Rv2016 Still unknown · low auto-curated
H37Rv Rv2016 · MTBC0 mtbc0_002146 ·
191 aa · 2287039–2287614 (+) ·
RefSeq NP_216532.1
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: 2e2l-assembly1_E Helicobacter pylori formamidase AmiF contains a fine- (prob 0.13, TM 0.52). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53462
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2BFQR |
|---|
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 | 0.587 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 11 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)
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 89.6 (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 |
|---|---|---|---|---|
2e2l-assembly1_E |
0.13 | 0.52 | 1.6e+00 | 2e2l-assembly1_E Helicobacter pylori formamidase AmiF contains a fine-tuned cysteine-glutamate-lysine catalytic triad |
2e2k-assembly1_C |
0.12 | 0.52 | 1.7e+00 | 2e2k-assembly1_C Helicobacter pylori formamidase AmiF contains a fine-tuned cysteine-glutamate-lysine catalytic triad |
2vhh-assembly1_A-2 |
0.08 | 0.53 | 2.8e+00 | 2vhh-assembly1_A-2 Crystal structure of a pyrimidine degrading enzyme from Drosophila melanogaster |
2dyu-assembly1_B |
0.06 | 0.52 | 5.5e+00 | 2dyu-assembly1_B Helicobacter pylori formamidase AmiF contains a fine-tuned cysteine-glutamate-lysine catalytic triad |
2e2k-assembly1_A |
0.06 | 0.57 | 6.6e+00 | 2e2k-assembly1_A Helicobacter pylori formamidase AmiF contains a fine-tuned cysteine-glutamate-lysine catalytic triad |
2e2l-assembly1_D |
0.06 | 0.52 | 5.9e+00 | 2e2l-assembly1_D Helicobacter pylori formamidase AmiF contains a fine-tuned cysteine-glutamate-lysine catalytic triad |
7t10-assembly1_R |
0.05 | 0.43 | 7.5e+00 | 7t10-assembly1_R CryoEM structure of somatostatin receptor 2 in complex with somatostatin-14 and Gi3 |
2vhi-assembly1_A |
0.05 | 0.53 | 5.9e+00 | 2vhi-assembly1_A Crystal structure of a pyrimidine degrading enzyme from Drosophila melanogaster |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2017 (transcriptional regulator), high confidence from genomic context alone (score 846 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) |
|---|---|---|---|---|
Rv2017 |
transcriptional regulator | 927 | 846 ctx | neighborhood:809 textmining:544 |
Rv2018 vapB45 hyp |
hypothetical protein | 470 | 470 ctx | neighborhood:443 |
Rv2019 vapC45 hyp |
hypothetical protein | 577 | 430 ctx | neighborhood:427 |
Rv2515c hyp |
hypothetical protein | 476 | 102 | textmining:441 |
Rv2165c rsmH |
rRNA small subunit methyltransferase H | 444 | 55 | textmining:436 |
Rv1765c hyp |
hypothetical protein | 442 | 51 | textmining:437 |
Rv3641c fic |
cell filamentation protein Fic | 654 | 50 | textmining:651 |
Rv0208c trmB |
tRNA (guanine-N(7)-)-methyltransferase | 440 | 50 | textmining:435 |
Rv2514c hyp |
hypothetical protein | 624 | 47 | textmining:622 |
Rv0078A hyp |
hypothetical protein | 441 | 47 | textmining:438 |
Rv0207c hyp |
hypothetical protein | 436 | 47 | textmining:433 |
Rv0229c vapC51 hyp |
hypothetical protein | 651 | 46 | textmining:650 |
Rv0268c hyp |
hypothetical protein | 631 | 46 | textmining:630 |
Rv3383c idsB |
polyprenyl synthetase IdsB | 654 | 44 | textmining:653 |
Rv1469 ctpD |
cobalt/nickel-exporting P-type ATPase | 653 | 44 | textmining:652 |
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: 2e2l-assembly1_E Helicobacter pylori formamidase AmiF contains a fine-tuned cyst (prob 0.13, E=2e+00, TM=0.52)
- (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_216532.1)
- 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
2BFQR - Curated reference: UniProt O53462 (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 89.6, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
25 functional partner(s); context anchor
Rv2017 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002146|Rv2016| MTELGDKFLAALVGTIRDTRFDIADMRNWRPGWFPTMHSRCLSNLIHDRIWAHLVTLIASNPGTSIKDKGATREIVVGAHLRLRIKRHHAGDEISTYPTRTAIEFWQQGSQPAFPGLEEVRIAVGYRWDPDTREIGAPLLSLRDGKDHVIWVVELDEPAAGVKITWTPIEPTLPSIDFGDLGEDSGASGER