{PDOC50330} {PS50330; UIM} {BEGIN} **************************************************** * Ubiquitin-interacting motif (UIM) domain profile * **************************************************** Covalent modification of proteins by the small, evolutionary conserved protein ubiquitin (see ) 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 ) 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 ), UBX (see ), ENTH, EH (see ), VHS (see ), SH3 (see ), HECT (see ), VWFA (see ), EF-hand calcium- binding (see ), WD-40 (see ), F-box (see ), LIM (see ), protein kinase (see ), ankyrin (see ), PX (see ), phosphatidylinositol 3- and 4-kinase (see ), C2 (see ), OTU (see ), dnaJ (see ), RING-finger (see ) or FYVE-finger (see ). 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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: October 2014 / Text revised. [ 1] Hofmann K., Falquet L. "A ubiquitin-interacting motif conserved in components of the proteasomal and lysosomal protein degradation systems." Trends Biochem. Sci. 26:347-350(2001). PubMed=11406394 [ 2] Buchberger A. "From UBA to UBX: new words in the ubiquitin vocabulary." Trends Cell Biol. 12:216-221(2002). PubMed=12062168 [ 3] Oldham C.E., Mohney R.P., Miller S.L.H., Hanes R.N., O'Bryan J.P. "The ubiquitin-interacting motifs target the endocytic adaptor protein epsin for ubiquitination." Curr. Biol. 12:1112-1116(2002). PubMed=12121618 [ 4] Riezman H. "Cell biology: the ubiquitin connection." Nature 416:381-383(2002). PubMed=11919614; DOI=10.1038/416381a [ 5] Polo S., Sigismund S., Faretta M., Guidi M., Capua M.R., Bossi G., Chen H., De Camilli P., Di Fiore P.P. "A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins." Nature 416:451-455(2002). PubMed=11919637; DOI=10.1038/416451a -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}