Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|
| MTBC0 PGAP re-annotation | 5-oxoprolinase/urea amidolyase family protein |
|---|
| Revised (this work) | Carboxyltransferase / 5-oxoprolinase (A/B) subunit (Pfam CT_A_B PF02626; PGAP 5-oxoprolinase/urea-amidolyase family). Putative ATP-dependent amide-bond-hydrolysing subunit, partnering Rv0264c. |
|---|
Curated reference (UniProt)
| UniProt |
P95220
TrEMBL · unreviewed
· Evidence at protein level
|
|---|
| UniProt name | Carboxyltransferase domain-containing protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|
| eggNOG description | Allophanate hydrolase subunit 2 |
|---|
| Orthologous group | COG1984 |
|---|
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 |
0.373 · purifying
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
3 synonymous, 3 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 |
|---|
CT_A_B | PF02626.21 |
1.2e-79 | 26–283 |
Carboxyltransferase domain, subdomain A and B |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
aac (aminoglycoside 2'-N-acetyltransferase),
high confidence from genomic context alone
(score 967 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) |
|---|
Rv0264c hyp |
hypothetical protein |
999 |
1000 ctx |
neighborhood:865 fusion:899 cooccurence:774 coexpression:975 experimental:997 textmining:929 |
Rv0262c aac |
aminoglycoside 2'-N-acetyltransferase |
995 |
967 ctx |
neighborhood:882 coexpression:731 textmining:860 |
Rv2501c accA1 |
acetyl/propionyl-CoA carboxylase subuit alpha |
851 |
845 ctx |
fusion:819 |
Rv3285 accA3 |
bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA |
829 |
823 ctx |
fusion:793 |
Rv0265c |
iron ABC transporter substrate-binding lipoprotein |
768 |
768 ctx |
neighborhood:766 |
Rv0973c accA2 |
acetyl/propionyl-CoA carboxylase subuit alpha |
768 |
759 ctx |
fusion:717 |
Rv1249c |
membrane protein |
791 |
746 |
coexpression:725 |
Rv0516c oprA |
anti-anti-sigma factor |
716 |
716 |
coexpression:716 |
Rv1719 |
transcriptional regulator |
658 |
658 |
coexpression:646 |
Rv1773c |
transcriptional regulator |
657 |
657 |
coexpression:645 |
Rv2989 |
transcriptional regulator |
657 |
657 |
coexpression:645 |
Rv0266c oplA |
5-oxoprolinase OplA |
543 |
542 ctx |
neighborhood:542 |
Rv0261c narK3 |
nitrate/nitrite transporter |
516 |
516 ctx |
neighborhood:513 |
Rv0924c mntH |
divalent metal cation transporter MntH |
515 |
489 |
coexpression:403 |
Rv0319 pcp |
pyrrolidone-carboxylate peptidase |
482 |
460 |
|
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: '5-oxoprolinase/urea amidolyase family protein'
- Pfam: CT_A_B PF02626 (E=1.2e-79)
ESM Atlas signal (exploratory)
Ancestral protein hash cb06b8bd8ff370dd23f53fb1b0bae030 ·
10 ESM-space neighbours (max similarity 0.906).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|
| 1 | 5326 |
1.41 |
Conserved His/Asp catalytic landmark |
| 2 | 6102 |
1.25 |
Active-site glycine-rich phosphate-binding loops |
| 3 | 8028 |
1.11 |
Catalytic-core active-site belt |
| 4 | 8133 |
0.91 |
Basic disordered tails/linkers |
| 5 | 11723 |
0.89 |
Noncatalytic flexible linker segments |
| 6 | 8703 |
0.85 |
Terminal helical scaffold detector |
| 7 | 11781 |
0.84 |
Anionic cofactor-binding α/β cores |
| 8 | 7867 |
0.83 |
Active-site-proximal C-terminal segments |
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_214777.1)
- Domains: Pfam-A via hmmscan --cut_ga — CT_A_B (PF02626.21)
- 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
COG1984
- Curated reference: UniProt
P95220
(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 —
28 functional partner(s); context anchor
aac
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000279|Rv0263c|
MTTLEILRSGPLALVEDLGRAGLAHLGVGRSGAADRRSHTLANRLVANPDDWATVEVTFGGFSARVRGGDVDIAVTGADTDPTVNGIMVGTNSIHHVRDGQVISLGTPRAGLRTYLAVRGGVCVEPVLGSRSYDVMSAIGPSPLRAGDVLPVGEHTDDYPELDQAPVAAIEEHLVELRVVPGPRDDWLVDPDALVHTIWMASNRSDRVGMRLQGRPLQHRWPDRQLPGEGVTRGAIQVPPNGLPVILGPDHPITGSYPVVGVITDEDIDKVAQIRPGQYVRLHWARPRSRLPGQGVTQAW
Spot an error? Suggest an improvement