Rv1984a Family assigned · low auto-curated · to review
H37Rv Rv1984a · MTBC0 - ·
76 aa ·
2228676–2228906 H37Rv
(+) ·
RefSeq YP_009030034.1
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Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | No Pfam domain above threshold; Foldseek indicates a fold similar to 1n91-assembly1_A Solution NMR Structure of Protein yggU from Escherichia coli. N (prob 1.00, TM 0.70). Structure-based, putative. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
In the literature (TB corpus sweep) never studied
No publication in PubMed mentions this gene in its title or abstract — not under its H37Rv locus tag, nor under any of its ortholog identifiers (M. bovis, M. marinum, M. smegmatis, M. leprae, M. abscessus). The atlas annotation rests on sequence/structure evidence, not on a primary study of this gene.
A verified absence of literature is itself information: it flags an annotation with no primary study behind it. This distinguishes a gene that is dark because nobody has looked from one that is dark despite having been studied. Source: PubMed (whole), MULTI-ALIAS sweep: H37Rv locus tag AND every ortholog identifier (M. bovis Mb…, M. marinum MMAR_…, M. smegmatis MSMEG_…, M. leprae ML…, M. abscessus MAB_…), each hit VERIFIED against the abstract text (word-boundary regex). phase73/phase75, 2026-07-13.
CRISPRi vulnerability
Vulnerability index 0.78 (95% CI -0.43 to 2.60). A more negative index = more vulnerable to knockdown (better drug-target quality); indicative threshold VI ≤ -6 = highly vulnerable.
Quantitative CRISPRi knockdown, graded (finer than binary Tn-seq essentiality). Source: CRISPRi vulnerability index (Bosch 2021, pebble.rockefeller.edu).
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Belongs to the UPF0235 family |
| Orthologous group | COG1872 |
| KEGG orthology |
K09131
|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 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.
Outgroup conservation (beyond the MTBC) Corynebacteriales
| Genus-wide presence (~53 non-MTBC Mycobacterium) |
present in 25/53 (47%) · mean identity 74.5%
· 2/4 closest MTBAP relatives present in a subset of the genus (25/53 NTM; in 2 of the 4 closest MTBAP relatives) — partial/intermediate conservation |
|---|---|
| Phylostratum (deepest detected homolog) |
MTBC-specific → Mycobacterium → Mycobacteriaceae → Corynebacteriales → Actinomycetia → Bacteria detected in 3/13 non-Mycobacterium reference genomes (down to Corynebacteriales) · mean identity 61.9% detected across the order Corynebacteriales (Corynebacterium/Nocardia/Rhodococcus/…) but not in more distant Actinomycetia — a Corynebacteriales-level gene |
Two orthogonal outgroup signals. M. canettii (the immediate outgroup) gives a deep-divergence dN/dS (a low value confirms a constrained, real gene; shown as confident only at ≥8 substitutions, else flagged low-power). Genus-wide presence/absence (tblastn vs assembled non-MTBC genomes) places the gene on the ancient-core ↔ MTBC-specific axis: a gene absent even from the closest MTBAP relatives is a candidate MTBC-specific innovation (possible host-adaptation factor, to confirm by synteny). The phylostratum extends that axis outside the genus (tblastn vs 13 reference genomes spanning Mycobacteriaceae → Corynebacteriales → Actinomycetia → outside the phylum): it is the deepest clade in which a homolog is still detected, i.e. a proxy for gene age. Read it with the null model in mind: a shallow (young) stratum can also reflect homology-detection failure for short or fast-evolving ORFs, so it is a descriptive axis, not a proof of novelty.
Proteomics (mass spectrometry) not detected
Not detected in the mass-spectrometry datasets integrated by PaxDb. This is not evidence of absence: low-abundance, condition-specific, or MS-refractory proteins (e.g. small, highly hydrophobic, or repetitive PE/PPE families with few tryptic peptides) are systematically under-sampled.
Physico-chemical properties (computed, ProtParam)
| Length | 76 aa |
|---|---|
| Molecular weight | 8.3 kDa |
| Theoretical pI | 10.97 |
| GRAVY | -0.154 (hydrophilic) |
| Aliphatic index | 102.5 |
| Aromaticity | 0.039 |
| Instability index | 24.4 (stable) |
Computed from the ancestral MTBC0 sequence with the ExPASy ProtParam method (Biopython). Descriptive biophysical context: a positive GRAVY flags a hydrophobic (often membrane) protein, a high instability index (>40) predicts a short in-vitro half-life, an extreme pI hints at compartment or binding partner.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF167 | PF02594.22 | 2.3e-19 | 5–74 | Uncharacterised ACR, YggU family COG1872 |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 88.7 (confident). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
1n91-assembly1_A |
1.00 | 0.70 | 1.4e-04 sig | 1n91-assembly1_A Solution NMR Structure of Protein yggU from Escherichia coli. Northeast Structural Genomics Consortium Target ER14. |
1yh5-assembly1_A |
1.00 | 0.66 | 2.2e-04 sig | 1yh5-assembly1_A Solution NMR Structure of Protein yggU from Escherichia coli. Northeast Structural Genomics Consortium Target ER14. |
2m0x-assembly1_A |
0.18 | 0.40 | 4.3e-01 | 2m0x-assembly1_A Solution structure of U14Ub1, an engineered ubiquitin variant with increased affinity for USP14 |
8rua-assembly1_A |
0.18 | 0.68 | 2.2e+00 | 8rua-assembly1_A Crystal structure of Rhizobium etli L-asparaginase ReAV C135A mutant |
8rud-assembly1_B |
0.14 | 0.69 | 3.1e+00 | 8rud-assembly1_B Crystal structure of Rhizobium etli L-asparaginase ReAV K138A mutant |
8rug-assembly1_B |
0.14 | 0.69 | 3.1e+00 | 8rug-assembly1_B Crystal structure of Rhizobium etli L-asparaginase ReAV C189A mutant |
8ruf-assembly1_A |
0.13 | 0.69 | 3.8e+00 | 8ruf-assembly1_A Crystal structure of Rhizobium etli L-asparaginase ReAV D187A mutant |
7os3-assembly1_AAA |
0.13 | 0.68 | 3.8e+00 | 7os3-assembly1_AAA Crystal structure of Rhizobium etli inducible L-asparaginase ReAV solved by S-SAD (orthorhombic form START) |
Evidence
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): DUF167 PF02594.22 (E=2e-19)
- Foldseek best: 1n91-assembly1_A Solution NMR Structure of Protein yggU from Escherichia coli. N (prob 1.00, E=1e-04, TM=0.70)
- (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 YP_009030034.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF167 (PF02594.22)
- 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
COG1872 - Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Model confidence: ESMFold per-residue pLDDT (mean 88.7, confident)
- Physico-chemical properties: ExPASy ProtParam method via Biopython (Gasteiger et al. 2005), computed from the MTBC0 sequence
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1984a| MTDSVVVRVKPGSHKGPLVEVGPNGELIIYVREPAIDGKANDAVTRLLAAHLQLPKSRVKLVSGATSRFKRFRLSR
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