Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
| MTBC0 PGAP re-annotation | DEAD/DEAH box helicase family protein |
| Revised (this work) | DEAD/DEAH box helicase family protein. Pfam: ResIII (PF04851.22). |
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O50435
TrEMBL · unreviewed
· Evidence at protein level
|
| UniProt name | Helicase ATP-binding domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
L Replication, recombination and repair
|
| eggNOG description | Type III restriction enzyme, res subunit |
| Orthologous group | COG1061 |
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 |
0.791 · relaxed/neutral
|
| Polymorphic sites (≥ 0.1% of strains) |
8 synonymous, 17 missense, 0 nonsense, 2 frameshift
|
| Disruption |
2 distinct premature-stop/frameshift site(s); most common in
0.39% of strains
(564) · clonal
|
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 |
ResIII | PF04851.22 |
3.7e-18 | 15–196 |
Type III restriction enzyme, res subunit |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
Rv1329c dinG |
ATP-dependent helicase DinG |
892 |
884 |
experimental:685 database:622 |
Rv0667 rpoB |
DNA-directed RNA polymerase subunit beta |
873 |
871 |
experimental:578 database:621 |
Rv3457c rpoA |
DNA-directed RNA polymerase subunit alpha |
853 |
853 |
experimental:627 database:621 |
Rv1390 rpoZ |
DNA-directed RNA polymerase subunit omega |
847 |
848 |
experimental:613 database:621 |
Rv1629 polA |
DNA polymerase I |
787 |
768 |
experimental:430 database:580 |
Rv2090 |
5'-3' exonuclease |
766 |
753 |
experimental:430 database:580 |
Rv1334 mec |
[CysO |
705 |
705 |
database:613 |
Rv2529 hyp |
hypothetical protein |
707 |
687 |
database:610 |
Rv0668 rpoC |
DNA-directed RNA polymerase subunit beta' |
686 |
686 |
database:620 |
Rv2101 helZ |
helicase HelZ |
694 |
671 |
database:615 |
Rv0832 PE_PGRS12 |
PE-PGRS family protein PE_PGRS12 |
620 |
621 |
database:563 |
Rv3812 PE_PGRS62 |
PE-PGRS family protein PE_PGRS62 |
620 |
621 |
database:563 |
Rv2328 PE23 |
PE family protein PE23 |
620 |
621 |
database:563 |
Rv3036c TB22.2 hyp |
hypothetical protein |
620 |
621 |
database:563 |
Rv0938 ligD |
multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD |
592 |
575 |
database:556 |
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: DEAD/DEAH box helicase family protein
- Pfam (hmmscan --cut_ga): ResIII PF04851.22 (E=4e-18)
- (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_215695.1)
- Domains: Pfam-A via hmmscan --cut_ga — ResIII (PF04851.22)
- 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
COG1061
- Curated reference: UniProt
O50435
(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 —
49 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001268|Rv1179c|
MDPHRDLESRAFAGNWRVYQQQALDAFDADVAAGDNRAYLVLPPGAGKTMIGLEAARRLGRRSLVLVPNTAVQAQWAAAWDNSFPSSDRSASKCGTERGLASAMNVLTYQSLAVIDAETDSTVRREVLRNRDQQALLDLLHPNGRAVIERAATLGPWTLVLDECHHLLATWGALVSALASVLGAQTALIGLTATPATELTAWQHTLHDELFGTADFVIPTPALVREGDLAPYQELVYLTQPTPEEQAWIGTHRARFADLMLALIDQKVGSMSLAAWLHTRIVDRATREGNQIAWSTFERAEPDLACSGLRFAYDGLIPLPDGVRLREQHRIAPDAQDWVNVLTDFSVGHLQQSADPRDAHALTAIKRVLPGLGYRLTSRGVRVATSPVDRLCALSESKIAATAHILDTEDAVLGARLRALVLCDFESMTGALPTSLKGAPVSEQSGSAQLVAAMLAASDHRRRTPLHALLVTGQTFACPAAIEDDLIAFCAERGALVTAEPLDAHPSLRVMRGTGGFTPRTWVALATEYFLAGRARVLVGTRSLLGEGWDCAAVNVNIDLTSATTQAAITQMRGRAIRNDPSDGHKVADNWSVCCIATEHPRGDADYLRLVRKHDGYYAATPQGLIESGVTHCDPSLSPYGPPVTDTHAITARALQRVAERAQARSWWRIGEPYEGVDVATIRVRSRQPLGVAAPRIPASALTPPVPGQFSPVRLARGAVAAVSVVGASTATAVASANLGMLAGAGTAGAIVAAGVGLVATAAAAESRRLDHAPNALEQLAAVVADALYAAGGAQRGSAALRLASDPEGWIRCQLDGVPTEQSLRFTAALDELLAPLAEPRYLIGRKILTPPARPVARRLFAVRAVVGLSLPGTVAWHAVPRWFARNKDRRQHLAQAWRKHIGPPRQLPADSPQGQAILDLFRGDNPLSVTTQLRTTWR
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