Rv3572 Still unknown · low auto-curated
H37Rv Rv3572 · MTBC0 mtbc0_003791 ·
176 aa · 4037188–4037718 (+) ·
RefSeq NP_218089.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 1f0l-assembly2_B 1.55 ANGSTROM CRYSTAL STRUCTURE OF WILD TYPE DIPHTHER (prob 0.92, TM 0.36). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6X7P2
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Secreted protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2ARAU |
|---|
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 | 0.452 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.19% of strains (283) · 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)
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 90.4 (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 |
|---|---|---|---|---|
1f0l-assembly2_B |
0.92 | 0.36 | 1.3e-02 | 1f0l-assembly2_B 1.55 ANGSTROM CRYSTAL STRUCTURE OF WILD TYPE DIPHTHERIA TOXIN |
6qh7-assembly1_M |
0.90 | 0.39 | 2.5e-02 | 6qh7-assembly1_M AP2 clathrin adaptor mu2T156-phosphorylated core with two cargo peptides in open+ conformation |
1f0l-assembly1_A |
0.90 | 0.32 | 6.7e-03 sig | 1f0l-assembly1_A 1.55 ANGSTROM CRYSTAL STRUCTURE OF WILD TYPE DIPHTHERIA TOXIN |
7k7c-assembly1_A |
0.89 | 0.34 | 1.2e-02 | 7k7c-assembly1_A Crystal structure of diphtheria toxin from crystals obtained at pH 5.5 |
7oi5-assembly2_D |
0.85 | 0.33 | 1.2e-02 | 7oi5-assembly2_D Crystal structure of AP2 Mu2 - FCHO2 chimera (GST cleaved) |
3ml6-assembly3_C |
0.85 | 0.36 | 1.6e-02 | 3ml6-assembly3_C a complex between Dishevelled2 and clathrin adaptor AP-2 |
7k7d-assembly1_A |
0.84 | 0.33 | 1.7e-02 | 7k7d-assembly1_A Crystal structure of diphtheria toxin from crystals obtained at pH 6.0 |
8g0f-assembly1_B |
0.84 | 0.31 | 1.1e-02 | 8g0f-assembly1_B Crystal structure of diphtheria toxin H223Q/H257Q double mutant (pH 5.5) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: kshB (3-ketosteroid-9-alpha-hydroxylase reductase subunit), high confidence from genomic context alone (score 857 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) |
|---|---|---|---|---|
Rv3571 kshB |
3-ketosteroid-9-alpha-hydroxylase reductase subunit | 857 | 857 ctx | neighborhood:855 |
Rv3567c hsaB |
flavin-dependent monooxygenase reductase subunit HsaB | 749 | 748 ctx | neighborhood:745 |
Rv3569c hsaD |
4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolase | 733 | 734 ctx | neighborhood:731 |
Rv3568c hsaC |
extradiol dioxygenase | 675 | 676 ctx | neighborhood:671 |
Rv3570c hsaA |
flavin-dependent monooxygenase oxygenase subunit HsaA | 565 | 566 ctx | neighborhood:560 |
Rv3527 hyp |
hypothetical protein | 757 | 55 | textmining:754 |
Rv1139c hyp |
hypothetical protein | 656 | 47 | textmining:654 |
Rv3668c |
protease | 653 | 46 | textmining:652 |
Rv1887 hyp |
hypothetical protein | 542 | 46 | textmining:540 |
Rv2781c |
oxidoreductase | 724 | 44 | textmining:724 |
Rv3036c TB22.2 hyp |
hypothetical protein | 629 | 41 | textmining:629 |
Rv0196 |
HTH-type transcriptional regulator | 618 | 41 | textmining:618 |
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: hypothetical protein
- Foldseek best: 1f0l-assembly2_B 1.55 ANGSTROM CRYSTAL STRUCTURE OF WILD TYPE DIPHTHERIA TOXIN (prob 0.92, E=1e-02, TM=0.36)
- (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_218089.1)
- 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
2ARAU - Curated reference: UniProt I6X7P2 (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 90.4, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
12 functional partner(s); context anchor
kshB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003791|Rv3572| MTRLIPGCTLVGLMLTLLPAPTSAAGSNTATTLFPVDEVTQLETHTFLDCHPNGSCDFVAGANLRTPDGPTGFPPGLWARQTTEIRSTNRLAYLDAHATSQFERVMKAGGSDVITTVYFGEGPPDKYQTTGVIDSTNWSTGQPMTDVNVIVCTHMQVVYPGVNLTSPSTCAQANFS