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 767942028 261 LMCRVCLEDKPIKPLPCCKKAVCEECLKVYLSAQ 294
Cdd:cd16622    1 LTCRVCLEDKQIKPLPCCKKAVCEECLKRYLSSQ 34

Variant RING finger, HC subclass (C4C4-type), found in RING finger protein 217 (RNF217) and similar proteins; RNF217, also known as IBR domain-containing protein 1 (IBRDC1), is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase mainly expressed in testis and skeletal muscle, as different splice variants. It interacts with the anti-apoptotic protein HAX1, and is adjacent to a translocation breakpoint involving ETV6 in childhood acute lymphoblastic leukemia (ALL). RNF217 contains a RBR domain followed by TMs. The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a variant C4C4-type RING finger whose overall folding is similar to that of the C3HC4-type RING-HC finger. It is required for RBR-mediated ubiquitination.

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                 ....*....|....*....|....*....|....
gi 767942028 261 LMCRVCLEDKPIKPLPCCKKAVCEECLKVYLSAQ 294
Cdd:cd16622    1 LTCRVCLEDKQIKPLPCCKKAVCEECLKRYLSSQ 34

Variant RING finger, HC subclass (C4C4-type), found in RING finger protein 217 (RNF217) and similar proteins; RNF217, also known as IBR domain-containing protein 1 (IBRDC1), is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase mainly expressed in testis and skeletal muscle, as different splice variants. It interacts with the anti-apoptotic protein HAX1, and is adjacent to a translocation breakpoint involving ETV6 in childhood acute lymphoblastic leukemia (ALL). RNF217 contains a RBR domain followed by TMs. The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a variant C4C4-type RING finger whose overall folding is similar to that of the C3HC4-type RING-HC finger. It is required for RBR-mediated ubiquitination.

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                 ....*....|....*....|....*....|....
gi 767942028 261 LMCRVCLEDKPIKPLPCCKKAVCEECLKVYLSAQ 294
Cdd:cd16622    1 LTCRVCLEDKQIKPLPCCKKAVCEECLKRYLSSQ 34

transcriptional regulator ICP4; Provisional

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767942028   15 QESQTLASGTAGHPEPPRPQGDSARAPPLRAASAEPSGGGC-----GSDWGCADTSAPEPARSLGPPGWSKSRAPAQPAG 89
Cdd:PHA03307  820 KSRSHTPDGGSESSGPARPPGAAARPPPARSSESSKSKPAAaggraRGKNGRRRPRPPEPRARPGAAAPPKAAAAAPPAG 899

                          90
                  ....*....|....
gi 767942028   90 LALTGPLNPQTLPL 103
Cdd:PHA03307  900 APAPRPRPAPRVKL 913

DNA polymerase III subunits gamma and tau; Validated

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767942028   6 STVSGGGGPQESQtlASGTAGHPEPPRPQGDSARAPPLRAASAEPSGGGCGSDWG------CADTSAPEPARSLGPPGWS 79
Cdd:PRK07764 616 AAPAAPAAPAAPA--PAGAAAAPAEASAAPAPGVAAPEHHPKHVAVPDASDGGDGwpakagGAAPAAPPPAPAPAAPAAP 693

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767942028  80 KSRAPAQPAGLALTGPLNPQTLPLQLELEEEEEEAGDRKEGGDEQQEAPPGEELEPRTRVGAADG 144
Cdd:PRK07764 694 AGAAPAQPAPAPAATPPAGQADDPAAQPPQAAQGASAPSPAADDPVPLPPEPDDPPDPAGAPAQP 758