Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|
| MTBC0 PGAP re-annotation | alpha/beta hydrolase |
|---|
| Revised (this work) | Alpha/beta hydrolase. Pfam: Abhydrolase_1 (PF00561.27), Abhydrolase_6 (PF12697.14). |
|---|
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53363
TrEMBL · unreviewed
· Predicted
|
|---|
| UniProt name | AB hydrolase-1 domain-containing protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|
| eggNOG description | Alpha beta hydrolase |
|---|
| Orthologous group | COG0596 |
|---|
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 |
0.522 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
2 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 |
|---|
Abhydrolase_1 | PF00561.27 |
8.1e-11 | 45–289 |
alpha/beta hydrolase fold |
Abhydrolase_6 | PF12697.14 |
1.0e-09 | 45–296 |
Alpha/beta hydrolase family |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase |
530 |
503 |
experimental:441 |
Rv2048c pks12 |
polyketide synthase |
529 |
501 |
experimental:441 |
Rv1527c pks5 |
polyketide synthase |
527 |
500 |
experimental:441 |
Rv2940c mas |
multifunctional mycocerosic acid synthase |
526 |
498 |
experimental:441 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC |
526 |
498 |
experimental:441 |
Rv1043c hyp |
hypothetical protein |
461 |
461 |
|
Rv2946c pks1 |
polyketide synthase |
487 |
457 |
|
Rv2307c hyp |
hypothetical protein |
451 |
431 |
|
Rv1181 pks4 |
polyketide beta-ketoacyl synthase |
454 |
429 |
|
Rv1661 pks7 |
polyketide synthase |
452 |
428 |
|
Rv1663 pks17 |
polyketide synthase |
435 |
414 |
|
Rv0976c hyp |
hypothetical protein |
401 |
399 |
|
Rv3312A mtp |
pilin |
549 |
394 |
|
Rv3314c deoA |
thymidine phosphorylase |
911 |
322 |
textmining:875 |
Rv3315c cdd |
cytidine deaminase |
861 |
315 |
textmining:806 |
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
- Legacy H37Rv annotation: hypothetical protein
- MTBC0 PGAP product: alpha/beta hydrolase
- Pfam (hmmscan --cut_ga): Abhydrolase_1 PF00561.27 (E=8e-11), Abhydrolase_6 PF12697.14 (E=1e-09)
- (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_217829.1)
- Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_1 (PF00561.27), Abhydrolase_6 (PF12697.14)
- 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
COG0596
- Curated reference: UniProt
O53363
(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 —
20 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003520|Rv3312c|
MTGPPPSLPERIRTDEADVLMLPDGRALAYLEWGDSTGYPAFYFHGTPSSRLEGAFADGAARRTGFRLIAIDRPGYGRSTFQAGRNFRDWPADVCALADAFELEEFGVVGHSGAGPHLFACGAVIPRTRLAFVGALGPWGPLATPDIMRSLNAADRCYARLARSGPRLFGALFAPLGWCAKYTPGLFSTLLAAAVPAADKHLLSDERFGRHLRAIQLEAFRQGSRGAAYESFLQFRPWGFDLAEVAVPTHIWLGDRDSFVPRAMGEYLQRAIPHVDLHWAHGKGHFNIEDWDAILAACALDIGKRRGG
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