Rv1439c Family assigned · medium auto-curated
H37Rv Rv1439c · MTBC0 mtbc0_001540 ·
141 aa ·
1626326–1626751 MTBC0
(-) ·
RefSeq NP_215955.1
Genomic neighbourhood (genome browser)
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Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | nuclear transport factor 2 family protein |
| Revised (this work) | Nuclear transport factor 2 family protein. Pfam: SnoaL_2 (PF12680.14). |
| Functional category (TubercuList) | conserved hypotheticals |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
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 1.44 (95% CI -0.13 to 3.82). 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).
Orthologues (reciprocal best hits across mycobacteria)
| M. bovis |
Mb1474c
· 100.0% identity |
|---|---|
| M. orygis |
RJtmp_001520
· 100.0% identity |
Reciprocal-best-hit orthologues (DIAMOND) against the Mycobrowser reference proteomes. A missing species is informative: e.g. a gene absent from M. leprae was likely lost in its reductive genome evolution. Locus tags link to Mycobrowser.
Curated reference (UniProt)
| UniProt |
O06820
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | SnoaL-like domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | SnoaL-like domain |
| Orthologous group | COG3631 |
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 | 0.846 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 5 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.10% of strains (151) · clonal |
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) Mycobacterium
| M. canettii dN/dS (deep-divergence selection) |
inf (low power)
· 2 consensus substitution(s) low power (2 canettii-consensus substitution(s)); present in M. canettii but dN/dS not reliable |
|---|---|
| Genus-wide presence (~53 non-MTBC Mycobacterium) |
present in 7/53 (13%) · mean identity 51.7%
· 1/4 closest MTBAP relatives present in a subset of the genus (7/53 NTM; in 1 of the 4 closest MTBAP relatives) — partial/intermediate conservation |
| Phylostratum (deepest detected homolog) |
MTBC-specific → Mycobacterium → Mycobacteriaceae → Corynebacteriales → Actinomycetia → Bacteria present across the genus Mycobacterium (NTM) but not detected in any non-Mycobacterium genome — a Mycobacterium-genus 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.
Essentiality (transposon mutagenesis)
| DeJesus 2017 call | NE · non-essential |
|---|---|
| What the call means | non-essential |
| TA sites (Himar1) | 7 in the ORF — 0 in the essential state, 0 growth-defect, 7 non-essential, 0 growth-advantage. Saturation 1.000, mean read count 217.857142857. A region of the protein devoid of TA sites is invisible to this assay: nothing can be inferred about it, in either direction. |
| Caveat | Read with some caution: only 7 TA (Himar1) sites in the whole ORF (atlas median 13). The DeJesus 2017 call rests on fewer independent observations than for a longer gene. If this gene overlaps a neighbour (see Genomic-neighbour overlap section below), some of these 7 sites may fall inside the neighbour's ORF rather than its own, leaving even fewer truly informative sites than the raw count suggests. (P20.3) |
Genome-wide Himar1 transposon essentiality in H37Rv (DeJesus 2017). An essential call (ES/ESD/GD) is strong, independent evidence that a "hypothetical" locus encodes a functional, selectively required gene — orthogonal to intra-species conservation.
Mutant phenotypes (conditional Tn-seq, MtbTnDB)
| Condition | log2FC | q | Effect |
|---|---|---|---|
| fitness after prolonged in vitro passage (in vitro passage) | -1.80 | 0.013 | required |
Conditional fitness of transposon-disruption mutants across 1 significant condition(s) (|log2FC|≥1, q≤0.05), from the standardized MtbTnDB compendium. A negative log2FC means the mutant is depleted — the gene contributes to fitness in that condition. An in-vivo defect for a "hypothetical" is strong evidence it matters for infection, even without a known molecular function. Disruption (Tn insertion), not a clean deletion; genetic-interaction screens excluded.
Proteomics (mass spectrometry) detected
| MS detection | detected in 11 of 16 independent MS datasets |
|---|---|
| Integrated abundance | 47.3 ppm · rank 1788/3519 (49.2th percentile) |
Detection by mass spectrometry is direct, experimental evidence that the protein product exists — orthogonal to sequence conservation and to Tn-seq essentiality, and especially decisive for a "hypothetical" locus. Reproducible detection across several independent datasets (PaxDb) makes the existence claim robust; the integrated abundance places the protein in the proteome's dynamic range.
