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 1409286790 710 FKCLICMEQYKKPVTSVCCWHVHCEQCWLHTLsgrpttspaakaakkrrllsvlqGAKKLCPQCNMITSPSDLRR 784
Cdd:cd16563     1 YKCLICMDSYTMPLVSIQCWHVHCEECWLRTL-----------------------GAKKLCPQCNTITSPADLRR 52

RING finger, HC subclass, found in RING finger protein 220 (RNF220) and similar proteins; RNF220 is an E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of Sin3B, a scaffold protein of the Sin3/HDAC (histone deacetylase) corepressor complex. It can also bind E2 and mediate auto-ubiquitination of itself. Moreover, RNF220 specifically interacts with beta-catenin, and enhances canonical Wnt signaling through ubiquitin-specific protease 7 (USP7)-mediated deubiquitination and stabilization of beta-catenin, which is independent of its E3 ligase activity. RNF220 contains a characteristic C3HC4-type RING-HC finger at its C-terminus.

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gi 1409286790 710 FKCLICMEQYKKPVTSVCCWHVHCEQCWLHTLsgrpttspaakaakkrrllsvlqGAKKLCPQCNMITSPSDLRR 784
Cdd:cd16563     1 YKCLICMDSYTMPLVSIQCWHVHCEECWLRTL-----------------------GAKKLCPQCNTITSPADLRR 52

Uncharacterized conserved protein, contains RING and CCCH-type Zn-fingers [General function prediction only];

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gi 1409286790 709 PFKCLICMEQYKKPVTSVcCWHVHCEQCWLHTLSGRPTTSPAAKAAKKR 757
Cdd:COG5152   196 PFLCGICKKDYESPVVTE-CGHSFCSLCAIRKYQKGDECGVCGKATYGR 243

RING finger, HC subclass, found in RING finger protein 220 (RNF220) and similar proteins; RNF220 is an E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of Sin3B, a scaffold protein of the Sin3/HDAC (histone deacetylase) corepressor complex. It can also bind E2 and mediate auto-ubiquitination of itself. Moreover, RNF220 specifically interacts with beta-catenin, and enhances canonical Wnt signaling through ubiquitin-specific protease 7 (USP7)-mediated deubiquitination and stabilization of beta-catenin, which is independent of its E3 ligase activity. RNF220 contains a characteristic C3HC4-type RING-HC finger at its C-terminus.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1409286790 710 FKCLICMEQYKKPVTSVCCWHVHCEQCWLHTLsgrpttspaakaakkrrllsvlqGAKKLCPQCNMITSPSDLRR 784
Cdd:cd16563     1 YKCLICMDSYTMPLVSIQCWHVHCEECWLRTL-----------------------GAKKLCPQCNTITSPADLRR 52

HC subclass of RING (RING-HC) finger and its variants; 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 a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in 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 enables efficient transfer of ubiquitin from E2 to the substrates.

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gi 1409286790 710 FKCLICMEQYKKPVTsVCCWHVHCEQCWLHTLSGRPTT 747
Cdd:cd16449     1 LECPICLERLKDPVL-LPCGHVFCRECIRRLLESGSIK 37

RING finger, HC subclass, found in RING finger proteins RNF113A, RNF113B, and similar proteins; RNF113A, also known as zinc finger protein 183 (ZNF183), is an E3 ubiquitin-protein ligase that physically interacts with the E2 protein, UBE2U. A nonsense mutation in RNF113A is associated with an X-linked trichothiodystrophy (TTD). Its yeast ortholog Cwc24p is predicted to have a spliceosome function and acts in a complex with Cef1p to participate in pre-U3 snoRNA splicing, indirectly affecting pre-rRNA processing. It is also important for the U2 snRNP binding to primary transcripts and co-migrates with spliceosomes. Moreover, the ortholog of RNF113A in fruit flies may also act as a spliceosome and is hypothesized to be involved in splicing, namely within the central nervous system. The ortholog in Caenorhabditis elegans is involved in DNA repair of inter-strand crosslinks. RNF113B, also known as zinc finger protein 183-like 1, shows high sequence similarity with RNF113A. Both RNF113A and RNF113B contain a CCCH-type zinc finger, which is commonly found in RNA-binding proteins involved in splicing, and a C3HC4-type RING-HC finger, which is frequently found in E3 ubiquitin ligases.

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gi 1409286790 709 PFKCLICMEQYKKPVTSVCCwHVHCEQCWL 738
Cdd:cd16539     5 PFACFICRKPFKNPVVTKCG-HYFCEKCAL 33

Uncharacterized conserved protein, contains RING and CCCH-type Zn-fingers [General function prediction only];

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gi 1409286790 709 PFKCLICMEQYKKPVTSVcCWHVHCEQCWLHTLSGRPTTSPAAKAAKKR 757
Cdd:COG5152   196 PFLCGICKKDYESPVVTE-CGHSFCSLCAIRKYQKGDECGVCGKATYGR 243

RING finger, HC subclass, found in RING finger protein 166 (RNF166) and similar proteins; RNF166 is encoded by the gene RNF166 targeted by thyroid hormone receptor alpha1 (TRalpha1), which is important in brain development. It plays an important role in RNA virus-induced interferon-beta production by enhancing the ubiquitination of TRAF3 and TRAF6. RNF166, together with three closely related proteins: RNF114, RNF125 and RNF138, 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 1409286790 710 FKCLICMEQYKKPVTSVCCWHVHCEQCwlhtlsgrpttspaakaakkrrLLSVLQGAKKLCPQCNM 775
Cdd:cd16549     2 FSCPICLEVYHKPVVITSCGHTFCGEC----------------------LQPCLQVASPLCPLCRM 45