Rv1354c Resolved · high auto-curated
H37Rv Rv1354c · MTBC0 mtbc0_001454 ·
623 aa · 1530707–1532578 (-) ·
RefSeq NP_215870.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional diguanylate cyclase/phosphodiesterase |
| Revised (this work) | Bifunctional diguanylate cyclase/phosphodiesterase. Pfam: GAF_2 (PF13185.13), GAF (PF01590.33), GGDEF (PF00990.27), EAL (PF00563.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WM13
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein Rv1354c |
UniProt still lists this protein as Uncharacterized protein Rv1354c; 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 | GGDEF domain |
| Orthologous group | COG2203 |
| Gene Ontology (63) |
GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006725, GO:0006753, GO:0006793, GO:0006796, GO:0006807, GO:0008081 +51 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 | 0.926 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
GAF_2 | PF13185.13 | 9.1e-08 | 27–169 | GAF domain |
GAF | PF01590.33 | 3.9e-07 | 31–169 | GAF domain |
GGDEF | PF00990.27 | 5.8e-39 | 184–337 | Diguanylate cyclase, GGDEF domain |
EAL | PF00563.26 | 1.6e-67 | 361–595 | EAL domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1364c (sigma factor regulatory protein), high confidence from genomic context alone (score 1000 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1364c |
sigma factor regulatory protein | 999 | 1000 ctx | neighborhood:544 coexpression:999 textmining:735 |
Rv1355c moeY |
molybdopterin biosynthesis protein MoeY | 990 | 973 ctx | neighborhood:779 coexpression:866 textmining:656 |
Rv1353c |
HTH-type transcriptional regulator | 981 | 970 ctx | neighborhood:793 coexpression:805 textmining:426 |
Rv1356c hyp |
hypothetical protein | 991 | 968 ctx | neighborhood:811 coexpression:839 textmining:742 |
Rv1358 |
transcriptional regulator | 968 | 925 ctx | neighborhood:544 coexpression:842 textmining:593 |
Rv1357c hyp |
hypothetical protein | 948 | 903 | coexpression:858 textmining:487 |
Rv0041 leuS |
leucine--tRNA ligase | 900 | 897 | experimental:875 |
Rv3287c rsbW |
anti-sigma factor RsbW | 846 | 821 | coexpression:692 |
Rv0895 |
diacyglycerol O-acyltransferase | 809 | 809 | coexpression:803 |
Rv1173 fbiC |
FO synthase | 789 | 758 | coexpression:726 |
Rv1904 hyp |
hypothetical protein | 758 | 743 | coexpression:649 |
Rv1365c rsfA |
anti-sigma-F factor antagonist RsfA | 750 | 735 | coexpression:648 |
Rv3242c hyp |
hypothetical protein | 746 | 735 | coexpression:649 |
Rv0894 |
transcriptional regulator | 742 | 733 | coexpression:733 |
Rv0696 mftF |
mycofactocin biosynthesis glycosyltransferase MftF | 887 | 720 ctx | neighborhood:544 coexpression:411 textmining:614 |
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: hypothetical protein
- MTBC0 PGAP product: bifunctional diguanylate cyclase/phosphodiesterase
- Pfam (hmmscan --cut_ga): GAF_2 PF13185.13 (E=9e-08), GAF PF01590.33 (E=4e-07), GGDEF PF00990.27 (E=6e-39), EAL PF00563.26 (E=2e-67)
- (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_215870.1)
- Domains: Pfam-A via hmmscan --cut_ga — GAF_2 (PF13185.13), GAF (PF01590.33), GGDEF (PF00990.27), EAL (PF00563.26)
- 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
COG2203 - Curated reference: UniProt P9WM13 (SwissProt, reviewed; Predicted)
- 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 —
134 functional partner(s); context anchor
Rv1364c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001454|Rv1354c| MCNDTATPQLEELVTTVANQLMTVDAATSAEVSQRVLAYLVEQLGVDVSFLRHNDRDRRATRLVAEWPPRLNIPDPDPLRLIYFADADPVFALCEHAKEPLVFRPEPATEDYQRLIEEARGVPVTSAAAVPLVSGEITTGLLGFIKFGDRKWHEAELNALMTIATLFAQVQARVAAEARLRYLADHDDLTGLHNRRALLQHLDQRLAPGQPGPVAALFLDLDRLKAINDYLGHAAGDQFIHVFAQRIGDALVGESLIARLGGDEFVLIPASPMSADAAQPLAERLRDQLKDHVAIGGEVLTRTVSIGVASGTPGQHTPSDLLRRADQAALAAKHAGGDSVAIFTADMSVSGELRNDIELHLRRGIESDALRLVYLPEVDLRTGDIVGTEALVRWQHPTRGLLAPGCFIPVAESINLAGELDRWVLRRACNEFSEWQSAGLGHDALLRINVSAGQLVTGGFVDFVADTIGQHGLDASSVCLEITENVVVQDLHTARATLARLKEVGVHIAIDDFGTGYSAISLLQTLPIDTLKIDKTFVRQLGTNTSDLVIVRGIMTLAEGFQLDVVAEGVETEAAARILLDQRCYRAQGFLFSRPVPGEAMRHMLSARRLPPTCIPATDPALS