The PFU (for PLAA family ubiquitin binding domain) is an ubiquitin binding domain with no homology to several known ubiquitin binding domains (e.g., UIM, NZF, UBA, UEV, UBP, or CUE domains). The PFU domain appears to be unique to the PLAA family of proteins. A single member of this family of proteins exists in every eukaryotic species examined. Each of these homologues possesses identical domain structure: an N-terminal domain containing seven WD40 repeats (see <PDOC00574>), a central PFU domain, and a C-terminal PUL domain, which directly binds to Cdc48, a member of the AAA-ATPase family of molecular chaperone [1]. In addition to ubiquitin, the PFU domain of DOA1 has been shown to bind to the SH3 domain (see <PDOC50002>) [2].

Secondary structure predictions of the PFU domain suggest the presence of an extensive length of β-sheet, N-terminal to an α-helical region [1].

Some proteins known to contain a PFU domain are listed below:

• Saccharomyces cerevisiae DOA1 (UFD3, ZZZ4), involved in ubiquitin conjugation pathway. DOA1 participates in the regulation of the ubiquin conjugation pathway involving CDC48 by hindering multiubiquitination of substrates at the CDC48 chaperone.
• Schizosaccharomyces pombe ubiquitin homeostasis protein lub1, acts as a negative regulator of vacuole-dependent ubiquitin degradation.
• Mammalian phospholipase A-2-activating protein (PLA2P, PLAA), the homologue of DOA1. PLA2P plays an important role in the regulation of specific inflammatory disease processes.

The profile we developed covers the entire PFU domain.