This family consists of several short bacterial proteins formely known as (DUF797). It was recently shown that Mycobacterium tuberculosis contains a small protein, Pup (Rv2111c), that is covalently conjugated to the e-NH2 groups of lysines on several target proteins (pupylation) such as the malonyl CoA acyl carrier protein (FabD) [[cite:PUB00053383]]. Pupylation of FabD was shown to result in its recruitment to the mycobacterial proteasome and subsequent degradation analogous to eukaryotic ubiquitin-conjugated proteins. Searches recovered Pup orthologs in all major actinobacteria lineages including the basal bifidobacteria and also sporadically in certain other bacterial lineages. [[cite:PUB00053382]] The Pup proteins were all between 50-90 residues in length and a multiple alignment shows that they all contain a conserved motif with a G [EQ] signature at the C-terminus. Thus, all of them are suitable for conjugation via the terminal glutamate or the deamidated glutamine (as shown in the case of the Mycobacterium Pup [[cite:PUB00053382]]). The conserved globular core of Pup is predicted to form a bihelical unit with the extreme C-terminal 6-7 residues forming a tail in the extended conformation. Thus, Pup is structurally unrelated to the ubiquitin fold and has convergently evolved the function of protein modifier.
","llm":false,"checked":false,"updated":false}],"wikipedia":[{"title":"Prokaryotic_ubiquitin-like_protein","extract":"Prokaryotic ubiquitin-like protein (Pup) is a functional analog of ubiquitin found in the prokaryote Mycobacterium tuberculosis. Like ubiquitin, Pup serves to direct proteins to the proteasome for degradation in the Pup-proteasome system (PPS). However, the enzymology of ubiquitylation and pupylation is different, owing to their distinct evolutionary origins. In contrast to the three-step reaction of ubiquitylation, pupylation requires only two steps, and thus only two enzymes are involved in pupylation. The enzymes involved in pupylation are descended from glutamine synthetase.
","thumbnail":null}],"literature":{"PUB00053383":{"PMID":18832610,"ISBN":null,"volume":"322","issue":"5904","year":2008,"title":"Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis.","URL":null,"raw_pages":"1104-7","medline_journal":"Science","ISO_journal":"Science","authors":["Pearce MJ","Mintseris J","Ferreyra J","Gygi SP","Darwin KH."],"DOI_URL":"http://dx.doi.org/10.1126/science.1163885"},"PUB00053382":{"PMID":18980670,"ISBN":null,"volume":"3","issue":null,"year":2008,"title":"Unraveling the biochemistry and provenance of pupylation: a prokaryotic analog of ubiquitination.","URL":null,"raw_pages":"45","medline_journal":"Biol Direct","ISO_journal":"Biol. Direct","authors":["Iyer LM","Burroughs AM","Aravind L."],"DOI_URL":"http://dx.doi.org/10.1186/1745-6150-3-45"}},"set_info":null,"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":4,"interactions":0,"matches":3495,"pathways":0,"proteins":3495,"proteomes":3401,"sets":0,"structural_models":{"alphafold":2101},"structures":12,"taxa":4136},"entry_annotations":{"hmm":0,"logo":0,"alignment:seed":21,"alignment:full":1682},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":{"accession":"7oxy","name":"Crystal structure of depupylase Dop in complex with Pup and AMP-PCP"}}}