Rv3491 Family assigned · medium
H37Rv Rv3491 · MTBC0 mtbc0_003706 ·
192 aa · 3934472–3935050 (+) ·
RefSeq NP_218008.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Membrane-anchored protein with a PknI-sensor-domain-like extracytoplasmic sensor fold; distinct from PknI/Rv2914c (fold-paralogue safeguard); ligand/partner undetermined RefSeq leaves this locus uncharacterised. |
Curated reference (UniProt)
| UniProt |
I6XHD1
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Secreted protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2AQE9 |
|---|
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 | 0.08 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 1 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)
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 79.8 (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 |
|---|---|---|---|---|
8ass-assembly2_C |
0.80 | 0.50 | 2.4e-01 | 8ass-assembly2_C The Crystal structure of F46Y mutant of the agroavidin-biotin complex |
1iiu-assembly1_A |
0.38 | 0.38 | 3.4e-01 | 1iiu-assembly1_A Chicken plasma retinol-binding protein (RBP) |
4h8p-assembly1_A |
0.33 | 0.31 | 1.3e-01 | 4h8p-assembly1_A NEAT5 domain of IsdX2, a B. anthracis hemophore in complex with heme |
4h8q-assembly1_A |
0.23 | 0.32 | 2.9e-01 | 4h8q-assembly1_A Structure of the Q29T IsdX2-NEAT5 mutant in complex with heme |
1l3a-assembly1_C |
0.13 | 0.29 | 9.9e-01 | 1l3a-assembly1_C Structure of the plant transcriptional regulator PBF-2 |
2lfu-assembly1_A |
0.11 | 0.30 | 1.2e+00 | 2lfu-assembly1_A The structure of a N. meningitides protein targeted for vaccine development |
1qab-assembly1_F |
0.11 | 0.33 | 1.9e+00 | 1qab-assembly1_F The structure of human retinol binding protein with its carrier protein transthyretin reveals interaction with the carboxy terminus of RBP |
8huy-assembly1_B |
0.10 | 0.20 | 1.3e-01 | 8huy-assembly1_B N-acetyl-(R)-beta-phenylalanine acylase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: otsA (trehalose-phosphate synthase), medium confidence from genomic context alone (score 559 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) |
|---|---|---|---|---|
Rv2006 otsB1 |
trehalose-6-phosphate phosphatase OtsB | 821 | 747 | coexpression:651 |
Rv3372 otsB2 |
trehalose 6-phosphate phosphatase | 737 | 692 | coexpression:650 |
Rv3490 otsA |
trehalose-phosphate synthase | 559 | 559 ctx | neighborhood:539 |
Rv3489 hyp |
hypothetical protein | 523 | 523 ctx | neighborhood:511 |
Rv1954A |
Rv1954A, len: 100 aa. Hypothetical unknown protein. | 432 | 432 | coexpression:432 |
Rv2771c hyp |
hypothetical protein | 418 | 419 | coexpression:418 |
Rv0007 |
membrane protein | 415 | 416 | coexpression:416 |
Rv0888 spmT hyp |
hypothetical protein | 412 | 413 | coexpression:413 |
Rv1884c rpfC |
resuscitation-promoting factor RpfC | 431 | 410 | coexpression:410 |
Rv1449c tkt |
transketolase | 407 | 408 | coexpression:408 |
Rv0925c hyp |
hypothetical protein | 404 | 405 | coexpression:404 |
Rv2450c rpfE |
resuscitation-promoting factor RpfE | 424 | 403 | coexpression:403 |
Rv3835 hyp |
hypothetical protein | 809 | 74 | textmining:803 |
Rv2799 |
membrane protein | 873 | 70 | textmining:870 |
Rv1887 hyp |
hypothetical protein | 757 | 57 | textmining:753 |
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
- HHpred (Neff 6.07, signal peptide+TM): top hit 5XLM_B PknI extracellular sensor domain Prob 99.6%, E 3.2e-14, 125 cols (also 5XLL); NOT PknI (=Rv2914c); same sensor fold as Rv2253
- HHpred web (MPI Bioinformatics Toolkit, profile-profile remote homology), interpreted in project 'Still unknown gene function', 2026-06-10. A fold/family-level assignment, not a demonstrated 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_218008.1)
- 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
2AQE9 - Curated reference: UniProt I6XHD1 (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 79.8, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
24 functional partner(s); context anchor
otsA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003706|Rv3491| MNIRCGLAAGAVICSAVALGIALHSGDPARALGPPPDGSYSFNQAGVSGVTWTITALCDQPSGTRNMNDYSDPIVWAFNCALNVVSTTPQQITRTDRLQNFSGRARMSSMLWTFQVNQADGVACPDGSTAPSSETYAFSDETLTGTHTTVHGAVCGLQPKLSKQPFSLQLIGPPPSPVQRYPLYCNNIAMCY