hsaA Family assigned · medium auto-curated
H37Rv Rv3570c · MTBC0 mtbc0_003789 ·
394 aa · 4034763–4035947 (-) ·
RefSeq NP_218087.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | flavin-dependent monooxygenase oxygenase subunit HsaA |
|---|---|
| MTBC0 PGAP re-annotation | flavin-dependent monooxygenase oxygenase subunit HsaA |
| Revised (this work) | Flavin-dependent monooxygenase oxygenase subunit HsaA. Pfam: Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_2 (PF08028.17). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJA1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Flavin-dependent monooxygenase, oxygenase subunit HsaA |
| EC (curated) |
EC 1.14.14.12
|
| Curated function | Catalyzes the o-hydroxylation of 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione (3-HSA) to 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione (3,4-DHSA) in the catabolism of cholesterol. Can also use 3,17-dihydroxy-9,10-seconandrost-1,3,5(10)-triene-9-one (3,17-DHSA), but it has higher specificity for 3-HSA than for 3,17-DHSA. Can use either FADH(2) or FMNH(2) as flavin cosubstrate. Also catalyzes the o-hydroxylation of a range of p-substituted phenols to generate the corresponding catechols. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| Preferred name | hsaA |
| eggNOG description | acyl-CoA dehydrogenase |
| Orthologous group | COG1960 |
| EC number |
EC 1.14.14.12
|
| KEGG orthology |
K16047
|
| KEGG pathways |
map00984, map01100, map01120
|
| Gene Ontology (59) |
GO:0000166, GO:0003674, GO:0003824, GO:0004497, GO:0005488, GO:0005575, GO:0005623, GO:0005886, GO:0006066, GO:0006629, GO:0006694, GO:0006706 +47 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 | 0.131 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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 |
|---|---|---|---|---|
Acyl-CoA_dh_N | PF02771.22 | 4.5e-05 | 22–104 | Acyl-CoA dehydrogenase, N-terminal domain |
Acyl-CoA_dh_2 | PF08028.17 | 2.1e-42 | 240–372 | Acyl-CoA dehydrogenase, C-terminal domain |
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:869 cooccurence:770 coexpression:807 database:900 textmining:883 |
Rv3569c hsaD |
4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase | 999 | 994 ctx | neighborhood:869 cooccurence:668 coexpression:862 textmining:870 |
Rv3567c hsaB |
flavin-dependent monooxygenase reductase subunit HsaB | 999 | 992 ctx | neighborhood:858 database:900 textmining:915 |
Rv3571 kshB |
3-ketosteroid-9-alpha-hydroxylase reductase subunit | 945 | 880 ctx | neighborhood:772 cooccurence:472 textmining:563 |
Rv3541c chsH1 hyp |
hypothetical protein | 842 | 837 ctx | cooccurence:690 |
Rv3550 echA20 |
enoyl-CoA hydratase EchA20 | 934 | 809 ctx | cooccurence:572 textmining:670 |
Rv3526 kshA |
3-ketosteroid-9-alpha-monooxygenase oxygenase subunit | 959 | 801 ctx | cooccurence:772 textmining:806 |
Rv3537 kstD |
3-oxosteroid 1-dehydrogenase | 938 | 789 ctx | cooccurence:756 textmining:720 |
Rv0860 fadB |
fatty oxidation protein FadB | 803 | 788 | coexpression:647 |
Rv3531c hyp |
hypothetical protein | 769 | 769 ctx | cooccurence:735 |
Rv3529c hyp |
hypothetical protein | 763 | 764 ctx | cooccurence:726 |
Rv1817 |
flavoprotein | 770 | 750 ctx | cooccurence:710 |
Rv0310c hyp |
hypothetical protein | 744 | 735 ctx | cooccurence:560 |
Rv3522 ltp4 |
lipid transfer protein | 816 | 729 ctx | cooccurence:539 |
Rv3542c chsH2 hyp |
hypothetical protein | 717 | 717 ctx | cooccurence:706 |
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: flavin-dependent monooxygenase oxygenase subunit HsaA
- MTBC0 PGAP product: flavin-dependent monooxygenase oxygenase subunit HsaA
- Pfam (hmmscan --cut_ga): Acyl-CoA_dh_N PF02771.22 (E=5e-05), Acyl-CoA_dh_2 PF08028.17 (E=2e-42)
- (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_218087.1)
- Domains: Pfam-A via hmmscan --cut_ga — Acyl-CoA_dh_N (PF02771.22), Acyl-CoA_dh_2 (PF08028.17)
- 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
COG1960 - Curated reference: UniProt P9WJA1 (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 —
145 functional partner(s); context anchor
hsaC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003789|Rv3570c|hsaA MTSIQQRDAQSVLAAIDDLLPEIRDRAQATEDLRRLPDETVKALDDVGFFTLLQPQQWGGLQCDPALFFEATRRLASVCGSTGWVSSIVGVHNWHLALFDQRAQEEVWGEDPSTRISSSYAPMGAGVVVDGGYLVNGSWNWSSGCDHASWTFVGGPVIKDGRPVDFGSFLIPRSEYEIKDVWYVVGLRGTGSNTLVVKDVFVPRHRFLSYKAMNDHTAGGLATNSAPVYKMPWGTMHPTTISAPIVGMAYGAYAAHVEHQGKRVRAAFAGEKAKDDPFAKVRIAEAASDIDAAWRQLIGNVSDEYALLAAGKEIPFELRARARRDQVRATGRSIASIDRLFEASGATALSNEAPIQRFWRDAHAGRVHAANDPERAYVIFGNHEFGLPPGDTMV