Rv0898c Family assigned · low auto-curated
H37Rv Rv0898c · MTBC0 mtbc0_000952 ·
87 aa ·
1005655–1005918 MTBC0
(-) ·
RefSeq NP_215413.1
Genomic neighbourhood (genome browser)
Open in full genome browser →This gene (outlined) in its genomic context; arrows are neighbouring genes coloured by verdict. Click any gene to navigate. Pan and zoom in the full browser.
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF2630 family protein |
| Revised (this work) | DUF2630 family protein. |
| 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.
Intrinsic disorder (sequence + structure) partially disordered
| Predicted disorder | 37% of residues (metapredict) · mean AlphaFold pLDDT 84.6 |
|---|---|
| Disordered regions | 1 IDR(s), longest 21 aa [66-87] |
carries a substantial disordered region (21/87 residues); disorder is a property, not a function
A property (biophysics), not a function. No LLPS/condensate claim is made from disorder alone. Verdict unchanged. Source: metapredict v3 (Emenecker/Holehouse) per-residue disorder + AlphaFold mean pLDDT (annotation_mtbc P16.13).
CRISPRi vulnerability
Vulnerability index 0.32 (95% CI -0.54 to 1.38). 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).
Legacy record & comparison (Mycobrowser)
| Mycobrowser function | Function unknown |
|---|
The legacy Mycobrowser record is shown for verification. Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.
Orthologues (reciprocal best hits across mycobacteria)
| M. bovis |
Mb0922c
· 100.0% identity |
|---|---|
| M. marinum |
MMAR_4638
· 82.8% identity |
| M. smegmatis |
MSMEG_5666
· 46.8% identity |
| M. orygis |
RJtmp_000947
· 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 |
P9WKP5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv0898c |
UniProt still lists this protein as Uncharacterized protein Rv0898c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF2630) |
| Orthologous group | 2E3KN |
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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 0 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) Actinomycetia
| Genus-wide presence (~53 non-MTBC Mycobacterium) |
present in 44/53 (83%) · mean identity 76.3%
· 2/4 closest MTBAP relatives conserved across the genus (present in 44/53 non-MTBC Mycobacterium genomes, incl. distant relatives) — an ancient core gene predating the genus radiation |
|---|---|
| Phylostratum (deepest detected homolog) |
MTBC-specific → Mycobacterium → Mycobacteriaceae → Corynebacteriales → Actinomycetia → Bacteria detected in 5/13 non-Mycobacterium reference genomes (down to Actinomycetia) · mean identity 48.7% detected across the class Actinomycetia (beyond Corynebacteriales) but not outside the phylum — an Actinobacteria-level ancient 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 | Uncertain · uncertain |
|---|---|
| What the call means | uncertain (short or TA-poor ORF): no call possible |
| TA sites (Himar1) | 2 in the ORF — 0 in the essential state, 0 growth-defect, 2 non-essential, 0 growth-advantage. Saturation 1.000, mean read count 78. A region of the protein devoid of TA sites is invisible to this assay: nothing can be inferred about it, in either direction. |
| Caveat | Statistically thin call: only 2 TA (Himar1) sites in the whole ORF (atlas median 13; genes under 300 nt typically have very few). A DeJesus 2017 call built on so few independent observations is less robust than the same call on a longer gene, in either direction. Cross-check against the CRISPRi vulnerability index (independent of TA-site density) and, if this gene overlaps a neighbour (see Genomic-neighbour overlap section below), verify how many of its TA sites actually fall inside its own ORF. (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.
Proteomics (mass spectrometry) detected
| MS detection | detected in 13 of 16 independent MS datasets |
|---|---|
| Integrated abundance | 306.0 ppm · rank 631/3519 (82.1th 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 | 87 aa |
|---|---|
| Molecular weight | 9.9 kDa |
| Theoretical pI | 6.11 |
| GRAVY | -0.983 (hydrophilic) |
| Aliphatic index | 79.7 |
| Aromaticity | 0.023 |
| Instability index | 79.9 (unstable) |
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 |
|---|---|---|---|---|
DUF2630 | PF10944.14 | 7.8e-33 | 8–86 | Protein of unknown function (DUF2630) |
Genomic context (neighbours & predicted operon) operon of 2
| Upstream (5' on genome) | Rv0897c (- strand, 25 bp gap) |
|---|---|
| Downstream (3' on genome) | arfA (+ strand, 107 bp gap) |
| Predicted operon |
Rv0897c · Rv0898c
|
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).
Functional interaction network (STRING v12, guilt-by-association)
Explore full network →Node colour = verdict, dashed = hypothetical; edge colour = evidence (green experimental, orange genomic-context, grey co-expression), width ∝ score. Click a partner to open its page; "Explore full network" to walk the graph.
Closest characterised functional partner: Rv0897c (oxidoreductase), high confidence from genomic context alone (score 851 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) |
|---|---|---|---|---|
Rv0897c |
oxidoreductase | 851 | 851 ctx | neighborhood:847 |
Rv0899 arfA |
peptidoglycan-binding protein ArfA | 780 | 780 ctx | neighborhood:779 |
Rv0901 arfC |
membrane protein | 605 | 606 ctx | neighborhood:606 |
Rv0900 arfB |
membrane protein | 570 | 570 ctx | neighborhood:570 |
Rv1265 hyp |
hypothetical protein | 468 | 468 ctx | cooccurence:465 |
Rv3687c rsfB |
anti-anti-sigma factor RsfB | 450 | 451 ctx | cooccurence:448 |
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 exp badge marks an experimentally-supported partner (measured interaction, experimental/database channel ≥400) as opposed to a purely predicted one — but note that the M. tuberculosis experimental interactome is dominated by a noisy bacterial-two-hybrid screen, so a strong measured link that contradicts the operon/localisation context is likely a false positive. 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: DUF2630 family protein
- Pfam (hmmscan --cut_ga): DUF2630 PF10944.14 (E=8e-33)
- (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_215413.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF2630 (PF10944.14)
- 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
2E3KN - Curated reference: UniProt P9WKP5 (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)
- 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 84.6)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
6 functional partner(s); context anchor
Rv0897c - 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)
- 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_000952|Rv0898c| MGKGRKPTDSETLAHIRDLVAEEKALRAQLRHGGISESEEQQQLRRIEIELDQCWDLLRQRRALRQTGGDPREAVVRPADQVEGYTG
Spot an error? Suggest an improvement
Found a mistake, a missing reference, or have a better functional hypothesis for Rv0898c? Email the maintainer — the message is pre-filled with this gene's details.