choD Resolved · high auto-curated
H37Rv Rv3409c · MTBC0 mtbc0_003623 ·
578 aa · 3852430–3854166 (-) ·
RefSeq NP_217926.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cholesterol oxidase |
|---|---|
| MTBC0 PGAP re-annotation | cholesterol oxidase |
| Revised (this work) | Cholesterol oxidase. Pfam: FAD_binding_2 (PF00890.31), NAD_binding_8 (PF13450.13), GMC_oxred_N (PF00732.26), GMC_oxred_C (PF05199.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WMV9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cholesterol oxidase |
| EC (curated) |
EC 1.1.3.6, EC 5.3.3.1
|
| Curated function | Bifunctional enzyme that catalyzes the oxidation and isomerization of cholesterol to cholestenone (cholest-4-en-3-one), an initial step in the cholesterol degradation process. Contributes to virulence. ChoD does not appear to play an essential role in cholesterol degradation in M.tuberculosis, and is probably important for pathogenesis not as a cholesterol-degrading enzyme, but rather as a virulence factor. Required for interference with the host Toll-like receptor 2 (TLR2)-mediated signaling pathway and subsequent intracellular growth and survival of the pathogen in human macrophages. Acts as. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | choD |
| eggNOG description | oxidoreductase |
| Orthologous group | COG2303 |
| EC number |
EC 1.1.3.6
|
| KEGG orthology |
K03333
|
| KEGG pathways |
map00984, map01120
|
| Gene Ontology (12) |
GO:0003674, GO:0003824, GO:0008150, GO:0008152, GO:0009405, GO:0016491, GO:0016614, GO:0016899, GO:0016995, GO:0044419, GO:0051704, GO:0055114
|
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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 0 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.23% of strains (330) · 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 |
|---|---|---|---|---|
FAD_binding_2 | PF00890.31 | 3.1e-04 | 6–39 | FAD binding domain |
NAD_binding_8 | PF13450.13 | 5.5e-05 | 9–39 | NAD(P)-binding Rossmann-like domain |
GMC_oxred_N | PF00732.26 | 5.0e-05 | 190–277 | GMC oxidoreductase |
GMC_oxred_C | PF05199.20 | 1.5e-10 | 468–522 | GMC oxidoreductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: guaB2 (inosine-5'-monophosphate dehydrogenase), high confidence from genomic context alone (score 794 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1106c |
3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase | 987 | 900 | database:900 textmining:875 |
Rv3518c cyp142 |
cytochrome P450 monooxygenase Cyp142 | 944 | 900 | database:900 textmining:471 |
Rv3545c cyp125 |
steroid C26-monooxygenase | 933 | 900 | database:900 |
Rv3411c guaB2 |
inosine-5'-monophosphate dehydrogenase | 806 | 794 ctx | neighborhood:791 |
Rv2194 qcrC |
ubiquinol-cytochrome C reductase cytochrome subunit C | 787 | 776 | experimental:762 |
Rv2267c stf3 hyp |
hypothetical protein | 755 | 744 | experimental:411 database:583 |
Rv3529c hyp |
hypothetical protein | 754 | 744 | experimental:411 database:583 |
Rv1691 hyp |
hypothetical protein | 754 | 744 | experimental:411 database:583 |
Rv2328 PE23 |
PE family protein PE23 | 739 | 729 | database:573 |
Rv3812 PE_PGRS62 |
PE-PGRS family protein PE_PGRS62 | 739 | 729 | database:573 |
Rv3036c TB22.2 hyp |
hypothetical protein | 739 | 729 | database:573 |
Rv0832 PE_PGRS12 |
PE-PGRS family protein PE_PGRS12 | 739 | 729 | database:573 |
Rv0200 |
transmembrane protein | 698 | 687 | database:536 |
Rv3410c guaB3 |
oxidoreductase | 720 | 685 ctx | neighborhood:682 |
Rv0178 |
Mce associated membrane protein | 694 | 682 | database:536 |
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: cholesterol oxidase
- MTBC0 PGAP product: cholesterol oxidase
- Pfam (hmmscan --cut_ga): FAD_binding_2 PF00890.31 (E=3e-04), NAD_binding_8 PF13450.13 (E=6e-05), GMC_oxred_N PF00732.26 (E=5e-05), GMC_oxred_C PF05199.20 (E=1e-10)
- (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_217926.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_2 (PF00890.31), NAD_binding_8 (PF13450.13), GMC_oxred_N (PF00732.26), GMC_oxred_C (PF05199.20)
- 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
COG2303 - Curated reference: UniProt P9WMV9 (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 —
41 functional partner(s); context anchor
guaB2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003623|Rv3409c|choD MKPDYDVLIIGSGFGGSVTALRLTEKGYRVGVLEAGRRFSDEEFAKTSWDLRKFLWAPRLGCYGIQRIHPLRNVMILAGAGVGGGSLNYANTLYVPPEPFFADQQWSHITDWRGELMPHYQQAQRMLGVVQNPTFTDADRIVKEVADEMGFGDTWVPTPVGVFFGPDGTKTPGKTVPDPYFGGAGPARTGCLECGCCMTGCRHGAKNTLVKNYLGLAESAGAQVIPMTTVKGFERRSDGLWEVRTVRTGSWLRRDRRTFTATQLVLAAGTWGTQHLLFKMRDRGRLPGLSKRLGVLTRTNSESIVGAATLKVNPDLDLTHGVAITSSIHPTADTHIEPVRYGKGSNAMGLLQTLMTDGSGPQGTDVPRWRQLLQTASQDPRGTIRMLNPRQWSERTVIALVMQHLDNSITTFTKRGKLGIRWYSSKQGHGEPNPTWIPIGNQVTRRIAAKIDGVAGGTWGELFNIPLTAHFLGGAVIGDDPEHGVIDPYHRVYGYPTLYVVDGAAISANLGVNPSLSIAAQAERAASLWPNKGETDRRPPQGEPYRRLAPIQPAHPVVPADAPGALRWLPIDPVSNAG