Rv3651 Family assigned · medium auto-curated
H37Rv Rv3651 · MTBC0 mtbc0_003868 ·
345 aa · 4115546–4116583 (+) ·
RefSeq NP_218168.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF5628 domain-containing protein |
| Revised (this work) | DUF5628 domain-containing protein. Pfam: Rv3651-like_N (PF18007.8), Rv3651-like_middle (PF18621.8), Rv3651-like_C (PF21043.4). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YCP0
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Triple sensor-domain protein Rv3651 |
| Curated function | Unusual sensor domain-only protein, which may integrate multiple different signals and serve as a scaffold to facilitate signal transfer. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2BH0Z |
|---|
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 | 2.06 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 6 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (173) · 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.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Rv3651-like_N | PF18007.8 | 1.5e-30 | 4–96 | Rv3651-like, N-terminal |
Rv3651-like_middle | PF18621.8 | 1.5e-54 | 99–208 | Rv3651-like, middle domain |
Rv3651-like_C | PF21043.4 | 4.0e-54 | 218–335 | Rv3651-like, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PE33 (PE family protein PE33), medium confidence from genomic context alone (score 419 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) |
|---|---|---|---|---|
Rv3650 PE33 |
PE family protein PE33 | 420 | 419 ctx | neighborhood:419 |
Rv1192 hyp |
hypothetical protein | 435 | 47 | textmining:432 |
Rv2313c hyp |
hypothetical protein | 870 | 41 | textmining:870 |
Rv1524 |
glycosyltransferase | 861 | 41 | textmining:861 |
Rv3351c hyp |
hypothetical protein | 809 | 41 | textmining:809 |
Rv1519 hyp |
hypothetical protein | 803 | 41 | textmining:803 |
Rv3737 |
transmembrane protein | 510 | 41 | textmining:510 |
Rv3179 hyp |
hypothetical protein | 434 | 41 | textmining:434 |
Rv1994c cmtR |
HTH-type transcriptional regulator CmtR | 433 | 41 | textmining:433 |
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
- Legacy H37Rv annotation: hypothetical protein
- MTBC0 PGAP product: DUF5628 domain-containing protein
- Pfam (hmmscan --cut_ga): Rv3651-like_N PF18007.8 (E=1e-30), Rv3651-like_middle PF18621.8 (E=2e-54), Rv3651-like_C PF21043.4 (E=4e-54)
- (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_218168.1)
- Domains: Pfam-A via hmmscan --cut_ga — Rv3651-like_N (PF18007.8), Rv3651-like_middle (PF18621.8), Rv3651-like_C (PF21043.4)
- 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
2BH0Z - Curated reference: UniProt I6YCP0 (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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
9 functional partner(s); context anchor
PE33 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003868|Rv3651| MTHDWLLVETLGDEPAVVARGRELKKLVPITTFLRRSPYLAAVRTAIAETLQTGQSLTSITPKHDRVIRTEPVIMTDGRMHGVQVWSGPTDAEPPDRPIPGPLKWDLTRGVATDTPESLTNSGKNPEVEITYGRAFAEDLPARELNPNETQVLAMAVKAKPGKTLCSIWDLTDWQGTPIRIGFVARSALEPGPNGRDHLVARAMNWRAETKAPAVPVDDLAQRILIGLAQAGVHRALVDLKTWTLLKWLDQPCSFYDWRRSAADGPRLHPDDQHVIDAMTRDLANGSASHVLRLPGHDVDWVPVHVTVNRIELEPDTFAGLVALRLPTDEELADAGLPKATDVTT