|PROSITE documentation PDOC50330|
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 . 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:
The profile we developed covers the entire UIM domain.Last update:
October 2014 / Text revised.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Hofmann K. Falquet L.|
|Title||A ubiquitin-interacting motif conserved in components of the proteasomal and lysosomal protein degradation systems.|
|Source||Trends Biochem. Sci. 26:347-350(2001).|
|Title||From UBA to UBX: new words in the ubiquitin vocabulary.|
|Source||Trends Cell Biol. 12:216-221(2002).|
|3||Authors||Oldham C.E. Mohney R.P. Miller S.L.H. Hanes R.N. O'Bryan J.P.|
|Title||The ubiquitin-interacting motifs target the endocytic adaptor protein epsin for ubiquitination.|
|Source||Curr. Biol. 12:1112-1116(2002).|
|Title||Cell biology: the ubiquitin connection.|
|5||Authors||Polo S. Sigismund S. Faretta M. Guidi M. Capua M.R. Bossi G. Chen H. De Camilli P. Di Fiore P.P.|
|Title||A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins.|