Rv3224 Resolved · high auto-curated
H37Rv Rv3224 · MTBC0 mtbc0_003431 ·
282 aa · 3621993–3622841 (+) ·
RefSeq NP_217740.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | iron-regulated short-chain dehydrogenase/reductase |
|---|---|
| MTBC0 PGAP re-annotation | NAD(P)-dependent oxidoreductase |
| Revised (this work) | NAD(P)-dependent 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 |
O05842
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible iron-regulated short-chain dehydrogenase/reductase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | Dehydrogenase |
| Orthologous group | COG1028 |
| KEGG orthology |
K13775
|
| KEGG pathways |
map00281
|
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 | 0.589 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 7 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 |
|---|---|---|---|---|
adh_short | PF00106.32 | 5.2e-29 | 6–203 | short chain dehydrogenase |
KR | PF08659.17 | 1.9e-07 | 7–132 | KR domain |
adh_short_C2 | PF13561.13 | 3.5e-27 | 12–215 | Enoyl-(Acyl carrier protein) reductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3224B (Rv3224B, len: 72 aa. Conserved hypothetical protein (possibly gene fragment), similar to C-terminal part of ML0799|AL583919_131 conserved hy), high confidence from genomic context alone (score 886 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3224B |
Rv3224B, len: 72 aa. Conserved hypothetical protein (possibly gene fragment), similar to C-terminal part of ML0799|AL583919_131 conserved hy | 886 | 886 ctx | neighborhood:881 |
Rv3224A |
Rv3224A, len: 62 aa. Conserved hypothetical protein (possibly gene fragment), overlaps Rv3224. Similar to N-terminus of ML0799|AL583919_131 | 849 | 849 ctx | neighborhood:781 |
Rv2524c fas |
fatty acid synthase | 829 | 803 | coexpression:513 experimental:475 |
Rv3274c fadE25 |
acyl-CoA dehydrogenase | 747 | 747 | coexpression:624 |
Rv0227c |
membrane protein | 734 | 734 | coexpression:734 |
Rv3223c sigH |
ECF RNA polymerase sigma factor SigH | 722 | 723 ctx | neighborhood:717 |
Rv3221A rshA |
anti-sigma factor RshA | 720 | 721 ctx | neighborhood:717 |
Rv3774 echA21 |
enoyl-CoA hydratase EchA21 | 651 | 639 | coexpression:498 |
Rv2477c ettA |
macrolide ABC transporter ATP-binding protein | 609 | 610 | coexpression:557 |
Rv1098c fum |
fumarate hydratase | 624 | 608 | coexpression:557 |
Rv3221c TB7.3 |
acetyl-CoA carboxylase biotin carboxyl carrier protein subunit | 609 | 595 ctx | neighborhood:591 |
Rv1436 gap |
glyceraldehyde 3-phosphate dehydrogenase | 607 | 591 | coexpression:536 |
Rv1937 |
oxygenase | 591 | 543 | |
Rv2299c htpG |
chaperone protein HtpG | 579 | 541 | database:450 |
Rv2564 glnQ |
glutamine ABC transporter ATP-binding protein | 539 | 518 | 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: iron-regulated short-chain dehydrogenase/reductase
- MTBC0 PGAP product: NAD(P)-dependent oxidoreductase
- Pfam (hmmscan --cut_ga): adh_short PF00106.32 (E=5e-29), KR PF08659.17 (E=2e-07), adh_short_C2 PF13561.13 (E=4e-27)
- (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_217740.1)
- 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 O05842 (TrEMBL, unreviewed; 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 —
115 functional partner(s); context anchor
Rv3224B - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003431|Rv3224| MSLNGKTMFISGASRGIGLAIAKRAARDGANIALIAKTAEPHPKLPGTVFTAAKELEEAGGQALPIVGDIRDPDAVASAVATTVEQFGGIDICVNNASAINLGSITEVPMKRFDLMNGIQVRGTYAVSQACIPHMKGRENPHILTLSPPILLEKKWLRPTAYMMAKYGMTLCALGIAEEMRADGIASNTLWPRTMVATAAVQNLLGGDEAMARSRKPEVYADAAYVIVNKPATEYTGKTLLCEDVLVESGVTDLSVYDCVPGATLGVDLWVEDANPPGYLPA