Rv3403c Family assigned · medium auto-curated
H37Rv Rv3403c · MTBC0 mtbc0_003617 ·
533 aa · 3847701–3849302 (-) ·
RefSeq NP_217920.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | FAD/NAD(P)-binding protein |
| Revised (this work) | FAD/NAD(P)-binding protein. Pfam: NAD_binding_9 (PF13454.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKZ5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv3403c |
UniProt still lists this protein as Uncharacterized protein Rv3403c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | FAD-NAD(P)-binding |
| Orthologous group | COG4529 |
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 | 0.797 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 12 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_9 | PF13454.13 | 3.0e-09 | 19–205 | FAD-NAD(P)-binding |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PPE55 (PPE family protein PPE55), high confidence from genomic context alone (score 772 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) |
|---|---|---|---|---|
Rv3404c hyp |
hypothetical protein | 798 | 799 ctx | neighborhood:746 |
Rv3347c PPE55 |
PPE family protein PPE55 | 772 | 772 ctx | cooccurence:772 |
Rv2209 |
integral membrane protein | 772 | 772 ctx | cooccurence:771 |
Rv3350c PPE56 |
PPE family protein PPE56 | 772 | 772 ctx | cooccurence:772 |
Rv0355c PPE8 |
PPE family protein PPE8 | 772 | 772 ctx | cooccurence:772 |
Rv0304c PPE5 |
PPE family protein PPE5 | 771 | 771 ctx | cooccurence:771 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 771 | 771 ctx | cooccurence:771 |
Rv1452c PE_PGRS28 |
PE-PGRS family protein PE_PGRS28 | 771 | 771 ctx | cooccurence:771 |
Rv1917c PPE34 |
PPE family protein PPE34 | 770 | 771 ctx | cooccurence:770 |
Rv1004c |
membrane protein | 770 | 771 ctx | cooccurence:770 |
Rv3343c PPE54 |
PPE family protein PPE54 | 769 | 769 ctx | cooccurence:768 |
Rv1651c PE_PGRS30 |
PE-PGRS family protein PE_PGRS30 | 769 | 769 ctx | cooccurence:769 |
Rv0872c PE_PGRS15 |
PE-PGRS family protein PE_PGRS15 | 767 | 767 ctx | cooccurence:767 |
Rv2082 hyp |
hypothetical protein | 766 | 766 ctx | cooccurence:765 |
Rv0888 spmT hyp |
hypothetical protein | 764 | 765 ctx | cooccurence:599 coexpression:438 |
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: FAD/NAD(P)-binding protein
- Pfam (hmmscan --cut_ga): NAD_binding_9 PF13454.13 (E=3e-09)
- (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_217920.1)
- Domains: Pfam-A via hmmscan --cut_ga — NAD_binding_9 (PF13454.13)
- 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
COG4529 - Curated reference: UniProt P9WKZ5 (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 —
116 functional partner(s); context anchor
PPE55 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003617|Rv3403c| MLAFPYLMTMITPPTFDVAFIGSGAACSMTLLEMADALLSSPSASPKLRIAVVERDEQFWCGIPYGQRSSIGSLAIQKLDDFADEPEKAAYRIWLEQNKQRWLAFFQAEGGAAAARWICDNRDALDGNQWGELYLPRFLFGVFLSEQMIAAIAALGERDLAEIVTIRAEAMSAHSADGHYRIGLRPSGNGPTAIAAGKVVVAIGSPPTKAILASDSEPAFTYINDFYSPGGESNVARLRDSLDRVESWEKRNVLVVGSNATSLEALYLMRHDARIRARVRSITVISRSGVLPYMICNQPPEFDFPRLRTLLCTEAIAAADLMSAIRDDLATAEERSLNLADLYDAVAALFGQALHKMDLVQQEEFFCVHGMNFTKLVRRAGRDCRQASEELAADGTLSLLAGEVLRVDACASGQPFATMTYRAAGAEHTHPVPFAAVVNCGGFEELDTCSSPFLVSAMQNGLCRPNRTNRGLLVNDDFEASPGFCVIGPLVGGNFTPKIRFWHVESAPRVRSLAKSLAASLLASLQPVALAPC