Rv3467 Still unknown · low auto-curated
H37Rv Rv3467 · MTBC0 - ·
317 aa · 3883964–3884917 (+) ·
RefSeq NP_217984.1
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: 4h9d-assembly1_C Crystal Structure of Mn-dependent Gme HNH nicking end (prob 0.25, TM 0.74). |
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 |
Q50655
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | HNH nuclease domain-containing 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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 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 | 1.3e-71 | 2–223 | Domain of unknown function (DUF222) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 87.8 (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 |
|---|---|---|---|---|
4h9d-assembly1_C |
0.25 | 0.74 | 3.5e+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_F |
0.18 | 0.62 | 3.1e+00 | 5zmm-assembly1_F Structure of the Type IV phosphorothioation-dependent restriction endonuclease ScoMcrA |
5zmm-assembly1_E |
0.18 | 0.62 | 3.5e+00 | 5zmm-assembly1_E Structure of the Type IV phosphorothioation-dependent restriction endonuclease ScoMcrA |
5zmm-assembly1_B |
0.18 | 0.62 | 3.5e+00 | 5zmm-assembly1_B Structure of the Type IV phosphorothioation-dependent restriction endonuclease ScoMcrA |
5zmm-assembly1_A |
0.16 | 0.62 | 3.7e+00 | 5zmm-assembly1_A Structure of the Type IV phosphorothioation-dependent restriction endonuclease ScoMcrA |
5zmm-assembly1_C |
0.15 | 0.62 | 4.1e+00 | 5zmm-assembly1_C Structure of the Type IV phosphorothioation-dependent restriction endonuclease ScoMcrA |
4h9d-assembly1_B |
0.14 | 0.71 | 6.1e+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 |
5ls6-assembly3_G |
0.04 | 0.22 | 4.3e+00 | 5ls6-assembly3_G Structure of Human Polycomb Repressive Complex 2 (PRC2) with inhibitor |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rmlB (dTDP-glucose 4,6-dehydratase), medium confidence from genomic context alone (score 557 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) |
|---|---|---|---|---|
Rv0094c hyp |
hypothetical protein | 831 | 832 | coexpression:831 |
Rv1587c hyp |
hypothetical protein | 809 | 809 | coexpression:806 |
Rv3466 hyp |
hypothetical protein | 793 | 793 ctx | neighborhood:774 |
Rv3776 hyp |
hypothetical protein | 757 | 757 ctx | cooccurence:688 |
Rv1702c hyp |
hypothetical protein | 747 | 747 | coexpression:740 |
Rv0336 hyp |
hypothetical protein | 741 | 742 ctx | cooccurence:730 |
Rv0515 hyp |
hypothetical protein | 741 | 742 ctx | cooccurence:730 |
Rv0393 hyp |
hypothetical protein | 733 | 734 ctx | cooccurence:726 |
Rv2100 hyp |
hypothetical protein | 706 | 707 ctx | cooccurence:677 |
Rv1765c hyp |
hypothetical protein | 665 | 665 ctx | cooccurence:657 |
Rv2015c hyp |
hypothetical protein | 631 | 631 ctx | cooccurence:626 |
Rv3464 rmlB |
dTDP-glucose 4,6-dehydratase | 556 | 557 ctx | neighborhood:555 |
Rv3465 rmlC |
dTDP-4-dehydrorhamnose 3,5-epimerase | 554 | 555 ctx | neighborhood:551 |
Rv1378c hyp |
hypothetical protein | 548 | 549 ctx | cooccurence:542 |
Rv3074 hyp |
hypothetical protein | 547 | 548 ctx | cooccurence:532 |
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=1e-71)
- Foldseek best: 4h9d-assembly1_C Crystal Structure of Mn-dependent Gme HNH nicking endonuclease (prob 0.25, E=3e+00, TM=0.74)
- (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_217984.1)
- 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 Q50655 (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 87.8, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
27 functional partner(s); context anchor
rmlB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3467| MSTRQAAEADLAGKAAQYRPDELARYAQRVMDWLHPDGDLTDTERARKRGITLSNQQYDGMSRLSGYLTPQARATFEAVLAKLAAPGATNPDDHTPVIDTTPDAAAIDRDTRSQAQRNHDGLLAGLRALIASGKLGQHNGLPVSIVVTTTLTDLQTGAGKGFTGGGTLLPMADVIRMTSHAHHYSPASGRYPQAIFDHGTPLALYHTKRLASPAQRIMLFANDRGCTKPGCDAPAYHSQAHHVTAWTSTGRTDITELTLACGPDNRLAEKGWTTHNNTHGHTEWLPPPHLDHGQPRTNTFHHPERFLHNQDDDDKPD