hsaC Resolved · high auto-curated
H37Rv Rv3568c · MTBC0 mtbc0_003787 ·
300 aa · 4032974–4033876 (-) ·
RefSeq NP_218085.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | extradiol dioxygenase |
|---|---|
| MTBC0 PGAP re-annotation | iron-dependent extradiol dioxygenase HsaC |
| Revised (this work) | Iron-dependent extradiol dioxygenase HsaC. Pfam: BphC_D1 (PF22632.3), Glyoxalase (PF00903.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNW7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Iron-dependent extradiol dioxygenase |
| EC (curated) |
EC 1.13.11.25
|
| Curated function | Catalyzes the meta-cleavage of 3,4-dihydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione (3,4-DHSA) to produce 4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oic acid (4,9-DSHA). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | hsaC |
| eggNOG description | Glyoxalase bleomycin resistance protein dioxygenase |
| Orthologous group | COG0346 |
| EC number |
EC 1.13.11.25
|
| KEGG orthology |
K16049
|
| KEGG pathways |
map00984, map01100, map01120, map01220
|
| Gene Ontology (49) |
GO:0003674, GO:0003824, GO:0005488, GO:0005506, GO:0006066, GO:0006629, GO:0006706, GO:0006707, GO:0008150, GO:0008152, GO:0008202, GO:0008203 +37 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 | 0.331 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 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 |
|---|---|---|---|---|
BphC_D1 | PF22632.3 | 4.8e-26 | 6–56 | Dihydroxybiphenyl dioxygenase BphC D1 |
Glyoxalase | PF00903.32 | 3.2e-19 | 143–267 | Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hsaD (4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3569c hsaD |
4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase | 999 | 999 ctx | neighborhood:881 cooccurence:743 coexpression:827 database:900 textmining:873 |
Rv3570c hsaA |
flavin-dependent monooxygenase oxygenase subunit HsaA | 999 | 999 ctx | neighborhood:869 cooccurence:770 coexpression:807 database:900 textmining:883 |
Rv3567c hsaB |
flavin-dependent monooxygenase reductase subunit HsaB | 999 | 998 ctx | neighborhood:869 coexpression:838 database:900 textmining:913 |
Rv3571 kshB |
3-ketosteroid-9-alpha-hydroxylase reductase subunit | 977 | 887 ctx | neighborhood:765 cooccurence:484 textmining:811 |
Rv3537 kstD |
3-oxosteroid 1-dehydrogenase | 955 | 867 ctx | cooccurence:765 textmining:678 |
Rv1817 |
flavoprotein | 848 | 833 ctx | cooccurence:710 |
Rv3526 kshA |
3-ketosteroid-9-alpha-monooxygenase oxygenase subunit | 974 | 802 ctx | cooccurence:774 textmining:878 |
Rv3542c chsH2 hyp |
hypothetical protein | 763 | 761 ctx | cooccurence:756 |
Rv3529c hyp |
hypothetical protein | 739 | 740 ctx | cooccurence:710 |
Rv3527 hyp |
hypothetical protein | 754 | 739 ctx | cooccurence:696 |
Rv3541c chsH1 hyp |
hypothetical protein | 745 | 736 ctx | cooccurence:732 |
Rv3521 hyp |
hypothetical protein | 737 | 736 ctx | cooccurence:733 |
Rv3552 |
CoA-transferase subunit beta | 759 | 729 ctx | cooccurence:719 |
Rv3531c hyp |
hypothetical protein | 728 | 728 ctx | cooccurence:716 |
Rv3551 |
CoA-transferase subunit alpha | 726 | 726 ctx | cooccurence:716 |
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: extradiol dioxygenase
- MTBC0 PGAP product: iron-dependent extradiol dioxygenase HsaC
- Pfam (hmmscan --cut_ga): BphC_D1 PF22632.3 (E=5e-26), Glyoxalase PF00903.32 (E=3e-19)
- (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_218085.1)
- Domains: Pfam-A via hmmscan --cut_ga — BphC_D1 (PF22632.3), Glyoxalase (PF00903.32)
- 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
COG0346 - Curated reference: UniProt P9WNW7 (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 —
76 functional partner(s); context anchor
hsaD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003787|Rv3568c|hsaC MSIRSLGYLRIEATDMAAWREYGLKVLGMVEGKGAPEGALYLRMDDFPARLVVVPGEHDRLLEAGWECANAEGLQEIRNRLDLEGTPYKEATAAELADRRVDEMIRFADPSGNCLEVFHGTALEHRRVVSPYGHRFVTGEQGMGHVVLSTRDDAEALHFYRDVLGFRLRDSMRLPPQMVGRPADGPPAWLRFFGCNPRHHSLAFLPMPTSSGIVHLMVEVEQADDVGLCLDRALRRKVPMSATLGRHVNDLMLSFYMKTPGGFDIEFGCEGRQVDDRDWIARESTAVSLWGHDFTVGARG