C2HC Zing finger domain; This is a zinc finger domain together with a linker region found in RNF125, a small protein (25kD) that contains a RING domain, three zinc fingers (ZnFs) and a ubiquitin interacting motif (UIM). The C2HC ZnF plays an essential role in the interaction of RNF125 with the E2 UbcH5a, which originates from the requirement of the C2HC-ZnF for the structural stability of the RING domain. A mutation at one of the contact residues in the C2HC-ZnF, a highly conserved M112, resulted in the loss of ubiquitin ligase activity. Furthermore, mutations at the Zn2+ chelating cysteine residues, C100 and C103 of this domain resulted in a loss of activity.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 530413828   34 RKFSGSCRCCAKQIKFYRMRHHYKSCKKYQDEY 66
Cdd:pfam18574   1 ESTEGNCRGCEKQVCLSKMRAHYATCEKYQEYY 33

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.

                         10        20
                 ....*....|....*....|
gi 530413828   1 MRESGAHCPLCRGNVTRRER 20
Cdd:cd16544   34 LRSSGARCPLCRGPVGKTER 53

C2HC Zing finger domain; This is a zinc finger domain together with a linker region found in RNF125, a small protein (25kD) that contains a RING domain, three zinc fingers (ZnFs) and a ubiquitin interacting motif (UIM). The C2HC ZnF plays an essential role in the interaction of RNF125 with the E2 UbcH5a, which originates from the requirement of the C2HC-ZnF for the structural stability of the RING domain. A mutation at one of the contact residues in the C2HC-ZnF, a highly conserved M112, resulted in the loss of ubiquitin ligase activity. Furthermore, mutations at the Zn2+ chelating cysteine residues, C100 and C103 of this domain resulted in a loss of activity.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 530413828   34 RKFSGSCRCCAKQIKFYRMRHHYKSCKKYQDEY 66
Cdd:pfam18574   1 ESTEGNCRGCEKQVCLSKMRAHYATCEKYQEYY 33

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                         10        20
                 ....*....|....*....|
gi 530413828   1 MRESGAHCPLCRGNVTRRER 20
Cdd:cd16544   34 LRSSGARCPLCRGPVGKTER 53

C2HC Zing finger domain; This is a zinc finger domain together with a linker region found in RNF125, a small protein (25kD) that contains a RING domain, three zinc fingers (ZnFs) and a ubiquitin interacting motif (UIM). The C2HC ZnF plays an essential role in the interaction of RNF125 with the E2 UbcH5a, which originates from the requirement of the C2HC-ZnF for the structural stability of the RING domain. A mutation at one of the contact residues in the C2HC-ZnF, a highly conserved M112, resulted in the loss of ubiquitin ligase activity. Furthermore, mutations at the Zn2+ chelating cysteine residues, C100 and C103 of this domain resulted in a loss of activity.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 530413828   34 RKFSGSCRCCAKQIKFYRMRHHYKSCKKYQDEY 66
Cdd:pfam18574   1 ESTEGNCRGCEKQVCLSKMRAHYATCEKYQEYY 33

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                         10        20
                 ....*....|....*....|
gi 530413828   1 MRESGAHCPLCRGNVTRRER 20
Cdd:cd16544   34 LRSSGARCPLCRGPVGKTER 53