Rv2137c Still unknown · low auto-curated
H37Rv Rv2137c · MTBC0 - ·
137 aa · 2396902–2397315 (-) ·
RefSeq NP_216653.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 6hhm-assembly1_A Crystal structure of the family S1_7 ulvan-specific s (prob 0.63, TM 0.66). |
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 |
O06238
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 | 2B14F |
|---|
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 | 0.508 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 missense, 2 nonsense, 0 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.56% of strains (810) · 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 52.8 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.
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 |
|---|---|---|---|---|
6hhm-assembly1_A |
0.63 | 0.66 | 7.8e-01 | 6hhm-assembly1_A Crystal structure of the family S1_7 ulvan-specific sulfatase FA22070 from Formosa agariphila |
5c8b-assembly1_B |
0.57 | 0.59 | 5.2e-01 | 5c8b-assembly1_B Structural insights into the redesign of a sucrose phosphorylase by induced loop repositioning |
8ceo-assembly1_p |
0.20 | 0.56 | 2.4e+00 | 8ceo-assembly1_p Yeast RNA polymerase II transcription pre-initiation complex with core Mediator and the +1 nucleosome |
6ioz-assembly1_A |
0.16 | 0.55 | 3.4e+00 | 6ioz-assembly1_A Structural insights of idursulfase beta |
3a24-assembly1_A |
0.15 | 0.50 | 1.6e+00 | 3a24-assembly1_A Crystal structure of BT1871 retaining glycosidase |
5man-assembly1_B |
0.14 | 0.59 | 4.3e+00 | 5man-assembly1_B Structure of sucrose phosphorylase from Bifidobacterium adolescentis bound to nigerose |
4xf2-assembly2_Y |
0.13 | 0.48 | 1.6e+00 | 4xf2-assembly2_Y Tetragonal structure of Arp2/3 complex |
5fql-assembly1_A-2 |
0.12 | 0.52 | 4.1e+00 | 5fql-assembly1_A-2 Insights into Hunter syndrome from the structure of iduronate-2- sulfatase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: uppP (undecaprenyl-diphosphatase), high confidence from genomic context alone (score 801 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) |
|---|---|---|---|---|
Rv2136c uppP |
undecaprenyl-diphosphatase | 841 | 801 ctx | neighborhood:800 |
Rv2135c hyp |
hypothetical protein | 800 | 801 ctx | neighborhood:800 |
Rv2134c hyp |
hypothetical protein | 743 | 743 ctx | neighborhood:741 |
Rv2133c hyp |
hypothetical protein | 741 | 742 ctx | neighborhood:740 |
Rv2138 lppL |
lipoprotein LppL | 591 | 591 ctx | neighborhood:591 |
Rv2130c mshC |
cysteine:1D-myo-inosityl 2-amino-2-deoxy--D-glucopyranoside ligase | 546 | 547 ctx | neighborhood:544 |
Rv2131c cysQ |
3'(2'),5'-bisphosphate nucleotidase CysQ | 545 | 546 ctx | neighborhood:544 |
Rv2139 pyrD |
dihydroorotate dehydrogenase | 400 | 400 | |
Rv2694c hyp |
hypothetical protein | 629 | 44 | textmining:628 |
Rv3848 |
transmembrane protein | 490 | 44 | textmining:489 |
Rv1909c furA |
ferric uptake regulation protein FurA | 480 | 44 | textmining:479 |
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
- Foldseek best: 6hhm-assembly1_A Crystal structure of the family S1_7 ulvan-specific sulfatase F (prob 0.63, E=8e-01, TM=0.66)
- (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_216653.1)
- 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
2B14F - Curated reference: UniProt O06238 (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 52.8, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
11 functional partner(s); context anchor
uppP - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2137c| MRNMKSTSHESESGKLLSISSCRPREMVLQRYSLGMTVTADRHLADKREEFAVEDISTGIFASGYGQVGDGRSFSFHIEHRSLVVEIYRPRVAGPVPQAEDVVAMAVRGLVDIDLTDERSLAAAVRDSVASAAPVSR