yrbE4A Family assigned · medium auto-curated
H37Rv Rv3501c · MTBC0 mtbc0_003716 ·
254 aa · 3944679–3945443 (-) ·
RefSeq NP_218018.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | integral membrane 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 |
O53546
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved integral membrane protein YrbE4A. Possible ABC transporter |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | yrbE4A |
| 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 | 0.152 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 2 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
MlaE | PF02405.22 | 2.1e-61 | 36–247 | 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).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0655 mkl |
ABC transporter ATP-binding protein | 987 | 987 ctx | cooccurence:773 coexpression:458 experimental:505 database:800 |
Rv3497c mce4C |
Mce family protein Mce4C | 985 | 975 ctx | neighborhood:815 cooccurence:771 textmining:445 |
Rv3496c mce4D |
Mce family protein Mce4D | 985 | 974 ctx | neighborhood:815 cooccurence:769 textmining:470 |
Rv3495c lprN |
Mce family lipoprotein LprN | 979 | 973 ctx | neighborhood:815 cooccurence:759 |
Rv3494c mce4F |
Mce family protein Mce4 | 993 | 967 ctx | neighborhood:813 cooccurence:704 textmining:807 |
Rv3498c mce4B |
Mce family protein Mce4B | 982 | 962 ctx | neighborhood:722 cooccurence:771 textmining:563 |
Rv3499c mce4A |
Mce family protein Mce4A | 983 | 952 ctx | neighborhood:669 cooccurence:752 textmining:662 |
Rv3500c yrbE4B |
integral membrane protein | 960 | 936 ctx | neighborhood:833 textmining:407 |
Rv3492c |
Mce associated protein | 883 | 883 ctx | neighborhood:813 |
Rv0170 mce1B |
Mce family protein Mce1B | 877 | 872 ctx | cooccurence:770 |
Rv1971 mce3F |
Mce family protein Mce3F | 874 | 872 ctx | cooccurence:768 |
Rv0590 mce2B |
Mce-family protein Mce2B; Rv0590, (MTCY19H5.32c), len: 275 aa. Mce2B; belongs to 24-membered Mycobacterium tuberculosis Mce protein family ( | 900 | 871 ctx | cooccurence:770 |
Rv0592 mce2D |
Mce family protein Mce2D | 902 | 870 ctx | cooccurence:764 |
Rv1967 mce3B |
Mce family protein Mce3B | 875 | 870 ctx | cooccurence:768 |
Rv1968 mce3C |
Mce family protein Mce3C | 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: integral membrane protein
- MTBC0 PGAP product: ABC transporter permease
- Pfam (hmmscan --cut_ga): MlaE PF02405.22 (E=2e-61)
- (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_218018.1)
- 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 O53546 (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 —
50 functional partner(s); context anchor
mkl - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003716|Rv3501c|yrbE4A MIQQLAVPARAVGGFFEMSMDTARAAFRRPFQFREFLDQTWMVARVSLVPTLLVSIPFTVLVAFTLNILLREIGAADLSGAGTAFGTITQLGPVVTVLVVAGAGATAICADLGARTIREEIDAMRVLGIDPIQRLVVPRVLASTLVALLLNGLVCAIGLSGGYAFSVFLQGVNPGAFINGLTVLTGLRELILAEIKALLFGVMAGLVGCYRGLTVKGGPKGVGNAVNETVVYAFICLFVINVVMTAIGVRISAQ