ubiquitin-interacting motif

{{Infobox protein family

| Symbol = UIM

| Name = UIM

| image = PDB 1yx5 EBI.jpg

| width =

| caption = solution structure of s5a uim-1/ubiquitin complex

| Pfam = PF02809

| Pfam_clan =

| InterPro = IPR003903

| SMART =

| PROSITE =

| MEROPS =

| SCOP = 1p9d

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD =

}}

In molecular biology, the Ubiquitin-Interacting Motif (UIM), or 'LALAL-motif', is a sequence motif 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 journal |vauthors=Young P, Deveraux Q, Beal RE, Pickart CM, Rechsteiner M | title = Characterization of two polyubiquitin binding sites in the 26 S protease subunit 5a | journal = J. Biol. Chem. | volume = 273 | issue = 10 | pages = 5461–7 |date=March 1998 | pmid = 9488668 | doi = 10.1074/jbc.273.10.5461| doi-access = free }}{{cite journal |vauthors=Hofmann K, Falquet L | title = A ubiquitin-interacting motif conserved in components of the proteasomal and lysosomal protein degradation systems | journal = Trends Biochem. Sci. | volume = 26 | issue = 6 | pages = 347–50 |date=June 2001 | pmid = 11406394 | doi = 10.1016/s0968-0004(01)01835-7}} 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 journal | author = Buchberger A | title = From UBA to UBX: new words in the ubiquitin vocabulary | journal = Trends Cell Biol. | volume = 12 | issue = 5 | pages = 216–21 |date=May 2002 | pmid = 12062168 | doi = 10.1016/S0962-8924(02)02269-9}} In most of these proteins, the UIM occurs in multiple copies and in association with other domains such as UBA ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR015940 INTERPRO]), UBX ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR001012 INTERPRO]), ENTH domain, EH ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR000261 INTERPRO]), VHS ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR002014 INTERPRO]), SH3 domain, HECT, VWFA ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR002035 INTERPRO]), EF-hand calcium-binding, WD-40, F-box ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR001810 INTERPRO]), LIM, protein kinase, ankyrin, PX, phosphatidylinositol 3- and 4-kinase ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR000403 INTERPRO]), C2 domain, OTU ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR003323 INTERPRO]), DnaJ domain ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR001623 INTERPRO]), RING-finger ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR001841 INTERPRO]) or FYVE-finger ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR017455 INTERPRO]). 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 journal |vauthors=Oldham CE, Mohney RP, Miller SL, Hanes RN, O'Bryan JP | title = The ubiquitin-interacting motifs target the endocytic adaptor protein epsin for ubiquitination | journal = Curr. Biol. | volume = 12 | issue = 13 | pages = 1112–6 |date=July 2002 | pmid = 12121618 | doi = 10.1016/S0960-9822(02)00900-4| doi-access = free }}{{cite journal | author = Riezman H | title = Cell biology: the ubiquitin connection | journal = Nature | volume = 416 | issue = 6879 | pages = 381–3 |date=March 2002 | pmid = 11919614 | doi = 10.1038/416381a | doi-access = free }}{{cite journal |vauthors=Reece DE, Barnett MJ, Connors JM, Fairey RN, Fay JW, Greer JP, Herzig GP, Herzig RH, Klingemann HG, LeMaistre CF | title = Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease | journal = J. Clin. Oncol. | volume = 9 | issue = 10 | pages = 1871–9 |date=October 1991 | doi = 10.1200/JCO.1991.9.10.1871 | pmid = 1919637 }}

The UIM is unlikely to form an independent protein 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. Some proteins known to contain an UIM are listed below:

• Eukaryotic PSD4/RPN-10/S5, a multi-ubiquitin binding subunit of the 26S proteasome.
• 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).
• Vertebrate epsin and epsin2.
• Vertebrate hepatocyte growth factor-regulated tyrosine kinase substrate (HRS).
• Mammalian epidermal growth factor receptor substrate 15 (EPS15), which is involved in cell growth regulation.
• Mammalian epidermal growth factor receptor substrate EPS15R.
• Drosophila melanogaster (Fruit fly) liquid facets (lqf), an epsin.
• Yeast VPS27 vacuolar sorting protein, which is required for membrane traffic to the vacuole.