Rv2777c Resolved · high auto-curated
H37Rv Rv2777c · MTBC0 mtbc0_002956 ·
356 aa · 3106900–3107970 (-) ·
RefSeq NP_217293.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | metal-dependent hydrolase |
| Revised (this work) | Metal-dependent hydrolase. Pfam: Metal_hydrol (PF10118.15). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O33319
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Metal-dependent hydrolase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Metal-dependent hydrolase |
| Orthologous group | COG3687 |
| KEGG orthology |
K07044
|
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) pseudogene candidate
| pN/pS | 0.495 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 3 missense, 0 nonsense, 3 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 17.57% of strains (25519) · 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 |
|---|---|---|---|---|
Metal_hydrol | PF10118.15 | 3.6e-77 | 79–335 | Predicted metal-dependent hydrolase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2776c (oxidoreductase), high confidence from genomic context alone (score 876 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) |
|---|---|---|---|---|
Rv2776c |
oxidoreductase | 875 | 876 ctx | neighborhood:741 |
Rv2214c ephD |
oxidoreductase EphD | 627 | 627 ctx | cooccurence:535 |
Rv2778c hyp |
hypothetical protein | 560 | 560 ctx | neighborhood:471 |
Rv3229c desA3 |
stearoyl-CoA 9-desaturase | 508 | 509 ctx | cooccurence:493 |
Rv3434c |
transmembrane protein | 499 | 499 ctx | cooccurence:478 |
Rv2300c |
metallo-hydrolase | 446 | 446 ctx | cooccurence:446 |
Rv2779c |
Lrp/AsnC family transcriptional regulator | 425 | 425 ctx | neighborhood:421 |
Rv2740 ephG |
epoxide hydrolase | 410 | 411 ctx | cooccurence:410 |
Rv3252c alkB |
transmembrane alkane 1-monooxygenase AlkB | 407 | 407 | |
Rv2963 |
integral membrane protein | 405 | 406 ctx | cooccurence:404 |
Rv3082c virS |
HTH-type transcriptional regulator VirS | 400 | 401 | |
Rv2878c mpt53 |
soluble secreted antigen Mpt53 | 547 | 55 | textmining:541 |
Rv2557 hyp |
hypothetical protein | 804 | 49 | textmining:803 |
Rv1929c hyp |
hypothetical protein | 870 | 47 | textmining:870 |
Rv0787A purS hyp |
hypothetical protein | 662 | 47 | textmining:660 |
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: metal-dependent hydrolase
- Pfam (hmmscan --cut_ga): Metal_hydrol PF10118.15 (E=4e-77)
- (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_217293.1)
- Domains: Pfam-A via hmmscan --cut_ga — Metal_hydrol (PF10118.15)
- 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
COG3687 - Curated reference: UniProt O33319 (TrEMBL, unreviewed; 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 —
25 functional partner(s); context anchor
Rv2776c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002956|Rv2777c| MNVEVHSAPGWRAGSSPLGYAQLYLPTRDVYWGDMSGIYVNAVATFSEGAAMVSVDDRATGPHSSESRAADHERLVLEPRDVEFDWTNLPFHYVPNEPMATHVLNVLHMLLPAGEEFFVRVFKKTLPLIKDDQLRLDVQGFIGQEAMHSQAHSGVVDHFDAQGVDVTAFTNQIRWLFEKLLGESPRRSPRRQYSWLLEQVSFIAAIEHYTAVMGEWILNSPQLDAVGADPVMLDMLRWHGAEEVEHKAVAFDTMKHLRAGYWRQVRAQLTVTPVMLLLWIRGVRFMYSVDPYLPPGTKPRWRDYFKAARRGLVPGLPRLLRVVGHYYKPGFHPSQLGGLGAAVDYLAVSPAARASH