Mustela putorius furo

    The CUE family was first described as a region of homology between the yeast Cue1 (coupling of ubiquitin to ER degradation) and human Tollip proteins. The domain is approximately 40 amino acids in length and is found in proteins that have a variety of functions, including the degradation of misfolded proteins in the endoplasmic reticulum and protein sorting. CUE domains have been shown to both bind mono and polyubiquitin and some CUE domain-containing proteins are themselves ubiquitinylated in a CUE domain-dependent manner (1).

1. http://www.cellsignal.com/contents/resources-protein-domains-interactions/cue-protein-domain/domains-cue/

    The DUIM proteins form a single a-helix, which binds two ubiquitin molecules, one on either side. These two ubiquitin molecules are related by pseudo two-fold screw symmetry along the helical axis of the UIM, corresponding to a shift by two residues on the UIM helix. DUIMs belongs to a new subclass of double-sided UIMs (1).

1. Hirano et al., 2006. Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting. Nat Struct Mol Biol., 13(3):272-7. PMID: 16462748

    The GAT (GGA and Tom1) domains are known to interact with GTP-bound ARF and are crucial for membrane recruitment of GGAs to the trans-Golgi network. Results have found the GAT domain of GGAs to possess dual functions. The N-terminal subdomain of GAT is bound to GTP-ARF as the C-terminal subdomain is bound to ubiquitin. The GAT domain is found in 25 proteins from various species and contains a three-helix bundle with a hydrophobic core. Both GGAs and Tom1 are capable of binding ubiquitin via their GAT domains suggesting roles for these proteins in mediating intracellular trafficking and sorting(1).

1. http://www.ebi.ac.uk/interpro/entry/IPR004152

    The MIU (Motif Interacting with Ubiquitin) domain binds to ubiquitin in a manner almost identical to that of the UIM:Ub interaction, although in the opposite orientation.Similar to UIM domains, a critical Ala residue is required for binding to Ub. MIU-containing proteins have been reported to bind to polyUb chains linked through lysine-48 or lysine-63 of ubiquitin. The identification of MIU domains in proteins such as Myosin VI and Rabex-5 support their role in ubiquitin-dependant vesicular trafficking.

    The ubiquitin-associated (UBA) domain is an approximately 40 amino acid motif that was first recognized in proteins associated with ubiquitination but is also found in proteins involved in DNA nucleotide excision-repair and other proteins (1). UBA domains have been shown to bind mono-, di-, tri-, and tetra-ubiquitin in vitro but appear to bind to polyubiquitin with a higher affinity and it is thought that polyubiquitinated proteins represent the true in vivo binding substrates. As well, some UBA domains appear to homo and heterodimerize and to bind other substrates. Functionally, the UBA domain has been proposed to limit ubiquitin chain elongation and to target ubiquitinated proteins to the 26S proteasome for degradation. Evidence that ubiquitin binds to UBA domains leads to the prediction that the hydrophobic surface patch of UBA domains interacts with the hydrophobic surface on the five-stranded beta-sheet of ubiquitin (2).

1. http://pfam.xfam.org/family/PF00627

2. Mueller TD, Feigon J. (2002). Solution structures of UBA domains reveal a conserved hydrophobic surface for protein-protein interactions. J Mol Biol., 319(5):1243-55. PMID: 12079361

    UBAN (ubiquitin binding in ABIN and NEMO) motif of NEMO selectively binds linear (head-to-tail) ubiquitin chains. Crystal structures of the UBAN motif revealed a parallel coiled-coil dimer that formed a heterotetrameric complex with two linear diubiquitin molecules. The UBAN dimer contacted all four ubiquitin moieties, and the integrity of each binding site was required for efficient NF-kappaB activation. Binding occurred via a surface on the proximal ubiquitin moiety and the canonical Ile44 surface on the distal one, thereby providing specificity for linear chain recognition.

    UBM adopts a structural fold distinct from other ubiquitin-binding domains and binds to the hydrophobic surface of ubiquitin centered at L8. Human pol eta contains two functional UBMs, both contributing to replication foci formation. In contrast, only the second UBM of Saccharomyces cerevisiae Rev1 binds to ubiquitin and is essential for Rev1-dependent cell survival and mutagenesis.

    The ubiquitin-interacting motif (UIM) was first described as a region of sequence homology to the ubiquitin binding S5a subunit of the 26S proteasome. The motif is found in a number of proteins involved in endocytosis and protein trafficking and can bind monoubiquitin as well as polyubiquitin chains. It has been suggested that UIM binding to monoubiquitylated substrates limits polyubiquitin chain assembly by blocking subsequent ubiquitin attachment to Lys48 of ubiquitin. Interestingly, several UIM domain-containing proteins are themselves ubiquitylated in UIM domain-dependent manner.

    The UMI motif mediates interaction with ubiquitin with a preference for 'Lys-63'-linked ubiquitin(1). The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs.

1. Pinato S., Gatti M., Scandiuzzi C., Confalonieri S., Penengo L (2011). UMI, a novel RNF168 ubiquitin binding domain involved in the DNA damage signaling pathway. Mol. Cell. Biol., 31:118-126. PMID:21041483

    The VHS (Vps27, Hrs, and STAM) domain is approximately 140 residues long and occur in ESCRT-0 subunits Hrs and STAM, GGA adapters, and other trafficking proteins. The structure of the STAM VHS domain-ubiquitin complex was solved at 2.6 A resolution, revealing that determinants for ubiquitin recognition are conserved in nearly all VHS domains. VHS domains from all classes of VHS-domain containing proteins in yeast and humans, including both subunits of ESCRT-0, bound ubiquitin in vitro.

