cpdA Resolved · high auto-curated
H37Rv Rv0805 · MTBC0 mtbc0_000854 ·
318 aa · 901898–902854 (+) ·
RefSeq NP_215320.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA |
|---|---|
| MTBC0 PGAP re-annotation | 3'%2C5'-cyclic adenosine monophosphate phosphodiesterase CpdA |
| Revised (this work) | 3'%2C5'-cyclic adenosine monophosphate phosphodiesterase CpdA. Pfam: Metallophos (PF00149.34). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP65
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | cAMP/cGMP dual specificity phosphodiesterase Rv0805 |
| EC (curated) |
EC 3.1.4.16, EC 3.1.4.17
|
| Curated function | Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP. Can use 2',3'-cAMP, 2',3'-cGMP, 3',5'-cAMP, 3',5'-cGMP and 3',5'-cUMP. Hydrolysis of 2',3'-cAMP produces a mixture of 3'-AMP (major product) and 2'-AMP (minor product). In vitro, is 150-fold more active in hydrolyzing 2',3'-cAMP than 3',5'-cAMP. Can also hydrolyze the model substrates p-nitrophenyl phosphate (pNPP), bis-(p-nitrophenyl phosphate) (bis(pNPP)) and p-nitrophenyl phenylphosphonate (pNPPP). Plays an important regulatory role in modulating the intracellular concentration of cAMP, ther. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | cpdA |
| eggNOG description | Hydrolyzes cAMP to 5'-AMP. Plays an important regulatory role in modulating the intracellular concentration of cAMP, thereby influencing cAMP-dependent processes |
| Orthologous group | COG1409 |
| EC number |
EC 3.1.4.53
|
| KEGG orthology |
K03651
|
| KEGG pathways |
map00230, map02025
|
| Gene Ontology (94) |
GO:0003674, GO:0003824, GO:0004112, GO:0004114, GO:0004115, GO:0005488, GO:0005506, GO:0005575, GO:0005618, GO:0005623, GO:0006139, GO:0006163 +82 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 | 0.586 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 5 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 |
|---|---|---|---|---|
Metallophos | PF00149.34 | 2.3e-19 | 16–210 | Calcineurin-like phosphoesterase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cpsY (exopolysaccharide phosphotransferase CpsY), high confidence from genomic context alone (score 756 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2584c apt |
adenine phosphoribosyltransferase | 912 | 906 | database:900 |
Rv2202c adoK |
adenosine kinase | 906 | 906 | database:900 |
Rv3645 |
transmembrane protein | 918 | 903 | database:900 |
Rv1264 |
adenylyl cyclase | 906 | 901 | database:900 |
Rv0733 adk |
adenylate kinase | 906 | 901 | database:900 |
Rv0777 purB |
adenylosuccinate lyase PurB | 901 | 901 | database:900 |
Rv1625c cya |
adenylate cyclase | 947 | 900 | database:900 textmining:499 |
Rv1318c |
adenylate cyclase | 925 | 900 | database:900 |
Rv1320c |
adenylate cyclase | 924 | 900 | database:900 |
Rv1319c |
adenylate cyclase | 922 | 900 | database:900 |
Rv0806c cpsY |
exopolysaccharide phosphotransferase CpsY | 764 | 756 ctx | cooccurence:750 |
Rv0803 purL |
phosphoribosylformylglycinamidine synthase 2 | 676 | 676 ctx | neighborhood:669 |
Rv0804 hyp |
hypothetical protein | 804 | 511 ctx | neighborhood:508 textmining:616 |
Rv0178 |
Mce associated membrane protein | 438 | 414 | experimental:403 |
Rv1362c |
membrane protein | 436 | 412 | experimental: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: 3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA
- MTBC0 PGAP product: 3'%2C5'-cyclic adenosine monophosphate phosphodiesterase CpdA
- Pfam (hmmscan --cut_ga): Metallophos PF00149.34 (E=2e-19)
- (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_215320.1)
- Domains: Pfam-A via hmmscan --cut_ga — Metallophos (PF00149.34)
- 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
COG1409 - Curated reference: UniProt P9WP65 (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 —
37 functional partner(s); context anchor
cpsY - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000854|Rv0805|cpdA MHRLRAAEHPRPDYVLLHISDTHLIGGDRRLYGAVDADDRLGELLEQLNQSGLRPDAIVFTGDLADKGEPAAYRKLRGLVEPFAAQLGAELVWVMGNHDDRAELRKFLLDEAPSMAPLDRVCMIDGLRIIVLDTSVPGHHHGEIRASQLGWLAEELATPAPDGTILALHHPPIPSVLDMAVTVELRDQAALGRVLRGTDVRAILAGHLHYSTNATFVGIPVSVASATCYTQDLTVAAGGTRGRDGAQGCNLVHVYPDTVVHSVIPLGGGETVGTFVSPGQARRKIAESGIFIEPSRRDSLFKHPPMVLTSSAPRSPVD