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        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574957034   1 MKVKIKCWNGVATWLW-VANDENCGICRMAFNGCCPDCKVPGDDCPLVWGQCSHCFHMHCILKWLHAQQVQQHCPMCRQE 79
Cdd:pfam12861  1 MKVKIKEWNAVATWLWdVPSDDVCGICRVSFDGTCPDCKFPGDDCPLVWGKCSHNFHMHCILKWLHTETSKGLCPMCRQT 80

                 ....*
gi 574957034  80 WKFKE 84
Cdd:pfam12861 81 FKFAE 85

Anaphase-promoting complex subunit 11 RING-H2 finger; Apc11 is one of the subunits of the anaphase-promoting complex or cyclosome. The APC subunits are cullin family proteins with ubiquitin ligase activity. Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). Apc11 acts as an E3 enzyme and is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo. In Saccharomyces cerevisiae this RING-H2 finger protein defines the minimal ubiquitin ligase activity of the APC, and the integrity of the RING-H2 finger is essential for budding yeast cell viability.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574957034   1 MKVKIKCWNGVATWLW-VANDENCGICRMAFNGCCPDCKVPGDDCPLVWGQCSHCFHMHCILKWLHAQQVQQHCPMCRQE 79
Cdd:pfam12861  1 MKVKIKEWNAVATWLWdVPSDDVCGICRVSFDGTCPDCKFPGDDCPLVWGKCSHNFHMHCILKWLHTETSKGLCPMCRQT 80

                 ....*
gi 574957034  80 WKFKE 84
Cdd:pfam12861 81 FKFAE 85

Component of SCF ubiquitin ligase and anaphase-promoting complex [Posttranslational modification, protein turnover, chaperones / Cell division and chromosome partitioning];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574957034  1 MKVKIKCWNGVATWLWVANDENCGICRMAFNGCCPDCK---VPGDDCPLVWGQCSHCFHMHCILKWLHAQQVqqhCPMCR 77
Cdd:COG5194   1 MKVKIKKWHAVALWSWDIPIDVCAICRNHIMGTCPECQfgmTPGDECPVVWGVCNHAFHDHCIYRWLDTKGV---CPLDR 77

                ....*
gi 574957034 78 QEWKF 82
Cdd:COG5194  78 QTWVL 82

Anaphase-promoting complex subunit 11 RING-H2 finger; Apc11 is one of the subunits of the anaphase-promoting complex or cyclosome. The APC subunits are cullin family proteins with ubiquitin ligase activity. Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). Apc11 acts as an E3 enzyme and is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo. In Saccharomyces cerevisiae this RING-H2 finger protein defines the minimal ubiquitin ligase activity of the APC, and the integrity of the RING-H2 finger is essential for budding yeast cell viability.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574957034   1 MKVKIKCWNGVATWLW-VANDENCGICRMAFNGCCPDCKVPGDDCPLVWGQCSHCFHMHCILKWLHAQQVQQHCPMCRQE 79
Cdd:pfam12861  1 MKVKIKEWNAVATWLWdVPSDDVCGICRVSFDGTCPDCKFPGDDCPLVWGKCSHNFHMHCILKWLHTETSKGLCPMCRQT 80

                 ....*
gi 574957034  80 WKFKE 84
Cdd:pfam12861 81 FKFAE 85

Component of SCF ubiquitin ligase and anaphase-promoting complex [Posttranslational modification, protein turnover, chaperones / Cell division and chromosome partitioning];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 574957034  1 MKVKIKCWNGVATWLWVANDENCGICRMAFNGCCPDCK---VPGDDCPLVWGQCSHCFHMHCILKWLHAQQVqqhCPMCR 77
Cdd:COG5194   1 MKVKIKKWHAVALWSWDIPIDVCAICRNHIMGTCPECQfgmTPGDECPVVWGVCNHAFHDHCIYRWLDTKGV---CPLDR 77

                ....*
gi 574957034 78 QEWKF 82
Cdd:COG5194  78 QTWVL 82

modified RING finger, H2 subclass (C3H2C2D-type), found in RING-box protein 1 (RBX1) and similar proteins; RBX1, also known as Hrt1, protein ZYP, RING finger protein 75 (RNF75), or regulator of cullins 1 (ROC1), is an E3 ubiquitin-protein ligase necessary for ubiquitin ligation activity of multimeric cullin (Cul)-RING E3 ligases (CRLs). RBX1-containing CRLs are involved in the NEDD8 pathway; RBX1 specifically regulates NEDD8ylation of Cul1-4. It can also bind and activate HIV-1 Vif-Cullin5 E3 ligase complex in vitro. Moreover, RBX1 is an essential element of Skp1/Cullin/F-box (SCF) E3-ubiquitin ligase complexes that target diverse proteins for proteasome-mediated degradation. It is a direct functional target of miR-194 and plays an important role in proliferation and migration of gastric cancer (GC) cells. RBX1 is also an essential component of KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex that functions as a regulator of NFE2-related factor 2 (NRF2) and plays a key role in NRF2 pathway deregulation in multiple tumor types, including ovarian carcinomas (OVCA) and papillary thyroid carcinoma (PTC). Furthermore, RBX1 associates with DDB1, Cul4A, and Fbxw5 to form the Fbxw5-DDB1-Cul4A-Rbx1 complex that may function as a dual SUMO/ubiquitin ligase suppressing c-Myb activity through sumoylation or ubiquitination. RBX1 contains a C-terminal modified RING-H2 finger that is of C3H2C2D-type, rather than the canonical C3H2C3-type. The modified RING-H2 finger is essential for its ligase activity.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 574957034 21 ENCGICRMAFNGCCPDCK-----VPGDDCPLVWGQCSHCFHMHCILKWLHAQQVqqhCPMCRQEW 80
Cdd:cd16485   1 DNCAICRNHIMDLCIECQanqasATSEECTVAWGVCNHAFHFHCISRWLKTRQV---CPLDNREW 62

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        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 574957034 23 CGICRMAFNGCCPdckvpgddcpLVWGQCSHCFHMHCILKWLHAQqvQQHCPMC 76
Cdd:cd00162   1 CPICREEMNDRRP----------VVLLSCGHTFSRSAIARWLEGS--KQKCPFC 42

H2 subclass of RING (RING-H2) fingers 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 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). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger 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 serves as a scaffold 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 574957034 23 CGICRMAFngccpdckvpGDDCPLVWGQCSHCFHMHCILKWLhaQQVQQHCPMCR 77
Cdd:cd16448   1 CVICLEEF----------EEGDVVRLLPCGHVFHLACILRWL--ESGNNTCPLCR 43

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                         10        20
                 ....*....|....*....|....*....
gi 574957034  51 CSHCFHMHCILKWLHAQQVQqhCPMCRQE 79
Cdd:COG5540  344 CDHRFHVGCVDKWLLGYSNK--CPVCRTA 370

second RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the second RING-H2 finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 574957034 23 CGICRMAFNGC-CPDCKVPGDDCPLVWGQCSHCFHMHCILKW-LHAQQVQQHCPMCRQE 79
Cdd:cd16678   2 CPICLTPLQSSgDSSDAKRVSSRPTVLLSCSHVFHATCLEAFeEFSVGEELVCPVCRSH 60

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.

                        10        20
                ....*....|....*....|....*....
gi 574957034 51 CSHCFHMHCILKWLHaqQVQQHCPMCRQE 79
Cdd:cd16473  25 CGHVFHQNCIDVWLE--RDNHCCPVCRWP 51