Rv0776c Still unknown · low auto-curated
H37Rv Rv0776c · MTBC0 mtbc0_000825 ·
259 aa · 873408–874187 (-) ·
RefSeq NP_215290.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DUF429 domain-containing protein |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF429. Function unknown. Foldseek best (non-significant) hit: 4pht-assembly1_X ATPase GspE in complex with the cytoplasmic domain of (prob 0.60, TM 0.40). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6Y4S9
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | GTP pyrophosphokinase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Protein of unknown function (DUF429) |
| Orthologous group | COG4328 |
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 | 0.507 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 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 |
|---|---|---|---|---|
DUF429 | PF04250.20 | 1.5e-22 | 5–220 | Protein of unknown function (DUF429) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 95.7 (very high). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
4pht-assembly1_X |
0.60 | 0.40 | 4.6e-02 | 4pht-assembly1_X ATPase GspE in complex with the cytoplasmic domain of GspL from the Vibrio vulnificus type II Secretion system |
1kcf-assembly1_A |
0.35 | 0.32 | 4.6e-02 | 1kcf-assembly1_A Crystal Structure of the Yeast Mitochondrial Holliday Junction Resolvase, Ydc2 |
9eh2-assembly1_M |
0.15 | 0.26 | 1.5e-01 | 9eh2-assembly1_M RNA polymerase II-DSIF-SPT6-PAF1c-TFIIS-IWS1-SETD2-FACT nucleosome upstream |
8oeu-assembly1_S |
0.14 | 0.25 | 1.0e-01 | 8oeu-assembly1_S Structure of the mammalian Pol II-SPT6 complex (composite structure, Structure 4) |
7p54-assembly1_B |
0.08 | 0.31 | 1.2e+00 | 7p54-assembly1_B Cryo-EM structure of human TTYH2 in GDN |
2f9t-assembly1_A |
0.06 | 0.21 | 3.8e-01 | 2f9t-assembly1_A Structure of the type III CoaA from Pseudomonas aeruginosa |
2f9t-assembly1_B |
0.06 | 0.21 | 5.1e-01 | 2f9t-assembly1_B Structure of the type III CoaA from Pseudomonas aeruginosa |
7ai7-assembly1_B |
0.03 | 0.16 | 5.4e-01 | 7ai7-assembly1_B MutS in Intermediate state |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: purB (adenylosuccinate lyase PurB), medium confidence from genomic context alone (score 470 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) |
|---|---|---|---|---|
Rv0777 purB |
adenylosuccinate lyase PurB | 470 | 470 ctx | neighborhood:468 |
Rv0778 cyp126 |
cytochrome P450 Cyp126 | 469 | 469 ctx | neighborhood:468 |
Rv3700c egtE |
pyridoxal-phosphate-dependent protein EgtE | 406 | 406 ctx | cooccurence:403 |
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: DUF429 domain-containing protein
- Pfam (hmmscan --cut_ga): DUF429 PF04250.20 (E=1e-22)
- Foldseek best: 4pht-assembly1_X ATPase GspE in complex with the cytoplasmic domain of GspL from (prob 0.60, E=5e-02, TM=0.40)
- (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_215290.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF429 (PF04250.20)
- 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
COG4328 - Curated reference: UniProt I6Y4S9 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 95.7, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
3 functional partner(s); context anchor
purB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000825|Rv0776c| MYFVGVDLAWAGRNPTGVAAVDADGCLVGVGAARDDASVLAALRPYVVGDCLVAFDAPLVVANRTGQRPAEAALNRDFRQFEAGAYPANTEKPEFADVPRAARLARQLALDMDPLSSATRRAIEVYPHPATVALFRLPRALKYKAKPGRSVDLLKSELLRLMDGVEGLAQAGVRMQVAGQPDWVSLRRQVTVAQRKSDLRAAEDPIDAVVCAYVALYAQRRPADVTIYGDFTTGYIVTPSLPTDFRTAPDAGRRARARR