icl1 Resolved · high auto-curated
H37Rv Rv0467 · MTBC0 - ·
428 aa · 557527–558813 (+) ·
RefSeq YP_177728.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | isocitrate lyase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Isocitrate lyase. 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 |
P9WKK7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Isocitrate lyase |
| EC (curated) |
EC 4.1.3.1
|
| Curated function | Involved in the persistence and virulence of M.tuberculosis. Catalyzes the reversible formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle, which operates as an anaplerotic route for replenishing the tricarboxylic acid cycle during growth on fatty acid substrates. It could also catalyze the formation of pyruvate and succinate from 2-methylisocitrate, a key step in the methylcitrate cycle (propionate degradation route) (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | aceA |
| 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 (78) |
GO:0001101, GO:0001666, GO:0003674, GO:0003824, GO:0004451, GO:0005488, GO:0005515, GO:0005575, GO:0005576, GO:0005622, GO:0005623, GO:0005737 +66 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 | 0.188 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 3 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 |
|---|---|---|---|---|
ICL | PF00463.28 | 1.5e-52 | 12–251 | Isocitrate lyase family |
PEP_mutase | PF13714.13 | 1.1e-14 | 72–302 | Phosphoenolpyruvate phosphomutase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadB2 (3-hydroxybutyryl-CoA dehydrogenase), high confidence from genomic context alone (score 952 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1837c glcB |
malate synthase | 999 | 992 | coexpression:923 database:900 textmining:956 |
Rv0468 fadB2 |
3-hydroxybutyryl-CoA dehydrogenase | 954 | 952 ctx | neighborhood:783 coexpression:788 |
Rv1916 aceAb |
isocitrate lyase AceAb | 931 | 928 | database:900 |
Rv1915 aceAa |
isocitrate lyase AceAa | 925 | 923 | database:900 |
Rv1475c acn |
iron-regulated aconitate hydratase | 919 | 908 | database:900 |
Rv0409 ackA |
acetate kinase | 962 | 906 | coexpression:906 textmining:615 |
Rv1257c |
oxidoreductase | 904 | 901 | database:900 |
Rv2280 |
Rv2280, (MTCY339.30c), len: 459 aa. Probable dehydrogenase. Similar to D-lactate dehydrogenase (cytochrome) precursor e.g. G1061264 (587 aa) | 903 | 900 | database:900 |
Rv1905c aao |
D-amino acid oxidase | 807 | 800 | database:800 |
Rv0465c ramB |
HTH-type transcriptional regulator | 835 | 590 ctx | neighborhood:403 textmining:616 |
Rv0408 pta |
phosphate acetyltransferase | 689 | 560 | coexpression:560 |
Rv3853 rraA |
RNase E regulator RraA | 540 | 524 | |
Rv1862 adhA |
alcohol dehydrogenase A | 452 | 444 | coexpression:444 |
Rv0466 hyp |
hypothetical protein | 436 | 436 ctx | neighborhood:434 |
Rv3667 acs |
acetyl-CoAsynthetase | 577 | 411 | coexpression:409 |
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
- Pfam (hmmscan --cut_ga): ICL PF00463.28 (E=2e-52), PEP_mutase PF13714.13 (E=1e-14)
- (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 YP_177728.1)
- 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 P9WKK7 (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 —
42 functional partner(s); context anchor
fadB2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0467|icl1 MSVVGTPKSAEQIQQEWDTNPRWKDVTRTYSAEDVVALQGSVVEEHTLARRGAEVLWEQLHDLEWVNALGALTGNMAVQQVRAGLKAIYLSGWQVAGDANLSGHTYPDQSLYPANSVPQVVRRINNALQRADQIAKIEGDTSVENWLAPIVADGEAGFGGALNVYELQKALIAAGVAGSHWEDQLASEKKCGHLGGKVLIPTQQHIRTLTSARLAADVADVPTVVIARTDAEAATLITSDVDERDQPFITGERTREGFYRTKNGIEPCIARAKAYAPFADLIWMETGTPDLEAARQFSEAVKAEYPDQMLAYNCSPSFNWKKHLDDATIAKFQKELAAMGFKFQFITLAGFHALNYSMFDLAYGYAQNQMSAYVELQEREFAAEERGYTATKHQREVGAGYFDRIATTVDPNSSTTALTGSTEEGQFH