Rv0449c Resolved · high auto-curated
H37Rv Rv0449c · MTBC0 mtbc0_000471 ·
439 aa · 540594–541913 (-) ·
RefSeq NP_214963.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | NAD(P)/FAD-dependent oxidoreductase |
| Revised (this work) | NAD(P)/FAD-dependent oxidoreductase. Pfam: NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53734
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Amine oxidase domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Flavin containing amine oxidoreductase |
| Orthologous group | COG2907 |
| KEGG orthology |
K06954
|
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 | 0.181 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 2 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 |
|---|---|---|---|---|
NAD_binding_8 | PF13450.13 | 1.1e-08 | 11–84 | NAD(P)-binding Rossmann-like domain |
Amino_oxidase | PF01593.31 | 1.4e-46 | 16–423 | Flavin containing amine oxidoreductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ufaA1 (cyclopropane-fatty-acyl-phospholipid synthase UfaA), high confidence from genomic context alone (score 996 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0447c ufaA1 |
cyclopropane-fatty-acyl-phospholipid synthase UfaA | 996 | 996 ctx | neighborhood:803 fusion:899 cooccurence:756 |
Rv0446c |
transmembrane protein | 982 | 983 ctx | neighborhood:803 fusion:635 cooccurence:763 |
Rv0448c hyp |
hypothetical protein | 984 | 982 ctx | neighborhood:803 fusion:568 cooccurence:774 |
Rv3392c cmaA1 |
cyclopropane mycolic acid synthase CmaA | 896 | 891 ctx | fusion:867 |
Rv0445c sigK |
ECF RNA polymerase sigma factor SigK | 897 | 712 ctx | neighborhood:586 textmining:657 |
Rv0450c mmpL4 |
transmembrane transport protein MmpL4 | 668 | 667 ctx | neighborhood:667 |
Rv0451c mmpS4 |
membrane protein MmpS4 | 660 | 659 ctx | neighborhood:659 |
Rv0642c mmaA4 |
hydroxymycolate synthase MmaA4 | 667 | 651 ctx | fusion:560 |
Rv0645c mmaA1 |
mycolic acid methyltransferase MmaA1 | 584 | 565 ctx | fusion:466 |
Rv0444c rskA |
anti-sigma-K factor RskA | 774 | 522 ctx | neighborhood:517 textmining:547 |
Rv0644c mmaA2 |
cyclopropane mycolic acid synthase CmaA | 539 | 518 ctx | fusion:424 |
Rv0452 |
transcriptional regulator | 411 | 411 ctx | neighborhood:404 |
Rv0643c mmaA3 |
methoxy mycolic acid synthase MmaA3 | 429 | 403 | |
Rv0503c cmaA2 |
cyclopropane mycolic acid synthase | 428 | 401 | |
Rv0735 sigL |
ECF RNA polymerase sigma factor SigL | 424 | 248 |
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: hypothetical protein
- MTBC0 PGAP product: NAD(P)/FAD-dependent oxidoreductase
- Pfam (hmmscan --cut_ga): NAD_binding_8 PF13450.13 (E=1e-08), Amino_oxidase PF01593.31 (E=1e-46)
- (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_214963.1)
- Domains: Pfam-A via hmmscan --cut_ga — NAD_binding_8 (PF13450.13), Amino_oxidase (PF01593.31)
- 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
COG2907 - Curated reference: UniProt O53734 (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 —
22 functional partner(s); context anchor
ufaA1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000471|Rv0449c| MQQSLRRSVAVVGSGVAGLTAAYILSGRDRVTLYEADGRLGGHAHTHYLDNGGGPRGTDVVGVDSAFLVHNDRTYPTLCRLFAELGVATQESEMSMSVRADDIGLEYAGALGARGLFACRQSLRPRYLCMLAEILRFHRAAARLLREETDNAEDKPETLEAFLSRHHFSQYFVDYFITPLVAAVWSCGGADALRYPARYLFVFLDHHGMLSVFGSPTWRTVTGGSANYVQAIAAQLDEVSTRTPVHSLRRLPDGVLVGAGDGPSRRFDAAVVAVHPDQALLLLDEPTPAERAVLGAIAYSTNSAQLHTDESVLPRHHRARASWNYLVTPGQHQVVVSYDISRLMRLDGGRRYLVTLGGHDRVDPSSVIAEMTYSHPLYTPESVAAQRLLPTLGDNRVVFAGAYHGWGFHEDGAASGLRAARRLGADWPAAIPQEAMVAC