Rv3401 Family assigned · medium auto-curated
H37Rv Rv3401 · MTBC0 mtbc0_003614 ·
786 aa · 3843481–3845841 (+) ·
RefSeq NP_217918.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | glycosyl hydrolase |
|---|---|
| MTBC0 PGAP re-annotation | glycoside hydrolase family 65 protein |
| Revised (this work) | Glycoside hydrolase family 65 protein. Pfam: Glyco_hydro_65N (PF03636.22), Glyco_hydro_65m (PF03632.22), Glyco_hydro_65C (PF03633.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WN13
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized glycosyl hydrolase Rv3401 |
| EC (curated) |
EC 3.2.1.-
|
UniProt still lists this protein as Uncharacterized glycosyl hydrolase Rv3401; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
G Carbohydrate transport and metabolism
|
|---|---|
| eggNOG description | hydrolase family 65, central catalytic |
| Orthologous group | COG1554 |
| EC number |
EC 2.4.1.64
|
| KEGG orthology |
K05342
|
| KEGG pathways |
map00500, map01100
|
| CAZy family |
GH65
|
| Gene Ontology (11) |
GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0016787, GO:0030312, GO:0044464, GO:0071944
|
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 | 1.534 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 17 missense, 1 nonsense, 4 frameshift |
| Disruption | 5 distinct premature-stop/frameshift site(s); most common in 0.65% of strains (946) · convergent |
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 |
|---|---|---|---|---|
Glyco_hydro_65N | PF03636.22 | 2.2e-61 | 16–270 | Glycosyl hydrolase family 65, N-terminal domain |
Glyco_hydro_65m | PF03632.22 | 2.2e-139 | 327–678 | Glycosyl hydrolase family 65 central catalytic domain |
Glyco_hydro_65C | PF03633.21 | 1.0e-16 | 687–750 | Glycosyl hydrolase family 65, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3400 (hydrolase), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3400 |
hydrolase | 997 | 997 ctx | neighborhood:865 fusion:898 cooccurence:773 |
Rv2006 otsB1 |
trehalose-6-phosphate phosphatase OtsB | 971 | 962 | database:900 |
Rv3372 otsB2 |
trehalose 6-phosphate phosphatase | 963 | 950 | database:900 |
Rv1562c treZ |
malto-oligosyltrehalose trehalohydrolase | 925 | 923 | database:900 |
Rv0126 treS |
trehalose synthase/amylase TreS | 918 | 913 | database:900 |
Rv2402 |
trehalase | 906 | 901 | database:900 |
Rv1679 fadE16 |
acyl-CoA dehydrogenase FadE16 | 716 | 716 | coexpression:716 |
Rv3396c guaA |
GMP synthase | 695 | 695 ctx | neighborhood:686 |
Rv3399 |
S-adenosylmethionine-dependent methyltransferase | 620 | 621 ctx | neighborhood:609 |
Rv2335 cysE |
serine acetyltransferase | 457 | 458 | coexpression:458 |
Rv3398c idsA1 |
multifunctional dimethylallyltransferase/geranyltranstransferase/farnesyltranstransferase | 446 | 446 ctx | neighborhood:421 |
Rv3397c phyA |
phytoene synthase | 409 | 410 |
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: glycosyl hydrolase
- MTBC0 PGAP product: glycoside hydrolase family 65 protein
- Pfam (hmmscan --cut_ga): Glyco_hydro_65N PF03636.22 (E=2e-61), Glyco_hydro_65m PF03632.22 (E=2e-139), Glyco_hydro_65C PF03633.21 (E=1e-16)
- (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_217918.1)
- Domains: Pfam-A via hmmscan --cut_ga — Glyco_hydro_65N (PF03636.22), Glyco_hydro_65m (PF03632.22), Glyco_hydro_65C (PF03633.21)
- 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
COG1554 - Curated reference: UniProt P9WN13 (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 —
12 functional partner(s); context anchor
Rv3400 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003614|Rv3401| MITEDAFPVEPWQVRETKLNLNLLAQSESLFALSNGHIGLRGNLDEGEPFGLPGTYLNSFYEIRPLPYAEAGYGYPEAGQTVVDVTNGKIFRLLVGDEPFDVRYGELISHERILDLRAGTLTRRAHWRSPAGKQVKVTSTRLVSLAHRSVAAIEYVVEAIEEFVRVTVQSELVTNEDVPETSADPRVSAILDRPLQAVEHERTERGALLMHRTRASALMMAAGMEHEVEVPGRVEITTDARPDLARTTVICGLRPGQKLRIVKYLAYGWSSLRSRPALRDQAAGALHGARYSGWQGLLDAQRAYLDDFWDSADVEVEGDPECQQAVRFGLFHLLQASARAERRAIPSKGLTGTGYDGHAFWDTEGFVLPVLTYTAPHAVADALRWRASTLDLAKERAAELGLEGAAFPWRTIRGQESSAYWPAGTAAWHINADIAMAFERYRIVTGDGSLEEECGLAVLIETARLWLSLGHHDRHGVWHLDGVTGPDEYTAVVRDNVFTNLMAAHNLHTAADACLRHPEAAEAMGVTTEEMAAWRDAADAANIPYDEELGVHQQCEGFTTLAEWDFEANTTYPLLLHEAYVRLYPAQVIKQADLVLAMQWQSHAFTPEQKARNVDYYERRMVRDSSLSACTQAVMCAEVGHLELAHDYAYEAALIDLRDLHRNTRDGLHMASLAGAWTALVVGFGGLRDDEGILSIDPQLPDGISRLRFRLRWRGFRLIVDANHTDVTFILGDGPGTQLTMRHAGQDLTLHTDTPSTIAVRTRKPLLPPPPQPPGREPVHRRALAR