hsaF Resolved · high auto-curated
H37Rv Rv3534c · MTBC0 mtbc0_003751 ·
346 aa · 3996229–3997269 (-) ·
RefSeq NP_218051.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 4-hydroxy-2-oxovalerate aldolase |
|---|---|
| MTBC0 PGAP re-annotation | 4-hydroxy-2-oxovalerate aldolase |
| Revised (this work) | 4-hydroxy-2-oxovalerate aldolase. Pfam: HMGL-like (PF00682.26), DmpG_comm (PF07836.17). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMK5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 4-hydroxy-2-oxohexanoate aldolase |
| EC (curated) |
EC 4.1.3.39, EC 4.1.3.43
|
| Curated function | Involved in cholesterol degradation. Catalyzes the retro-aldol cleavage of 4-hydroxy-2-oxohexanoate (HOHA) to pyruvate and propanal. Can also catalyze the cleavage of 4-hydroxy-2-oxopentanoate (HOPA) to pyruvate and acetaldehyde. The aldehydes produced by this reaction are directly channeled to the dehydrogenase HsaG. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | bphI |
| eggNOG description | Catalyzes the retro-aldol cleavage of 4-hydroxy-2- oxopentanoate to pyruvate and acetaldehyde. Is involved in the meta-cleavage pathway for the degradation of aromatic compounds |
| Orthologous group | COG0119 |
| EC number |
EC 4.1.3.39
|
| KEGG orthology |
K01666
|
| KEGG pathways |
map00360, map00362, map00621, map00622, map01100, map01120, map01220
|
| KEGG modules |
M00545, M00569
|
| Gene Ontology (6) |
GO:0005575, GO:0005618, GO:0005623, 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 | 0.058 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 23 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 |
|---|---|---|---|---|
HMGL-like | PF00682.26 | 1.7e-45 | 7–265 | HMGL-like |
DmpG_comm | PF07836.17 | 2.0e-27 | 275–335 | DmpG-like communication domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hsaG (acetaldehyde dehydrogenase), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3535c hsaG |
acetaldehyde dehydrogenase | 999 | 1000 ctx | neighborhood:881 cooccurence:774 coexpression:802 experimental:999 database:900 textmining:932 |
Rv3536c hsaE |
hydratase | 999 | 998 ctx | neighborhood:879 cooccurence:771 database:900 textmining:880 |
Rv3469c mhpE |
4-hydroxy-2-oxovalerate aldolase MhpE | 923 | 923 | database:900 |
Rv3538 |
dehydrogenase | 920 | 918 ctx | neighborhood:606 coexpression:659 database:436 |
Rv3537 kstD |
3-oxosteroid 1-dehydrogenase | 929 | 808 ctx | neighborhood:607 coexpression:443 textmining:648 |
Rv2995c leuB |
3-isopropylmalate dehydrogenase | 763 | 738 | coexpression:696 |
Rv2988c leuC |
3-isopropylmalate dehydratase large subunit | 734 | 706 | coexpression:695 |
Rv2987c leuD |
3-isopropylmalate dehydratase small subunit | 733 | 704 | coexpression:693 |
Rv3001c ilvC |
ketol-acid reductoisomerase | 733 | 704 | coexpression:693 |
Rv0189c ilvD |
dihydroxy-acid dehydratase | 697 | 665 | coexpression:652 |
Rv2210c ilvE |
branched-chain amino acid aminotransferase | 682 | 662 | coexpression:607 |
Rv0812 |
4-amino-4-deoxychorismate lyase | 682 | 662 | coexpression:607 |
Rv3570c hsaA |
flavin-dependent monooxygenase oxygenase subunit HsaA | 872 | 628 | textmining:671 |
Rv1820 ilvG |
acetolactate synthase large subunit IlvG | 625 | 606 | |
Rv3003c ilvB1 |
acetolactate synthase large subunit IlvB | 624 | 605 |
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: 4-hydroxy-2-oxovalerate aldolase
- MTBC0 PGAP product: 4-hydroxy-2-oxovalerate aldolase
- Pfam (hmmscan --cut_ga): HMGL-like PF00682.26 (E=2e-45), DmpG_comm PF07836.17 (E=2e-27)
- (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_218051.1)
- Domains: Pfam-A via hmmscan --cut_ga — HMGL-like (PF00682.26), DmpG_comm (PF07836.17)
- 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
COG0119 - Curated reference: UniProt P9WMK5 (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 —
124 functional partner(s); context anchor
hsaG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003751|Rv3534c|hsaF MTDMWDVRITDTSLRDGSHHKRHQFTKDEVGAIVAALDAAGVPVIEVTHGDGLGGSSFNYGFSKTPEQELIKLAAATAKEARIAFLMLPGVGTKDDIKEARDNGGSICRIATHCTEADVSIQHFGLARELGLETVGFLMMAHTIAPEKLAAQARIMADAGCQCVYVVDSAGALVLDGVADRVSALVAELGEDAQVGFHGHENLGLGVANSVAAVRAGAKQIDGSCRRFGAGAGNAPVEALIGVFDKIGVKTGIDFFDIADAAEDVVRPAMPAECLLDRNALIMGYSGVYSSFLKHAVRQAERYGVPASALLHRAGQRKLIGGQEDQLIDIALEIKRELDSGAAVTH