<p>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 recognise ubiquitin [<cite idref="PUB00007601"/>,<cite idref="PUB00018255"/>]. 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 (ubiquitin carboxy-terminal hydrolase) 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 [<cite idref="PUB00018086"/>]. In most of these proteins, the UIM occurs in multiple copies and in association with other domains such as UBA (<db_xref db="INTERPRO" dbkey="IPR015940"/>), UBX (<db_xref db="INTERPRO" dbkey="IPR001012"/>), ENTH, EH (<db_xref db="INTERPRO" dbkey="IPR000261"/>), VHS (<db_xref db="INTERPRO" dbkey="IPR002014"/>), SH3 (<db_xref db="INTERPRO" dbkey="IPR001452"/>), HECT (<db_xref db="INTERPRO" dbkey="IPR000569"/>), VWFA (<db_xref db="INTERPRO" dbkey="IPR002035"/>), EF-hand calcium-binding, WD-40 (<db_xref db="INTERPRO" dbkey="IPR001680"/>), F-box (<db_xref db="INTERPRO" dbkey="IPR001810"/>), LIM (<db_xref db="INTERPRO" dbkey="IPR001781"/>), protein kinase (<db_xref db="INTERPRO" dbkey="IPR000719"/>), ankyrin (<db_xref db="INTERPRO" dbkey="IPR002110"/>), PX (<db_xref db="INTERPRO" dbkey="IPR001683"/>), phosphatidylinositol 3- and 4-kinase (<db_xref db="INTERPRO" dbkey="IPR000403"/>), C2 (<db_xref db="INTERPRO" dbkey="IPR000008"/>), OTU (<db_xref db="INTERPRO" dbkey="IPR003323"/>), dnaJ (<db_xref db="INTERPRO" dbkey="IPR001623"/>), RING-finger (<db_xref db="INTERPRO" dbkey="IPR001841"/>) or FYVE-finger (<db_xref db="INTERPRO" dbkey="IPR017455"/>). 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 [<cite idref="PUB00018256"/>, <cite idref="PUB00018257"/>, <cite idref="PUB00044081"/>]. </p><p>The UIM is unlikely to form an independent folding domain. Instead, based on the spacing of the conserved residues, the motif probably forms a short alpha-helix that can be embedded into different protein folds [<cite idref="PUB00018255"/>]. Some proteins known to contain an UIM are listed below: </p><p> <ul><li>Eukaryotic PSD4/RPN-10/S5, a multi-ubiquitin binding subunit of the 26S proteasome. </li><li>Vertebrate Machado-Joseph disease protein 1 (Ataxin-3), which acts as a histone-binding protein that regulates transcription; defects in Ataxin-3 cause the neurodegenerative disorder Machado-Joseph disease (MJD).</li><li>Vertebrate epsin and epsin2. </li><li>Vertebrate hepatocyte growth factor-regulated tyrosine kinase substrate (HRS). </li><li>Mammalian epidermal growth factor receptor substrate 15 (EPS15), which is involved in cell growth regulation. </li><li>Mammalian epidermal growth factor receptor substrate EPS15R. </li><li> <taxon tax_id="7227">Drosophila melanogaster</taxon> (Fruit fly) liquid facets (lqf), an epsin. </li><li>Yeast VPS27 vacuolar sorting protein, which is required for membrane traffic to the vacuole. </li></ul> </p> Ubiquitin interacting motif