aceAa Resolved · high auto-curated
H37Rv Rv1915 · MTBC0 - ·
367 aa · 2160463–2161566 (+) ·
RefSeq NP_216431.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | isocitrate lyase AceAa |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Isocitrate lyase AceAa. Pfam: ICL (PF00463.28), PEP_mutase (PF13714.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O07718
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative isocitrate lyase subunit A |
| EC (curated) |
EC 4.1.3.1
|
| Curated function | Together with AceAb, they could catalyze the formation of succinate and glyoxylate from isocitrate. |
UniProt still lists this protein as Putative isocitrate lyase subunit A; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | aceAb |
| eggNOG description | Isocitrate lyase |
| Orthologous group | COG2224 |
| EC number |
EC 4.1.3.1
|
| KEGG orthology |
K01637
|
| KEGG pathways |
map00630, map01100, map01110, map01120, map01200
|
| KEGG modules |
M00012
|
| Gene Ontology (25) |
GO:0003674, GO:0003824, GO:0004451, GO:0005975, GO:0006081, GO:0006082, GO:0006097, GO:0006102, GO:0008150, GO:0008152, GO:0009987, GO:0016829 +13 more
|
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 | 1.005 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 73.72% of strains (107049) · reference-fixed |
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 |
|---|---|---|---|---|
ICL | PF00463.28 | 9.4e-70 | 21–285 | Isocitrate lyase family |
PEP_mutase | PF13714.13 | 2.2e-10 | 172–257 | Phosphoenolpyruvate phosphomutase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: aceAb (isocitrate lyase AceAb), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1916 aceAb |
isocitrate lyase AceAb | 999 | 1000 ctx | neighborhood:773 fusion:900 cooccurence:774 database:900 |
Rv1837c glcB |
malate synthase | 993 | 973 | coexpression:696 database:900 textmining:757 |
Rv0467 icl1 |
isocitrate lyase | 925 | 923 | database:900 |
Rv1475c acn |
iron-regulated aconitate hydratase | 917 | 908 | database:900 |
Rv2280 |
Rv2280, (MTCY339.30c), len: 459 aa. Probable dehydrogenase. Similar to D-lactate dehydrogenase (cytochrome) precursor e.g. G1061264 (587 aa) | 908 | 905 | database:900 |
Rv1257c |
oxidoreductase | 903 | 900 | database:900 |
Rv1905c aao |
D-amino acid oxidase | 807 | 800 | database:800 |
Rv0409 ackA |
acetate kinase | 666 | 630 | coexpression:630 |
Rv0408 pta |
phosphate acetyltransferase | 689 | 561 | coexpression:561 |
Rv1914c hyp |
hypothetical protein | 552 | 552 ctx | neighborhood:552 |
Rv3667 acs |
acetyl-CoAsynthetase | 474 | 417 | coexpression:415 |
Rv0465c ramB |
HTH-type transcriptional regulator | 498 | 317 | |
Rv0889c citA |
citrate synthase 2 | 661 | 281 | textmining:549 |
Rv0896 gltA2 |
citrate synthase 1 | 493 | 280 | |
Rv1131 prpC |
methylcitrate synthase PrpC | 485 | 273 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): isocitrate lyase AceAa
- Pfam (hmmscan --cut_ga): ICL PF00463.28 (E=9e-70), PEP_mutase PF13714.13 (E=2e-10)
- (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_216431.1)
- Domains: Pfam-A via hmmscan --cut_ga — ICL (PF00463.28), PEP_mutase (PF13714.13)
- 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
COG2224 - Curated reference: UniProt O07718 (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 —
23 functional partner(s); context anchor
aceAb - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1915|aceAa MAIAETDTEVHTPFEQDFEKDVAATQRYFDSSRFAGIIRLYTARQVVEQRGTIPVDHIVAREAAGAFYERLRELFAARKSITTFGPYSPGQAVSMKRMGIEAIYLGGWATSAKGSSTEDPGPDLASYPLSQVPDDAAVLVRALLTADRNQHYLRLQMSERQRAATPAYDFRPFIIADAGTGHGGDPHVRNLIRRFVEVGVPGYHIEDQRPGTKKCGHQGGKVLVPSDEQIKRLNAARFQLDIMRVPGIIVARTDAEAANLIDSRADERDQPFLLGATKLDVPSYKSCFLAMVRRFTNWASRSSMVIFSMRLATASTRRPAVGLSAKAFSAWSPTRSTRGGRTASSRSTAFSTRSSRGSWRPGRTTRA