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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.

July 2008 / First entry.

PROSITE method (with tools and information) covered by this documentation:

PFU, PS51394; PFU domain profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE

• Domain architecture view of Swiss-Prot proteins matching PS51394 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS51394 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS51394 • Scan Swiss-Prot/TrEMBL entries against PS51394 • view ligand binding statistics

Matching PDB structures: 2K89 2K8A 2K8B 2K8C ... [ALL]

1	Authors	Mullally J.E., Chernova T., Wilkinson K.D.
	Title	Doa1 is a Cdc48 adapter that possesses a novel ubiquitin binding domain.
	Source	Mol. Cell. Biol. 26:822-830(2006).
	PubMed ID	16428438
	DOI	10.1128/MCB.26.3.822-830.2006

2	Authors	Ren J., Pashkova N., Winistorfer S., Piper R.C.
	Title	DOA1/UFD3 plays a role in sorting ubiquitinated membrane proteins into multivesicular bodies.
	Source	J. Biol. Chem. 0:0-0(2008).
	PubMed ID	18508771
	DOI	10.1074/jbc.M802982200

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