To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS.
To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017.
From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...]
View this page in https
PROSITE documentation PDOC50330 [for PROSITE entry PS50330]

Ubiquitin-interacting motif (UIM) domain profile





Description

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.

Last update:

October 2014 / Text revised.

Technical section

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

UIM, PS50330; Ubiquitin-interacting motif (UIM) domain profile  (MATRIX)


References

1AuthorsHofmann K., Falquet L.
TitleA ubiquitin-interacting motif conserved in components of the proteasomal and lysosomal protein degradation systems.
SourceTrends Biochem. Sci. 26:347-350(2001).
PubMed ID11406394

2AuthorsBuchberger A.
TitleFrom UBA to UBX: new words in the ubiquitin vocabulary.
SourceTrends Cell Biol. 12:216-221(2002).
PubMed ID12062168

3AuthorsOldham C.E., Mohney R.P., Miller S.L.H., Hanes R.N., O'Bryan J.P.
TitleThe ubiquitin-interacting motifs target the endocytic adaptor protein epsin for ubiquitination.
SourceCurr. Biol. 12:1112-1116(2002).
PubMed ID12121618

4AuthorsRiezman H.
TitleCell biology: the ubiquitin connection.
SourceNature 416:381-383(2002).
PubMed ID11919614
DOI10.1038/416381a

5AuthorsPolo S., Sigismund S., Faretta M., Guidi M., Capua M.R., Bossi G., Chen H., De Camilli P., Di Fiore P.P.
TitleA single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins.
SourceNature 416:451-455(2002).
PubMed ID11919637
DOI10.1038/416451a



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)