Rv2434c Resolved · high auto-curated
H37Rv Rv2434c · MTBC0 mtbc0_002592 ·
481 aa · 2753363–2754808 (-) ·
RefSeq NP_216950.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transmembrane protein |
|---|---|
| MTBC0 PGAP re-annotation | mechanosensitive ion channel |
| Revised (this work) | Mechanosensitive ion channel. Pfam: MS_channel_1st (PF21088.3), MS_channel_2nd (PF00924.25), MS_channel_3rd (PF21082.3), cNMP_binding (PF00027.36). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71915
TrEMBL · unreviewed
· Inferred from homology
|
|---|---|
| UniProt name | Probable conserved transmembrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesisT Signal transduction mechanisms
|
|---|---|
| eggNOG description | mechanosensitive |
| Orthologous group | COG0664 |
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 | 0.422 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 8 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (168) · 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 |
|---|---|---|---|---|
MS_channel_1st | PF21088.3 | 1.1e-05 | 117–158 | Mechanosensitive ion channel, transmembrane helices 2/3 |
MS_channel_2nd | PF00924.25 | 9.1e-20 | 159–225 | Mechanosensitive ion channel, beta-domain |
MS_channel_3rd | PF21082.3 | 9.9e-10 | 231–310 | Mechanosensitive ion channel MscS, C-terminal |
cNMP_binding | PF00027.36 | 1.5e-14 | 353–438 | Cyclic nucleotide-binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2435c (cyclase), high confidence from genomic context alone (score 988 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2435c |
cyclase | 988 | 988 ctx | neighborhood:881 cooccurence:753 experimental:408 |
Rv2433c nrtS hyp |
hypothetical protein | 897 | 897 ctx | neighborhood:882 |
Rv2432c hyp |
hypothetical protein | 887 | 887 ctx | neighborhood:882 |
Rv1320c |
adenylate cyclase | 700 | 681 ctx | neighborhood:496 |
Rv1358 |
transcriptional regulator | 687 | 654 | experimental:440 |
Rv0386 |
transcriptional regulator | 686 | 653 | experimental:440 |
Rv2488c |
LuxR family transcriptional regulator | 685 | 652 | experimental:440 |
Rv1856c |
oxidoreductase | 646 | 632 | database:431 |
Rv1832 gcvB |
glycine dehydrogenase | 605 | 606 | coexpression:602 |
Rv1625c cya |
adenylate cyclase | 608 | 596 | |
Rv2015c hyp |
hypothetical protein | 580 | 581 ctx | cooccurence:569 |
Rv1527c pks5 |
polyketide synthase | 631 | 572 | database:431 |
Rv2048c pks12 |
polyketide synthase | 629 | 569 | database:431 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 628 | 568 | database:431 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 628 | 568 | database:431 |
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
- Legacy H37Rv annotation: transmembrane protein
- MTBC0 PGAP product: mechanosensitive ion channel
- Pfam (hmmscan --cut_ga): MS_channel_1st PF21088.3 (E=1e-05), MS_channel_2nd PF00924.25 (E=9e-20), MS_channel_3rd PF21082.3 (E=1e-09), cNMP_binding PF00027.36 (E=1e-14)
- (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_216950.1)
- Domains: Pfam-A via hmmscan --cut_ga — MS_channel_1st (PF21088.3), MS_channel_2nd (PF00924.25), MS_channel_3rd (PF21082.3), cNMP_binding (PF00027.36)
- 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
COG0664 - Curated reference: UniProt P71915 (TrEMBL, unreviewed; Inferred from homology)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
98 functional partner(s); context anchor
Rv2435c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002592|Rv2434c| MNLLDSTWFYWAVGIAIGLPAGLIVLTELHNILVRRNSHLARQASLLRNYLLPLGAVLLLLVKASEVPAEDPTVRVLTTAFGFLVLVLLLSLLNATLFQGAPQQSWRKRLPAIFVDVARFALIGIGLAVILSYIWGVRVGGLFAALGVTSVVIGLMLQNSVGQIVSGLFMLFEQPFRIDDWLETPTARGRVVEVNWRAVHIDTGSGLQIMPNSMLATTAFTNLSRPAGAHECSITTTFSTSDPPDKVCAMLNRAASALPHVKPGVVPATIARGAAEYRTTVRLTSPADEGPTQATFLRWVWYAARREGLHLDEADDEFSTAERVESALRTVVGPELRLSSSDQQSLARYARLVRYGTDEIVQHAGVVPMGITFVIAGSVRLTVTTDDGSVVAIATLKKGTFLGLTALTRQPDPAGAVALEEVTALQIGREHLEQVVMNKPMLLQELGRVIDERQRKAQQAIRRDLHQSPAAAGEHRGPARR