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 569004244  14 DDFYCPVCQEVLKTPVRTAACQHV--------SSGHPTFKCPLCQESNFTRQR 58
Cdd:cd16544    1 AELTCPVCQEVLKDPVELPPCRHIfckacillALRSSGARCPLCRGPVGKTER 53

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).

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 569004244  14 DDFYCPVCQEVLKTPVRTAACQHV--------SSGHPTFKCPLCQESNFTRQR 58
Cdd:cd16544    1 AELTCPVCQEVLKDPVELPPCRHIfckacillALRSSGARCPLCRGPVGKTER 53

Zinc finger, C3HC4 type (RING finger);

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                  ....*....|....*....|....*....|....*....|
gi 569004244   17 YCPVCQEVLKTPVRTAACQHV---SSGHPTF----KCPLC 49
Cdd:pfam13923   1 MCPICMDMLKDPSTTTPCGHVfcqDCILRALragnECPLC 40

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).

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 569004244  14 DDFYCPVCQEVLKTPVRTAACQHV--------SSGHPTFKCPLCQESNFTRQR 58
Cdd:cd16544    1 AELTCPVCQEVLKDPVELPPCRHIfckacillALRSSGARCPLCRGPVGKTER 53

SP-RING finger found in the Siz/PIAS RING (SP-RING) family of SUMO E3 ligases; The SP-RING family includes PIAS (protein inhibitor of activated STAT) proteins, Zmiz proteins, and Siz proteins from plants and fungi. PIAS proteins modulate the activity of several transcription factors and act as E3 ubiquitin ligases in the sumoylation pathway. There are four members: PIAS1, PIAS2 (also known as PIASx), PIAS3, and PIAS4 (also known as PIASy). PIAS proteins were initially identified as inhibitors of activated STAT only, but are now known to interact with and modulate several other proteins, including androgen receptor (AR), tumor suppressor p53, and the transforming growth factor-beta (TGF-beta) signaling protein SMAD. They interact with STATs in a cytokine-dependent manner. PIAS proteins have SUMO E3-ligase activity and interaction of PIAS proteins with transcription factors often results in sumoylation of that protein. Zmiz1 (Zimp10) and its homolog Zmiz2 (Zimp7) were initially identified in humans as androgen receptor (AR) interacting proteins that function as transcriptional co-activators. They interact with BRG1, the catalytic subunit of the SWI-SNF remodeling complex. They also associate with other hormone nuclear receptors and transcription factors such as p53 and Smad3/Smad4, and regulate transcription of specific target genes by altering their chromatin structure. SIZ1 proteins from plants and fungi are also founding members of this family. SIZ1-mediated conjugation of SUMO1 and SUMO2 to other intracellular proteins is essential in Arabidopsis. Yeast SIZ proteins are SUMO E3 ligases involved in a novel pathway of chromosome maintenance. They enhance SUMO modification to many substrates in vivo, but also exhibit unique substrate specificity. PIAS proteins contain a specific RING finger known as Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, which is essential for SUMO ligase activity. The SP-RING finger is a variant of the RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It binds a single Zn ion, instead of two ions bound by typical RING fingers.

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gi 569004244  18 CPVCQEVLKTPVRTAACQH-----------VSSGHPTFKCPLCQE 51
Cdd:cd16650    4 CPLSLKRIKTPARGKHCKHlqcfdldsyleFNKRKPTWKCPICDK 48

Zinc finger, C3HC4 type (RING finger);

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gi 569004244   17 YCPVCQEVLKTPVRTAACQHV---SSGHPTF----KCPLC 49
Cdd:pfam13923   1 MCPICMDMLKDPSTTTPCGHVfcqDCILRALragnECPLC 40