inhA Resolved · high auto-curated
H37Rv Rv1484 · MTBC0 mtbc0_001587 ·
269 aa · 1684007–1684816 (+) ·
RefSeq NP_216000.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | NADH-dependent enoyl-[ACP |
|---|---|
| MTBC0 PGAP re-annotation | NADH-dependent enoyl-ACP reductase InhA |
| Revised (this work) | NADH-dependent enoyl-ACP reductase InhA. Pfam: adh_short_C2 (PF13561.13), adh_short (PF00106.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WGR1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Enoyl-[acyl-carrier-protein] reductase [NADH] |
| EC (curated) |
EC 1.3.1.9
|
| Curated function | Enoyl-ACP reductase of the type II fatty acid syntase (FAS-II) system, which is involved in the biosynthesis of mycolic acids, a major component of mycobacterial cell walls. Catalyzes the NADH-dependent reduction of the double bond of 2-trans-enoyl-[acyl-carrier protein], an essential step in the fatty acid elongation cycle of the FAS-II pathway. Shows preference for long-chain fatty acyl thioester substrates (>C16), and can also use 2-trans-enoyl-CoAs as alternative substrates. The mycobacterial FAS-II system utilizes the products of the FAS-I system as primers to extend fatty acyl chain leng. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | inhA |
| eggNOG description | Enoyl- acyl-carrier-protein reductase NADH |
| Orthologous group | COG0623 |
| EC number |
EC 1.3.1.10, EC 1.3.1.9
|
| KEGG orthology |
K00208, K11611
|
| KEGG pathways |
map00061, map00333, map00780, map01100, map01130, map01212
|
| KEGG modules |
M00083, M00572
|
| Gene Ontology (75) |
GO:0000166, GO:0003674, GO:0003824, GO:0004312, GO:0004318, GO:0005488, GO:0005504, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006082 +63 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 | 2.02 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 6 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 |
|---|---|---|---|---|
adh_short_C2 | PF13561.13 | 5.9e-58 | 14–265 | Enoyl-(Acyl carrier protein) reductase |
adh_short | PF00106.32 | 2.3e-11 | 18–198 | short chain dehydrogenase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fas (fatty acid synthase), high confidence from genomic context alone (score 984 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2524c fas |
fatty acid synthase | 994 | 984 ctx | neighborhood:476 coexpression:971 textmining:689 |
Rv1483 fabG1 |
3-oxoacyl-ACP reductase FabG | 997 | 976 ctx | neighborhood:857 coexpression:785 textmining:883 |
Rv0904c accD3 |
acetyl-CoAcarboxylase carboxyl transferase subunit beta | 986 | 974 | coexpression:959 textmining:511 |
Rv1485 hemZ |
ferrochelatase | 904 | 888 ctx | neighborhood:882 |
Rv0533c fabH |
3-oxoacyl-ACP synthase III | 976 | 852 ctx | cooccurence:549 coexpression:646 textmining:850 |
Rv2246 kasB |
3-oxoacyl-ACP synthase 2 | 982 | 840 ctx | cooccurence:477 coexpression:689 textmining:896 |
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 981 | 839 ctx | cooccurence:422 coexpression:707 textmining:890 |
Rv2245 kasA |
3-oxoacyl-ACP synthase 1 | 994 | 836 ctx | cooccurence:466 coexpression:688 textmining:965 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 771 | 688 | coexpression:438 experimental:403 |
Rv2048c pks12 |
polyketide synthase | 769 | 678 | coexpression:420 experimental:403 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 763 | 678 | coexpression:420 experimental:403 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 761 | 675 | coexpression:413 experimental:403 |
Rv1527c pks5 |
polyketide synthase | 761 | 675 | coexpression:413 experimental:403 |
Rv1663 pks17 |
polyketide synthase | 700 | 661 | coexpression:415 experimental:403 |
Rv3800c pks13 |
polyketide synthase | 959 | 601 | experimental:403 textmining:902 |
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: NADH-dependent enoyl-[ACP
- MTBC0 PGAP product: NADH-dependent enoyl-ACP reductase InhA
- Pfam (hmmscan --cut_ga): adh_short_C2 PF13561.13 (E=6e-58), adh_short PF00106.32 (E=2e-11)
- (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_216000.1)
- Domains: Pfam-A via hmmscan --cut_ga — adh_short_C2 (PF13561.13), adh_short (PF00106.32)
- 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
COG0623 - Curated reference: UniProt P9WGR1 (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 —
95 functional partner(s); context anchor
fas - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001587|Rv1484|inhA MTGLLDGKRILVSGIITDSSIAFHIARVAQEQGAQLVLTGFDRLRLIQRITDRLPAKAPLLELDVQNEEHLASLAGRVTEAIGAGNKLDGVVHSIGFMPQTGMGINPFFDAPYADVSKGIHISAYSYASMAKALLPIMNPGGSIVGMDFDPSRAMPAYNWMTVAKSALESVNRFVAREAGKYGVRSNLVAAGPIRTLAMSAIVGGALGEEAGAQIQLLEEGWDQRAPIGWNMKDATPVAKTVCALLSDWLPATTGDIIYADGGAHTQLL