acn Resolved · high auto-curated
H37Rv Rv1475c · MTBC0 mtbc0_001578 ·
943 aa · 1673020–1675851 (-) ·
RefSeq NP_215991.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | iron-regulated aconitate hydratase |
|---|---|
| MTBC0 PGAP re-annotation | iron-regulated aconitate hydratase Acn |
| Revised (this work) | Iron-regulated aconitate hydratase Acn. Pfam: Aconitase (PF00330.26), Aconitase_C (PF00694.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53166
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Aconitate hydratase A |
| EC (curated) |
EC 4.2.1.3, EC 4.2.1.99
|
| Curated function | Involved in the catabolism of short chain fatty acids (SCFA) via the tricarboxylic acid (TCA)(acetyl degradation route) and probably via the 2-methylcitrate cycle I (propionate degradation route). Catalyzes the reversible isomerization of citrate to isocitrate via cis-aconitate. The apo form of AcnA functions as a RNA-binding regulatory protein which binds to selected IRE-like sequences present within the UTRs (untranslated regions) of 3' trxC and 5' IdeR mRNA. Could catalyze the hydration of 2-methyl-cis-aconitate to yield (2R,3S)-2-methylisocitrate (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | acnA |
| eggNOG description | aconitate hydratase |
| Orthologous group | COG1048 |
| EC number |
EC 4.2.1.3
|
| KEGG orthology |
K01681
|
| KEGG pathways |
map00020, map00630, map00720, map01100, map01110, map01120, map01130, map01200, map01210, map01230
|
| KEGG modules |
M00009, M00010, M00012, M00173, M00740
|
| Gene Ontology (78) |
GO:0003674, GO:0003676, GO:0003723, GO:0003729, GO:0003730, GO:0003824, GO:0003994, GO:0005488, GO:0005506, GO:0005575, GO:0005576, GO:0005618 +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 | 0.215 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 4 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 |
|---|---|---|---|---|
Aconitase | PF00330.26 | 1.2e-165 | 73–606 | Aconitase family (aconitate hydratase) |
Aconitase_C | PF00694.26 | 9.0e-40 | 735–865 | Aconitase C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: prpC (methylcitrate synthase PrpC), high confidence from genomic context alone (score 993 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1131 prpC |
methylcitrate synthase PrpC | 995 | 993 ctx | cooccurence:489 coexpression:690 database:941 textmining:411 |
Rv0889c citA |
citrate synthase 2 | 995 | 991 | coexpression:692 database:941 textmining:533 |
Rv0896 gltA2 |
citrate synthase 1 | 995 | 990 | coexpression:699 database:941 textmining:527 |
Rv3339c icd1 |
isocitrate dehydrogenase | 988 | 983 | coexpression:806 database:900 |
Rv0066c icd2 |
isocitrate dehydrogenase | 965 | 919 | database:900 textmining:591 |
Rv0467 icl1 |
isocitrate lyase | 919 | 908 | database:900 |
Rv1915 aceAa |
isocitrate lyase AceAa | 917 | 908 | database:900 |
Rv1916 aceAb |
isocitrate lyase AceAb | 916 | 908 | database:900 |
Rv1474c |
transcriptional regulator | 905 | 906 ctx | neighborhood:879 |
Rv3846 sodA |
superoxide dismutase | 921 | 897 | experimental:830 |
Rv2904c rplS |
50S ribosomal protein L19 | 885 | 878 | experimental:863 |
Rv0979A rpmF |
50S ribosomal protein L32 | 863 | 864 | experimental:832 |
Rv2441c rpmA |
50S ribosomal protein L27 | 856 | 851 | experimental:832 |
Rv2909c rpsP |
30S ribosomal protein S16 | 850 | 849 | experimental:832 |
Rv3456c rplQ |
50S ribosomal protein L17 | 850 | 843 | experimental:832 |
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: iron-regulated aconitate hydratase
- MTBC0 PGAP product: iron-regulated aconitate hydratase Acn
- Pfam (hmmscan --cut_ga): Aconitase PF00330.26 (E=1e-165), Aconitase_C PF00694.26 (E=9e-40)
- (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_215991.1)
- Domains: Pfam-A via hmmscan --cut_ga — Aconitase (PF00330.26), Aconitase_C (PF00694.26)
- 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
COG1048 - Curated reference: UniProt O53166 (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 —
172 functional partner(s); context anchor
prpC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001578|Rv1475c|acn MTSKSVNSFGAHDTLKVGEKSYQIYRLDAVPNTAKLPYSLKVLAENLLRNEDGSNITKDHIEAIANWDPKAEPSIEIQYTPARVVMQDFTGVPCIVDLATMREAIADLGGNPDKVNPLAPADLVIDHSVIADLFGRADAFERNVEIEYQRNGERYQFLRWGQGAFDDFKVVPPGTGIVHQVNIEYLASVVMTRDGVAYPDTCVGTDSHTTMVNGLGVLGWGVGGIEAEAAMLGQPVSMLIPRVVGFRLTGEIQPGVTATDVVLTVTEMLRQHGVVGKFVEFYGEGVAEVPLANRATLGNMSPEFGSTAAIFPIDEETIKYLRFTGRTPEQVALVEAYAKAQGMWHDPKHEPEFSEYLELNLSDVVPSIAGPKRPQDRIALAQAKSTFREQIYHYVGNGSPDSPHDPHSKLDEVVEETFPASDPGQLTFANDDVATDETVHSAAAHADGRVSNPVRVKSDELGEFVLDHGAVVIAAITSCTNTSNPEVMLGAALLARNAVEKGLTSKPWVKTTIAPGSQVVNDYYDRSGLWPYLEKLGFYLVGYGCTTCIGNSGPLPEEISKAVNDNDLSVTAVLSGNRNFEGRINPDVKMNYLASPPLVIAYALAGTMDFDFQTQPLGQDKDGKNVFLRDIWPSQQDVSDTIAAAINQEMFTRNYADVFKGDDRWRNLPTPSGNTFEWDPNSTYVRKPPYFEGMTAKPEPVGNISGARVLALLGDSVTTDHISPAGAIKPGTPAARYLDEHGVDRKDYNSFGSRRGNHEVMIRGTFANIRLRNQLLDDVSGGYTRDFTQPGGPQAFIYDAAQNYAAQHIPLVVFGGKEYGSGSSRDWAAKGTLLLGVRAVIAESFERIHRSNLIGMGVIPLQFPEGKSASSLGLDGTEVFDITGIDVLNDGKTPKTVCVQATKGDGATIEFDAVVRIDTPGEADYYRNGGILQYVLRNILKSG