RING Domain
Class:Ubiquitin processes
Structure:

No Image RING finger domains are defined by the consensus sequence CX2CX(9-39)CX(1-3)HX(2-3)C/HX2CX(4-48)CX2C with the Cys and His representing zinc binding residues. RING fingers are further divided into RING-HC and RING-H2, depending on whether a Cys or His occupies the fifth coordination site. While RING fingers are structurally diverse, all contain two interleaved Zn2+ binding sites. Binding of the Cbl RING domain to the E2 protein, UbcH7, occurs between a groove within the RING domain and two loops in the E2 fold of UbcH7. Van der Waals interactions involving hydrophobic residues in both the E2 and RING domains support the Cbl-UbcH7 binding, though this is not universal as the RING-E2 pair of Rad18p and Rad6p/Ubc2p interact by hydrogen bonding of polar residues. The figure shows the structure of the RING finger domain of c-Cbl with the interleaved zinc ions indicated in black.

Structure Reference:
Zheng et al. (2000) Cell. 102:533-539. PDB: 1FBV.

Domain binding and function:
structure The RING finger is a specialized type of Zn-finger consisting of 40 to 60 residues that binds two atoms of zinc, and is involved in mediating protein-protein interactions. The presence of a RING finger domain is a characteristic of RING-class E3 ubiquitin protein ligases capable of transfering ubiquitin from an E2 enzyme to a substrate protein. The RING domain mediates the interaction with the appropriate E2 enzyme. Unlike HECT E3s that form a thiol-ester with ubiquitin, RING fingers likely mediate ubiquitination by facilitating the direct transfer of ubiquitin from E2s to lysine residues on the target substrate. RING finger proteins include the Hrt1/Roc1/Rbx1 proteins found in both the SCF and VCB-like E3 complexes, the APC1 component of the Anaphase Promoting Complex, Cbl family proteins, Mdm2 and many other proteins with demonstrated E3 activity, E2 binding or involvement in ubiquitination. In addition to the involvement of RING finger domains in ubiquitin transfer, this domain has also been associated with certain transcription factors such as TIF1b, the PML-family, NFX1 and XPRF.
Examples of Proteins: 
RING domain protein
 Binding partner
Cbl UbcH7
RAD5 UBC13-MMS2 complex
RAD6 RAD18
HHARI UbcH7
Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors: Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada