Rv2012 Family assigned · low auto-curated · to review
H37Rv Rv2012 · MTBC0 - ·
164 aa · 2259326–2259820 (+) ·
RefSeq NP_216528.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | No Pfam domain above threshold; Foldseek indicates a fold similar to 2hh8-assembly1_A Solution NMR structure of the ydfO protein from Escherichia col (prob 1.00, TM 0.74). Structure-based, putative. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
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 |
P9WLM3
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein Rv2012 |
UniProt still lists this protein as Uncharacterized protein Rv2012; 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 (DUF1398) |
| Orthologous group | COG5562 |
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 | 0.509 · 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 |
|---|---|---|---|---|
DUF1398 | PF07166.17 | 7.4e-09 | 44–147 | Protein of unknown function (DUF1398) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 76.0 (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 |
|---|---|---|---|---|
2hh8-assembly1_A |
1.00 | 0.74 | 1.9e-05 sig | 2hh8-assembly1_A Solution NMR structure of the ydfO protein from Escherichia coli. Northeast Structural Genomics target ER251. |
4qt6-assembly1_A |
0.15 | 0.64 | 2.0e+00 | 4qt6-assembly1_A Crystal structure of the SPRY domain of human HERC1 |
6qh1-assembly1_A |
0.06 | 0.22 | 4.5e-01 | 6qh1-assembly1_A The structure of Schizosaccharomyces pombe PCNA in complex with an Spd1 derived peptide |
6qh1-assembly1_B |
0.06 | 0.24 | 5.5e-01 | 6qh1-assembly1_B The structure of Schizosaccharomyces pombe PCNA in complex with an Spd1 derived peptide |
3b8b-assembly1_A |
0.06 | 0.48 | 5.1e+00 | 3b8b-assembly1_A Crystal structure of CysQ from Bacteroides thetaiotaomicron, a bacterial member of the inositol monophosphatase family |
8p9o-assembly1_A |
0.05 | 0.24 | 1.0e+00 | 8p9o-assembly1_A PCNA from Chaetomium thermophilum in complex with PolD3 peptide |
2zvv-assembly2_B |
0.05 | 0.25 | 7.9e-01 | 2zvv-assembly2_B Crystal structure of Proliferating cellular nuclear antigen 1 and Short peptide from human P21 |
6oaq-assembly1_B |
0.05 | 0.23 | 9.6e-01 | 6oaq-assembly1_B Crystal structure of a dual sensor histidine kinase in BeF3- bound state |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2011c hyp |
hypothetical protein | 598 | 598 ctx | neighborhood:587 |
Rv0991c hyp |
hypothetical protein | 553 | 55 | textmining:547 |
Rv0990c hyp |
hypothetical protein | 801 | 49 | textmining:800 |
Rv3224 |
iron-regulated short-chain dehydrogenase/reductase | 809 | 42 | textmining:809 |
Rv3729 |
transferase | 803 | 42 | textmining:803 |
Rv2541 hyp |
hypothetical protein | 803 | 41 | textmining:803 |
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): DUF1398 PF07166.17 (E=7e-09)
- Foldseek best: 2hh8-assembly1_A Solution NMR structure of the ydfO protein from Escherichia col (prob 1.00, E=2e-05, 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_216528.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF1398 (PF07166.17)
- 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
COG5562 - Curated reference: UniProt P9WLM3 (SwissProt, reviewed; 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 76.0, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 6 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2012| MLSKSKRSCRRRETLRIGEKMSAPITNLQAAQRDAIMNRPAVNGFPHLAETLRRAGVRTNTWWLPAMQSLYETDYGPVLDQGVPLIDGVAEVPAFDRTALVTALRADQAGQTSFREFAAAAWRAGVLRYVVDLENRTCTYFGLHDQTYMEHYAAVEPSGGAPTS