kstD Resolved · high auto-curated
H37Rv Rv3537 · MTBC0 mtbc0_003754 ·
563 aa · 3999046–4000737 (+) ·
RefSeq NP_218054.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-oxosteroid 1-dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | 3-oxosteroid 1-dehydrogenase |
| Revised (this work) | 3-oxosteroid 1-dehydrogenase. Pfam: FAD_binding_3 (PF01494.26), FAD_binding_2 (PF00890.31), FAD_oxidored (PF12831.14), DAO (PF01266.31), NAD_binding_8 (PF13450.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71864
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-oxosteroid 1-dehydrogenase |
| EC (curated) |
EC 1.3.99.4
|
| Curated function | Involved in the degradation of cholesterol. Catalyzes the elimination of the C-1 and C-2 hydrogen atoms of the A-ring from the polycyclic ring structure of 3-ketosteroids. Has a clear preference for 3-ketosteroids with a saturated A-ring, displaying highest activity on 5alpha-AD (5alpha-androstane-3,17-dione) and 5alpha-T (5alpha-testosterone, also known as 17beta-hydroxy-5alpha-androstane-3-one). Is also involved in the formation of 3-keto-1,4-diene-steroid from 3-keto-4-ene-steroid. Catalyzes the conversion of 3-oxo-23,24-bisnorchol-4-en-22-oyl-coenzyme A thioester (4-BNC-CoA) to 3-oxo-23,24. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | kstD |
| eggNOG description | Succinate dehydrogenase fumarate reductase flavoprotein subunit |
| Orthologous group | COG1053 |
| EC number |
EC 1.3.99.4
|
| KEGG orthology |
K05898
|
| KEGG pathways |
map00984, map01100, map01120
|
| Gene Ontology (42) |
GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006066, GO:0006629, GO:0006694, GO:0006706, GO:0006707, GO:0008150, GO:0008152 +30 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 | 0.417 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 5 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 |
|---|---|---|---|---|
FAD_binding_3 | PF01494.26 | 1.4e-05 | 6–93 | FAD binding domain |
FAD_binding_2 | PF00890.31 | 1.6e-86 | 7–541 | FAD binding domain |
FAD_oxidored | PF12831.14 | 4.6e-11 | 7–82 | FAD dependent oxidoreductase |
DAO | PF01266.31 | 7.8e-09 | 7–52 | FAD dependent oxidoreductase |
NAD_binding_8 | PF13450.13 | 4.6e-06 | 10–45 | NAD(P)-binding Rossmann-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3538 (dehydrogenase), high confidence from genomic context alone (score 981 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3538 |
dehydrogenase | 980 | 981 ctx | neighborhood:882 coexpression:818 |
Rv3526 kshA |
3-ketosteroid-9-alpha-monooxygenase oxygenase subunit | 998 | 978 ctx | cooccurence:753 database:900 textmining:932 |
Rv3316 sdhC |
succinate dehydrogenase cytochrome B-556 subunit | 962 | 959 | coexpression:650 experimental:707 database:621 |
Rv0760c hyp |
hypothetical protein | 940 | 938 ctx | cooccurence:404 database:900 |
Rv3571 kshB |
3-ketosteroid-9-alpha-hydroxylase reductase subunit | 992 | 936 | database:900 textmining:895 |
Rv1817 |
flavoprotein | 947 | 935 | database:900 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 937 | 918 | coexpression:894 |
Rv3319 sdhB |
succinate dehydrogenase iron-sulphur protein subunit | 881 | 875 | coexpression:484 experimental:454 database:578 |
Rv0247c |
succinate dehydrogenase iron-sulfur subunit | 881 | 875 | coexpression:484 experimental:454 database:578 |
Rv1553 frdB |
fumarate reductase iron-sulfur subunit | 881 | 875 | coexpression:487 experimental:454 database:578 |
Rv3568c hsaC |
extradiol dioxygenase | 955 | 867 ctx | cooccurence:765 textmining:678 |
Rv3540c ltp2 |
lipid transfer protein | 848 | 815 ctx | cooccurence:546 database:500 |
Rv3534c hsaF |
4-hydroxy-2-oxovalerate aldolase | 929 | 808 ctx | neighborhood:607 coexpression:443 textmining:648 |
Rv3535c hsaG |
acetaldehyde dehydrogenase | 892 | 808 ctx | neighborhood:673 textmining:465 |
Rv3317 sdhD |
succinate dehydrogenase hydrophobic membrane anchor subunit | 812 | 797 | coexpression:647 experimental:430 |
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: 3-oxosteroid 1-dehydrogenase
- MTBC0 PGAP product: 3-oxosteroid 1-dehydrogenase
- Pfam (hmmscan --cut_ga): FAD_binding_3 PF01494.26 (E=1e-05), FAD_binding_2 PF00890.31 (E=2e-86), FAD_oxidored PF12831.14 (E=5e-11), DAO PF01266.31 (E=8e-09), NAD_binding_8 PF13450.13 (E=5e-06)
- (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_218054.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_3 (PF01494.26), FAD_binding_2 (PF00890.31), FAD_oxidored (PF12831.14), DAO (PF01266.31), NAD_binding_8 (PF13450.13)
- 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
COG1053 - Curated reference: UniProt P71864 (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 —
110 functional partner(s); context anchor
Rv3538 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003754|Rv3537|kstD MTVQEFDVVVVGSGAAGMVAALVAAHRGLSTVVVEKAPHYGGSTARSGGGVWIPNNEVLKRRGVRDTPEAARTYLHGIVGEIVEPERIDAYLDRGPEMLSFVLKHTPLKMCWVPGYSDYYPEAPGGRPGGRSIEPKPFNARKLGADMAGLEPAYGKVPLNVVVMQQDYVRLNQLKRHPRGVLRSMKVGARTMWAKATGKNLVGMGRALIGPLRIGLQRAGVPVELNTAFTDLFVENGVVSGVYVRDSHEAESAEPQLIRARRGVILACGGFEHNEQMRIKYQRAPITTEWTVGASANTGDGILAAEKLGAALDLMDDAWWGPTVPLVGKPWFALSERNSPGSIIVNMSGKRFMNESMPYVEACHHMYGGEHGQGPGPGENIPAWLVFDQRYRDRYIFAGLQPGQRIPSRWLDSGVIVQADTLAELAGKAGLPADELTATVQRFNAFARSGVDEDYHRGESAYDRYYGDPSNKPNPNLGEVGHPPYYGAKMVPGDLGTKGGIRTDVNGRALRDDGSIIDGLYAAGNVSAPVMGHTYPGPGGTIGPAMTFGYLAALHIADQAGKR