7.3 |
acetyl-CoA carboxylase biotin carboxyl carrier protein subunit | 982 | 964 | database:958 textmining:524 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 959 | 957 | coexpression:433 database:900 |
Rv3710 leuA |
2-isopropylmalate synthase | 945 | 942 | coexpression:428 database:900 |
Rv2504c scoA |
succinyl-CoA:3-ketoacid-CoA transferase subunit A | 969 | 936 ctx | neighborhood:882 coexpression:483 textmining:543 |
Rv2499c |
oxidase regulatory-like protein | 939 | 933 ctx | neighborhood:881 |
Rv2503c scoB |
succinyl-CoA:3-ketoacid-CoA transferase subunit B | 936 | 932 ctx | neighborhood:881 |
Rv2790c ltp1 |
lipid-transfer protein | 928 | 925 | 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: acetyl/propionyl-CoA carboxylase subuit alpha
- MTBC0 PGAP product: acetyl/propionyl/methylcrotonyl-CoA carboxylase subunit alpha
- Pfam (hmmscan --cut_ga): Biotin_carb_N PF00289.29 (E=2e-42), CPSase_L_D2 PF02786.23 (E=9e-81), Dala_Dala_lig_C PF07478.19 (E=4e-08), Biotin_carb_C PF02785.26 (E=7e-32), BT_MCC_alpha PF21139.4 (E=1e-22), Biotin_lipoyl PF00364.29 (E=4e-15)
- (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_217017.1)
- Domains: Pfam-A via hmmscan --cut_ga — Biotin_carb_N (PF00289.29), CPSase_L_D2 (PF02786.23), Dala_Dala_lig_C (PF07478.19), Biotin_carb_C (PF02785.26), BT_MCC_alpha (PF21139.4), 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 P9WPQ3 (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 —
91 functional partner(s); context anchor
accD1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002663|Rv2501c|accA1 MFDTVLVANRGEIAVRVIRTLRRLGIRSVAVYSDPDVDARHVLEADAAVRLGPAPARESYLDIGKVLDAAARTGAQAIHPGYGFLAENADFAAACERARVVFLGPPARAIEVMGDKIAAKNAVAAFDVPVVPGVARAGLTDDALVTAAAEVGYPVLIKPSAGGGGKGMRLVQDPARLPEALVSARREAMSSFGDDTLFLERFVLRPRHIEVQVLADAHGNVVHLGERECSLQRRHQKVIEEAPSPLLDPQTRERIGVAACNTARCVDYVGAGTVEFIVSAQRPDEFFFMEMNTRLQVEHPVTEAITGLDLVEWQLRVGAGEKLGFAQNDIELRGHAIEARVYAEDPAREFLPTGGRVLAVFEPAGPGVRVDSSLLGGTVVGSDYDPLLTKVIAHGADREEALDRLDQALARTAVLGVQTNVEFLRFLLADERVRVGDLDTAVLDERSADFTARPAPDDVLAAGGLYRQWALARRAQGDLWAAPSGWRGGGHMAPVRTAMRTPLRSETVSVWGPPESAQVQVGDGEIDCASVQVTREQMSVTISGLRRDYRWAEADRHLWIADERGTWHLREAEEHKIHRAVGARPAEVVSPMPGSVIAVQVESGSQISAGDVVVVVEAMKMEHSLEAPVSGRVQVLVSVGDQVKVEQVLARIKD