Rv2251 Resolved · high auto-curated
H37Rv Rv2251 · MTBC0 - ·
475 aa · 2525565–2526992 (+) ·
RefSeq NP_216767.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | flavoprotein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Flavoprotein. Pfam: FAD_binding_4 (PF01565.29), FAD-oxidase_C (PF02913.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
L0TBR2
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible flavoprotein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | eapA |
| eggNOG description | FAD linked |
| Orthologous group | COG0277 |
| EC number |
EC 2.5.1.26
|
| KEGG orthology |
K00803
|
| KEGG pathways |
map00565, map01100, map04146
|
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 | 0.489 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 98.76% of strains (143404) · reference-fixed |
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 |
|---|---|---|---|---|
FAD_binding_4 | PF01565.29 | 1.3e-30 | 51–183 | FAD binding domain |
FAD-oxidase_C | PF02913.25 | 1.4e-44 | 223–473 | FAD linked oxidases, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2250A (Possible flavoprotein; Rv2250A, len: 139 aa. Conserved hypothetical protein, possibly flavoprotein. Similar to N-terminus of SCF91.28c|AL132), high confidence from genomic context alone (score 995 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2250A |
Possible flavoprotein; Rv2250A, len: 139 aa. Conserved hypothetical protein, possibly flavoprotein. Similar to N-terminus of SCF91.28c|AL132 | 998 | 995 ctx | neighborhood:773 fusion:625 cooccurence:622 coexpression:857 textmining:803 |
Rv2252 dagK |
diacylglycerol kinase | 976 | 973 ctx | neighborhood:799 coexpression:831 |
Rv3107c agpS |
alkyldihydroxyacetonephosphate synthase | 915 | 915 | database:900 |
Rv2250c |
HTH-type transcriptional regulator | 794 | 794 ctx | neighborhood:600 cooccurence:480 |
Rv2249c glpD1 |
glycerol-3-phosphate dehydrogenase | 764 | 755 ctx | neighborhood:602 |
Rv2253 hyp |
hypothetical protein | 613 | 614 ctx | neighborhood:611 |
Rv1551 plsB1 |
acyltransferase PlsB | 621 | 605 | database:549 |
Rv2482c plsB2 |
glycerol-3-phosphate acyltransferase | 619 | 603 | database:549 |
Rv3806c ubiA |
decaprenyl-phosphate phosphoribosyltransferase | 590 | 570 | database:552 |
Rv1310 atpD |
ATP synthase subunit beta | 573 | 558 | database:538 |
Rv1305 atpE |
ATP synthase subunit C | 537 | 537 | database:526 |
Rv3633 hyp |
hypothetical protein | 547 | 531 | database:463 |
Rv1501 hyp |
hypothetical protein | 543 | 526 | database:463 |
Rv0694 mftD |
mycofactocin system heme/flavin oxidoreductase MftD | 537 | 517 | |
Rv1872c lldD2 |
L-lactate dehydrogenase | 534 | 514 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): flavoprotein
- Pfam (hmmscan --cut_ga): FAD_binding_4 PF01565.29 (E=1e-30), FAD-oxidase_C PF02913.25 (E=1e-44)
- (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_216767.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_4 (PF01565.29), FAD-oxidase_C (PF02913.25)
- 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
COG0277 - Curated reference: UniProt L0TBR2 (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 —
43 functional partner(s); context anchor
Rv2250A - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2251| MRWRASSAPSISAPPIATGCCTPAASPPQTCCGAKTPVSRMRPTRCCCPAAPTGEDAVADILHYCSDHGIAVVPFGGGTSVVGGLDPVRNDFRAVISLDMRRFDRLHRIDEVSGEAELEAGVTGPEAERLLGEHGFSLGHFPQSFEFATIGGFAATRSSGQDSAGYGRFNDMILGLRMITPVGVLDLGRVPASAAGPDLRQLAIGSEGVFGVITRVRLRVHRIPESTRYEAWSFPDFATGVAALRTITQTGTGPTVVRLSDEAETGVNLATTEAIGETQITGGCLGITVFEGTQEHTESRHAETRALLAARGGTSLGEGPARAWERGRFAAPYLRDSLLAAGALCETLETATVWSNTPVLKAAVTEALTTSLAASGTPALVMCHVSHVYPTGASLYFTVVAGQRGDPIEQWLAAKKAASDAIMATGGTITHHHAVGSDHRPWMRAEVGDLGVTLLRTIKATLDPAGILNPGKLIP