acs Resolved · high auto-curated
H37Rv Rv3667 · MTBC0 mtbc0_003886 ·
651 aa · 4131622–4133577 (+) ·
RefSeq NP_218184.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | acetyl-CoAsynthetase |
|---|---|
| MTBC0 PGAP re-annotation | acetate--CoA ligase |
| Revised (this work) | Acetate--CoA ligase. Pfam: ACAS_N (PF16177.12), AMP-binding (PF00501.35), AMP-binding_C (PF13193.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQD1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Acetyl-coenzyme A synthetase |
| EC (curated) |
EC 6.2.1.1
|
| Curated function | Catalyzes the conversion of acetate into acetyl-CoA (AcCoA), an essential intermediate at the junction of anabolic and catabolic pathways. AcsA undergoes a two-step reaction. In the first half reaction, AcsA combines acetate with ATP to form acetyl-adenylate (AcAMP) intermediate. In the second half reaction, it can then transfer the acetyl group from AcAMP to the sulfhydryl group of CoA, forming the product AcCoA. M.tuberculosis may use AcsA for both acetate and propionate assimilation. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | acsA |
| eggNOG description | Catalyzes the conversion of acetate into acetyl-CoA (AcCoA), an essential intermediate at the junction of anabolic and catabolic pathways. AcsA undergoes a two-step reaction. In the first half reaction, AcsA combines acetate with ATP to form acetyl-adenylate (AcAMP) intermediate. In the second half reaction, it can then transfer the acetyl group from AcAMP to the sulfhydryl group of CoA, forming the product AcCoA |
| Orthologous group | COG0365 |
| EC number |
EC 6.2.1.1
|
| KEGG orthology |
K01895
|
| KEGG pathways |
map00010, map00620, map00640, map00680, map00720, map01100, map01110, map01120, map01130, map01200
|
| KEGG modules |
M00357
|
| Gene Ontology (8) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, 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 | 0.447 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 11 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.20% of strains (289) · 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 |
|---|---|---|---|---|
ACAS_N | PF16177.12 | 1.6e-22 | 26–79 | Acetyl-coenzyme A synthetase N-terminus |
AMP-binding | PF00501.35 | 4.6e-91 | 86–471 | AMP-binding enzyme |
AMP-binding_C | PF13193.13 | 1.1e-26 | 539–617 | AMP-binding enzyme C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0896 gltA2 |
citrate synthase 1 | 974 | 969 | coexpression:649 database:900 |
Rv1131 prpC |
methylcitrate synthase PrpC | 974 | 969 | coexpression:649 database:900 |
Rv0889c citA |
citrate synthase 2 | 971 | 969 | coexpression:649 database:900 |
Rv1837c glcB |
malate synthase | 975 | 968 | coexpression:651 database:900 |
Rv0147 |
aldehyde dehydrogenase | 952 | 947 | coexpression:418 database:900 |
Rv0223c |
aldehyde dehydrogenase | 952 | 947 | coexpression:417 database:900 |
Rv0458 |
aldehyde dehydrogenase | 951 | 947 | coexpression:416 database:900 |
Rv3293 pcd |
piperideine-6-carboxylic acid dehydrogenase | 950 | 947 | coexpression:420 database:900 |
Rv0753c mmsA |
methylmalonate-semialdehyde dehydrogenase | 950 | 947 | coexpression:419 database:900 |
Rv0768 aldA |
aldehyde dehydrogenase AldA | 950 | 947 | coexpression:418 database:900 |
Rv0859 fadA |
acyltransferase | 953 | 941 | coexpression:413 database:900 |
Rv3546 fadA5 |
acetyl-CoA acetyltransferase FadA | 950 | 941 | coexpression:415 database:900 |
Rv1074c fadA3 |
beta-ketoacyl CoA thiolase FadA | 948 | 941 | coexpression:415 database:900 |
Rv0914c |
lipid carrier protein or keto acyl-CoA thiolase | 944 | 941 | coexpression:414 database:900 |
Rv1323 fadA4 |
acetyl-CoA acetyltransferase | 944 | 941 | coexpression:416 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-CoAsynthetase
- MTBC0 PGAP product: acetate--CoA ligase
- Pfam (hmmscan --cut_ga): ACAS_N PF16177.12 (E=2e-22), AMP-binding PF00501.35 (E=5e-91), AMP-binding_C PF13193.13 (E=1e-26)
- (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_218184.1)
- Domains: Pfam-A via hmmscan --cut_ga — ACAS_N (PF16177.12), AMP-binding (PF00501.35), AMP-binding_C (PF13193.13)
- 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
COG0365 - Curated reference: UniProt P9WQD1 (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 — 193 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003886|Rv3667|acs MSESTPEVSSSYPPPAHFAEHANARAELYREAEEDRLAFWAKQANRLSWTTPFTEVLDWSGAPFAKWFVGGELNVAYNCVDRHVEAGHGDRVAIHWEGEPVGDRRTLTYSDLLAEVSKAANALTDLGLVAGDRVAIYLPLIPEAVIAMLACARLGIMHSVVFGGFTAAALQARIVDAQAKLLITADGQFRRGKPSPLKAAADEALAAIPDCSVEHVLVVRRTGIEMAWSEGRDLWWHHVVGSASPAHTPEPFDSEHPLFLLYTSGTTGKPKGIMHTSGGYLTQCCYTMRTIFDVKPDSDVFWCTADIGWVTGHTYGVYGPLCNGVTEVLYEGTPDTPDRHRHFQIIEKYGVTIYYTAPTLIRMFMKWGREIPDSHDLSSLRLLGSVGEPINPEAWRWYRDVIGGGRTPLVDTWWQTETGSAMISPLPGIAAAKPGSAMTPLPGISAKIVDDHGDPLPPHTEGAQHVTGYLVLDQPWPSMLRGIWGDPARYWHSYWSKFSDKGYYFAGDGARIDPDGAIWVLGRIDDVMNVSGHRISTAEVESALVAHSGVAEAAVVGVTDETTTQAICAFVVLRANYAPHDRTAEELRTEVARVISPIARPRDVHVVPELPKTRSGKIMRRLLRDVAENRELGDTSTLLDPTVFDAIRAAK