RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.

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gi 40226324   1 LNKLHRKACPFDQT 14
Cdd:cd16782  36 LNKLHRKACPFDQT 49

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-2; Roquin-2, also known as membrane-associated nucleic acid-binding protein (MNAB), RING finger and CCCH-type zinc finger domain-containing protein 2 (RC3H2), or RING finger protein 164 (RNF164), is an E3 ubiquitin ligase that is localized to the cytoplasm and upon stress, is concentrated in stress granules. It is required for reactive oxygen species (ROS)-induced ubiquitination and degradation of apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5). Roquin-2 interacts with the 3'UTR of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) and tumor-necrosis factor-alpha (TNFalpha), and modulates immune responses. Moreover, Roquin-2 shares functions with its paralog Roquin-1 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Roquin-2 contains an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 ubiquitin-ligase function, a highly conserved ROQ domain required for RNA binding and localization to stress granules, a coiled-coil (CC1), and a CCCH-type zinc finger that is involved in RNA recognition.

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gi 40226324   1 LNKLHRKACPFDQT 14
Cdd:cd16782  36 LNKLHRKACPFDQT 49

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-2; Roquin-2, also known as membrane-associated nucleic acid-binding protein (MNAB), RING finger and CCCH-type zinc finger domain-containing protein 2 (RC3H2), or RING finger protein 164 (RNF164), is an E3 ubiquitin ligase that is localized to the cytoplasm and upon stress, is concentrated in stress granules. It is required for reactive oxygen species (ROS)-induced ubiquitination and degradation of apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5). Roquin-2 interacts with the 3'UTR of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) and tumor-necrosis factor-alpha (TNFalpha), and modulates immune responses. Moreover, Roquin-2 shares functions with its paralog Roquin-1 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Roquin-2 contains an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 ubiquitin-ligase function, a highly conserved ROQ domain required for RNA binding and localization to stress granules, a coiled-coil (CC1), and a CCCH-type zinc finger that is involved in RNA recognition.

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gi 40226324   1 LNKLHRKACPFDQT 14
Cdd:cd16782  36 LNKLHRKACPFDQT 49

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1, Roquin-2, and similar proteins; The ROQUIN family includes Roquin-1, Roquin-2, and similar proteins, which localize to the cytoplasm and upon stress, are concentrated in stress granules. They may play essential roles in preventing T-cell-mediated autoimmune disease and in microRNA-mediated repression of inducible costimulator (Icos) mRNA. They function as E3 ubiquitin ligases consisting of an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 activity, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger involved in RNA recognition.

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gi 40226324   1 LNKLHRKACPFDQ 13
Cdd:cd16638  32 LSKLHRKQCPFDQ 44