Rv2456c Resolved · high auto-curated
H37Rv Rv2456c · MTBC0 mtbc0_002615 ·
418 aa · 2781184–2782440 (-) ·
RefSeq NP_216972.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | MFS-type transporter |
|---|---|
| MTBC0 PGAP re-annotation | MFS transporter |
| Revised (this work) | MFS transporter. Pfam: MFS_1 (PF07690.22), MFS_1_like (PF12832.14). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJX1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized MFS-type transporter Rv2456c |
UniProt still lists this protein as Uncharacterized MFS-type transporter Rv2456c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolismG Carbohydrate transport and metabolismP Inorganic ion transport and metabolism
|
|---|---|
| eggNOG description | Thought to be involved in transport of undeterminated substrate (possibly sugar) across the membrane. responsible for the translocation of the substrate across the membrane |
| Orthologous group | COG0477 |
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 | 1.001 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 8 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 |
|---|---|---|---|---|
MFS_1 | PF07690.22 | 2.2e-33 | 21–344 | Major Facilitator Superfamily |
MFS_1_like | PF12832.14 | 4.6e-15 | 30–372 | MFS_1 like family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: clpX (ATP-dependent CLP protease ATP-binding subunit ClpX), high confidence from genomic context alone (score 821 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2457c clpX |
ATP-dependent CLP protease ATP-binding subunit ClpX | 912 | 821 ctx | neighborhood:812 textmining:530 |
Rv2454c korB |
2-oxoglutarate oxidoreductase subunit KorB | 692 | 659 ctx | neighborhood:659 |
Rv2453c mobA |
molybdenum cofactor guanylyltransferase | 796 | 568 ctx | neighborhood:563 textmining:547 |
Rv2289 cdh |
CDP-diacylglycerol pyrophosphatase | 503 | 504 ctx | cooccurence:489 |
Rv2455c korA |
2-oxoglutarate oxidoreductase subunit KorA | 563 | 501 ctx | neighborhood:501 |
Rv2458 mmuM |
homocysteine S-methyltransferase MmuM | 431 | 431 ctx | neighborhood:419 |
Rv3190c hyp |
hypothetical protein | 413 | 413 ctx | cooccurence:410 |
Rv2452c hyp |
hypothetical protein | 402 | 402 | |
Rv3402c hyp |
hypothetical protein | 892 | 233 | textmining:866 |
Rv2425c hyp |
hypothetical protein | 871 | 53 | textmining:870 |
Rv1624c |
membrane protein | 870 | 47 | textmining:870 |
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: MFS-type transporter
- MTBC0 PGAP product: MFS transporter
- Pfam (hmmscan --cut_ga): MFS_1 PF07690.22 (E=2e-33), MFS_1_like PF12832.14 (E=5e-15)
- (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_216972.1)
- Domains: Pfam-A via hmmscan --cut_ga — MFS_1 (PF07690.22), MFS_1_like (PF12832.14)
- 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
COG0477 - Curated reference: UniProt P9WJX1 (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 —
11 functional partner(s); context anchor
clpX - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002615|Rv2456c| MSGTVVAVPPRVARALDLLNFSLADVRDGLGPYLSIYLLLIHDWDQASIGFVMAVGGIAAIVAQTPIGALVDRTTAKRALVVAGAVLVTAAAVAMPLFAGLYSISVLQAVTGIASSVFAPALAAITLGAVGPQFFARRIGRNEAFNHAGNASAAGATGALAYFFGPVVVFWVLAGMALISVLATLRIPPDAVDHDLARGMDHAPGEPHPQPSRFTVLAHNRELVIFGAAVVAFHFANAAMLPLVGELLALHNRDEGTALMSSCIVAAQVVMVPVAYVVGTRADAWGRKPIFLVGFAVLTARGFLYTLSDNSYWLVGVQLLDGIGAGIFGALFPLVVQDVTHGTGHFNISLGAVTTATGIGAALSNLVAGWIVVVAGYDAAFMSLGALAGAGFLLYLVAMPETVDSDVRVRSRPTLGGK