pup Family assigned · medium auto-curated
H37Rv Rv2111c · MTBC0 - ·
64 aa · 2370598–2370792 (-) ·
RefSeq NP_216627.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ubiquitin-like protein Pup |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Ubiquitin-like protein Pup. Pfam: Pup (PF05639.17). |
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 |
P9WHN5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Prokaryotic ubiquitin-like protein Pup |
| Curated function | Protein modifier that is covalently attached to lysine residues of substrate proteins, thereby targeting them for proteasomal degradation. The tagging system is termed pupylation. Among the identified substrates are the FabD, PanB and Mpa proteins. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | pup |
| eggNOG description | Protein modifier that is covalently attached to lysine residues of substrate proteins, thereby targeting them for proteasomal degradation. The tagging system is termed pupylation |
| Orthologous group | 2E9C2 |
| KEGG orthology |
K13570
|
| Gene Ontology (39) |
GO:0003674, GO:0005488, GO:0006464, GO:0006508, GO:0006807, GO:0008150, GO:0008152, GO:0009056, GO:0009057, GO:0009987, GO:0010498, GO:0018193 +27 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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 0 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 |
|---|---|---|---|---|
Pup | PF05639.17 | 3.5e-22 | 5–64 | Pup-like protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: prcB (proteasome subunit beta), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2110c prcB |
proteasome subunit beta | 999 | 997 ctx | neighborhood:882 cooccurence:749 experimental:898 textmining:735 |
Rv2109c prcA |
proteasome subunit alpha | 998 | 997 ctx | neighborhood:881 cooccurence:750 experimental:898 textmining:684 |
Rv2115c mpa |
proteasome-associated ATPase | 997 | 996 ctx | cooccurence:764 experimental:982 |
Rv2112c dop |
pup deamidase/depupylase | 967 | 948 ctx | neighborhood:766 cooccurence:768 textmining:411 |
Rv2097c pafA |
proteasome accessory factor PafA | 926 | 905 ctx | neighborhood:504 cooccurence:769 |
Rv3780 bpa hyp |
hypothetical protein | 694 | 681 ctx | cooccurence:679 |
Rv1457c |
antibiotic ABC transporter permease | 463 | 463 ctx | cooccurence:463 |
Rv0819 mshD |
mycothiol acetyltransferase | 460 | 461 ctx | cooccurence:458 |
Rv2466c hyp |
hypothetical protein | 435 | 436 ctx | cooccurence:434 |
Rv1082 mca |
mycothiol S-conjugate amidase | 433 | 433 ctx | cooccurence:425 |
Rv2286c hyp |
hypothetical protein | 425 | 426 ctx | cooccurence:424 |
Rv1331 clpS |
ATP-dependent Clp protease adapter protein ClpS | 420 | 421 | |
Rv3221A rshA |
anti-sigma factor RshA | 413 | 414 ctx | cooccurence:412 |
Rv2113 |
integral membrane protein | 405 | 406 ctx | neighborhood:406 |
Rv3118 sseC1 hyp |
hypothetical protein | 630 | 222 | textmining:544 |
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): ubiquitin-like protein Pup
- Pfam (hmmscan --cut_ga): Pup PF05639.17 (E=4e-22)
- (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_216627.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pup (PF05639.17)
- 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
2E9C2 - Curated reference: UniProt P9WHN5 (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 —
16 functional partner(s); context anchor
prcB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2111c|pup MAQEQTKRGGGGGDDDDIAGSTAAGQERREKLTEETDDLLDEIDDVLEENAEDFVRAYVQKGGQ