accA2 Family assigned · medium auto-curated
H37Rv Rv0973c · MTBC0 mtbc0_001039 ·
667 aa · 1090962–1092965 (-) ·
RefSeq NP_215488.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acetyl/propionyl-CoA carboxylase subuit alpha |
|---|---|
| MTBC0 PGAP re-annotation | biotin carboxylase N-terminal domain-containing protein |
| Revised (this work) | Biotin carboxylase N-terminal domain-containing protein. 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 |
P71538
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Biotin-dependent 3-methylcrotonyl-coenzyme A carboxylase alpha1 subunit |
| 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 | accA2 |
| eggNOG description | carboxylase |
| Orthologous group | COG4770 |
| EC number |
EC 6.4.1.1, EC 6.4.1.3, EC 6.4.1.4
|
| KEGG orthology |
K01959, K01965, K01968
|
| KEGG pathways |
map00020, map00280, map00620, map00630, map00640, map00720, map01100, map01120, map01130, map01200, map01230
|
| KEGG modules |
M00036, M00173, M00373, M00620, 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 | 0.79 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 11 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.25% of strains (360) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Biotin_carb_N | PF00289.29 | 8.6e-40 | 3–107 | Biotin carboxylase, N-terminal domain |
CPSase_L_D2 | PF02786.23 | 3.2e-56 | 133–317 | Carbamoyl-phosphate synthase L chain, ATP binding domain |
Dala_Dala_lig_C | PF07478.19 | 9.6e-07 | 136–286 | D-ala D-ala ligase C-terminus |
Biotin_carb_C | PF02785.26 | 7.5e-26 | 329–445 | Biotin carboxylase C-terminal domain |
BT_MCC_alpha | PF21139.4 | 2.1e-10 | 466–571 | Methylcrotonyl-CoA carboxylase, alpha-subunit, BT domain |
Biotin_lipoyl | PF00364.29 | 5.8e-18 | 590–653 | Biotin-requiring enzyme |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: accD2 (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) |
|---|---|---|---|---|
Rv0974c accD2 |
acetyl-/propionyl-CoA carboxylase subunit beta | 999 | 1000 ctx | neighborhood:881 coexpression:918 experimental:454 database:956 textmining:898 |
Rv0904c accD3 |
acetyl-CoAcarboxylase carboxyl transferase subunit beta | 998 | 993 | coexpression:486 experimental:975 textmining:759 |
Rv2247 accD6 |
acetyl-/propionyl-CoA carboxylase subunit beta | 995 | 988 | coexpression:435 experimental:454 database:956 textmining:634 |
Rv3280 accD5 |
propionyl-CoA carboxylase subunit beta | 995 | 987 | coexpression:435 experimental:454 database:956 textmining:693 |
Rv0972c fadE12 |
acyl-CoA dehydrogenase fadE12 | 993 | 986 ctx | neighborhood:882 coexpression:874 textmining:584 |
Rv0975c fadE13 |
acyl-CoA dehydrogenase FadE13 | 984 | 984 ctx | neighborhood:882 coexpression:856 |
Rv0976c hyp |
hypothetical protein | 984 | 983 ctx | neighborhood:881 coexpression:832 |
Rv0971c echA7 |
enoyl-CoA hydratase EchA7 | 967 | 930 ctx | neighborhood:882 textmining:555 |
Rv2790c ltp1 |
lipid-transfer protein | 928 | 925 | database:900 |
Rv3667 acs |
acetyl-CoAsynthetase | 925 | 918 | database:900 |
Rv3285 accA3 |
bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA | 942 | 916 | database:900 |
Rv2501c accA1 |
acetyl/propionyl-CoA carboxylase subuit alpha | 924 | 913 | database:900 |
Rv0408 pta |
phosphate acetyltransferase | 917 | 905 | database:900 |
Rv1322A hyp |
hypothetical protein | 909 | 905 | database:900 |
Rv0753c mmsA |
methylmalonate-semialdehyde dehydrogenase | 906 | 902 | 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: biotin carboxylase N-terminal domain-containing protein
- Pfam (hmmscan --cut_ga): Biotin_carb_N PF00289.29 (E=9e-40), CPSase_L_D2 PF02786.23 (E=3e-56), Dala_Dala_lig_C PF07478.19 (E=1e-06), Biotin_carb_C PF02785.26 (E=7e-26), BT_MCC_alpha PF21139.4 (E=2e-10), Biotin_lipoyl PF00364.29 (E=6e-18)
- (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_215488.1)
- 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 P71538 (TrEMBL, unreviewed; 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 —
71 functional partner(s); context anchor
accD2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001039|Rv0973c|accA2 MGITRVLVANRGEIARRVFATCRRLGLGTVAVYTDPDAAAPHVAEADARVRLPQTTDYLNAEAIIAAAQAAGADAVHPGYGFLSENAEFAAAVQEAGLTWVGPPVDAVRAMGSKIESKKLMAAAGVPVLEELDPDAVTTAQLPVLVKASAGGGGRGMRVVHELSALPAEVEAARREAQSAFGDPTVFCERYLPTGHHVEVQVMADTHGTVWAVGERECSIQRRHQKIIEEAPSPLVERVPGMRAKLFDAARLAASAIGYTGAGTVEFLADDSPGREGEFYFLEMNTRLQVEHPVTEETTGLDLVELQLMIADCGRLDTEPPPAQGYSIEARLYAEDPAHGWQPQAGVMHTIEVPGVRAQFDSLGQRTGIRLDSGIVDGSTVSIHYDPMLAKVVSYGATRRQAALVLADALVRARLHGLRTNRELLVNVLRHPAFLDGATDTGFFDTHGMAELSTPLADTATLRLSAIAAALADAEHNRASAGVFSSIPSGWRNLASGYQVKTYRDDADTEHRVEYRFTRTGLALPGDPVVQLVSADVDQVVLAQDGVAHGFTVARHGPDVYVDSARGPVHLVALSRFPEPSSAVEQGSLVAPMPGNVIRIGAEVGDTVTAGQPLIWLEAMKMEHTIAAPADGVLTHVSVNTGQQVEVGAILARVEAPQNGPAEGDSP