Rv1989c Family assigned · medium auto-curated
H37Rv Rv1989c · MTBC0 mtbc0_002113 ·
186 aa · 2256352–2256912 (-) ·
RefSeq NP_216505.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | RES family NAD+ phosphorylase |
| Revised (this work) | RES family NAD+ phosphorylase. Pfam: RES (PF08808.18). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WLP9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | NAD(+) phosphorylase MbcT |
| EC (curated) |
EC 2.4.2.-
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. Neutralized by cognate antitoxin MbcA. Degrades NAD(+) by phosphorolysis. Expression in the absence of its cognate antitoxin MbcA causes dramatic reduction of intracellular NAD(+) levels and is deleterious to cell growth, causing cell death. In a SCID mouse infection model, mice infected with bacteria overexpressing this protein survive longer. Overexpression of this protein in a mouse infection model at 21 days leads to bacterial death, and shows a synergistic 100-fold increase in mouse survival when combined with isoniazid treatment. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | RES |
| Orthologous group | COG5654 |
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 | 0.682 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 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 |
|---|---|---|---|---|
RES | PF08808.18 | 8.8e-18 | 25–148 | RES domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mbcA (transcriptional regulator), high confidence from genomic context alone (score 1000 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1990c mbcA |
transcriptional regulator | 999 | 1000 ctx | neighborhood:882 experimental:999 textmining:870 |
Rv3188 hyp |
hypothetical protein | 985 | 959 | experimental:956 textmining:652 |
Rv1990A |
Rv1990A, len: 111 aa. Possible dehydrogenase (fragment), similar to N-terminal part of several dehydrogenases and hypothetical proteins, e.g | 454 | 454 ctx | neighborhood:425 |
Rv2034 |
ArsR family HTH-type transcriptional repressor | 457 | 83 | textmining:433 |
Rv1330c pncB1 |
nicotinic acid phosphoribosyltransferase PncB1 | 422 | 61 | textmining:410 |
Rv3189 hyp |
hypothetical protein | 658 | 55 | textmining:653 |
Rv2035 hyp |
hypothetical protein | 546 | 55 | textmining:540 |
Rv1985c lysG |
HTH-type transcriptional regulator | 445 | 55 | textmining:437 |
Rv0837c hyp |
hypothetical protein | 437 | 52 | textmining:431 |
Rv0918 hyp |
hypothetical protein | 652 | 47 | textmining:650 |
Rv1981c nrdF1 |
ribonucleoside-diphosphate reductase subunit beta NrdF1 | 632 | 47 | textmining:630 |
Rv3698 hyp |
hypothetical protein | 626 | 47 | textmining:624 |
Rv3697c vapC48 |
ribonuclease VapC48 | 512 | 46 | textmining:510 |
Rv1545 hyp |
hypothetical protein | 414 | 46 | textmining:411 |
Rv1978 hyp |
hypothetical protein | 513 | 45 | textmining:511 |
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: hypothetical protein
- MTBC0 PGAP product: RES family NAD+ phosphorylase
- Pfam (hmmscan --cut_ga): RES PF08808.18 (E=9e-18)
- (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_216505.1)
- Domains: Pfam-A via hmmscan --cut_ga — RES (PF08808.18)
- 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
COG5654 - Curated reference: UniProt P9WLP9 (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 —
20 functional partner(s); context anchor
mbcA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002113|Rv1989c| MSDALDEGLVQRIDARGTIEWSETCYRYTGAHRDALSGEGARRFGGRWNPPLLFPAIYLADSAQACMVEVERAAQAASTTAEKMLEAAYRLHTIDVTDLAVLDLTTPQAREAVGLENDDIYGDDWSGCQAVGHAAWFLHMQGVLVPAAGGVGLVVTAYEQRTRPGQLQLRQSVDLTPALYQELRAT