Rv2134c Still unknown · low
H37Rv Rv2134c · MTBC0 - ·
195 aa · 2394650–2395237 (-) ·
RefSeq NP_216650.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical; function unknown. Structure-based hint rejected: weak fold hit (DUF3090); function unknown. |
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 |
O06241
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 (DUF3090) |
| Orthologous group | 298YA |
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 | 0.359 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 2 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (379) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF3090 | PF11290.14 | 2.0e-69 | 6–175 | Protein of unknown function (DUF3090) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 84.3 (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 |
|---|---|---|---|---|
3k44-assembly1_A |
0.99 | 0.52 | 5.6e-03 sig | 3k44-assembly1_A Crystal Structure of Drosophila melanogaster Pur-alpha |
6l4l-assembly1_A |
0.20 | 0.28 | 1.1e-01 | 6l4l-assembly1_A Crystal structure of S. aureus CntK in inactive state |
3p0c-assembly3_B-2 |
0.15 | 0.41 | 4.0e-01 | 3p0c-assembly3_B-2 Nischarin PX-domain |
6jis-assembly1_A-2 |
0.15 | 0.27 | 2.3e-01 | 6jis-assembly1_A-2 Crystal structure of the histidine racemase CntK in cobalt and nickel transporter system of staphylococcus aureus |
6koi-assembly8_O |
0.13 | 0.40 | 7.8e-01 | 6koi-assembly8_O Crystal structure of SNX11-PXe domain in dimer form. |
6jiw-assembly1_A-2 |
0.12 | 0.28 | 3.2e-01 | 6jiw-assembly1_A-2 Crystal structure of S. aureus CntK with C72S mutation |
3p0c-assembly3_A |
0.10 | 0.38 | 8.3e-01 | 3p0c-assembly3_A Nischarin PX-domain |
4a9c-assembly1_A |
0.10 | 0.37 | 9.9e-01 | 4a9c-assembly1_A Crystal structure of human SHIP2 in complex with biphenyl 2,3',4,5',6- pentakisphosphate |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: uppP (undecaprenyl-diphosphatase), high confidence from genomic context alone (score 807 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) |
|---|---|---|---|---|
Rv2133c hyp |
hypothetical protein | 975 | 975 ctx | neighborhood:879 cooccurence:773 |
Rv2135c hyp |
hypothetical protein | 933 | 934 ctx | neighborhood:800 cooccurence:677 |
Rv2136c uppP |
undecaprenyl-diphosphatase | 806 | 807 ctx | neighborhood:800 |
Rv2137c hyp |
hypothetical protein | 743 | 743 ctx | neighborhood:741 |
Rv2130c mshC |
cysteine:1D-myo-inosityl 2-amino-2-deoxy--D-glucopyranoside ligase | 723 | 723 ctx | neighborhood:544 |
Rv1170 mshB |
1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase | 615 | 615 ctx | cooccurence:613 |
Rv2131c cysQ |
3'(2'),5'-bisphosphate nucleotidase CysQ | 563 | 563 ctx | neighborhood:544 |
Rv1082 mca |
mycothiol S-conjugate amidase | 514 | 515 ctx | cooccurence:509 |
Rv0819 mshD |
mycothiol acetyltransferase | 455 | 455 ctx | cooccurence:447 |
Rv2138 lppL |
lipoprotein LppL | 437 | 437 ctx | neighborhood:433 |
Rv2466c hyp |
hypothetical protein | 440 | 419 ctx | cooccurence:416 |
Rv3753c hyp |
hypothetical protein | 411 | 412 ctx | cooccurence:405 |
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
- Structural Foldseek hit not propagated -- weak fold hit (DUF3090); function unknown
- Reviewed against literature (extended structural cross-check, 2026-06-02)
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_216650.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3090 (PF11290.14)
- 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
298YA - Curated reference: UniProt O06241 (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 84.3, confident)
- 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
uppP - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2134c| MARAIHVFRTPDRFVAGTVGQPGNRTFYLQAVHDSRVVSVVLEKQQVAVLAERIGALLFEVNRRFGTPVPPEPTEIDDLSPLIMPVDAEFRVGTMGLGWDSEAQSVVVELLAVTDAEFDASVVLDDTEEGPDAVRVFLTPESARQFATRSYRVISAGRPPCPLCDEPLDPEGHICARTNGYRRDVLLGSGDDPAG