Rv1025 Still unknown · low auto-curated
H37Rv Rv1025 · MTBC0 - ·
155 aa · 1146561–1147028 (+) ·
RefSeq NP_215541.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF501. Function unknown. Foldseek best (non-significant) hit: 4xku-assembly1_A E coli BFR variant Y114F (prob 0.01, TM 0.19). |
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 |
P96375
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF501) |
| Orthologous group | COG1507 |
| KEGG orthology |
K09009
|
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 | 0.581 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 3 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 |
|---|---|---|---|---|
DUF501 | PF04417.18 | 1.3e-36 | 17–136 | Protein of unknown function (DUF501) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 86.8 (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 |
|---|---|---|---|---|
4xku-assembly1_A |
0.01 | 0.19 | 7.7e+00 | 4xku-assembly1_A E coli BFR variant Y114F |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1024 (membrane protein), high confidence from genomic context alone (score 885 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) |
|---|---|---|---|---|
Rv1026 ppx2 hyp |
hypothetical protein | 993 | 993 ctx | neighborhood:881 fusion:899 coexpression:500 |
Rv1024 |
membrane protein | 885 | 885 ctx | neighborhood:861 |
Rv1023 eno |
enolase | 876 | 877 ctx | neighborhood:861 |
Rv1022 lpqU |
lipoprotein LpqU | 763 | 763 ctx | neighborhood:762 |
Rv1021 mazG |
nucleoside triphosphate pyrophosphohydrolase | 686 | 687 ctx | neighborhood:682 |
Rv3219 whiB1 |
transcriptional regulator WhiB1 | 656 | 656 ctx | cooccurence:656 |
Rv3260c whiB2 |
transcriptional regulator WhiB2 | 622 | 622 ctx | cooccurence:620 |
Rv1020 mfd |
transcription-repair coupling factor | 620 | 620 ctx | neighborhood:610 |
Rv1830 |
HTH-type transcriptional regulator | 619 | 619 ctx | cooccurence:594 |
Rv1390 rpoZ |
DNA-directed RNA polymerase subunit omega | 594 | 595 ctx | cooccurence:591 |
Rv3195 hyp |
hypothetical protein | 702 | 585 ctx | cooccurence:583 |
Rv1321 nucS |
endonuclease NucS | 532 | 532 ctx | cooccurence:530 |
Rv0807 hyp |
hypothetical protein | 505 | 505 ctx | cooccurence:503 |
Rv1440 secG |
protein-export membrane protein SecG | 491 | 491 ctx | cooccurence:458 |
Rv0004 hyp |
hypothetical protein | 477 | 477 ctx | cooccurence:474 |
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): DUF501 PF04417.18 (E=1e-36)
- Foldseek best: 4xku-assembly1_A E coli BFR variant Y114F (prob 0.01, E=8e+00, TM=0.19)
- (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_215541.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF501 (PF04417.18)
- 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
COG1507 - Curated reference: UniProt P96375 (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 86.8, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
22 functional partner(s); context anchor
Rv1024 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1025| MVTRQLGRAPRGVLAIAYRCPNGEPGVVKTAPRLPDGTPFPTLYYLTHPVLTAAASRLETTGLMREMNRRLGQDAELAAAYRRAHESYLSERDALEPLGTTVSAGGMPDRVKCLHVLIAHSLAKGPGLNPFGDEALALLAAEPRTAATLVAGQWR