(ThiS has 14% identity to ubiquitin), share the same protein fold. These proteins also share sulfur chemistry with ubiquitin. MoaD, which is involved in molybdopterin biosynthesis, interacts with MoeB, which acts like an E1 ubiquitin-activating enzyme for MoaD, strengthening the link between these prokaryotic proteins and the ubiquitin system. A similar system exists for ThiS, with its E1-like enzyme ThiF. It is also believed that the Saccharomyces cerevisiae protein Urm1, a ubiquitin-related modifier, is a "molecular fossil" that connects the evolutionary relation with the prokaryotic ubiquitin-like molecules and ubiquitin. Archaea have a functionally closer homolog of the ubiquitin modification system, where "sampylation" with SAMPs (small archaeal modifier proteins) is performed. The sampylation system only uses E1 to guide proteins to the proteosome. Proteoarchaeota, which are related to the ancestor of eukaryotes, possess all of the E1, E2, and E3 enzymes plus a regulated Rpn11 system. Unlike SAMP which are more similar to ThiS or MoaD, Proteoarchaeota ubiquitin are most similar to eukaryotic homologs. Prokaryotic ubiquitin-like protein (Pup) and ubiquitin bacterial (UBact) Prokaryotic ubiquitin-like protein (Pup) is a functional analog of ubiquitin which has been found in the gram-positive bacterial phylum Actinomycetota. It serves the same function (targeting proteins for degradations), although the enzymology of ubiquitination and pupylation is different, and the two families share no homology. In contrast to the three-step reaction of ubiquitination, pupylation requires two steps, therefore only two enzymes are involved in pupylation. In 2017, homologs of Pup were reported in five phyla of gram-negative bacteria, in seven candidate bacterial phyla and in one archaeon The sequences of the Pup homologs are very different from the sequences of Pup in gram-positive bacteria and were termed Ubiquitin bacterial (UBact), although the distinction has yet not been proven to be phylogenetically supported by a separate evolutionary origin and is without experimental evidence. The finding of the Pup/UBact-proteasome system in both gram-positive and gram-negative bacteria suggests that either the Pup/UBact-proteasome system evolved in bacteria prior to the split into gram positive and negative clades over 3000 million years ago or, that these systems were acquired by different bacterial lineages through horizontal gene transfer(s) from a third, yet unknown, organism. In support of the second possibility, two UBact loci were found in the genome of an uncultured anaerobic methanotrophic Archaeon (ANME-1;locus CBH38808.1 and locus CBH39258.1). Human proteins containing ubiquitin domain These include ubiquitin-like proteins. ANUBL1; BAG1; BAT3/BAG6; C1orf131; DDI1; DDI2; FAU;