Rv1587c Still unknown · low auto-curated
H37Rv Rv1587c · MTBC0 - ·
333 aa · 1788162–1789163 (-) ·
RefSeq NP_216103.2
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: 4h9d-assembly1_B Crystal Structure of Mn-dependent Gme HNH nicking end (prob 0.23, TM 0.72). |
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 |
O06603
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Partial REP13E12 repeat protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| eggNOG description | Domain of unknown function (DUF222) |
| Orthologous group | COG1403 |
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 | 1.847 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 4 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.13% of strains (192) · 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 |
|---|---|---|---|---|
DUF222 | PF02720.23 | 5.7e-40 | 2–145 | Domain of unknown function (DUF222) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 67.8 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.
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 |
|---|---|---|---|---|
4h9d-assembly1_B |
0.23 | 0.72 | 2.8e+00 | 4h9d-assembly1_B Crystal Structure of Mn-dependent Gme HNH nicking endonuclease from Geobacter metallireducens GS-15, Northeast Structural Genomics Consortium (NESG) Target GmR87 |
7mpz-assembly1_A |
0.21 | 0.42 | 4.8e-01 | 7mpz-assembly1_A HNH Nuclease Domain from G. stearothermophilus Cas9 |
4h9d-assembly1_C |
0.16 | 0.77 | 6.0e+00 | 4h9d-assembly1_C Crystal Structure of Mn-dependent Gme HNH nicking endonuclease from Geobacter metallireducens GS-15, Northeast Structural Genomics Consortium (NESG) Target GmR87 |
5zmm-assembly1_E |
0.14 | 0.46 | 1.8e+00 | 5zmm-assembly1_E Structure of the Type IV phosphorothioation-dependent restriction endonuclease ScoMcrA |
5zmm-assembly1_F |
0.12 | 0.42 | 1.8e+00 | 5zmm-assembly1_F Structure of the Type IV phosphorothioation-dependent restriction endonuclease ScoMcrA |
5zmm-assembly1_B |
0.12 | 0.43 | 2.0e+00 | 5zmm-assembly1_B Structure of the Type IV phosphorothioation-dependent restriction endonuclease ScoMcrA |
5zmm-assembly1_C |
0.11 | 0.39 | 1.8e+00 | 5zmm-assembly1_C Structure of the Type IV phosphorothioation-dependent restriction endonuclease ScoMcrA |
5zmm-assembly1_D |
0.09 | 0.40 | 2.6e+00 | 5zmm-assembly1_D Structure of the Type IV phosphorothioation-dependent restriction endonuclease ScoMcrA |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1586c (phage integrase), high confidence from genomic context alone (score 882 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) |
|---|---|---|---|---|
Rv1586c |
phage integrase | 882 | 882 ctx | neighborhood:780 |
Rv3467 hyp |
hypothetical protein | 809 | 809 | coexpression:806 |
Rv1585c |
phage protein | 788 | 788 ctx | neighborhood:773 |
Rv1588c hyp |
hypothetical protein | 787 | 787 ctx | neighborhood:773 |
Rv0393 hyp |
hypothetical protein | 745 | 746 ctx | cooccurence:742 |
Rv0515 hyp |
hypothetical protein | 726 | 727 ctx | cooccurence:720 |
Rv0336 hyp |
hypothetical protein | 726 | 726 ctx | cooccurence:719 |
Rv3776 hyp |
hypothetical protein | 716 | 717 ctx | cooccurence:703 |
Rv2100 hyp |
hypothetical protein | 703 | 704 ctx | cooccurence:695 |
Rv1765c hyp |
hypothetical protein | 681 | 681 ctx | cooccurence:677 |
Rv2015c hyp |
hypothetical protein | 645 | 645 ctx | cooccurence:642 |
Rv1582c |
phage protein | 630 | 627 ctx | neighborhood:617 |
Rv1584c |
phage protein | 616 | 616 ctx | neighborhood:605 |
Rv1583c |
phage protein | 608 | 607 ctx | neighborhood:605 |
Rv1378c hyp |
hypothetical protein | 591 | 591 ctx | cooccurence:584 |
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-40)
- Foldseek best: 4h9d-assembly1_B Crystal Structure of Mn-dependent Gme HNH nicking endonuclease (prob 0.23, E=3e+00, TM=0.72)
- (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_216103.2)
- 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 O06603 (TrEMBL, unreviewed; Predicted)
- 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 67.8, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
18 functional partner(s); context anchor
Rv1586c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1587c| MLAKLAAPGATNPDDHTPVIDTTPDAAAIDRDTRSQAQRNHDGLLAGLRALIASGKLGQHNGLPVSIVVTTTLTDLQTGAGKGFTGGGTLLPMADVIRMTSHAHHYSPASGRYPQAIFDHGTPLALYHTKRLASPAQRIMLFANDRGCTKPGCDAPAYHSQAHHVTAWTSTGRTDITELTLACGPDNRLAEKGWTTHNNTHGHTEWLPPPHLDHGQPWTCEIHYTCACCCLPPNLRRPLRRTARRGPPTRGLPKAVRAAKMGARRVPRQRRQRINRQAPPRLRADVGRHHRRQDRRRGGLGPGPAPSPSHRAGSLHVISRREAAGPGHRRRRR