Rv3433c Resolved · high auto-curated
H37Rv Rv3433c · MTBC0 mtbc0_003652 ·
473 aa · 3877678–3879099 (-) ·
RefSeq NP_217950.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase |
|---|---|
| MTBC0 PGAP re-annotation | NAD(P)H-hydrate dehydratase |
| Revised (this work) | NAD(P)H-hydrate dehydratase. Pfam: YjeF_N (PF03853.22), Carb_kinase (PF01256.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WF11
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Bifunctional NAD(P)H-hydrate repair enzyme Nnr |
| EC (curated) |
EC 4.2.1.136, EC 5.1.99.6
|
| Curated function | Bifunctional enzyme that catalyzes the epimerization of the S- and R-forms of NAD(P)HX and the dehydration of the S-form of NAD(P)HX at the expense of ADP, which is converted to AMP. This allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
G Carbohydrate transport and metabolism
|
|---|---|
| Preferred name | nnrD |
| eggNOG description | Bifunctional enzyme that catalyzes the epimerization of the S- and R-forms of NAD(P)HX and the dehydration of the S-form of NAD(P)HX at the expense of ADP, which is converted to AMP. This allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration |
| Orthologous group | COG0062 |
| EC number |
EC 4.2.1.136, EC 5.1.99.6
|
| KEGG orthology |
K17758, K17759
|
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 | 0.105 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 23 synonymous, 6 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 |
|---|---|---|---|---|
YjeF_N | PF03853.22 | 3.0e-33 | 25–182 | YjeF-related protein N-terminus |
Carb_kinase | PF01256.23 | 2.1e-76 | 234–462 | NAD(P)H-hydrate dehydratase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gadB (glutamate decarboxylase GadB), high confidence from genomic context alone (score 906 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1700 |
NUDIX hydrolase | 952 | 946 | experimental:787 database:643 |
Rv3672c hyp |
hypothetical protein | 941 | 933 | experimental:787 database:643 |
Rv2609c |
membrane protein | 941 | 933 | experimental:787 database:643 |
Rv3211 rhlE |
ATP-dependent RNA helicase RhlE | 934 | 927 | experimental:781 database:659 |
Rv1253 deaD |
ATP-dependent RNA helicase DeaD | 933 | 926 | experimental:781 database:659 |
Rv3432c gadB |
glutamate decarboxylase GadB | 910 | 906 ctx | neighborhood:829 coexpression:408 |
Rv3434c |
transmembrane protein | 945 | 883 ctx | neighborhood:882 textmining:550 |
Rv3422c tsaE |
tRNA threonylcarbamoyladenosine biosynthesis protein | 885 | 805 ctx | neighborhood:544 coexpression:412 textmining:438 |
Rv3435c |
transmembrane protein | 828 | 797 ctx | neighborhood:796 |
Rv3417c groEL1 |
chaperonin GroEL | 734 | 735 | coexpression:648 |
Rv0440 groEL2 |
molecular chaperone GroEL | 730 | 730 | coexpression:648 |
Rv2524c fas |
fatty acid synthase | 749 | 725 ctx | neighborhood:541 coexpression:425 |
Rv3423c alr |
alanine racemase | 690 | 691 ctx | neighborhood:544 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 681 | 681 ctx | neighborhood:534 |
Rv3148 nuoD |
NADH-quinone oxidoreductase subunit D | 692 | 678 | experimental:465 |
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: bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase
- MTBC0 PGAP product: NAD(P)H-hydrate dehydratase
- Pfam (hmmscan --cut_ga): YjeF_N PF03853.22 (E=3e-33), Carb_kinase PF01256.23 (E=2e-76)
- (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_217950.1)
- Domains: Pfam-A via hmmscan --cut_ga — YjeF_N (PF03853.22), Carb_kinase (PF01256.23)
- 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
COG0062 - Curated reference: UniProt P9WF11 (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 —
140 functional partner(s); context anchor
gadB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003652|Rv3433c| MRHYYSVDTIRAAEAPLLASLPDGALMRRAAFGLATEIGRELTARTGGVVGRRVCAVVGSGDNGGDALWAATFLRRRGAAADAVLLNPDRTHRKALAAFTKSGGRLVESVSAATDLVIDGVVGISGSGPLRPAAAQVFAAVQAAAIPVVAVDIPSGIDVATGAITGPAVHAALTVTFGGLKPVHALADCGRVVLVDIGLDLAHTDVLGFEATDVAARWPVPGPRDDKYTQGVTGVLAGSSTYPGAAVLCTGAAVAATSGMVRYAGTAHAEVLAHWPEVIASPTPAAAGRVQAWVVGPGLGTDEAGAAALWFALDTDLPVLVDADGLTMLADHPDLVAGRNAPTVLTPHAGEFARLAGAPPGDDRVGACRQLADALGATVLLKGNVTVIADPGGPVYLNPAGQSWAATAGSGDVLSGMIGALLASGLPSGEAAAAAAFVHARAAAAAAADPGPGDAPTSASRISGHIRAALAAL