Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|
| MTBC0 PGAP re-annotation | PIN domain nuclease |
|---|
| Revised (this work) | PIN-domain ribonuclease, VapC-family toxin (Pfam PIN PF01850): the toxin of a VapBC-type toxin-antitoxin module, a metal-dependent mRNA interferase that cleaves RNA. |
|---|
Curated reference (UniProt)
| UniProt |
L0T5V6
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Ribonuclease VapC51 |
|---|
| EC (curated) |
EC 3.1.-.-
|
|---|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. An RNase. Its cognate antitoxin is VapB51. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|
| eggNOG description | toxic component of a |
|---|
| Orthologous group | COG1487 |
|---|
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 |
1.371 · diversifying/relaxed
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
1 synonymous, 4 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 |
|---|
PIN | PF01850.28 |
6.6e-11 | 5–120 |
PIN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
php (phosphotriesterase),
high confidence from genomic context alone
(score 799 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) |
|---|
Rv0230c php |
phosphotriesterase |
902 |
799 ctx |
neighborhood:799 textmining:532 |
Rv0231 fadE4 |
acyl-CoA dehydrogenase FadE4 |
562 |
562 ctx |
neighborhood:562 |
Rv0582 vapC26 |
ribonuclease VapC26 |
483 |
483 ctx |
cooccurence:474 |
Rv0300 vapB2 |
antitoxin VapB2 |
444 |
445 |
experimental:412 |
Rv1607 chaA |
ionic transporter integral membrane protein ChaA |
440 |
440 ctx |
cooccurence:439 |
Rv2601A vapB41 |
antitoxin VapB41 |
434 |
412 |
|
Rv1952 vapB14 |
antitoxin VapB14 |
429 |
407 |
|
Rv0595c vapC4 |
ribonuclease VapC4 |
440 |
265 |
|
Rv0268c hyp |
hypothetical protein |
470 |
69 |
textmining:454 |
Rv0366c hyp |
hypothetical protein |
731 |
62 |
textmining:726 |
Rv0207c hyp |
hypothetical protein |
803 |
55 |
textmining:801 |
Rv3662c hyp |
hypothetical protein |
515 |
52 |
textmining:510 |
Rv3641c fic |
cell filamentation protein Fic |
871 |
50 |
textmining:870 |
Rv0078A hyp |
hypothetical protein |
804 |
50 |
textmining:803 |
Rv2165c rsmH |
rRNA small subunit methyltransferase H |
804 |
47 |
textmining:803 |
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: 'PIN domain nuclease'
- Pfam: PIN PF01850 (E=6.6e-11) -- VapC-type metal-dependent RNase
ESM Atlas signal (exploratory)
Ancestral protein hash a578a5f3c4bce26c8788866c3281b74f ·
10 ESM-space neighbours (max similarity 0.924).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|
| 1 | 12085 |
1.20 |
Acidic N-terminal nuclease motif |
| 2 | 304 |
1.06 |
PIN/NYN endoribonuclease catalytic core |
| 3 | 6726 |
1.06 |
Divalent-metal active-site loops |
| 4 | 15824 |
1.02 |
VapC PINc RNase scaffold |
| 5 | 765 |
1.01 |
Acidic PIN/NYN endonuclease regions |
| 6 | 5964 |
0.87 |
Metallo-phosphoesterase active-site entry |
| 7 | 15408 |
0.86 |
Acidic phosphate-binding catalytic helix |
| 8 | 15033 |
0.79 |
Acidic metal-binding nuclease active site |
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_214743.2)
- Domains: Pfam-A via hmmscan --cut_ga — PIN (PF01850.28)
- 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
COG1487
- Curated reference: UniProt
L0T5V6
(SwissProt, reviewed; 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 —
20 functional partner(s); context anchor
php
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000243|Rv0229c|
MALKYLLDTSVIKRLSRPAVRRAVEPLAEAGAVARTQITDLEVGYSARNETEWQRLMVALSAFDLIESTASHHRRALGIQRLLAARSQRGRKIPDLLIAAAGEEHGLVVLHYDADFDLIAAVTGQPCQWIVPAGTID
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