Rv2963 Resolved · high auto-curated
H37Rv Rv2963 · MTBC0 mtbc0_003146 ·
406 aa · 3336411–3337631 (+) ·
RefSeq NP_217479.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | integral membrane protein |
|---|---|
| MTBC0 PGAP re-annotation | permease |
| Revised (this work) | Permease. Pfam: ArsP_1 (PF03773.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YET7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative permease Rv2963 |
UniProt still lists this protein as Putative permease Rv2963; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Predicted permease |
| Orthologous group | COG0701 |
| KEGG orthology |
K07089
|
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 | 1.771 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 5 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 4.90% of strains (7115) · 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 |
|---|---|---|---|---|
ArsP_1 | PF03773.20 | 9.8e-85 | 18–329 | Predicted permease |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: purU (formyltetrahydrofolate deformylase), high confidence from genomic context alone (score 796 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0848 cysK2 |
cysteine synthase CysK | 880 | 841 | coexpression:841 |
Rv0849 |
MFS-type transporter | 936 | 825 | coexpression:822 textmining:654 |
Rv0847 lpqS |
lipoprotein LpqS | 974 | 813 | coexpression:813 textmining:870 |
Rv0846c mmcO |
oxidase | 973 | 803 | coexpression:770 textmining:870 |
Rv2964 purU |
formyltetrahydrofolate deformylase | 796 | 796 ctx | neighborhood:790 |
Rv0090 |
membrane protein | 668 | 668 ctx | cooccurence:665 |
Rv3310 sapM |
acid phosphatase | 645 | 645 ctx | cooccurence:645 |
Rv0180c |
transmembrane protein | 589 | 589 ctx | cooccurence:588 |
Rv2962c |
PGL/p-HBAD biosynthesis rhamnosyltransferase | 571 | 571 ctx | neighborhood:554 |
Rv3434c |
transmembrane protein | 568 | 568 ctx | cooccurence:568 |
Rv2925c rnc |
ribonuclease III | 551 | 552 ctx | neighborhood:540 |
Rv2927c sepIVA hyp |
hypothetical protein | 545 | 545 ctx | neighborhood:544 |
Rv2926c hyp |
hypothetical protein | 544 | 544 ctx | neighborhood:540 |
Rv2924c fpg |
formamidopyrimidine-DNA glycosylase | 534 | 534 ctx | neighborhood:529 |
Rv0208c trmB |
tRNA (guanine-N(7)-)-methyltransferase | 484 | 485 | coexpression:483 |
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: permease
- Pfam (hmmscan --cut_ga): ArsP_1 PF03773.20 (E=1e-84)
- (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_217479.1)
- Domains: Pfam-A via hmmscan --cut_ga — ArsP_1 (PF03773.20)
- 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
COG0701 - Curated reference: UniProt I6YET7 (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 —
35 functional partner(s); context anchor
purU - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003146|Rv2963| MTSTKVEDRVTAAVLGAIGHALALTASMTWEILWALILGFALSAVVQAVVRRSTIVTLLGDDRPRTLVIATGLGAASSSCSYAAVALARSLFRKGANFTAAMAFEIGSTNLVVELGIILALLMGWQFTAAEFVGGPIMILVLAVLFRLFVGARLIDAAREQAERGLAGSMEGHAAMDMSIKREGSFWRRLLSPPGFTSIAHVFVMEWLAILRDLILGLLIAGAIAAWVPESFWQSFFLANHPAWSAVWGPIIGPIVAIVSFVCSIGNVPLAAVLWNGGISFGGVIAFIFADLLILPILNIYRKYYGARMMLVLLGTFYASMVVAGYLIELLFGTTNLIPSQRSATVMTAEISWNYTTWLNVIFLVIAAALVVRFITSGGLPMLRMMGGSPDAPHDHHDRHDDHLGH