Rv1937 Resolved · high auto-curated
H37Rv Rv1937 · MTBC0 mtbc0_002051 ·
839 aa · 2207612–2210131 (+) ·
RefSeq NP_216453.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | oxygenase |
|---|---|
| MTBC0 PGAP re-annotation | FAD-binding oxidoreductase |
| Revised (this work) | FAD-binding oxidoreductase. Pfam: Fer2 (PF00111.33), FAD_binding_6 (PF00970.31), NAD_binding_1 (PF00175.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P95277
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Possible oxygenase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| eggNOG description | Oxidoreductase FAD-binding domain |
| Orthologous group | COG0543 |
| KEGG orthology |
K05784
|
| KEGG pathways |
map00362, map00364, map00622, map01100, map01120, map01220
|
| KEGG modules |
M00551
|
| Gene Ontology (13) |
GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0009507, GO:0009536, GO:0043226, GO:0043227, GO:0043229, GO:0043231, GO:0044424, GO:0044444 +1 more
|
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 | 0.176 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 17 synonymous, 9 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.10% of strains (146) · 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 |
|---|---|---|---|---|
Fer2 | PF00111.33 | 3.8e-14 | 12–84 | 2Fe-2S iron-sulfur cluster binding domain |
FAD_binding_6 | PF00970.31 | 1.7e-19 | 108–201 | Oxidoreductase FAD-binding domain |
NAD_binding_1 | PF00175.27 | 7.9e-17 | 212–314 | Oxidoreductase NAD-binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ephB (epoxide hydrolase EphB), high confidence from genomic context alone (score 982 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1175c fadH |
NADPH dependent 2,4-dienoyl-CoA reductase FadH | 996 | 992 | experimental:973 database:568 textmining:647 |
Rv0886 fprB |
ferredoxin/ferredoxin--NADP reductase | 995 | 990 | experimental:973 database:568 textmining:519 |
Rv3106 fprA |
NADPH-ferredoxin reductase FprA | 992 | 989 | experimental:973 database:568 |
Rv3858c gltD |
glutamate synthase small subunit | 992 | 989 | experimental:973 database:568 |
Rv1938 ephB |
epoxide hydrolase EphB | 983 | 982 ctx | neighborhood:774 cooccurence:437 coexpression:864 |
Rv1940 ribA1 |
riboflavin biosynthesis protein RibA | 983 | 981 ctx | neighborhood:882 coexpression:845 |
Rv1936 |
monooxygenase | 981 | 979 ctx | neighborhood:792 cooccurence:468 coexpression:829 |
Rv2139 pyrD |
dihydroorotate dehydrogenase | 969 | 958 | coexpression:770 experimental:814 |
Rv1939 |
oxidoreductase | 958 | 955 ctx | neighborhood:779 coexpression:805 |
Rv1941 |
short-chain type dehydrogenase/reductase | 950 | 945 ctx | neighborhood:872 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 977 | 925 | coexpression:408 experimental:786 textmining:713 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 977 | 924 | coexpression:404 experimental:786 textmining:713 |
Rv2048c pks12 |
polyketide synthase | 977 | 924 | coexpression:402 experimental:786 textmining:713 |
Rv1527c pks5 |
polyketide synthase | 977 | 924 | coexpression:402 experimental:786 textmining:713 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 977 | 924 | coexpression:404 experimental:786 textmining:713 |
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: oxygenase
- MTBC0 PGAP product: FAD-binding oxidoreductase
- Pfam (hmmscan --cut_ga): Fer2 PF00111.33 (E=4e-14), FAD_binding_6 PF00970.31 (E=2e-19), NAD_binding_1 PF00175.27 (E=8e-17)
- (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_216453.1)
- Domains: Pfam-A via hmmscan --cut_ga — Fer2 (PF00111.33), FAD_binding_6 (PF00970.31), NAD_binding_1 (PF00175.27)
- 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
COG0543 - Curated reference: UniProt P95277 (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 —
340 functional partner(s); context anchor
ephB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002051|Rv1937| MAVRQVTVGYSDGTHKTMPVRCDQTVLDAAEEHGVAIVNECQSGICGTCVATCTAGRYQMGRTEGLSDVERAARKILTCQTFVTSDCRIELQYPVDDNAALLVTGDGVVTAVELVSPSTAILRVDTSGMAGALRYRAGQFAQLQVPGTNVWRNYSYAHPADGRGECEFIIRLLPDGVMSNYLRDRAQPGDHIALRCSKGSFYLRPIVRPVILVAGGTGLSAILAMAQSLDADVAHPVYLLYGVERTEDLCKLDELTELRRRVGRLEVHVVVARPDPDWDGRTGLVTDLLDERMLASGDADVYLCGPVAMVDAARTWLDHNGFHRVGLYYEKFVASGAARRRTPARLDYAGVDIAEVCRRGRGTAVVIGGSIAGIAAAKMLSETFDRVIVLEKDGPHRRREGRPGAAQGWHLHHLLTAGQIELERIFPGIVDDMVREGAFKVDMAAQYRIRLGGTWKKPGTSDIEIVCAGRPLLEWCVRRRLDDEPRIDFRYESEVADLAFDRANNAIVGVAVDNGDADGGDGLQVVPAEFVVDASGKNTRVPEFLERLGVGAPEAEQDIINCFYSTMQHRVPPERRWQDKVMVICYAYRPFEDTYAAQYYTDSSRTILSTSLVAYNCYSPPRTAREFRAFADLMPSPVIGENIDGLEPASPIYNFRYPNMLRLRYEKKRNLPRALLAVGDAYTSADPVSGLGMSLALKEVREMQALLAKYGAGHRDLPRRYYRAIAKMADTAWFVIREQNLRFDWMKDVDKKRPFYFGVLTWYMDRVLELVHDDLDAYREFLAVVHLVKPPSALMRPRIASRVLGKWARTRLSGQKTLIARNYENHPIPAEPADQLVNA