Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-alpha(or 20-beta)-hydroxysteroid dehydrogenase |
|---|
| MTBC0 PGAP re-annotation | SDR family oxidoreductase |
|---|
| Revised (this work) | SDR family oxidoreductase. Pfam: adh_short (PF00106.32), KR (PF08659.17), adh_short_C2 (PF13561.13). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WGT1
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | 3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase |
|---|
| EC (curated) |
EC 1.1.1.53
|
|---|
| Curated function | Probably involved in steroid metabolism. Catalyzes the oxidation of androsterone (3alpha-hydroxy-5alpha-androstan-17-one) and 20beta-hydroxyprogesterone (4-pregnen-20beta-ol-3-one), and the reduction of progesterone (4-pregnen-3,20-dione). Shows a preference for NADH. Has no detectable activity for oxidation of L-3-hydroxybutyric acid and only an insignificant activity for reduction of acetoacetyl-CoA. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|
| Preferred name | fabG3 |
|---|
| eggNOG description | Dehydrogenase |
|---|
| Orthologous group | COG1028 |
|---|
| EC number |
EC 1.1.1.53
|
|---|
| KEGG orthology |
K00038
|
|---|
| KEGG pathways |
map00140, map01100
|
|---|
| Gene Ontology (22) |
GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006629, GO:0008150, GO:0008152, GO:0008202, GO:0016020, GO:0016229, GO:0016491 +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 |
0.175 · strong purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
4 synonymous, 2 missense, 0 nonsense, 1 frameshift
|
|---|
| Disruption |
1 distinct premature-stop/frameshift site(s); most common in
0.14% of strains
(203) · clonal
|
|---|
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 |
|---|
adh_short | PF00106.32 |
1.1e-56 | 8–193 |
short chain dehydrogenase |
KR | PF08659.17 |
2.3e-09 | 10–164 |
KR domain |
adh_short_C2 | PF13561.13 |
2.8e-60 | 16–237 |
Enoyl-(Acyl carrier protein) reductase |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv2524c fas |
fatty acid synthase |
827 |
802 |
coexpression:509 experimental:475 |
Rv2000 hyp |
hypothetical protein |
650 |
650 ctx |
neighborhood:605 |
Rv2001 hyp |
hypothetical protein |
636 |
630 ctx |
neighborhood:611 |
Rv2299c htpG |
chaperone protein HtpG |
621 |
605 |
database:450 |
Rv1937 |
oxygenase |
591 |
543 |
|
Rv2564 glnQ |
glutamine ABC transporter ATP-binding protein |
553 |
532 |
database:431 |
Rv0073 |
glutamine ABC transporter ATP-binding protein |
533 |
512 |
database:431 |
Rv3239c |
transmembrane transport protein |
534 |
509 |
database:431 |
Rv3728 |
membrane protein |
531 |
506 |
database:431 |
Rv2565 |
NTE family protein |
520 |
501 |
database:431 |
Rv2434c |
transmembrane protein |
515 |
496 |
database:431 |
Rv2946c pks1 |
polyketide synthase |
534 |
488 |
|
Rv3676 crp |
cAMP receptor protein |
489 |
488 |
database:431 |
Rv0998 |
acetyltransferase Pat |
488 |
487 |
database:431 |
Rv0104 hyp |
hypothetical protein |
488 |
487 |
database:431 |
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-alpha(or 20-beta)-hydroxysteroid dehydrogenase
- MTBC0 PGAP product: SDR family oxidoreductase
- Pfam (hmmscan --cut_ga): adh_short PF00106.32 (E=1e-56), KR PF08659.17 (E=2e-09), adh_short_C2 PF13561.13 (E=3e-60)
- (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_216518.1)
- Domains: Pfam-A via hmmscan --cut_ga — adh_short (PF00106.32), KR (PF08659.17), adh_short_C2 (PF13561.13)
- 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
COG1028
- Curated reference: UniProt
P9WGT1
(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 —
85 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002129|Rv2002|fabG3
MSGRLIGKVALVSGGARGMGASHVRAMVAEGAKVVFGDILDEEGKAVAAELADAARYVHLDVTQPAQWTAAVDTAVTAFGGLHVLVNNAGILNIGTIEDYALTEWQRILDVNLTGVFLGIRAVVKPMKEAGRGSIINISSIEGLAGTVACHGYTATKFAVRGLTKSTALELGPSGIRVNSIHPGLVKTPMTDWVPEDIFQTALGRAAEPVEVSNLVVYLASDESSYSTGAEFVVDGGTVAGLAHNDFGAVEVSSQPEWVT
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