Rv1647 Resolved · high auto-curated
H37Rv Rv1647 · MTBC0 - ·
316 aa · 1856774–1857724 (+) ·
RefSeq NP_216163.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | adenylate cyclase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Adenylate cyclase. Pfam: Guanylate_cyc (PF00211.26). |
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 |
P94982
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Adenylate cyclase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | Guanylate cyclase |
| Orthologous group | COG2114 |
| EC number |
EC 4.6.1.1
|
| KEGG orthology |
K01768
|
| KEGG pathways |
map00230, map02025, map04113, map04213
|
| KEGG modules |
M00695
|
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 | 0.749 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.23% of strains (334) · 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 |
|---|---|---|---|---|
Guanylate_cyc | PF00211.26 | 1.4e-08 | 127–264 | Adenylate and Guanylate cyclase catalytic domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1648 (transmembrane protein), high confidence from genomic context alone (score 885 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1648 |
transmembrane protein | 885 | 885 ctx | neighborhood:882 |
Rv1646 PE17 |
PE family protein PE17 | 786 | 787 ctx | neighborhood:787 |
Rv1649 pheS |
phenylalanine--tRNA ligase subunit alpha | 738 | 738 ctx | neighborhood:737 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 738 | 738 ctx | neighborhood:737 |
Rv3645 |
transmembrane protein | 701 | 702 ctx | cooccurence:654 |
Rv1320c |
adenylate cyclase | 690 | 679 ctx | cooccurence:675 |
Rv1645c hyp |
hypothetical protein | 671 | 672 ctx | neighborhood:670 |
Rv1318c |
adenylate cyclase | 699 | 663 ctx | cooccurence:663 |
Rv1319c |
adenylate cyclase | 678 | 660 ctx | cooccurence:660 |
Rv0955 |
integral membrane protein | 591 | 592 ctx | cooccurence:576 |
Rv0804 hyp |
hypothetical protein | 571 | 571 ctx | cooccurence:570 |
Rv1652 argC |
N-acetyl-gamma-glutamyl-phoshate reductase | 546 | 547 ctx | neighborhood:544 |
Rv1653 argJ |
bifunctional glutamate N-acetyltransferase/amino-acid acetyltransferase | 546 | 547 ctx | neighborhood:544 |
Rv1654 argB |
acetylglutamate kinase | 546 | 546 ctx | neighborhood:544 |
Rv1655 argD |
acetylornithine aminotransferase | 541 | 542 ctx | neighborhood:539 |
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): adenylate cyclase
- Pfam (hmmscan --cut_ga): Guanylate_cyc PF00211.26 (E=1e-08)
- (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_216163.1)
- Domains: Pfam-A via hmmscan --cut_ga — Guanylate_cyc (PF00211.26)
- 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
COG2114 - Curated reference: UniProt P94982 (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 —
42 functional partner(s); context anchor
Rv1648 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1647| MAGSARTTYPCHVEVGPQDSESGAPDETATAMASPVPRQRSALRWLRTVNRSPGLVSFIHRARRLLPGDPEFGDPLSTAGEGGPRAAARAADRLLRDRDAASREVGLSVLQVWQALTEAVSRRPANPEVTLVFTDLVGFSTWSLHAGDDATLTLLRQVARAVESPLLDAGGHIVKRLGDGIMAVFRNPTVALRAVLVAQDAVKSLEVQGYTPRMRIGIHTGRPQRLAADWLGVDVNIAARVMERATKGGIMISQPTLDLIPQSELDALGVVARRVRKPVFASKPTGIPPDLAIYRIKTVSESTAADNFDEMSPDAQ