Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
| MTBC0 PGAP re-annotation | allophanate hydrolase subunit 1 |
| Revised (this work) | Allophanate hydrolase / 5-oxoprolinase (C/D) subunit (Pfam CT_C_D PF02682). With Rv0263c forms a urea-amidolyase / 5-oxoprolinase-type complex that hydrolyses amide bonds (e.g. allophanate or 5-oxoproline). |
Curated reference (UniProt)
| UniProt |
P95221
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
|
| Preferred name | kipI |
| eggNOG description | Allophanate hydrolase subunit 1 |
| Orthologous group | COG2049 |
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 |
0.719 · 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 |
CT_C_D | PF02682.22 |
3.1e-50 | 9–199 |
Carboxyltransferase domain, subdomain C and D |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
aac (aminoglycoside 2'-N-acetyltransferase),
high confidence from genomic context alone
(score 899 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) |
Rv0263c hyp |
hypothetical protein |
999 |
1000 ctx |
neighborhood:865 fusion:899 cooccurence:774 coexpression:975 experimental:997 textmining:929 |
Rv0262c aac |
aminoglycoside 2'-N-acetyltransferase |
979 |
899 ctx |
neighborhood:865 textmining:804 |
Rv0265c |
iron ABC transporter substrate-binding lipoprotein |
954 |
778 ctx |
neighborhood:776 textmining:803 |
Rv1249c |
membrane protein |
814 |
778 |
coexpression:760 |
Rv0516c oprA |
anti-anti-sigma factor |
716 |
716 |
coexpression:716 |
Rv1773c |
transcriptional regulator |
714 |
715 |
coexpression:655 |
Rv1719 |
transcriptional regulator |
710 |
711 |
coexpression:656 |
Rv2989 |
transcriptional regulator |
667 |
668 |
coexpression:656 |
Rv0266c oplA |
5-oxoprolinase OplA |
748 |
564 ctx |
neighborhood:564 textmining:445 |
Rv0269c hyp |
hypothetical protein |
531 |
532 ctx |
neighborhood:529 |
Rv0261c narK3 |
nitrate/nitrite transporter |
496 |
496 ctx |
neighborhood:493 |
Rv0924c mntH |
divalent metal cation transporter MntH |
509 |
491 |
coexpression:405 |
Rv0319 pcp |
pyrrolidone-carboxylate peptidase |
467 |
448 |
|
Rv2230c |
GTP cyclohydrolase |
463 |
440 |
coexpression:421 |
Rv3063 cstA |
carbon starvation protein A |
400 |
401 |
|
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: 'allophanate hydrolase subunit 1'
- Pfam: CT_C_D PF02682 (E=3.1e-50)
ESM Atlas signal (exploratory)
Ancestral protein hash 7f6a123950adb9eb789880d463d33e84 ·
10 ESM-space neighbours (max similarity 0.911).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
| 1 | 5326 |
1.29 |
Conserved His/Asp catalytic landmark |
| 2 | 6102 |
1.25 |
Active-site glycine-rich phosphate-binding loops |
| 3 | 8028 |
1.06 |
Catalytic-core active-site belt |
| 4 | 7104 |
0.82 |
C-terminal beta-to-alpha module |
| 5 | 11781 |
0.67 |
Anionic cofactor-binding α/β cores |
| 6 | 13388 |
0.57 |
Generic N-terminal segment detector |
| 7 | 14837 |
0.55 |
N-terminal beta-1 edge motifs |
| 8 | 8703 |
0.53 |
Terminal helical scaffold detector |
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_214778.1)
- Domains: Pfam-A via hmmscan --cut_ga — CT_C_D (PF02682.22)
- 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
COG2049
- Curated reference: UniProt
P95221
(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 —
25 functional partner(s); context anchor
aac
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000280|Rv0264c|
MDAALACTVLDYGDHALMLQCDSTADAMAWTDALRAAALPGVVDIVAASRTVLVKLDAPRYQGVTRQRLRRLRVTPEAVAAADHRCDLVIDVVYDGPDLAEVARCTGLTTAAVINAHTATGWRAGFSGSAPGFAYLIDGDPSLRVPRRPERRTSMPPGSVALADGFSAIYPSQAPSDWQIIGHTDAVLWDVDRPQPALLTPGMWVQFRAA
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