Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|
| MTBC0 PGAP re-annotation | NYN domain-containing protein |
|---|
| Revised (this work) | NYN-domain ribonuclease (Pfam NYN PF01936), of the PIN/NYN metal-dependent RNase superfamily. Putative ribonuclease. |
|---|
Curated reference (UniProt)
| UniProt |
P96389
TrEMBL · unreviewed
· Evidence at protein level
|
|---|
| UniProt name | NYN domain-containing protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|
| eggNOG description | NYN domain |
|---|
| Orthologous group | COG1432 |
|---|
| KEGG orthology |
K06860
|
|---|
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 |
0.725 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
1 synonymous, 2 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 |
|---|
NYN | PF01936.25 |
2.3e-07 | 40–202 |
NYN domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
trmB (tRNA (guanine-N(7)-)-methyltransferase),
high confidence from genomic context alone
(score 973 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) |
|---|
Rv0208c trmB |
tRNA (guanine-N(7)-)-methyltransferase |
989 |
973 ctx |
neighborhood:882 coexpression:783 textmining:604 |
Rv0206c mmpL3 |
transmembrane transport protein MmpL3 |
874 |
850 ctx |
neighborhood:798 |
Rv0210 hyp |
hypothetical protein |
775 |
775 ctx |
neighborhood:775 |
Rv2673 aftC |
alpha-(1->3)-arabinofuranosyltransferase |
742 |
742 ctx |
cooccurence:742 |
Rv3802c |
membrane protein |
749 |
735 ctx |
cooccurence:729 |
Rv3805c aftB |
terminal beta-(1->2)-arabinofuranosyltransferase |
742 |
733 ctx |
cooccurence:729 |
Rv0209 hyp |
hypothetical protein |
730 |
730 ctx |
neighborhood:729 |
Rv1100 hyp |
hypothetical protein |
702 |
702 ctx |
cooccurence:698 |
Rv2342 hyp |
hypothetical protein |
690 |
691 ctx |
cooccurence:686 |
Rv3793 embC |
arabinosyltransferase C |
667 |
666 ctx |
cooccurence:664 |
Rv3795 embB |
arabinosyltransferase B |
652 |
652 ctx |
cooccurence:649 |
Rv3794 embA |
arabinosyltransferase A |
651 |
651 ctx |
cooccurence:648 |
Rv0010c |
membrane protein |
648 |
648 ctx |
cooccurence:645 |
Rv0531 |
membrane protein |
634 |
634 ctx |
cooccurence:632 |
Rv3792 aftA |
arabinofuranosyltransferase |
600 |
601 ctx |
cooccurence:567 |
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: 'NYN domain-containing protein'
- Pfam: NYN PF01936 (E=2.3e-07)
ESM Atlas signal (exploratory)
Ancestral protein hash ffbc698a06f95a3b3ada3ea5c7918dda ·
10 ESM-space neighbours (max similarity 0.900).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|
| 1 | 12599 |
1.43 |
Mg2+-assisted phosphodiester subdomains |
| 2 | 15169 |
1.25 |
Terminal and boundary accessory regions |
| 3 | 11726 |
1.23 |
Acidic two-metal nuclease cores |
| 4 | 13093 |
1.10 |
Charged nuclease-like catalytic cleft |
| 5 | 2645 |
0.72 |
N-terminal extension/subdomain marker |
| 6 | 3881 |
0.48 |
Metal-dependent phosphohydrolase cores and tails |
| 7 | 6472 |
0.46 |
Noncatalytic N-terminal accessory modules |
| 8 | 13129 |
0.42 |
VWA alpha7 gating helix |
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_214721.1)
- Domains: Pfam-A via hmmscan --cut_ga — NYN (PF01936.25)
- 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
COG1432
- Curated reference: UniProt
P96389
(TrEMBL, unreviewed; 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 —
67 functional partner(s); context anchor
trmB
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000221|Rv0207c|
MSLTEDVTSQTSESLARHSVLAEDLSQDGLTSLGAPGARVLLVWDAPNLDMGLGSILGRRPTALERPRFDALGRWLLARTAEIVAGRPGISTEPEATVFTNIAPGSAEVVRPWVDALRNVGFAVFAKPKVDEDSDVDRDMLAHIDERYREGLAALVVASADGQAFRQPLEAVARSGTPVQVLGFREHASWALASDTLEFVDLEDIAGVFREPLPRIGLDSLPEQGAWLQPFRPLSSLLTSRV
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