Rv1999c Family assigned · medium auto-curated
H37Rv Rv1999c · MTBC0 mtbc0_002126 ·
440 aa · 2267429–2268751 (-) ·
RefSeq NP_216515.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transporter |
|---|---|
| MTBC0 PGAP re-annotation | APC family permease |
| Revised (this work) | APC family permease. Pfam: AA_permease_2 (PF13520.13), AA_permease (PF00324.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQM3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized transporter Rv1999c |
| Curated function | Probable amino-acid or metabolite transport protein. |
UniProt still lists this protein as Uncharacterized transporter Rv1999c; the revised annotation above is ahead of the current UniProt record.
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) pseudogene candidate
| pN/pS | 0.917 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 9 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 1.47% of strains (2136) · 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 | 6.1e-44 | 18–403 | Amino acid permease |
AA_permease | PF00324.28 | 3.8e-35 | 23–344 | Amino acid permease |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0541c (integral membrane protein), medium confidence from genomic context alone (score 547 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0650 |
sugar kinase | 824 | 823 | coexpression:822 |
Rv0218 |
transmembrane protein | 788 | 781 | coexpression:774 |
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 |
Rv0126 treS |
trehalose synthase/amylase TreS | 774 | 763 | experimental:451 database:577 |
Rv0648 |
alpha-mannosidase | 734 | 733 | coexpression:733 |
Rv1998c hyp |
hypothetical protein | 636 | 637 ctx | neighborhood:583 |
Rv2000 hyp |
hypothetical protein | 556 | 555 ctx | neighborhood:554 |
Rv2001 hyp |
hypothetical protein | 547 | 547 ctx | neighborhood:547 |
Rv0541c |
integral membrane protein | 546 | 547 ctx | neighborhood:544 |
Rv0649 fabD2 |
malonyl CoA-acyl carrier protein transacylase | 441 | 441 | coexpression:441 |
Rv0689c hyp |
hypothetical protein | 431 | 431 | coexpression:431 |
Rv0178 |
Mce associated membrane protein | 441 | 419 | |
Rv1973 |
Mce associated membrane protein | 440 | 419 | |
Rv1972 |
Mce associated membrane protein | 439 | 417 |
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: transporter
- MTBC0 PGAP product: APC family permease
- Pfam (hmmscan --cut_ga): AA_permease_2 PF13520.13 (E=6e-44), AA_permease PF00324.28 (E=4e-35)
- (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_216515.1)
- Domains: Pfam-A via hmmscan --cut_ga — AA_permease_2 (PF13520.13), AA_permease (PF00324.28)
- 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 P9WQM3 (SwissProt, reviewed; 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 —
34 functional partner(s); context anchor
Rv0541c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002126|Rv1999c| MRRPLDPRDIPDELRRRLGLLDAVVIGLGSMIGAGIFAALAPAAYAAGSGLLLGLAVAAVVAYCNAISSARLAARYPASGGTYVYGRMRLGDFWGYLAGWGFVVGKTASCAAMALTVGFYVWPAQAHAVAVAVVVALTAVNYAGIQKSAWLTRSIVAVVLVVLTAVVVAAYGSGAADPARLDIGVDAHVWGMLQAAGLLFFAFAGYARIATLGEEVRDPARTIPRAIPLALGITLAVYALVAVAVIAVLGPQRLARAAAPLSEAMRVAGVNWLIPVVQIGAAVAALGSLLALILGVSRTTLAMARDRHLPRWLAAVHPRFKVPFRAELVVGAVVAALAATADIRGAIGFSSFGVLVYYAIANASALTLGLDEGRPRRLIPLVGLIGCVVLAFALPLSSVAAGAAVLGVGVAAYGVRRIITRRARQTDSGDTQRSGHPSAT