Rv2435c Family assigned · medium auto-curated
H37Rv Rv2435c · MTBC0 mtbc0_002593 ·
730 aa · 2754805–2756997 (-) ·
RefSeq NP_216951.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cyclase |
|---|---|
| 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 |
P71914
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable cyclase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | Guanylate cyclase |
| Orthologous group | COG2114 |
| Gene Ontology (142) |
GO:0000287, GO:0003674, GO:0003824, GO:0004016, GO:0004383, GO:0005488, GO:0005515, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +130 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 | 0.224 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 6 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 | 1.7e-17 | 462–513 | HAMP domain |
Guanylate_cyc | PF00211.26 | 5.0e-36 | 550–721 | Adenylate and Guanylate cyclase catalytic domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2434c (transmembrane protein), high confidence from genomic context alone (score 988 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2434c |
transmembrane protein | 988 | 988 ctx | neighborhood:881 cooccurence:753 experimental:408 |
Rv2432c hyp |
hypothetical protein | 804 | 804 ctx | neighborhood:801 |
Rv2433c nrtS hyp |
hypothetical protein | 804 | 804 ctx | neighborhood:801 |
Rv1354c hyp |
hypothetical protein | 788 | 689 ctx | neighborhood:544 |
Rv0998 |
acetyltransferase Pat | 651 | 635 | experimental:408 |
Rv1675c cmr |
HTH-type transcriptional regulator Cmr | 649 | 611 | experimental:408 |
Rv3676 crp |
cAMP receptor protein | 772 | 594 | experimental:408 textmining:464 |
Rv0104 hyp |
hypothetical protein | 609 | 591 | experimental:408 |
Rv2565 |
NTE family protein | 602 | 579 | experimental:408 |
Rv0073 |
glutamine ABC transporter ATP-binding protein | 592 | 570 | experimental:408 |
Rv2564 glnQ |
glutamine ABC transporter ATP-binding protein | 589 | 567 | experimental:408 |
Rv1364c |
sigma factor regulatory protein | 594 | 550 ctx | neighborhood:544 |
Rv3728 |
membrane protein | 574 | 535 | experimental:408 |
Rv3239c |
transmembrane transport protein | 571 | 532 | experimental:408 |
Rv2212 |
adenylyl cyclase | 745 | 530 ctx | cooccurence:529 textmining:481 |
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: cyclase
- MTBC0 PGAP product: adenylate/guanylate cyclase domain-containing protein
- Pfam (hmmscan --cut_ga): HAMP PF00672.31 (E=2e-17), Guanylate_cyc PF00211.26 (E=5e-36)
- (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_216951.1)
- 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 P71914 (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 —
51 functional partner(s); context anchor
Rv2434c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002593|Rv2435c| MTSGEALDSVAESESTPAKKRHKNVLRRRPRFRASIQSKLMVLLLLTSIVSVAAIAAIVYQSGRTSLRAAAYERLTQLRESQKRAVETLFSDLTNSLVIYERGLTVVDAVVRFTAGFDQLADATISPAQQQAIVNYYNNEFITPVERTTGDKLDITALLPTSPAQRYLQAYYTAPFTSDQDAMRLDDAGDGSAWSAANAQFNSYFREIVTRFDYDDAVLLDTRGNIVYTLSKDPDLGTNILTGPYRESNLRDAYLKALGANAVDFTWITDFKPYQPQLGVPTAWLVAPVEAGGKTQGVLALPLPIDKINKIMTADRQWQAAGMGSGTETYLAGPDSLMRSDSRLFLQDPEEYRKQVVAAGTSLDVVNRAIQFGGTTLLQPVATEGLRAAQRGQTGTVTSTDYTGSRELEAYAPLNVPDSDLHWSILATRNDSEAFAAVASFSRALVLVTVGIIVVICVASMLIAHAMVRPIRRLEVGTQKISAGDYEVNIPVKSRDEIGDLTAAFNEMSRNLQTKEELLNEQRKENDRLLLSMMPEPVVERYRLGEQTIAQEHQDVTVLFADILGVDEISSGLSGNELVKIVDELVRQFDSAAEHLGVERIRTLHNGYLAGCGVTTPRLDNIPRTVDFALEMRRIVDRFNCQTGNDLHLRVGINTGDVISGLVGRSSVVYDMWGAAVSLAYQMHSGSPQPGIYVTSQVYEAMRDVWQFTAAGTISVGGLEEPIYRLSERS