Rv1378c Still unknown · low auto-curated
H37Rv Rv1378c · MTBC0 - ·
475 aa · 1551228–1552655 (-) ·
RefSeq NP_215894.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF222. Function unknown. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
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 |
P71806
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | HNH nuclease domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| eggNOG description | endonuclease |
| Orthologous group | COG1403 |
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 | 1.115 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.16% of strains (234) · 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 |
|---|---|---|---|---|
DUF222 | PF02720.23 | 5.5e-12 | 74–337 | Domain of unknown function (DUF222) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1377c (transferase), high confidence from genomic context alone (score 819 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) |
|---|---|---|---|---|
Rv1377c |
transferase | 819 | 819 ctx | neighborhood:776 |
Rv3776 hyp |
hypothetical protein | 852 | 811 | coexpression:703 |
Rv3074 hyp |
hypothetical protein | 806 | 804 | coexpression:801 |
Rv2633c hyp |
hypothetical protein | 665 | 666 ctx | cooccurence:663 |
Rv1128c hyp |
hypothetical protein | 777 | 626 ctx | cooccurence:620 textmining:430 |
Rv1379 pyrR |
bifunctional pyrimidine operon regulatory protein/uracil phosphoribosyltransferase | 621 | 606 ctx | neighborhood:604 |
Rv1381 pyrC |
dihydroorotase | 606 | 606 ctx | neighborhood:604 |
Rv1702c hyp |
hypothetical protein | 697 | 605 ctx | cooccurence:592 |
Rv1383 carA |
carbamoyl-phosphate synthase small subunit | 605 | 605 ctx | neighborhood:604 |
Rv1384 carB |
carbamoyl-phosphate synthase large subunit | 605 | 605 ctx | neighborhood:604 |
Rv1380 pyrB |
aspartate carbamoyltransferase | 604 | 604 ctx | neighborhood:604 |
Rv1385 pyrF |
orotidine 5'-phosphate decarboxylase | 600 | 600 ctx | neighborhood:597 |
Rv1382 hyp |
hypothetical protein | 597 | 596 ctx | neighborhood:595 |
Rv1978 hyp |
hypothetical protein | 594 | 594 ctx | cooccurence:594 |
Rv1587c hyp |
hypothetical protein | 591 | 591 ctx | cooccurence:584 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): DUF222 PF02720.23 (E=6e-12)
- (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_215894.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF222 (PF02720.23)
- 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 P71806 (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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
34 functional partner(s); context anchor
Rv1377c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1378c| MGNLDLLLRLSGRIVKGCRPLGSVALARCGPAVRWPRWPRPAILEHMFDLVSLAGVDSRDDEASLTARIAELERVKSAAAAGQARAAAALDKLRRCNEADAGVPARRRGRGVASEVALARRDSPARGGRHLGFAKALVYEMPHTLAALEVGRLSEWRATLIVRESACLDVEDRRALDAELCADMSALDGMGDARIAAAARAIAYRLDAQAVVERAARAETERTVTIRPAPDTMTWVTALLPVARGVSVYAALKRAADTTFDDRTRGQVMADTLVERVTGQPAEAAQPVAVNLVLSDETLLAGDRAPAVVDGYGPIPAAVARNLVRDAVADTRSRATLRRLYRHPRSGALVAMESRARRFPKGLAAFIGLRDQRCRMPYCDAPIRHRDHAQPHHRGGPTTATNGLGSCERCNYVKEAPGWRVSTDTDETGRHTAEFTTPTGMYYHCTAPPLPGPLEIDVSQVEARIGVALTHLHAA