Physico-chemical properties (computed, ProtParam)
| Length | 141 aa |
|---|---|
| Molecular weight | 16.0 kDa |
| Theoretical pI | 8.23 |
| GRAVY | -0.077 (hydrophilic) |
| Aliphatic index | 96.7 |
| Aromaticity | 0.099 |
| Instability index | 37.3 (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 |
|---|---|---|---|---|
SnoaL_2 | PF12680.14 | 2.1e-13 | 10–109 | SnoaL-like domain |
Structural search (AlphaFold DB model, Foldseek vs PDB — genome-wide) pLDDT 88.8
| PDB hit | prob | TM-score | E-value | Description |
|---|---|---|---|---|
3kkg-assembly1_A-2 |
1.00 | 0.76 | 8.1e-09 sig | 3kkg-assembly1_A-2 Crystal structure of Putative SnoaL-like polyketide cyclase (YP_509242.1) from Jannaschia Sp. CCS1 at 1.40 A resolution |
4hvn-assembly1_B |
1.00 | 0.87 | 1.4e-07 sig | 4hvn-assembly1_B Crystal structure of hypothetical protein with ketosteroid isomerase-like protein fold from Catenulispora acidiphila DSM 44928 in complex with Trimethylamine. |
5yqt-assembly2_B |
1.00 | 0.80 | 8.4e-08 sig | 5yqt-assembly2_B Crystal Structure of the L74F/M78V/I80V/L114F mutant of LEH complexed with cyclopentene oxide |
5cf1-assembly3_D |
1.00 | 0.81 | 2.2e-07 sig | 5cf1-assembly3_D Crystal Structure of the M32V/M78V/I80V/L114F mutant of LEH |
4xdw-assembly2_F |
1.00 | 0.79 | 2.0e-07 sig | 4xdw-assembly2_F Crystal Structure of the L74F/M78V/I80V/L114F mutant of LEH |
Foldseek search of the AlphaFold DB model (mean pLDDT 88.8, gated at 70) against the PDB — a genome-wide extension of the ESMFold dark-gene search that also covers proteins beyond the single-sequence length limit. Confident structural neighbours (E < 0.01) shown.
Genomic context (neighbours & predicted operon)
| Upstream (5' on genome) | tpi (+ strand, 611 bp gap) |
|---|---|
| Downstream (3' on genome) | secG (+ strand, 450 bp gap) |
Neighbours from the H37Rv annotation (- strand). The operon is predicted by co-directional intergenic distance (same strand, gaps ≤50 bp) — a transcription-unit hypothesis, not a mapped TSS. For a "hypothetical", co-transcription with a characterised operon is a concrete functional lead (complements the STRING neighborhood channel below).
Evidence
- Legacy H37Rv annotation: hypothetical protein
- MTBC0 PGAP product: nuclear transport factor 2 family protein
- Pfam (hmmscan --cut_ga): SnoaL_2 PF12680.14 (E=2e-13)
- (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_215955.1)
- Domains: Pfam-A via hmmscan --cut_ga — SnoaL_2 (PF12680.14)
- 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
COG3631 - Curated reference: UniProt O06820 (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)
- Genome-wide structure: AlphaFold DB model (Jumper et al. 2021, doi:10.1038/s41586-021-03819-2; Varadi et al. 2024, doi:10.1093/nar/gkad1011) searched vs PDB with Foldseek (mean pLDDT 88.8)
- Essentiality: genome-wide transposon mutagenesis in H37Rv — DeJesus et al. 2017 (mBio, doi:10.1128/mBio.02133-16, CC BY)
- Proteomics: integrated mass-spectrometry abundance from PaxDb 5.0 (Huang et al. 2023, doi:10.1016/j.mcpro.2023.100640), taxon 83332 — weighted average of 16 datasets, incl. Schubert et al. 2013 (doi:10.1016/j.chom.2013.04.008) and Albrethsen et al. 2013 (doi:10.1074/mcp.M112.018846)
- Functional category: TubercuList scheme (Cole et al. 1998, doi:10.1038/31159), via Mycobrowser (Kapopoulou et al. 2011, doi:10.1016/j.tube.2010.09.006)
- Orthologues: reciprocal best hits (DIAMOND, Buchfink et al. 2021, doi:10.1038/s41592-021-01101-x) against Mycobrowser release 5 reference proteomes
- Genomic context / operon: H37Rv annotation; operon predicted by co-directional intergenic distance (Salgado et al. 2000, doi:10.1073/pnas.030539397)
- Mutant phenotypes: standardized Tn-seq compendium MtbTnDB (Jinich et al. 2025, doi:10.1111/mmi.15370), aggregating many primary Tn-seq studies across conditions
- 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
>mtbc0_001540|Rv1439c| MQMSASNAFVEGFADFWKAPSPDRLTDHLHPDVVLVRPLSPPRHGLGAAQREFTRILGLLPDLHGEVDRWSQAGDVVFIEFRLIARLGSEVVEWPVVDRFLLRGDKAVERVSYFDSLPLLIKVVKHPSAWRGWLTTMRSRA
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