Rv2690c Family assigned · medium auto-curated
H37Rv Rv2690c · MTBC0 - ·
657 aa · 3007236–3009209 (-) ·
RefSeq NP_217206.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | integral membrane protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Integral membrane protein. Pfam: AA_permease_2 (PF13520.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
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 |
I6Y1H7
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable conserved integral membrane alanine and valine and leucine rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| eggNOG description | amino acid |
| Orthologous group | COG0531 |
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 | 0.983 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 11 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.46% of strains (661) · 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 |
|---|---|---|---|---|
AA_permease_2 | PF13520.13 | 7.9e-21 | 60–455 | Amino acid permease |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ceoB (TRK system potassium uptake protein CeoB), high confidence from genomic context alone (score 915 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2691 ceoB |
TRK system potassium uptake protein CeoB | 919 | 915 ctx | neighborhood:775 cooccurence:633 |
Rv2692 ceoC |
TRK system potassium uptake protein CeoC | 914 | 911 ctx | neighborhood:741 cooccurence:665 |
Rv0126 treS |
trehalose synthase/amylase TreS | 776 | 765 | experimental:451 database:577 |
Rv1327c glgE |
alpha-1,4-glucan:maltose-1-phosphate maltosyltransferase | 775 | 764 | experimental:451 database:577 |
Rv2471 aglA |
alpha-glucosidase AglA | 774 | 763 | experimental:451 database:577 |
Rv2689c hyp |
hypothetical protein | 760 | 749 ctx | neighborhood:743 |
Rv2694c hyp |
hypothetical protein | 747 | 747 ctx | cooccurence:740 |
Rv1973 |
Mce associated membrane protein | 502 | 483 | |
Rv0342 iniA |
isoniazid inductible protein IniA | 428 | 429 | |
Rv1362c |
membrane protein | 438 | 416 | |
Rv1363c |
membrane protein | 438 | 416 | |
Rv0200 |
transmembrane protein | 436 | 414 | |
Rv0199 |
membrane protein | 436 | 414 | |
Rv3492c |
Mce associated protein | 435 | 413 | |
Rv2390c hyp |
hypothetical protein | 435 | 413 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): integral membrane protein
- Pfam (hmmscan --cut_ga): AA_permease_2 PF13520.13 (E=8e-21)
- (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_217206.1)
- Domains: Pfam-A via hmmscan --cut_ga — AA_permease_2 (PF13520.13)
- 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
COG0531 - Curated reference: UniProt I6Y1H7 (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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
25 functional partner(s); context anchor
ceoB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2690c| MSKLSTAARRLLIGRPFRSDRLSHTLLPKRIALPVFASDAMSSIAYAPEEIFLVLSVAGLAAYSMAPLIGLAVAAVLLVVVSSYRQNVHAYPSGGGDYEVVTTNLGATGGLVVASALMVDYVLTVAVSISSAASNIGSVSPFVYEHKVLFAVGAIVLIMAMNLRGVRESGLAFAIPTYAFIAGIGTMLVWGLFRIFVLGNPVRAESAAFEMHAEHGQIVGFALVFLVARSFSSGCAALTGVEAISNGVPAFQKPKSRNAATTLLMLGIIAVSMFMGMIVLAVETGVQVVDDPDTQLTGAPPGYQQKTLVAQLAQAVFGGFYLGFLLIAAVTALILVLAANTAFNGFPVLGSVLAQHSYLPRQLHTRGDRLAFSNGILFLAAAAIGAVVAFRAELTALIQLYIVGVFISFTMSQVGMVRHWTRLLSAETDPRARRAMLRSRAVNTVGFVSTGTVLLIVLVTKFLAGAWIAIVAMGGFFMMMKLIHRHYDAVNRELAEQAEEAEITLPSRNHAVVLVSKLHLPTLRALTYARATRPDVLEAVTVNVDDAETRELVRQWQDSDVSVPLKVIASPYREITRPVLDYVKRVSKESPRTVVTVFIPEYVVGRWWEQLLHNQSALRLKGRLLFMPGVMVTSVPWQLTSSERIKTLQPHAAPGDT