Rv1106c Resolved · high auto-curated

H37Rv Rv1106c · MTBC0 mtbc0_001188 · 370 aa · 1241284–1242396 (-) · RefSeq NP_215622.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase
MTBC0 PGAP re-annotation3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase
Revised (this work)3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase. Pfam: KR (PF08659.17), RmlD_sub_bind (PF04321.24), NmrA (PF05368.20), Epimerase (PF01370.28), Polysacc_synt_2 (PF02719.22), 3Beta_HSD (PF01073.26), GDP_Man_Dehyd (PF16363.12), NAD_binding_10 (PF13460.13), NAD_binding_4 (PF07993.19).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WQP7 SwissProt · reviewed · Evidence at protein level
UniProt name3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase
EC (curated) EC 1.1.1.145, EC 5.3.3.1
Curated function3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidation and isomerization of cholesterol, pregnenolone, and dehydroepiandrosterone (DHEA) into cholest-4-en-3-one, progesterone, and androsterone, respectively.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
eggNOG description3-beta hydroxysteroid dehydrogenase isomerase
Orthologous groupCOG0451
EC number EC 1.1.1.145, EC 1.1.1.412, EC 5.3.3.1
KEGG orthology K16045, K22320
KEGG pathways map00984, map01120
Gene Ontology (44) GO:0000166, GO:0003674, GO:0003824, GO:0003854, GO:0004769, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +32 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 0.112 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 2 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.62% of strains (905) · 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)

PfamAccessioni-EvalueResiduesDescription
KRPF08659.17 6.2e-0615–139 KR domain
RmlD_sub_bindPF04321.24 3.2e-1216–273 RmlD substrate binding domain
NmrAPF05368.20 5.5e-0916–131 NmrA-like family
EpimerasePF01370.28 2.1e-3117–238 NAD dependent epimerase/dehydratase family
Polysacc_synt_2PF02719.22 5.5e-0717–136 Polysaccharide biosynthesis protein
3Beta_HSDPF01073.26 3.0e-5718–277 3-beta hydroxysteroid dehydrogenase/isomerase family
GDP_Man_DehydPF16363.12 1.1e-1518–342 GDP-mannose 4,6 dehydratase
NAD_binding_10PF13460.13 2.5e-1521–134 NAD(P)H-binding
NAD_binding_4PF07993.19 1.1e-0953–221 Male sterility protein

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: xseB (exodeoxyribonuclease VII small subunit), high confidence from genomic context alone (score 884 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3518c cyp142 cytochrome P450 monooxygenase Cyp142 968 917 database:900 textmining:633
Rv3545c cyp125 steroid C26-monooxygenase 960 917 database:900 textmining:546
Rv3409c choD cholesterol oxidase 987 900 database:900 textmining:875
Rv1107c xseB exodeoxyribonuclease VII small subunit 888 884 ctx neighborhood:882
Rv1108c xseA exodeoxyribonuclease VII large subunit 883 883 ctx neighborhood:882
Rv1109c hyp hypothetical protein 882 882 ctx neighborhood:882
Rv0705 rpsS 30S ribosomal protein S19 817 817 experimental:463 database:574
Rv0682 rpsL 30S ribosomal protein S12 814 806 experimental:463 database:573
Rv0710 rpsQ 30S ribosomal protein S17 804 798 experimental:463 database:578
Rv0707 rpsC 30S ribosomal protein S3 803 796 experimental:463 database:578
Rv0721 rpsE 30S ribosomal protein S5 797 790 experimental:463 database:575
Rv2056c rpsN2 30S ribosomal protein S14 788 788 experimental:436 database:548
Rv0717 rpsN1 30S ribosomal protein S14 788 788 experimental:436 database:548
Rv0718 rpsH 30S ribosomal protein S8 793 786 experimental:463 database:578
Rv0700 rpsJ 30S ribosomal protein S10 789 785 experimental:463 database:557

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 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase
  • MTBC0 PGAP product: 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase
  • Pfam (hmmscan --cut_ga): KR PF08659.17 (E=6e-06), RmlD_sub_bind PF04321.24 (E=3e-12), NmrA PF05368.20 (E=5e-09), Epimerase PF01370.28 (E=2e-31), Polysacc_synt_2 PF02719.22 (E=6e-07), 3Beta_HSD PF01073.26 (E=3e-57), GDP_Man_Dehyd PF16363.12 (E=1e-15), NAD_binding_10 PF13460.13 (E=2e-15), NAD_binding_4 PF07993.19 (E=1e-09)
  • (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_215622.1)
  • Domains: Pfam-A via hmmscan --cut_ga — KR (PF08659.17), RmlD_sub_bind (PF04321.24), NmrA (PF05368.20), Epimerase (PF01370.28), Polysacc_synt_2 (PF02719.22), 3Beta_HSD (PF01073.26), GDP_Man_Dehyd (PF16363.12), NAD_binding_10 (PF13460.13), NAD_binding_4 (PF07993.19)
  • 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 COG0451
  • Curated reference: UniProt P9WQP7 (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 — 92 functional partner(s); context anchor xseB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001188|Rv1106c|
MLRRMGDASLTTELGRVLVTGGAGFVGANLVTTLLDRGHWVRSFDRAPSLLPAHPQLEVLQGDITDADVCAAAVDGIDTIFHTAAIIELMGGASVTDEYRQRSFAVNVGGTENLLHAGQRAGVQRFVYTSSNSVVMGGQNIAGGDETLPYTDRFNDLYTETKVVAERFVLAQNGVDGMLTCAIRPSGIWGNGDQTMFRKLFESVLKGHVKVLVGRKSARLDNSYVHNLIHGFILAAAHLVPDGTAPGQAYFINDAEPINMFEFARPVLEACGQRWPKMRISGPAVRWVMTGWQRLHFRFGFPAPLLEPLAVERLYLDNYFSIAKARRDLGYEPLFTTQQALTECLPYYVSLFEQMKNEARAEKTAATVKP