Rv3253c Resolved · high auto-curated
H37Rv Rv3253c · MTBC0 mtbc0_003461 ·
495 aa · 3654240–3655727 (-) ·
RefSeq NP_217770.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cationic amino acid transport integral membrane protein |
|---|---|
| MTBC0 PGAP re-annotation | amino acid permease |
| Revised (this work) | Amino acid permease. Pfam: AA_permease_2 (PF13520.13), AA_permease (PF00324.28), AA_permease_C (PF13906.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05896
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Possible cationic amino acid transport integral membrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| eggNOG description | amino acid |
| Orthologous group | COG0531 |
| KEGG orthology |
K03294
|
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 | 0.372 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 5 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 |
|---|---|---|---|---|
AA_permease_2 | PF13520.13 | 4.0e-55 | 28–452 | Amino acid permease |
AA_permease | PF00324.28 | 6.0e-40 | 33–451 | Amino acid permease |
AA_permease_C | PF13906.13 | 6.2e-18 | 430–480 | C-terminus of AA_permease |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rubB (rubredoxin RubB), high confidence from genomic context alone (score 769 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3250c rubB |
rubredoxin RubB | 769 | 769 ctx | neighborhood:768 |
Rv1327c glgE |
alpha-1,4-glucan:maltose-1-phosphate maltosyltransferase | 775 | 764 | experimental:451 database:577 |
Rv0126 treS |
trehalose synthase/amylase TreS | 774 | 763 | experimental:451 database:577 |
Rv2471 aglA |
alpha-glucosidase AglA | 774 | 763 | experimental:451 database:577 |
Rv3254 hyp |
hypothetical protein | 856 | 598 ctx | neighborhood:553 textmining:658 |
Rv3252c alkB |
transmembrane alkane 1-monooxygenase AlkB | 586 | 585 ctx | neighborhood:577 |
Rv3251c rubA |
rubredoxin RubA | 576 | 576 ctx | neighborhood:575 |
Rv3249c |
TetR family transcriptional regulator | 555 | 556 ctx | neighborhood:553 |
Rv3248c sahH |
adenosylhomocysteinase | 482 | 462 ctx | neighborhood:441 |
Rv0178 |
Mce associated membrane protein | 445 | 424 | |
Rv1363c |
membrane protein | 441 | 419 | |
Rv0200 |
transmembrane protein | 440 | 419 | |
Rv0199 |
membrane protein | 438 | 416 | |
Rv3492c |
Mce associated protein | 438 | 416 | |
Rv2390c hyp |
hypothetical protein | 436 | 414 |
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: cationic amino acid transport integral membrane protein
- MTBC0 PGAP product: amino acid permease
- Pfam (hmmscan --cut_ga): AA_permease_2 PF13520.13 (E=4e-55), AA_permease PF00324.28 (E=6e-40), AA_permease_C PF13906.13 (E=6e-18)
- (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_217770.1)
- Domains: Pfam-A via hmmscan --cut_ga — AA_permease_2 (PF13520.13), AA_permease (PF00324.28), AA_permease_C (PF13906.13)
- 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 O05896 (TrEMBL, unreviewed; Predicted)
- 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 —
26 functional partner(s); context anchor
rubB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003461|Rv3253c| MAGRRRMKSVEQSIADTDEPTTRLRKDLTWWDLVVFGVSVVIGAGIFTVTASTAGDITGPAIWISFLIAAATCALAALCYAEFASTLPVAGSAYTFSYATFGEFLAWVIGWNLVLELAMGAAVVAKGWSSYLGTVFGFGNGTGHLGSLQLDWGALVIVTLVATLIALGTKLSSRFSAVVTAIKVSVVVLVVVVGAFYIRAANYSPFIPEPEVQHHGGGLDQSVFSLLTGAQGSHYGWYGVLAGASIVFFAFIGFDIVATMAEETKRPQRDVPRGILASLGVVTLLYVAVSVVLSGMVPYTQLRTVPGRGPANLATAFQANGVYWASGIISVGALAGLTTVVMVLMLGQCRVLFAMARDGLVPRQLAKTGSRGTPVRVTVLVAVLVATTASVFPITKLEEMVNVGTLFAFILVSAGVVVLRRTRPDLQRGFTAPWVPLLPIAAVCACLWLMLNLTALTWIRFGIWLVAGTAIYVGYGRRHSAQGLRQARESATRRC