Rv1588c Still unknown · low auto-curated
H37Rv Rv1588c · MTBC0 - ·
222 aa · 1789168–1789836 (-) ·
RefSeq NP_216104.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF222. Function unknown. Foldseek best (non-significant) hit: 2qww-assembly3_F Crystal structure of multiple antibiotic-resistance r (prob 0.18, TM 0.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WLT9
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Uncharacterized protein Rv1588c |
UniProt still lists this protein as Uncharacterized protein Rv1588c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| eggNOG description | Domain of unknown function (DUF222) |
| Orthologous group | COG1403 |
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 0.323 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 5 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF222 | PF02720.23 | 6.4e-22 | 38–138 | Domain of unknown function (DUF222) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 84.1 (confident). 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 |
|---|---|---|---|---|
2qww-assembly3_F |
0.18 | 0.26 | 3.3e-01 | 2qww-assembly3_F Crystal structure of multiple antibiotic-resistance repressor (MarR) (YP_013417.1) from Listeria monocytogenes 4b F2365 at 2.07 A resolution |
2bke-assembly1_A |
0.15 | 0.54 | 5.3e+00 | 2bke-assembly1_A Conformational Flexibility Revealed by the Crystal Structure of a Crenarchaeal RadA |
1lnw-assembly2_C |
0.03 | 0.21 | 4.4e+00 | 1lnw-assembly2_C CRYSTAL STRUCTURE OF THE MEXR REPRESSOR OF THE MEXAB-OPRM MULTIDRUG EFFLUX OPERON OF PSEUDOMONAS AERUGINOSA |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1586c (phage integrase), high confidence from genomic context alone (score 786 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) |
|---|---|---|---|---|
Rv1587c hyp |
hypothetical protein | 787 | 787 ctx | neighborhood:773 |
Rv1586c |
phage integrase | 786 | 786 ctx | neighborhood:780 |
Rv1585c |
phage protein | 778 | 778 ctx | neighborhood:773 |
Rv3466 hyp |
hypothetical protein | 762 | 761 | coexpression:761 |
Rv1582c |
phage protein | 622 | 619 ctx | neighborhood:617 |
Rv1583c |
phage protein | 609 | 609 ctx | neighborhood:605 |
Rv1584c |
phage protein | 608 | 607 ctx | neighborhood:605 |
Rv1578c |
phage protein | 549 | 549 | |
Rv1148c hyp |
hypothetical protein | 444 | 359 | |
Rv3776 hyp |
hypothetical protein | 453 | 339 | |
Rv0336 hyp |
hypothetical protein | 844 | 233 | textmining:806 |
Rv2100 hyp |
hypothetical protein | 837 | 203 | textmining:804 |
Rv0515 hyp |
hypothetical protein | 701 | 161 | textmining:659 |
Rv2719c chiZ |
membrane protein | 540 | 101 | textmining:510 |
Rv2593c ruvA |
Holliday junction ATP-dependent DNA helicase RuvA | 535 | 67 | textmining:523 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): DUF222 PF02720.23 (E=6e-22)
- Foldseek best: 2qww-assembly3_F Crystal structure of multiple antibiotic-resistance repressor ( (prob 0.18, E=3e-01, TM=0.26)
- (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_216104.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF222 (PF02720.23)
- 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
COG1403 - Curated reference: UniProt P9WLT9 (SwissProt, reviewed; Inferred from homology)
- 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 84.1, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
19 functional partner(s); context anchor
Rv1586c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1588c| MLANSREELVEVFDALDAELDRLDEVSFEVLTTPERLRSLERLECLVRRLPAVGHALINQLDAQASEEELGGTLCCALANRLRITKPDAARRIADAADLGPRRALTGEPLAPQLTATATAQRQGLIGEAHVKVIRALFRPPARRGGCVHPPGRRSRPGRQSRSISSRRAGPLRPAGHGLATPRRRPHRHRTRPQTRHHPEQPAIRRHVTAKWLPDPPSAGHL