    WD40-repeat Beta-Prp are found in a wide range of proteins involved in distinct biological activities.Recently, a large subset of WD40 Beta-Prp were identified as a class of ubiquitin-binding domains. For example, the Doa1 Beta-Prp could bind the hydrophobic patch of ubiquitin centered on residues I44, L8, and V70.

    CARD is a special ubiquitin binding domain. The CARD domains of many proteins, such as NOD1, NOD2, DDX58 and IFIH1, have been shown to bind polyubiquitin chains.

    Jab_MPN domain binds directly to ubiquitin with an affinity comparable to other known UBDs, Proteins with this domain include proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors. They are metalloenzymes that function as the ubiquitin isopeptidase/ deubiquitinase in the ubiquitin-based signaling and protein turnover pathways in eukaryotes (1).

1. Verma R , Aravind L , Oania R , McDonald WH , Yates JR 3rd , Koonin EV , Deshaies RJ(2002). Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science., 298(5593):611-5. PMID:12183636

    UBD/Other/Other family is a collection of unconventional ubiquitin-binding domain containing proteins. ZRF1-UBD, UT3, PBR and many other undescribed UBDs consist this family.

    The GLUE (GRAM-like ubiquitin-binding in EAP45) domain structure has a typical PH domain architecture with two curved beta sheets forming a barrel-like structure and one long alpha helix. Although the GLUE domain structurally resembles a split PH domain, the phosphoinositide pocket is clearly different that of the PH domain. The major components of the ESCRT complex consists of proteins recruited at different stages of the vesicular transport pathway. The GLUE domain plays a critical role in its ability to bind PtdIns3p and translocate Vps36 to endosomes. The affinity of the GLUE domain to bind PtdIns3p-containing vesicles is approximately 0.1uM. Mutations within the GLUE domain inhibit lipid binding and result in defects in the sorting of ubiquitinated cargo. Furthermore, the GLUE domain of Vps36 contains two integral NSF domains that recognize ubiquitin.

    The PRU family was thought originally to be involved in cell-adhesion (1, 2), but the members are now known to be proteasome subunit Rpn13, a novel ubiquitin receptor. Rpn13 binds ubiquitin via a conserved amino-terminal region called the pleckstrin-like receptor for ubiquitin, termed Pru, domain (3, 4). The domain forms two contiguous anti-parallel beta-sheets with a configuration similar to the pleckstrin-homology domain (PHD) fold. Rpn13's ability to bind ubiquitin and the proteasome subunit Rpn2/S1 simultaneously supports evidence of its role as a ubiquitin receptor. Finally, when complexed to di-ubiquitin, via the Pru, and Uch37 via the C-terminal part, it frees up the distal ubiquitin for de-ubiquitination by the Uch37 (5).

1. Hasegawa et al., 1999. Xoom: a novel oocyte membrane protein maternally expressed and involved in the gastrulation movement of Xenopus embryos. Int J Dev Biol., 43(6):479-85. PMID: 10610020

2. Simins et al., 1999. Functional cloning of ARM-1, an adhesion-regulating molecule upregulated in metastatic tumor cells. Clin Exp Metastasis., 17(8):641-8. PMID: 10919708

3. Husnjak et al., 2008. Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature., 453(7194):481-8. PMID: 18497817

4. http://www.ebi.ac.uk/interpro/entry/IPR006773

5. Schreiner et al., 2008. Ubiquitin docking at the proteasome through a novel pleckstrin-homology domain interaction. Nature., ;453(7194):548-52. PMID: 18497827

    The SH3 domains constitute a new type of ubiquitin-binding domains. Like many other ubiquitin-binding motifs, the SH3 domain engages the Ile44 hydrophobic patch of ubiquitin. A phenylalanine residue located at the heart of the ubiquitin-binding surface of the SH3 domain serves as a key specificity determinant. The structure of the SH3-ubiquitin complex explains how a subset of SH3 domains has acquired this non-traditional function.

    UBD_UBC is a family aslo exists in E2 group, which is the abbreviation of ubiquitin-conjugating and mediates the ubiquitin binding and poly-ub chain formation.

    UBD_UEV is a family aslo exists in E2 group. UEV represents the Ubiquitin E2 variant (UEV) proteins which have a UBC domain but lack the active-site cysteine residue.

    The NZF domain (Npl4 zinc finger) is a compact zinc-binding module found in many proteins that function in ubiquitin-dependent processes. Present in more than 100 proteins, NZF domains conform to the consensus sequence: x(4)-W-x-C-x(2)-C-x(3)-N-x(6)-C-x(2)-C-x(5), with many more proteins containing recognizable variants of the NZF motif. Consisting of ~35 amino acids, the NZF domain forms a compact module composed of four antiparallel beta-strands linked by three ordered loops and organized about a rubredoxin-like Zn(Cys)4 metal-binding site. While many NZF domains have shown to bind mono- and polyubiquitin, not all NZF domains appear capable of binding ubiquitin.

    The ubiquitin-binding zinc finger (UBZ) domain binds polyubiquitin but not monoubiquitin and appears to show no specificity for polyubiquitin chain linkage. A homologous zinc finger domain in RAD18 also binds polyubiquitin, suggesting a wider role for the UBZ domain in DNA repair.

    ZnF_A20 domain has may functions. It has been reported to determine the ubiquitin ligase activity. Also, Using an alternative UBD, the A20 ZnF domain from the ZNF216 protein, which binds the Asp58 residue of Ub.

    The ZnF_UBP domain is present in several conserved protein families:deubiquitinating enzymes such as mammalian USP3, USP5, USP13, USP44, USP45, USP49, and USP51.Unlike other ubiquitin binding domains, ZnF_UBP contains a deep binding pocket where the C-terminal diglycine motif of ubiquitin is inserted.