cya Resolved · high auto-curated
H37Rv Rv1625c · MTBC0 mtbc0_001732 ·
443 aa · 1838578–1839909 (-) ·
RefSeq NP_216141.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | adenylate cyclase |
|---|---|
| MTBC0 PGAP re-annotation | adenylate cyclase |
| Revised (this work) | Adenylate cyclase. Pfam: MASE7 (PF20967.3), Guanylate_cyc (PF00211.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQ35
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Adenylate cyclase |
| EC (curated) |
EC 4.6.1.1
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | cya |
| eggNOG description | Belongs to the adenylyl cyclase class-4 guanylyl cyclase family |
| Orthologous group | COG2114 |
| EC number |
EC 4.6.1.1
|
| KEGG orthology |
K01768
|
| KEGG pathways |
map00230, map02025, map04113, map04213
|
| KEGG modules |
M00695
|
| Gene Ontology (76) |
GO:0000287, GO:0003674, GO:0003824, GO:0004016, GO:0005488, GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006163, GO:0006164, GO:0006171 +64 more
|
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 | 0.994 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 14 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.83% of strains (1203) · 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 |
|---|---|---|---|---|
MASE7 | PF20967.3 | 9.0e-75 | 34–215 | MASE7 |
Guanylate_cyc | PF00211.26 | 5.2e-59 | 244–422 | Adenylate and Guanylate cyclase catalytic domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1624c (membrane protein), high confidence from genomic context alone (score 842 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2583c relA |
bifunctional (p)ppGpp synthase/hydrolase RelA | 912 | 913 | database:900 |
Rv1617 pykA |
pyruvate kinase | 911 | 902 | database:900 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 911 | 902 | database:900 |
Rv0805 cpdA |
3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA | 947 | 900 | database:900 textmining:499 |
Rv1624c |
membrane protein | 842 | 842 ctx | neighborhood:840 |
Rv1415 ribA2 |
bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase | 811 | 812 | database:800 |
Rv0869c moaA2 |
molybdenum cofactor biosynthesis protein MoaA | 809 | 809 | database:800 |
Rv3109 moaA1 |
cyclic pyranopterin monophosphate synthase | 808 | 809 | database:800 |
Rv1940 ribA1 |
riboflavin biosynthesis protein RibA | 804 | 805 | database:800 |
Rv3609c folE |
GTP cyclohydrolase I | 802 | 803 | database:800 |
Rv2212 |
adenylyl cyclase | 728 | 713 ctx | cooccurence:712 |
Rv2434c |
transmembrane protein | 608 | 596 | |
Rv3676 crp |
cAMP receptor protein | 784 | 594 | textmining:491 |
Rv0998 |
acetyltransferase Pat | 687 | 587 | |
Rv0104 hyp |
hypothetical protein | 596 | 581 |
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: adenylate cyclase
- MTBC0 PGAP product: adenylate cyclase
- Pfam (hmmscan --cut_ga): MASE7 PF20967.3 (E=9e-75), Guanylate_cyc PF00211.26 (E=5e-59)
- (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_216141.2)
- Domains: Pfam-A via hmmscan --cut_ga — MASE7 (PF20967.3), 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 P9WQ35 (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 —
45 functional partner(s); context anchor
Rv1624c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001732|Rv1625c|cya MAARKCGAPPIAADGSTRRPDCVTAVRTQARAPTQHYAESVARRQRVLTITAWLAVVVTGSFALMQLATGAGGWYIALINVFTAVTFAIVPLLHRFGGLVAPLTFIGTAYVAIFAIGWDVGTDAGAQFFFLVAAALVVLLVGIEHTALAVGLAAVAAGLVIALEFLVPPDTGLQPPWAMSVSFVLTTVSACGVAVATVWFALRDTARAEAVMEAEHDRSEALLANMLPASIAERLKEPERNIIADKYDEASVLFADIVGFTERASSTAPADLVRFLDRLYSAFDELVDQHGLEKIKVSGDSYMVVSGVPRPRPDHTQALADFALDMTNVAAQLKDPRGNPVPLRVGLATGPVVAGVVGSRRFFYDVWGDAVNVASRMESTDSVGQIQVPDEVYERLKDDFVLRERGHINVKGKGVMRTWYLIGRKVAADPGEVRGAEPRTAGV