Rv2562 Family assigned · low auto-curated · to review
H37Rv Rv2562 · MTBC0 ·
129 aa ·
2881758–2882147 H37Rv
(+) ·
RefSeq
Genomic neighbourhood (genome browser)
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Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Conserved hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Protein of unknown function (DUF2652) |
| Functional category (TubercuList) | conserved hypotheticals |
Curation note: Added P16.5d: Mycobrowser-annotated gene absent from RefSeq NC_000962.3 (the atlas' original 3906-CDS reference). Foundation record from the Mycobrowser release + translated H37Rv sequence; heavy enrichment layers (structure, orthology, conservation, interaction) pending.
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
In the literature (TB corpus sweep)
This distinguishes a gene that is dark because nobody has looked from one that is dark despite having been studied. Source: .
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 Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.
Curated reference (UniProt)
| UniProt |
Q50737
TrEMBL · unreviewed
|
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | Protein of unknown function (DUF2652) |
| Orthologous group | COG2114 |
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 | 0.935 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 3 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.
Essentiality (transposon mutagenesis)
| DeJesus 2017 call | NE · non-essential |
|---|---|
| What the call means | non-essential |
| TA sites (Himar1) | 9 in the ORF — 0 in the essential state, 0 growth-defect, 9 non-essential, 0 growth-advantage. Saturation 1.000, mean read count 238. 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 9 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 9 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.
Proteomics (mass spectrometry) detected
| MS detection | detected in 6 of 16 independent MS datasets |
|---|---|
| Integrated abundance | 42.5 ppm · rank 1864/3519 (47.1th 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 | 129 aa |
|---|---|
| Molecular weight | 14.3 kDa |
| Theoretical pI | 5.12 |
| GRAVY | -0.011 (hydrophilic) |
| Aliphatic index | 89.9 |
| Aromaticity | 0.093 |
| Instability index | 41.9 (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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Transcriptional regulation (signed TRN: ChIP-seq + TFOE)
| Regulated by (4 TF) |
Rv0081 (activates) · tcrA (activates) · whiA (activates) · kstR (represses)
|
|---|
Regulatory edges from the ISB signed transcriptional regulatory network (TF ChIP-seq binding, Minch 2015 + TF-overexpression response, Rustad 2014). An edge is regulatory evidence (binding and/or expression change), not necessarily direct. For a "hypothetical", membership in a known regulon (e.g. DosR dormancy, PhoP virulence) is a strong physiological-context lead.
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: Rv2561 (Rv2561, (MTCY9C4.07c), len: 97 aa. Conserved hypothetical protein, highly similar in part (and longer 33 aa) to upstream ORF AAK46951|RV2562), high confidence from genomic context alone (score 948 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) |
|---|---|---|---|---|
Rv2561 |
Rv2561, (MTCY9C4.07c), len: 97 aa. Conserved hypothetical protein, highly similar in part (and longer 33 aa) to upstream ORF AAK46951|RV2562 | 992 | 948 ctx | neighborhood:601 fusion:867 textmining:870 |
Rv2564 glnQ |
glutamine ABC transporter ATP-binding protein | 692 | 681 ctx | neighborhood:498 |
Rv2565 |
NTE family protein | 581 | 564 | |
Rv2563 |
glutamine ABC transporter permease | 496 | 495 ctx | neighborhood:493 |
Rv0104 hyp |
hypothetical protein | 437 | 423 | |
Rv2434c |
transmembrane protein | 435 | 421 | |
Rv3728 |
membrane protein | 437 | 414 | |
Rv0073 |
glutamine ABC transporter ATP-binding protein | 432 | 411 | |
Rv3239c |
transmembrane transport protein | 431 | 408 | |
Rv0998 |
acetyltransferase Pat | 415 | 401 | |
Rv1675c cmr |
HTH-type transcriptional regulator Cmr | 414 | 400 | |
Rv3676 crp |
cAMP receptor protein | 414 | 399 | |
Rv1264 |
adenylyl cyclase | 514 | 50 | textmining:510 |
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.
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 )
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
COG2114 - Curated reference: UniProt Q50737 (TrEMBL, unreviewed)
- 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 —
13 functional partner(s); context anchor
Rv2561 - 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)
- Transcriptional regulation: ISB signed TRN — TF ChIP-seq (Minch et al. 2015, doi:10.1038/ncomms6829) + TF overexpression (Rustad et al. 2014, doi:10.1186/gb-2014-15-11-502)
- 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
>|Rv2562|Rv2562 VAEQKVKRNVELAGVDVILVHRMLKNEVPVSEYLFMTDVVAQCLDESVRKLATPLTHDFEGIGETSTHYIDLATSDMPPAVPDHSFFGLLWADVKFEWHALPYLLGFKKACAGFRSLGRGATEEPAEMG
Spot an error? Suggest an improvement
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