Rv3645 Family assigned · medium auto-curated
H37Rv Rv3645 · MTBC0 mtbc0_003862 ·
549 aa · 4106512–4108161 (+) ·
RefSeq NP_218162.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transmembrane protein |
|---|---|
| MTBC0 PGAP re-annotation | adenylate/guanylate cyclase domain-containing protein |
| Revised (this work) | Adenylate/guanylate cyclase domain-containing protein. Pfam: HAMP (PF00672.31), 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 |
I6X7Z3
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable conserved transmembrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | cya |
| eggNOG description | COG2114 Adenylate cyclase, family 3 (some proteins contain HAMP domain) |
| 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 | 0.421 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 8 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 |
|---|---|---|---|---|
HAMP | PF00672.31 | 2.7e-09 | 275–326 | HAMP domain |
Guanylate_cyc | PF00211.26 | 4.8e-13 | 359–504 | Adenylate and Guanylate cyclase catalytic domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2212 (adenylyl cyclase), high confidence from genomic context alone (score 718 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0805 cpdA |
3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA | 918 | 903 | database:900 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 911 | 903 | database:900 |
Rv1617 pykA |
pyruvate kinase | 908 | 903 | database:900 |
Rv2583c relA |
bifunctional (p)ppGpp synthase/hydrolase RelA | 909 | 902 | database:900 |
Rv1415 ribA2 |
bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase | 814 | 814 | database:800 |
Rv1940 ribA1 |
riboflavin biosynthesis protein RibA | 812 | 812 | database:800 |
Rv0869c moaA2 |
molybdenum cofactor biosynthesis protein MoaA | 808 | 808 | database:800 |
Rv3609c folE |
GTP cyclohydrolase I | 808 | 808 | database:800 |
Rv3109 moaA1 |
cyclic pyranopterin monophosphate synthase | 807 | 807 | database:800 |
Rv2212 |
adenylyl cyclase | 718 | 718 ctx | cooccurence:674 |
Rv1647 |
adenylate cyclase | 701 | 702 ctx | cooccurence:654 |
Rv1675c cmr |
HTH-type transcriptional regulator Cmr | 790 | 625 | textmining:465 |
Rv3676 crp |
cAMP receptor protein | 725 | 621 | |
Rv0998 |
acetyltransferase Pat | 697 | 611 | |
Rv0104 hyp |
hypothetical protein | 735 | 572 | textmining:407 |
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: transmembrane protein
- MTBC0 PGAP product: adenylate/guanylate cyclase domain-containing protein
- Pfam (hmmscan --cut_ga): HAMP PF00672.31 (E=3e-09), Guanylate_cyc PF00211.26 (E=5e-13)
- (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_218162.1)
- Domains: Pfam-A via hmmscan --cut_ga — HAMP (PF00672.31), 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 I6X7Z3 (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 —
47 functional partner(s); context anchor
Rv2212 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003862|Rv3645| MDAEAFVGFRQVPAARYGGLMATTAALPRRIHAFVRWVVRTPWPLFSLSMLQSDIIGALFVLGFLRYGLPPQDNIQLQDLPPVNLLIFVSTVIILFLAGAVVNLKLLMPVFRWQRRDNLLTEPDPAATELARSRALRMPLYRTLISLAVWATGGGVFILASWSVAKHAAPVVAVATALGATATAIIGYLQSERVLRPVAVAALRSGVPENVNAPGVILRLMLAWIPSTGVPLLAIVLAVAADKIALLHATPEALFNPILMMALAALGIGSVSTLLVAMSIADPLRQLRWALSEVQRGNYNAHMQIYDASELGLLQAGFNDMVRELSERQRLRDLFGRYVGEDVARRALERGTELGGQERDVAVLFVDLVGSTQLAATRPPAEVVQLLNEFFRVVVETVARHGGFVNKFQGDAALAIFGAPIEHPDGAGAALSAARELHDELIPVLGSAEFGIGVSAGRAIAGHIGAQARFEYTVIGDPVNEAARLTELAKLEDGHVLASAIAVSGALDAEALCWDVGEVVELRGRAAPTQLARPMNLAAPEEVSSEVRG