PROSITE documentation PDOC50330

Ubiquitin-interacting motif (UIM) domain profile

Covalent modification of proteins by the small, evolutionary conserved protein ubiquitin (see <PDOC00271>) plays a central role in a variety of cellular processes, including bulk protein degradation, cell-cycle control, stress response, DNA repair, signal transduction, transcriptional regulation and vesicular traffic. A cascade of three enzymes (called E1, E2 and E3) catalyzes the conjugation of ubiquitin to lysine side-chains of target proteins. Ubiquitination is a reversible process: several specific ubiquitin carboxy-terminal hydrolases (UBPs) (see <PDOC00750>) can remove ubiquitin from proteins. The variety of cellular processes regulated by ubiquitination demands a high substrate specificity of the ubiquitination machinery as well as the existence of diverse downstream effector proteins interacting with ubiquitinated substrates. Most of these cellular effectors are characterized by a modular composition of ubiquitin-binding motifs and further domains mediating specific functions.

The ubiquitin-interacting motif (UIM), or 'LALAL-motif', is a stretch of about 20 amino acid residues, which was first described in the 26S proteasome subunit PSD4/RPN-10 that is known to recognize ubiquitin [1]. In addition, the UIM is found, often in tandem or triplet arrays, in a variety of proteins either involved in ubiquitination and ubiquitin metabolism, or known to interact with ubiquitin-like modifiers. Among the UIM proteins are two different subgroups of the UBP family of deubiquitinating enzymes, one F-box protein, one family of HECT-containing ubiquitin-ligases (E3s) from plants, and several proteins containing ubiquitin-associated UBA and/or UBX domains. In most of these proteins, the UIM occurs in multiple copies and in association with other domains such as UBA (see <PDOC50030>), UBX (see <PDOC50033>), ENTH, EH (see <PDOC50031>), VHS (see <PDOC50179>), SH3 (see <PDOC50002>), HECT (see <PDOC50237>), VWFA (see <PDOC50234>), EF-hand calcium-binding (see <PDOC50031>), WD-40 (see <PDOC00574>), F-box (see <PDOC50181>), LIM (see <PDOC00382>), protein kinase (see <PDOC00100>), ankyrin (see <PDOC50088>), PX (see <PDOC50195>), phosphatidylinositol 3- and 4-kinase (see <PDOC00710>), C2 (see <PDOC00380>), OTU (see <PDOC50802>), dnaJ (see <PDOC00553>), RING-finger (see <PDOC00449>) or FYVE-finger (see <PDOC50178>). UIMs have been shown to bind ubiquitin and to serve as a specific targeting signal important for monoubiquitination. Thus, UIMs may have several functions in ubiquitin metabolism each of which may require different numbers of UIMs [3,4,5].

Some proteins known to contain an UIM domain are listed below:

• Eukaryotic PSD4/RPN-10/S5a multiubiquitin binding subunit of the 26S proteasome.
• Vertebrate Machado-Joseph disease protein 1 (Ataxin-3). It acts as a histone-binding protein that regulates transcription. In human, defects Ataxin-3 the cause of Machado-Joseph disease (MJD), a neurodegenerative disorder characterized by cerebellar ataxia, pyramidal and extrapyramidal signs, peripheral nerve palsy, external ophtalmoplegia, facial and lingual fasciculation and bulging.
• Vertebrate epsin and epsin2.
• Vertebrate hepatocyte growth factor-regulated tyrosine kinase substrate (HRS).
• Mammalian epidermal growth factor receptor substrate 15 (EPS15). It is involved in cell growth regulation.
• Mammalian epidermal growth factor receptor substrate EPS15R.
• Drosophila melanogaster liquid facets (lqf), an epsin.
• Yeast VPS27 vacuolar sorting protein. It is required for membrane traffic to the vacuole.

The profile we developed covers the entire UIM domain.