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PROSITE documentation PDOC51140CUE domain profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC51140
The Coupling of Ubiquitin conjugation to ER degradation or CUE domain is a ~44 residue ubiquitin binding domain, present in eukaryotic proteins of trafficking and ubiquitination pathways. Ubiquitin is a 76 amino acid polypeptide that can be attached to proteins to alter their activity or location (see <PDOC00271>). Monoubiquitination and the addition of polyubiquitin chains are important cellular regulatory signals. The CUE domain was named after baker's yeast Cue1 protein [1]. Some domains which can occur in combination with the CUE domain are the RING-type zinc finger (see <PDOC00449>), the Smr domain (see <PDOC50828>) or the C2 domain (see <PDOC00380>). CUE domains can bind monoubiquitin and can be required for ubiquitination of the protein in which they are found [2,3,4].
The 3D structure of the CUE domain comprises three α helices arranged in a bundle (see <PDB:1OTR>), similar to the fold of the UBA domain (see <PDOC50030>). The binding surface is a hydrophobic patch that is complementary to the ubiquitin hydrophobic surface. The CUE domain contains two conserved motifs that bind ubiquitin, i.e. (MF)P, C-terminal to the first helix, and a di-leucine-like motif in the third helix.
Some proteins known to contain a CUE domain:
- Yeast Cue1 (YMR264W) protein, which recruits the ubiquitin-conjugating enzyme Ubc7p to the endoplasmic reticulum (ER), where it is essential for the degradation of misfolded proteins. The Cue1 CUE domain lacks parts of the motifs and shows a relatively low affinity for ubiquitin [2].
- Yeast Cue2, Cue3 (YGL110C), Cue4 (YML101C) and Cue5 (YOR042w) proteins, which have different ubiquitin-binding affinities [2]. Cue2 contains a tandem of two ubiquitin binding CUE domains near its N-terminus.
- Yeast Def1 (YKL054C) protein, which is involved in ubiquitination of RNA polymerase II and mediating its degradation through interaction with Rad26.
- Fungal Vacuolar Protein Sorting-associated protein Vps9, a guanine nucleotide exchange factor for the Rab-like GTPase Vps21. Vps9 is needed for the transport of proteins from biosynthetic and endocytic pathways into the vacuole. Its C-terminal CUE domain forms a dimer which binds a single ubiquitin molecule.
- Mammalian Toll-interacting protein tollip and TAB2, proteins involved in signaling from the interleukin-1 receptor.
- Human autocrine motility factor receptor (AMFR), a cytokine receptor that regulates tumor cell motility and promotes metastasis. AMFR is conserved among metazoans.
- Human ancient ubiquitous protein 1 (AUP1), involved in integrin signaling. Aup1 is conserved among metazoans.
- Japanese pufferfish BAW (Between AKAP84 and WSBB1 genes) protein.
The profile we developed covers the entire CUE domain.
Last update:July 2005 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Ponting C.P. |
| Title | Proteins of the endoplasmic-reticulum-associated degradation pathway: domain detection and function prediction. | |
| Source | Biochem. J. 351:527-535(2000). | |
| PubMed ID | 11023840 |
| 2 | Authors | Shih S.C. Prag G. Francis S.A. Sutanto M.A. Hurley J.H. Hicke L. |
| Title | A ubiquitin-binding motif required for intramolecular monoubiquitylation, the CUE domain. | |
| Source | EMBO J. 22:1273-1281(2003). | |
| PubMed ID | 12628920 | |
| DOI | 10.1093/emboj/cdg140 |
| 3 | Authors | Prag G. Misra S. Jones E.A. Ghirlando R. Davies B.A. Horazdovsky B.F. Hurley J.H. |
| Title | Mechanism of ubiquitin recognition by the CUE domain of Vps9p. | |
| Source | Cell 113:609-620(2003). | |
| PubMed ID | 12787502 |
| 4 | Authors | Kang R.S. Daniels C.M. Francis S.A. Shih S.C. Salerno W.J. Hicke L. Radhakrishnan I. |
| Title | Solution structure of a CUE-ubiquitin complex reveals a conserved mode of ubiquitin binding. | |
| Source | Cell 113:621-630(2003). | |
| PubMed ID | 12787503 |
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