Rv1431 Family assigned · medium
H37Rv Rv1431 · MTBC0 mtbc0_001531 ·
589 aa · 1617427–1619196 (+) ·
RefSeq NP_215947.1
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 |
O06827
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 | 0.598 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 9 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.29% of strains (424) · 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 |
|---|---|---|---|---|
DUF3556 | PF12077.14 | 2.3e-275 | 1–580 | Transmembrane protein of unknown function (DUF3556) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 90.6 (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 |
|---|---|---|---|---|
5zm6-assembly1_B-2 |
0.23 | 0.76 | 6.0e+00 | 5zm6-assembly1_B-2 Crystal structure of ORP1-ORD in complex with PI(4,5)P2 |
5zm8-assembly1_A |
0.06 | 0.39 | 8.5e+00 | 5zm8-assembly1_A Crystal structure of ORP2-ORD in complex with PI(4,5)P2 |
8qyo-assembly1_P |
0.02 | 0.26 | 6.3e+00 | 8qyo-assembly1_P Human proteasome 20S core particle |
8th3-assembly1_A |
0.01 | 0.12 | 6.3e+00 | 8th3-assembly1_A Structure of AT118-H Nanobody Antagonist in Complex with the Angiotensin II Type I Receptor |
7qoa-assembly2_B |
0.01 | 0.13 | 5.1e+00 | 7qoa-assembly2_B Structure of CodB, a cytosine transporter in an outward-facing conformation |
4c5r-assembly1_A |
0.01 | 0.09 | 3.9e+00 | 4c5r-assembly1_A Structural Investigations into the Stereochemistry and Activity of a Phenylalanine-2,3-Aminomutase from Taxus chinensis |
2yii-assembly1_B |
0.01 | 0.09 | 3.4e+00 | 2yii-assembly1_B Manipulating the regioselectivity of phenylalanine aminomutase: new insights into the reaction mechanism of MIO-dependent enzymes from structure-guided directed evolution |
6afv-assembly1_A |
0.01 | 0.10 | 7.5e+00 | 6afv-assembly1_A Proton pyrophosphatase-L555K mutant |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1432 (dehydrogenase), high confidence from genomic context alone (score 931 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) |
|---|---|---|---|---|
Rv1432 |
dehydrogenase | 931 | 931 ctx | neighborhood:882 cooccurence:415 |
Rv1429 hyp |
hypothetical protein | 660 | 660 ctx | cooccurence:466 |
Rv1430 PE16 |
PE family protein PE16 | 551 | 551 ctx | neighborhood:551 |
Rv1428c hyp |
hypothetical protein | 527 | 527 | |
Rv3830c |
TetR family transcriptional regulator | 506 | 507 ctx | cooccurence:504 |
Rv3169 hyp |
hypothetical protein | 503 | 504 ctx | cooccurence:499 |
Rv1433 ldtMt3 hyp |
hypothetical protein | 497 | 497 ctx | neighborhood:495 |
Rv3829c |
dehydrogenase | 436 | 437 ctx | cooccurence:416 |
Rv2574 hyp |
hypothetical protein | 436 | 436 ctx | cooccurence:434 |
Rv1203c hyp |
hypothetical protein | 430 | 431 ctx | cooccurence:428 |
Rv0176 |
Mce associated transmembrane protein | 430 | 431 ctx | cooccurence:428 |
Rv1683 |
bifunctional long-chain acyl-CoA synthase/lipase | 417 | 417 ctx | cooccurence:414 |
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_215947.1)
- 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 O06827 (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 90.6, very high)
- 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
Rv1432 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001531|Rv1431| MGFLKPDLPDVDHDTWLTQPRRTRLQVVTRDWVEHGFGTPYAVYLLYLTKIAVYVAAGAAIISLTPGLGGLSRIGDWWTQPIVYQKVIVFTLLFEVLGFGCGSGPLTGRFWPPIGGFLYWLRPNTIRLPAWPDKVPFTQGDTRTVVDVALYAIVLIGGVWALLSPGSPGPGGTPVTAAGDVGLINPVLVVPTIVALGVLGLRDKTIFLAARGEHYWLKLFVFFFPFTDQIAAFKIIMLCLWWGAATSKLNHHFPYVVAVMTSNNALLRSRVFNPIKHLLYRDHANDLRPSWLPKLMAHGGGTTAEFLVPGILVLVADGHPWRWFLIGFMVLFHLNILSNLPMGVPLEWNVFFIFSLCYLFGHYGAITATDLRSPLLLAIVIAVVAVVIMGNLLPEKISFLPAMRYYAGNWATSIWCFRGDAEATMETSVVKSSALVVNQLAKLYDGATAEIMTDKVAAFRAMHTHGRALNGLLPRALDDEAHYRIREGEIVAGPLVGWNFGEGHLHNEQLVAAVQRRCNFADGDLRVIILEGQPIHVQKQWYRIVDAKTGLFEAGYVTVEDMLSRQPWPEPGDEFPVHVTTQRGTPSKP