Rv2635 Resolved · high
H37Rv Rv2635 · MTBC0 mtbc0_002805 ·
80 aa · 2986031–2986273 (+) ·
RefSeq NP_217151.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Nucleoid-associated protein (NAP); a small intrinsically disordered protein (IDP) that undergoes liquid-liquid phase separation. RefSeq leaves this locus 'hypothetical protein'. By in-silico analysis and circular dichroism Rv2635 is established as an IDP; GFP-tagged Rv2635 phase-separates into reversible condensates (FRAP); it binds DNA sequence-independently (EMSA) and, when over-expressed in E. coli, causes nucleoid compaction and co-localises with the condensed nucleoid. Its unstructured regions are required for phase separation and its C-terminus for DNA binding, indicating a phase-separating NAP role in mycobacteria (Chandra 2025). Experimentally characterised. |
Curated reference (UniProt)
| UniProt |
P9WL57
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DNA-binding protein Rv2635 |
| Curated function | Intrinsically disordered protein (IDP) that can bind to DNA in a sequence-independent fashion. Mediates chromatin compaction and may impose transcriptional regulation in bacteria during stress adaptation. |
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.314 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2636 (O-phosphotransferase), high confidence from genomic context alone (score 774 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) |
|---|---|---|---|---|
Rv2636 |
O-phosphotransferase | 775 | 774 ctx | neighborhood:773 |
Rv2634c PE_PGRS46 |
PE-PGRS family protein PE_PGRS46 | 575 | 575 ctx | neighborhood:575 |
Rv2637 dedA |
transmembrane protein DedA | 448 | 448 ctx | neighborhood:446 |
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
- RefSeq: hypothetical protein (small protein)
- Intrinsically disordered protein (in-silico + CD); reversible phase separation (GFP/FRAP) (Chandra 2025, PMID 40513736)
- Sequence-independent DNA binding (EMSA); nucleoid compaction and co-localisation on over-expression
- Unstructured regions required for phase separation; C-terminus for DNA binding; phase-separating NAP
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_217151.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Curated reference: UniProt P9WL57 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 38.0, very low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
3 functional partner(s); context anchor
Rv2636 - Primary literature: Chandra G, Sharma R, Venugopal U, Ghosal D, Akhtar MS, Krishnan MY (2025). Hypothetical protein Rv2635 of Mycobacterium tuberculosis is an intrinsically disordered nucleoid-associated protein that undergoes phase separation Int J Biol Macromol 319(Pt 1):145216. doi:10.1016/j.ijbiomac.2025.145216 PMID:40513736
Ancestral MTBC0 protein sequence
>mtbc0_002805|Rv2635| MVAADHRALGSNKSYPASQTAEAIWPPARTLRYDRQSPWLATGFDRRMSQTVTGVGVQNCAVSKRRCSAVDHSSRTPYRR