cmrA Resolved · high auto-curated
H37Rv Rv2509 · MTBC0 mtbc0_002671 ·
268 aa · 2847568–2848374 (+) ·
RefSeq NP_217025.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | short-chain type dehydrogenase/reductase |
|---|---|
| MTBC0 PGAP re-annotation | mycolate reductase |
| Revised (this work) | Mycolate reductase. 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 |
I6Y9I3
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable short-chain type dehydrogenase/reductase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| Preferred name | cmrA |
| eggNOG description | Dehydrogenase |
| Orthologous group | COG0300 |
| KEGG orthology |
K07124
|
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 | 0.498 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 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 | 1.2e-37 | 12–196 | short chain dehydrogenase |
KR | PF08659.17 | 2.8e-10 | 12–190 | KR domain |
adh_short_C2 | PF13561.13 | 1.9e-23 | 16–197 | Enoyl-(Acyl carrier protein) reductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2508c (integral membrane protein), high confidence from genomic context alone (score 784 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2508c |
integral membrane protein | 784 | 784 ctx | neighborhood:783 |
Rv3802c |
membrane protein | 621 | 602 ctx | cooccurence:599 |
Rv3549c |
short-chain type dehydrogenase/reductase | 606 | 591 ctx | cooccurence:536 |
Rv3530c |
oxidoreductase | 587 | 572 ctx | cooccurence:514 |
Rv2673 aftC |
alpha-(1->3)-arabinofuranosyltransferase | 571 | 572 ctx | cooccurence:567 |
Rv1882c |
short-chain type dehydrogenase/reductase | 553 | 553 ctx | cooccurence:544 |
Rv1865c |
short-chain type dehydrogenase | 527 | 527 ctx | cooccurence:527 |
Rv0687 |
NAD-dependent oxidoreductase | 560 | 523 ctx | cooccurence:458 |
Rv1350 fabG2 |
3-oxoacyl-ACP reductase FabG | 688 | 510 ctx | cooccurence:443 |
Rv3559c |
oxidoreductase | 522 | 504 ctx | cooccurence:435 |
Rv3794 embA |
arabinosyltransferase A | 508 | 488 ctx | cooccurence:468 |
Rv3793 embC |
arabinosyltransferase C | 497 | 477 ctx | cooccurence:455 |
Rv3795 embB |
arabinosyltransferase B | 494 | 474 ctx | cooccurence:454 |
Rv3805c aftB |
terminal beta-(1->2)-arabinofuranosyltransferase | 483 | 464 ctx | cooccurence:445 |
Rv1714 |
oxidoreductase | 476 | 463 |
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: short-chain type dehydrogenase/reductase
- MTBC0 PGAP product: mycolate reductase
- Pfam (hmmscan --cut_ga): adh_short PF00106.32 (E=1e-37), KR PF08659.17 (E=3e-10), adh_short_C2 PF13561.13 (E=2e-23)
- (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_217025.1)
- 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
COG0300 - Curated reference: UniProt I6Y9I3 (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 —
30 functional partner(s); context anchor
Rv2508c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002671|Rv2509|cmrA MPIPAPSPDARAVVTGASQNIGAALATELAARGHHLIVTARREDVLTELAARLADKYRVTVDVRPADLADPQERSKLADELAARPISILCANAGTATFGPIASLDLAGEKTQVQLNAVAVHDLTLAVLPGMIERKAGGILISGSAAGNSPIPYNATYAATKAFVNTFSESLRGELRGSGVHVTVLAPGPVRTELPDASEASLVEKLVPDFLWISTEHTARVSLNALERNKMRVVPGLTSKAMSVASQYAPRAIVAPIVGAFYKRLGGS