Rv3776 Still unknown · low auto-curated
H37Rv Rv3776 · MTBC0 - ·
519 aa · 4221089–4222648 (+) ·
RefSeq NP_218293.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF222. Function unknown. |
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 |
P72042
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein Rv3776 |
UniProt still lists this protein as Uncharacterized protein Rv3776; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| eggNOG description | HNH endonuclease |
| Orthologous group | COG1403 |
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, 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 | 0.729 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 16 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.19% of strains (281) · 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 |
|---|---|---|---|---|
DUF222 | PF02720.23 | 9.9e-58 | 28–355 | Domain of unknown function (DUF222) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3777 (oxidoreductase), medium confidence from genomic context alone (score 693 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) |
|---|---|---|---|---|
Rv3074 hyp |
hypothetical protein | 971 | 862 | coexpression:798 textmining:803 |
Rv1378c hyp |
hypothetical protein | 852 | 811 | coexpression:703 |
Rv2100 hyp |
hypothetical protein | 801 | 800 | coexpression:798 |
Rv1765c hyp |
hypothetical protein | 775 | 775 ctx | cooccurence:762 |
Rv2015c hyp |
hypothetical protein | 773 | 773 ctx | cooccurence:764 |
Rv1702c hyp |
hypothetical protein | 917 | 772 ctx | cooccurence:691 textmining:655 |
Rv0094c hyp |
hypothetical protein | 760 | 761 ctx | cooccurence:688 |
Rv3467 hyp |
hypothetical protein | 757 | 757 ctx | cooccurence:688 |
Rv1148c hyp |
hypothetical protein | 785 | 737 ctx | cooccurence:688 |
Rv1587c hyp |
hypothetical protein | 716 | 717 ctx | cooccurence:703 |
Rv1945 hyp |
hypothetical protein | 762 | 708 ctx | cooccurence:691 |
Rv1128c hyp |
hypothetical protein | 753 | 697 ctx | cooccurence:693 |
Rv3777 |
oxidoreductase | 693 | 693 ctx | neighborhood:625 |
Rv1073 hyp |
hypothetical protein | 648 | 648 ctx | cooccurence:644 |
Rv0756c hyp |
hypothetical protein | 592 | 592 ctx | cooccurence:587 |
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): hypothetical protein
- Pfam (hmmscan --cut_ga): DUF222 PF02720.23 (E=1e-57)
- (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_218293.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF222 (PF02720.23)
- 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
COG1403 - Curated reference: UniProt P72042 (SwissProt, reviewed; 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 —
54 functional partner(s); context anchor
Rv3777 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3776| MFEISLSDPVELRDADDAALLAAIEDCARAEVAAGARRLSAIAELTSRRTGNDQRADWACDGWDCAAAEVAAALTVSHRKASGQMHLSLTLNRLPQVAALFLAGQLSARLVSIIAWRTYLVRDPEALSLLDAALAKHATAWGPLSAPKLEKAIDSWIDRYDPAALRRTRISARSRDLCIGDPDEDAGTAALWGRLFATDAAMLDKRLTQLAHGVCDDDPRTIAQRRADALGALAAGADRLTCGCGNSDCPSSAGNHRQATGVVIHVVADAAALGAAPDPRLSGPEPALAPEAPATPAVKPPAALISGGGVVPAPLLAELIRGGAALSRMRHPGDLRSEPHYRPSAKLAEFVRIRDMTCRFPGCDQPTEFCDIDHTLPYPLGPTHPSNLKCLCRKHHLLKTFWTGWRDVQLPDGTIIWTAPNGHTYTTHPDSRIFLPSWHTTTAALPPAPSPPAIGPTHTLLMPRRRRTRAAELAHRIKRERAHVTQRNKPPPSGGDTAVAEGFEPPDGVSRLSLSRRVH