Rv3647c Family assigned · low
H37Rv Rv3647c · MTBC0 mtbc0_003864 ·
192 aa · 4111315–4111893 (-) ·
RefSeq NP_218164.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | WhiA-like cell-division / homeostasis protein (LAGLIDADG-derived DNA-binding fold). RefSeq leaves it 'hypothetical protein'. Distinct from whiA/Rv3641c. |
Curated reference (UniProt)
| UniProt |
I6Y469
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2EE2C |
|---|
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 | 0.198 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 95.0 (very high). 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 |
|---|---|---|---|---|
8dy9-assembly1_I |
1.00 | 0.61 | 2.1e-07 sig | 8dy9-assembly1_I Streptomyces venezuelae RNAP unconstrained open promoter complex with WhiA and WhiB transcription factors |
8dy7-assembly1_I |
1.00 | 0.59 | 1.1e-06 sig | 8dy7-assembly1_I Streptomyces venezuelae RNAP transcription open promoter complex with WhiA and WhiB transcription factors |
2dch-assembly1_X |
1.00 | 0.67 | 1.0e-04 sig | 2dch-assembly1_X Crystal structure of archaeal intron-encoded homing endonuclease I-Tsp061I |
1ef0-assembly2_A |
1.00 | 0.60 | 1.2e-04 sig | 1ef0-assembly2_A CRYSTAL STRUCTURE OF PI-SCEI MINIPRECURSOR |
1vde-assembly1_B |
1.00 | 0.54 | 1.2e-04 sig | 1vde-assembly1_B PI-SCEI, A HOMING ENDONUCLEASE WITH PROTEIN SPLICING ACTIVITY |
1vde-assembly1_A |
1.00 | 0.55 | 2.3e-04 sig | 1vde-assembly1_A PI-SCEI, A HOMING ENDONUCLEASE WITH PROTEIN SPLICING ACTIVITY |
1ef0-assembly2_B-2 |
1.00 | 0.58 | 5.3e-04 sig | 1ef0-assembly2_B-2 CRYSTAL STRUCTURE OF PI-SCEI MINIPRECURSOR |
1um2-assembly2_B |
1.00 | 0.58 | 5.9e-04 sig | 1um2-assembly2_B Crystal Structure of the Vma1-Derived Endonuclease with the Ligated Extein Segment |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cspA (cold shock protein A), high confidence from genomic context alone (score 759 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) |
|---|---|---|---|---|
Rv3648c cspA |
cold shock protein A | 868 | 759 ctx | neighborhood:755 textmining:474 |
Rv3646c topA |
DNA topoisomerase I | 715 | 715 ctx | neighborhood:711 |
Rv3849 espR |
ESX-1 transcriptional regulator EspR | 673 | 673 ctx | cooccurence:668 |
Rv0996 |
transmembrane protein | 620 | 620 ctx | cooccurence:616 |
Rv0383c ttfA hyp |
hypothetical protein | 597 | 597 ctx | cooccurence:597 |
Rv1303 hyp |
hypothetical protein | 588 | 589 ctx | cooccurence:586 |
Rv1109c hyp |
hypothetical protein | 580 | 580 ctx | cooccurence:576 |
Rv2732c |
transmembrane protein | 574 | 574 ctx | cooccurence:568 |
Rv3818 hyp |
hypothetical protein | 562 | 562 ctx | cooccurence:562 |
Rv0863 hyp |
hypothetical protein | 556 | 556 ctx | cooccurence:555 |
Rv0475 hbhA |
heparin binding hemagglutinin HbhA | 547 | 547 ctx | cooccurence:541 |
Rv2049c hyp |
hypothetical protein | 537 | 538 ctx | cooccurence:526 |
Rv2091c |
membrane protein | 537 | 537 ctx | cooccurence:531 |
Rv3212 hyp |
hypothetical protein | 535 | 536 ctx | cooccurence:525 |
Rv1836c hyp |
hypothetical protein | 526 | 526 ctx | cooccurence:505 |
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
- Foldseek vs AFDB-SwissProt: cell division protein WhiA, TM 0.64, E 3e-7
- Structural homology vs AlphaFold-Swiss-Prot (Foldseek; 542k curated SwissProt structures), project 'Still unknown gene function' phase13, 2026-06-10. Fold/family-level, not a demonstrated 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 NP_218164.1)
- 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
2EE2C - Curated reference: UniProt I6Y469 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 95.0, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
32 functional partner(s); context anchor
cspA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003864|Rv3647c| MSQLSFFAAESVPPAVADLSGVLAGPGQIVLVGCGARLSVVVAESWRASALAEMIQEAGLVPEVARTDENTPLVRTAVDPLLCGIAAEWTRGAVKTVPPRWLPGPRELRAWTLAAGSPEADRYLLGLDPHAPDTHSPLASALMRVGIAPTLIGTRGTRPALRISGRRRLSRLVENVGEPPDGAEAWVQWPRT