Rv0104 Family assigned · low
H37Rv Rv0104 · MTBC0 mtbc0_000113 ·
504 aa · 122480–123994 (+) ·
RefSeq NP_214618.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | cyclic nucleotide-binding domain-containing protein |
| Revised (this work) | Cyclic-nucleotide-binding (cNMP) domain protein (Pfam cNMP_binding PF00027). A large (504 aa) protein carrying a cNMP regulatory module, likely a cyclic-nucleotide-responsive regulator/effector; the precise function is not established. |
Curated reference (UniProt)
| UniProt |
P9WM61
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein Rv0104 |
UniProt still lists this protein as Uncharacterized protein Rv0104; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolismT Signal transduction mechanisms
|
|---|---|
| eggNOG description | Cyclic nucleotide-binding domain |
| Orthologous group | COG0499 |
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) pseudogene candidate
| pN/pS | 1.31 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 14 missense, 1 nonsense, 2 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 25.78% of strains (37432) · 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 |
|---|---|---|---|---|
cNMP_binding | PF00027.36 | 1.8e-19 | 397–475 | Cyclic nucleotide-binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1004c (membrane protein), high confidence from genomic context alone (score 765 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) |
|---|---|---|---|---|
Rv1552 frdA |
fumarate reductase flavoprotein subunit | 852 | 801 | coexpression:801 |
Rv1553 frdB |
fumarate reductase iron-sulfur subunit | 809 | 801 | coexpression:801 |
Rv1555 frdD |
fumarate reductase membrane anchor subunit | 783 | 775 | coexpression:740 |
Rv1004c |
membrane protein | 773 | 765 ctx | cooccurence:760 |
Rv0355c PPE8 |
PPE family protein PPE8 | 764 | 764 ctx | cooccurence:762 |
Rv3347c PPE55 |
PPE family protein PPE55 | 763 | 763 ctx | cooccurence:762 |
Rv3350c PPE56 |
PPE family protein PPE56 | 763 | 763 ctx | cooccurence:762 |
Rv1551 plsB1 |
acyltransferase PlsB | 770 | 762 | coexpression:762 |
Rv1917c PPE34 |
PPE family protein PPE34 | 761 | 762 ctx | cooccurence:756 |
Rv0304c PPE5 |
PPE family protein PPE5 | 760 | 761 ctx | cooccurence:759 |
Rv1753c PPE24 |
PPE family protein PPE24 | 759 | 760 ctx | cooccurence:756 |
Rv3343c PPE54 |
PPE family protein PPE54 | 759 | 759 ctx | cooccurence:759 |
Rv1452c PE_PGRS28 |
PE-PGRS family protein PE_PGRS28 | 759 | 759 ctx | cooccurence:759 |
Rv2209 |
integral membrane protein | 757 | 755 ctx | cooccurence:752 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 754 | 754 ctx | cooccurence:754 |
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
- MTBC0 PGAP product: 'cyclic nucleotide-binding domain-containing protein'
- Pfam: cNMP_binding PF00027 (E=1.8e-19)
ESM Atlas signal (exploratory)
Ancestral protein hash 6b880c3403de46e44952120bfe5e2b57 ·
10 ESM-space neighbours (max similarity 0.694).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 451 |
1.24 | Ligand pocket coupling helices |
| 2 | 4908 |
1.20 | Adenosine-phosphate binding glycine loop |
| 3 | 11534 |
1.20 | CNBD/CBS allosteric domains |
| 4 | 9189 |
1.20 | CNBD and flanking helices |
| 5 | 8044 |
1.14 | CNBD/GAF cNMP-binding pockets |
| 6 | 809 |
1.09 | Cyclic nucleotide-binding domains |
| 7 | 2649 |
1.09 | N-terminal nucleotide phosphate-binding loop |
| 8 | 5288 |
1.06 | Cytosolic CNB-like sensors and tails |
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_214618.1)
- Domains: Pfam-A via hmmscan --cut_ga — cNMP_binding (PF00027.36)
- 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
COG0499 - Curated reference: UniProt P9WM61 (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 —
173 functional partner(s); context anchor
Rv1004c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000113|Rv0104| MTPVTTFPLVDAILAGRDRNLDGVILIAAQHLLQTTHAMLRSLFRVGLDPRNVAVIGKCYSTHPGVVDAMRADGIYVDDCSDAYAPHESFDTQYTRHVERFFAESWARLTAGRTARVVLLDDGGSLLAVAGAMLDASADVIGIEQTSAGYAKIVGCALGFPVINIARSSAKLLYESPIIAARVTQTAFERTAGIDSSAAILITGAGAIGTALADVLRPLHDRVDVYDTRSGCMTPIDLPNAIGGYDVIIGATGATSVPASMHELLRPGVLLMSASSSDREFDAVALRRRTTPNPDCHADLRVADGSVDATLLNSGFPVNFDGSPMCGDASMALTMALLAAAVLYASVAVADEMSSDHPHLGLIDQGDIVASFLNIDVPLQALSRLPLLSIDGYRRLQVRSGHTLFRQGERADHFFVIESGELEALVDGKVILRLGAGDHFGEACLLGGMRRIATVRACEPSVLWELDGKAFGDALHGDAAMREIAYGVARTRLMHAGASESLMV