hsaD Resolved · high auto-curated
H37Rv Rv3569c · MTBC0 mtbc0_003788 ·
291 aa · 4033873–4034748 (-) ·
RefSeq NP_218086.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase |
|---|---|
| MTBC0 PGAP re-annotation | alpha/beta fold hydrolase |
| Revised (this work) | Alpha/beta fold hydrolase. Pfam: Hydrolase_4 (PF12146.16), Abhydrolase_1 (PF00561.27), Abhydrolase_6 (PF12697.14). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNH5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 4,5:9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase |
| EC (curated) |
EC 3.7.1.17, EC 3.7.1.8
|
| Curated function | Catalyzes the hydrolysis of a carbon-carbon bond in 4,5: 9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate (4,9-DSHA) to yield 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oate (DOHNAA) and 2-hydroxy-hexa-2,4-dienoate (HHD). Is also able to catalyze the hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) and the synthetic analog 8-(2-chlorophenyl)-2-hydroxy-5-methyl-6-oxoocta-2,4-dienoic acid (HOPODA). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | hsaD |
| eggNOG description | Alpha beta hydrolase |
| Orthologous group | COG2267 |
| EC number |
EC 3.1.1.24, EC 3.7.1.17
|
| KEGG orthology |
K01055, K16050
|
| KEGG pathways |
map00362, map00984, map01100, map01120, map01220
|
| KEGG modules |
M00568
|
| Gene Ontology (22) |
GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0016787, GO:0016822, GO:0016823, GO:0030312 +10 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 | 0.344 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 2 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 |
|---|---|---|---|---|
Hydrolase_4 | PF12146.16 | 9.1e-15 | 36–274 | Serine aminopeptidase, S33 |
Abhydrolase_1 | PF00561.27 | 3.1e-28 | 38–275 | alpha/beta hydrolase fold |
Abhydrolase_6 | PF12697.14 | 3.4e-21 | 39–280 | Alpha/beta hydrolase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hsaC (extradiol dioxygenase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3568c hsaC |
extradiol dioxygenase | 999 | 999 ctx | neighborhood:881 cooccurence:743 coexpression:827 database:900 textmining:873 |
Rv3570c hsaA |
flavin-dependent monooxygenase oxygenase subunit HsaA | 999 | 994 ctx | neighborhood:869 cooccurence:668 coexpression:862 textmining:870 |
Rv3567c hsaB |
flavin-dependent monooxygenase reductase subunit HsaB | 995 | 963 ctx | neighborhood:869 coexpression:731 textmining:870 |
Rv3561 fadD3 |
fatty-acid--CoA ligase FadD3 | 954 | 923 | database:900 textmining:432 |
Rv3571 kshB |
3-ketosteroid-9-alpha-hydroxylase reductase subunit | 939 | 831 ctx | neighborhood:765 textmining:657 |
Rv3572 hyp |
hypothetical protein | 733 | 734 ctx | neighborhood:731 |
Rv3526 kshA |
3-ketosteroid-9-alpha-monooxygenase oxygenase subunit | 945 | 719 ctx | cooccurence:682 textmining:815 |
Rv3536c hsaE |
hydratase | 886 | 693 | database:500 textmining:645 |
Rv3534c hsaF |
4-hydroxy-2-oxovalerate aldolase | 854 | 587 ctx | cooccurence:543 textmining:663 |
Rv3535c hsaG |
acetaldehyde dehydrogenase | 796 | 573 ctx | cooccurence:501 textmining:542 |
Rv3537 kstD |
3-oxosteroid 1-dehydrogenase | 879 | 565 ctx | cooccurence:557 textmining:733 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 529 | 501 | experimental:441 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 529 | 501 | experimental:441 |
Rv1527c pks5 |
polyketide synthase | 529 | 501 | experimental:441 |
Rv2048c pks12 |
polyketide synthase | 527 | 500 | experimental:441 |
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: 4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase
- MTBC0 PGAP product: alpha/beta fold hydrolase
- Pfam (hmmscan --cut_ga): Hydrolase_4 PF12146.16 (E=9e-15), Abhydrolase_1 PF00561.27 (E=3e-28), Abhydrolase_6 PF12697.14 (E=3e-21)
- (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_218086.1)
- Domains: Pfam-A via hmmscan --cut_ga — Hydrolase_4 (PF12146.16), Abhydrolase_1 (PF00561.27), Abhydrolase_6 (PF12697.14)
- 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
COG2267 - Curated reference: UniProt P9WNH5 (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 —
60 functional partner(s); context anchor
hsaC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003788|Rv3569c|hsaD MTATEELTFESTSRFAEVDVDGPLKLHYHEAGVGNDQTVVLLHGGGPGAASWTNFSRNIAVLARHFHVLAVDQPGYGHSDKRAEHGQFNRYAAMALKGLFDQLGLGRVPLVGNSLGGGTAVRFALDYPARAGRLVLMGPGGLSINLFAPDPTEGVKRLSKFSVAPTRENLEAFLRVMVYDKNLITPELVDQRFALASTPESLTATRAMGKSFAGADFEAGMMWREVYRLRQPVLLIWGREDRVNPLDGALVALKTIPRAQLHVFGQCGHWVQVEKFDEFNKLTIEFLGGGR