Rv1132 Family assigned · medium
H37Rv Rv1132 · MTBC0 mtbc0_001215 ·
576 aa · 1265765–1267495 (+) ·
RefSeq NP_215648.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF3556 domain-containing protein |
| Revised (this work) | Polytopic integral membrane protein with 11 predicted transmembrane helices (DeepTMHMM). RefSeq leaves it 'hypothetical protein'. A topological feature consistent with a membrane transporter/permease or membrane-embedded enzyme; the transported substrate and molecular function are undetermined. |
Curated reference (UniProt)
| UniProt |
O06583
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved membrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Transmembrane protein of unknown function (DUF3556) |
| Orthologous group | 2CB1C |
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 | 3.692 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 11 missense, 0 nonsense, 4 frameshift |
| Disruption | 4 distinct premature-stop/frameshift site(s); most common in 2.25% of strains (3269) · convergent |
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 |
|---|---|---|---|---|
DUF3556 | PF12077.14 | 2.7e-288 | 1–573 | Transmembrane protein of unknown function (DUF3556) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 92.9 (very high). 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 |
|---|---|---|---|---|
6l85-assembly1_A |
0.09 | 0.18 | 6.0e-01 | 6l85-assembly1_A The sodium-dependent phosphate transporter |
5cdh-assembly3_E |
0.01 | 0.16 | 6.1e+00 | 5cdh-assembly3_E Structure of Legionella pneumophila Histidine Acid Phosphatase complexed with L(+)-tartrate |
7doq-assembly2_D |
0.01 | 0.17 | 8.3e+00 | 7doq-assembly2_D Lp major histidine acid phosphatase mutant D281A/5'-AMP |
8ipr-assembly2_D |
0.01 | 0.12 | 9.4e+00 | 8ipr-assembly2_D Cryo-EM structure of heme transporter CydDC from Mycobacterium smegmatis in the outward facing ATP bound state |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: prpC (methylcitrate synthase PrpC), high confidence from genomic context alone (score 852 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) |
|---|---|---|---|---|
Rv1131 prpC |
methylcitrate synthase PrpC | 852 | 852 ctx | neighborhood:847 |
Rv1130 prpD |
2-methylcitrate dehydratase | 788 | 789 ctx | neighborhood:783 |
Rv3169 hyp |
hypothetical protein | 637 | 637 ctx | cooccurence:636 |
Rv1129c prpR |
transcriptional regulator | 606 | 606 ctx | neighborhood:553 |
Rv2574 hyp |
hypothetical protein | 572 | 573 ctx | cooccurence:570 |
Rv3830c |
TetR family transcriptional regulator | 525 | 525 ctx | cooccurence:525 |
Rv1125 hyp |
hypothetical protein | 481 | 482 ctx | cooccurence:477 |
Rv1683 |
bifunctional long-chain acyl-CoA synthase/lipase | 480 | 480 ctx | cooccurence:476 |
Rv1203c hyp |
hypothetical protein | 469 | 469 ctx | cooccurence:469 |
Rv0216 |
hydratase | 462 | 463 ctx | cooccurence:461 |
Rv0171 mce1C |
Mce family protein Mce1C | 454 | 455 ctx | cooccurence:452 |
Rv0276 hyp |
hypothetical protein | 448 | 448 ctx | cooccurence:448 |
Rv1429 hyp |
hypothetical protein | 442 | 442 | |
Rv1428c hyp |
hypothetical protein | 438 | 438 ctx | cooccurence:433 |
Rv0172 mce1D |
Mce family protein Mce1D | 437 | 438 ctx | cooccurence:433 |
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
- DeepTMHMM: 11 transmembrane helices (type TM)
- Integral membrane topology (localisation feature, not a function)
- DeepTMHMM topology prediction (project 'Still unknown gene function', phase8, 2026-06-10). A topological feature, not a demonstrated molecular function.
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_215648.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF3556 (PF12077.14)
- 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
2CB1C - Curated reference: UniProt O06583 (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 92.9, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
36 functional partner(s); context anchor
prpC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001215|Rv1132| MGFLQPRLPDIDLAEWSQGSRSQKIRPMAQHWAEVGFGTPVLLHLFYVAKILLYVLVGWLIVLTTKGIDGFTDAAAWYAEPIVFEKVVLYTMLFEVIGLGCGFGPLNNRFFPPMGSILYWMRFGTIRLPPWPDRVPWTRGTKRKPVDVALYALLVMMLLSALFTDGAGPIPELGTTVGLLPAWQIVLILLLLGVLGLRDKVIFLAARGEVYATLTVTFLFGRLNGIDMIVAAKLVFLVIWIGAATSKLNRHFPFVISTMMSNNPLFRPRFIKRMFFKKFPGDLRPGLLSRIVAHVSTVIEMCVPVVLFVAHGGWPTVVAATIMVCFHLGILTAIPMGVPLEWNVFMIFGVLSLFVGHACLGLADVKNPVPLAILIAVVAGIVIAGNVFPRKISFLAAMRYYAGNWDTTLWCIKPSAEDKINRGIVAIASMPAAQLERFYGKDRAQIPMYLGYAFRAMNSHGRALFTLAHRAMAGHDEDDYVITDGERVCSTAVGWNFGDGHLHNEQLIAAMQQRCGFQPGEVRVVLLDAQPIHRQTQEYRLVDAATGEFERGYVRVADMVNRQPWDDDVPVHVLPG