dop Resolved · high auto-curated
H37Rv Rv2112c · MTBC0 - ·
554 aa · 2370905–2372569 (-) ·
RefSeq NP_216628.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | pup deamidase/depupylase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Pup deamidase/depupylase. Pfam: Pup_ligase (PF03136.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WNU9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Pup deamidase/depupylase |
| EC (curated) |
EC 3.4.-.-, EC 3.5.1.119
|
| Curated function | Specifically catalyzes the deamidation of the C-terminal glutamine of the prokaryotic ubiquitin-like protein Pup to glutamate, thereby rendering Pup competent for conjugation. Also displays depupylase (DPUP) activity, removing conjugated Pup from target proteins; is thus involved in the recycling of Pup and may function similarly to deubiquitinases (DUBs) in eukaryotes to prevent or promote proteasomal degradation of certain proteins. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | dop |
| eggNOG description | proteasome accessory factor PafA2 |
| Orthologous group | COG4122 |
| EC number |
EC 3.5.1.119
|
| KEGG orthology |
K20814
|
| Gene Ontology (57) |
GO:0000166, GO:0003674, GO:0003824, GO:0005488, GO:0005524, GO:0006464, GO:0006508, GO:0006807, GO:0008144, GO:0008150, GO:0008152, GO:0008233 +45 more
|
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 | 0.239 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (177) · 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 |
|---|---|---|---|---|
Pup_ligase | PF03136.21 | 9.1e-185 | 52–507 | Pup-ligase protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pup (ubiquitin-like protein Pup), high confidence from genomic context alone (score 948 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2111c pup |
ubiquitin-like protein Pup | 967 | 948 ctx | neighborhood:766 cooccurence:768 textmining:411 |
Rv2109c prcA |
proteasome subunit alpha | 979 | 939 ctx | neighborhood:766 cooccurence:739 textmining:673 |
Rv2110c prcB |
proteasome subunit beta | 978 | 937 ctx | neighborhood:766 cooccurence:737 textmining:664 |
Rv2115c mpa |
proteasome-associated ATPase | 904 | 828 ctx | cooccurence:774 textmining:465 |
Rv3780 bpa hyp |
hypothetical protein | 786 | 687 ctx | cooccurence:685 |
Rv2097c pafA |
proteasome accessory factor PafA | 718 | 666 | database:500 |
Rv2239c hyp |
hypothetical protein | 663 | 664 ctx | cooccurence:659 |
Rv2114 hyp |
hypothetical protein | 606 | 605 ctx | neighborhood:604 |
Rv2113 |
integral membrane protein | 586 | 585 ctx | neighborhood:581 |
Rv3676 crp |
cAMP receptor protein | 536 | 519 ctx | cooccurence:501 |
Rv1830 |
HTH-type transcriptional regulator | 481 | 481 ctx | cooccurence:478 |
Rv3626c hyp |
hypothetical protein | 478 | 479 ctx | cooccurence:471 |
Rv1331 clpS |
ATP-dependent Clp protease adapter protein ClpS | 454 | 454 ctx | cooccurence:452 |
Rv2624c |
universal stress protein | 438 | 439 ctx | cooccurence:437 |
Rv1457c |
antibiotic ABC transporter permease | 426 | 427 ctx | cooccurence:412 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): pup deamidase/depupylase
- Pfam (hmmscan --cut_ga): Pup_ligase PF03136.21 (E=9e-185)
- (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_216628.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pup_ligase (PF03136.21)
- 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
COG4122 - Curated reference: UniProt P9WNU9 (SwissProt, reviewed; 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 —
33 functional partner(s); context anchor
pup - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2112c|dop MFWVGGPCLMPASSAARCAARIVGGRCLMPASSAARCAARIVGGPRLYGMQRIIGTEVEYGISSPSDPTANPILTSTQAVLAYAAAAGIQRAKRTRWDYEVESPLRDARGFDLSRSAGPPPVVDADEVGAANMILTNGARLYVDHAHPEYSAPECTDPLDAVIWDKAGERVMEAAARHVASVPGAAKLQLYKNNVDGKGASYGSHENYLMSRQTPFSAIITGLTPFLVSRQVVTGSGRVGIGPSGDEPGFQLSQRSDYIEVEVGLETTLKRGIINTRDEPHADADRYRRLHVIIGDANLAETSTYLKLGTTALVLDLIEEGPAHAIDLTDLALARPVHAVHAISRDPSLRATVALADGRELTGLALQRIYLDRVAKLVDSRDPDPRAADIVETWAHVLDQLERDPMDCAELLDWPAKLRLLDGFRQRENLSWSAPRLHLVDLQYSDVRLDKGLYNRLVARGSMKRLVTEHQVLSAVENPPTDTRAYFRGECLRRFGADIAAASWDSVIFDLGGDSLVRIPTLEPLRGSKAHVGALLDSVDSAVELVEQLTAEPR