yrbE2A Family assigned · medium auto-curated
H37Rv Rv0587 · MTBC0 mtbc0_000617 ·
265 aa · 688680–689477 (+) ·
RefSeq NP_215101.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | ABC transporter permease |
| Revised (this work) | ABC transporter permease. Pfam: MlaE (PF02405.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6Y870
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved hypothetical integral membrane protein YrbE2A |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | yrbE1A |
| eggNOG description | ABC-type transport system involved in resistance to organic solvents, permease component |
| Orthologous group | COG0767 |
| KEGG orthology |
K02066
|
| KEGG pathways |
map02010
|
| KEGG modules |
M00210, M00669, M00670
|
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 | 0.147 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 3 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (205) · 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 |
|---|---|---|---|---|
MlaE | PF02405.22 | 9.7e-57 | 47–256 | Permease MlaE |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mkl (ABC transporter ATP-binding protein), high confidence from genomic context alone (score 987 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) |
|---|---|---|---|---|
Rv0588 yrbE2B hyp |
hypothetical protein | 991 | 989 ctx | neighborhood:882 coexpression:806 |
Rv0655 mkl |
ABC transporter ATP-binding protein | 987 | 987 ctx | cooccurence:773 coexpression:455 experimental:505 database:800 |
Rv0591 mce2C |
Mce family protein Mce2C | 982 | 982 ctx | neighborhood:881 cooccurence:749 |
Rv0589 mce2A |
Mce family protein Mce2A | 991 | 974 ctx | neighborhood:786 cooccurence:733 textmining:667 |
Rv0590 mce2B |
Mce-family protein Mce2B; Rv0590, (MTCY19H5.32c), len: 275 aa. Mce2B; belongs to 24-membered Mycobacterium tuberculosis Mce protein family ( | 973 | 972 ctx | neighborhood:786 cooccurence:769 |
Rv0592 mce2D |
Mce family protein Mce2D | 970 | 968 ctx | neighborhood:781 cooccurence:761 |
Rv0593 lprL |
Mce family lipoprotein LprL | 968 | 968 ctx | neighborhood:781 cooccurence:756 |
Rv0594 mce2F |
Mce family protein Mce2F | 991 | 967 ctx | neighborhood:785 cooccurence:751 textmining:734 |
Rv0586 mce2R |
HTH-type transcriptional regulator Mce2R | 985 | 889 ctx | neighborhood:882 textmining:870 |
Rv0174 mce1F |
Mce family protein Mce1F | 914 | 888 ctx | cooccurence:734 |
Rv0171 mce1C |
Mce family protein Mce1C | 888 | 885 ctx | cooccurence:727 |
Rv0590A |
Mce-family related protein; Rv0590A, len: 84 aa. Probable continuation of mce2B|Rv0590. Can find no frameshift to account for this. Possible | 881 | 877 ctx | neighborhood:786 |
Rv3497c mce4C |
Mce family protein Mce4C | 876 | 874 ctx | cooccurence:768 |
Rv1967 mce3B |
Mce family protein Mce3B | 876 | 872 ctx | cooccurence:766 |
Rv0170 mce1B |
Mce family protein Mce1B | 874 | 870 ctx | cooccurence:768 |
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: hypothetical protein
- MTBC0 PGAP product: ABC transporter permease
- Pfam (hmmscan --cut_ga): MlaE PF02405.22 (E=1e-56)
- (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_215101.1)
- Domains: Pfam-A via hmmscan --cut_ga — MlaE (PF02405.22)
- 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
COG0767 - Curated reference: UniProt I6Y870 (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 —
44 functional partner(s); context anchor
mkl - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000617|Rv0587|yrbE2A MTTHAVIITYLRDQTQPAVDAIGGFYRTCVLTGKALVRRPFHWREAIEQGWFITSVSLLPTLAVSIPLTVLIIFTLNILLAEFGAADISGAGAALGAVTQLGPLTTVLVIAGAGATAICADLGARTIREEIDAMEVLGIDPIHRLVVPRVVAATIVAALLNGAVITIGLVGGFVFSVFIQHVSAGAYVGTLTLVTGLPEVIISVVKSATFGLIAGLVGCYRGLTTKGGPKGVGTAVNETLVLCVIALFATNVVLTTIGVRFGTGH