Rv2212 Resolved · high auto-curated
H37Rv Rv2212 · MTBC0 mtbc0_002348 ·
378 aa · 2503347–2504483 (+) ·
RefSeq NP_216728.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | adenylyl cyclase |
|---|---|
| MTBC0 PGAP re-annotation | adenylyl cyclase |
| Revised (this work) | Adenylyl 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.
Curated reference (UniProt)
| UniProt |
P9WMU7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2212 |
UniProt still lists this protein as Uncharacterized protein Rv2212; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | Adenylyl- / guanylyl cyclase, catalytic domain |
| Orthologous group | COG2114 |
| EC number |
EC 4.6.1.1
|
| KEGG orthology |
K01768
|
| KEGG pathways |
map00230, map02025, map04113, map04213
|
| KEGG modules |
M00695
|
| Gene Ontology (64) |
GO:0003674, GO:0003824, GO:0004016, GO:0005488, GO:0005504, GO:0006139, GO:0006163, GO:0006164, GO:0006171, GO:0006725, GO:0006753, GO:0006793 +52 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 | 0.42 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 7 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.65% of strains (948) · 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 | 1.3e-12 | 206–350 | Adenylate and Guanylate cyclase catalytic domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pepB (cytosol aminopeptidase), high confidence from genomic context alone (score 874 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2213 pepB |
cytosol aminopeptidase | 880 | 874 ctx | neighborhood:872 |
Rv2211c gcvT |
aminomethyltransferase | 794 | 794 ctx | neighborhood:792 |
Rv2210c ilvE |
branched-chain amino acid aminotransferase | 730 | 730 ctx | neighborhood:730 |
Rv3645 |
transmembrane protein | 718 | 718 ctx | cooccurence:674 |
Rv1625c cya |
adenylate cyclase | 728 | 713 ctx | cooccurence:712 |
Rv1320c |
adenylate cyclase | 683 | 672 ctx | cooccurence:668 |
Rv1319c |
adenylate cyclase | 687 | 667 ctx | cooccurence:667 |
Rv0998 |
acetyltransferase Pat | 646 | 635 ctx | cooccurence:414 |
Rv3676 crp |
cAMP receptor protein | 753 | 610 | |
Rv1675c cmr |
HTH-type transcriptional regulator Cmr | 686 | 589 | |
Rv2434c |
transmembrane protein | 563 | 550 | |
Rv2435c |
cyclase | 745 | 530 ctx | cooccurence:529 textmining:481 |
Rv0104 hyp |
hypothetical protein | 520 | 505 | |
Rv2564 glnQ |
glutamine ABC transporter ATP-binding protein | 520 | 502 | |
Rv0073 |
glutamine ABC transporter ATP-binding protein | 517 | 499 |
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: adenylyl cyclase
- MTBC0 PGAP product: adenylyl cyclase
- Pfam (hmmscan --cut_ga): Guanylate_cyc PF00211.26 (E=1e-12)
- (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_216728.1)
- 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 P9WMU7 (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 —
27 functional partner(s); context anchor
pepB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002348|Rv2212| MYDSLDFDALEAAGIANPRERAGLLTYLDELGFTVEEMVQAERRGRLFGLAGDVLLWSGPPIYTLATAADELGLSADDVARAWSLLGLTVAGPDVPTLSQADVDALATWVALKALVGEDGAFGLLRVLGTAMARLAEAESTMIRAGSPNIQMTHTHDELATARAYRAAAEFVPRIGALIDTVHRHHLASARTYFEGVIGDTSASVTCGIGFADLSSFTALTQALTPAQLQDLLTEFDAAVTDVVHADGGRLVKFIGDAVMWVSSSPERLVRAAVDLVDHPGARAAELQVRAGLAYGTVLALNGDYFGNPVNLAARLVAAAAPGQILAAAQLRDMLPDWPALAHGPLTLKGFDAPVMAFELHDNPRARDADTPSPAASD