Rv0397 Family assigned · medium
H37Rv Rv0397 · MTBC0 - ·
122 aa · 475816–476184 (+) ·
RefSeq NP_214911.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | HNH endonuclease (eggNOG COG1403, defense COG category V), a member of the conserved 13E12-repeat protein family of M. tuberculosis. RefSeq leaves it 'hypothetical protein'. The HNH motif marks a nuclease active site; the cleavage target is undetermined. |
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P95205
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Conserved 13E12 repeat family protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| eggNOG description | HNH endonuclease |
| Orthologous group | COG1403 |
| Gene Ontology (8) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, GO:0044464, GO:0071944
|
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 | 0.36 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 5 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 59.4 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
6tmf-assembly1_F |
0.47 | 0.72 | 1.9e+00 | 6tmf-assembly1_F Structure of an archaeal ABCE1-bound ribosomal post-splitting complex |
6th6-assembly1_Af |
0.44 | 0.61 | 1.4e+00 | 6th6-assembly1_Af Cryo-EM Structure of T. kodakarensis 70S ribosome |
2i5c-assembly3_C |
0.20 | 0.61 | 4.0e+00 | 2i5c-assembly3_C Crystal structure of the C-terminal PH domain of pleckstrin in complex with D-myo-Ins(1,2,3,4,5)P5 |
1bes-assembly1_A |
0.16 | 0.36 | 1.3e+00 | 1bes-assembly1_A INTERACTION BETWEEN PROXIMAL AND DISTALS REGIONS OF CYTOCHROME C PEROXIDASE |
3d0f-assembly1_B |
0.15 | 0.56 | 4.2e+00 | 3d0f-assembly1_B Structure of the BIG_1156.2 domain of putative penicillin-binding protein MrcA from Nitrosomonas europaea ATCC 19718 |
8hx7-assembly1_B |
0.14 | 0.62 | 4.8e+00 | 8hx7-assembly1_B Crystal structure of 4-amino-4-deoxychorismate synthase from Streptomyces venezuelae co-crystallized with L-glutamine |
1j9o-assembly1_A |
0.13 | 0.40 | 1.8e+00 | 1j9o-assembly1_A SOLUTION STRUCTURE OF HUMAN LYMPHOTACTIN |
6p41-assembly2_C |
0.11 | 0.36 | 2.2e+00 | 6p41-assembly2_C Yeast cytochrome c peroxidase (W191Y:L232E) in complex with iso-1 cytochrome c |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3354 hyp |
hypothetical protein | 694 | 675 | experimental:470 |
Rv0395 hyp |
hypothetical protein | 619 | 619 ctx | neighborhood:615 |
Rv0396 hyp |
hypothetical protein | 619 | 619 ctx | neighborhood:615 |
Rv3103c hyp |
hypothetical protein | 618 | 594 | experimental:512 |
Rv2564 glnQ |
glutamine ABC transporter ATP-binding protein | 619 | 584 | |
Rv0073 |
glutamine ABC transporter ATP-binding protein | 615 | 579 | |
Rv0986 |
adhesion component ABC transporter ATP-binding protein | 598 | 578 | |
Rv0397A hyp |
hypothetical protein | 469 | 469 ctx | neighborhood:469 |
Rv0394c hyp |
hypothetical protein | 434 | 433 ctx | neighborhood:431 |
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
- eggNOG COG1403 = HNH endonuclease (COG category V, defense)
- 13E12 (REP13E12) repeat family
- eggNOG-mapper orthology (COG functional assignment, under-propagated by the auto-curation). A family/activity-level assignment from orthology, not a substrate demonstrated in M. tuberculosis.
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_214911.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
COG1403 - Curated reference: UniProt P95205 (TrEMBL, unreviewed; 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)
- Model confidence: ESMFold per-residue pLDDT (mean 59.4, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 9 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0397| MLATFWGWRAQQLPDGTVIWTLPGDQTYVTTPGSALLFPALCTPTGDPPRPDPARADRRGQRTAMMPRRASTRAQNRAHYIAAERHRNHQARRIAHVVTQTATTAPETNGPPPDPDDDPPPF