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 17509663 366 SRIFCSLSGKLCDDDkNIPFLFPSGHVIGSAAIERL-KRDDNKLYDPIHKK 415
Cdd:cd16659   1 SRLVCRITGEVMNEH-NPPLALPNGYVYSEKALEEMaEKNDGKVVCPRTGE 50

CT11-RanBPM; protein-protein interaction domain present in crown eukaryotes (plants, animals, fungi)

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gi 17509663    240 GNIPEAVAYVKKYIAPIAK--GKFTEDLKKTMGAIAC--TLEQSRLRNpELHAADRYQKCAAL---FIEEAHRIfeiHGN 312
Cdd:smart00757   1 GKIEEALAYARELLAPFAKehEKFLKELEKTMALLAYpdPTEPSPYKE-LLSPSQREKLAEELnsaILELLHGK---SSE 76

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gi 17509663    313 TALATLIQYGLATQKTPSCHNDE 335
Cdd:smart00757  77 SPLEILLSAGLAALKTLLEKGGV 99

CT11-RanBPM; protein-protein interaction domain present in crown eukaryotes (plants, animals, fungi)

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509663    240 GNIPEAVAYVKKYIAPIAK--GKFTEDLKKTMGAIAC--TLEQSRLRNpELHAADRYQKCAAL---FIEEAHRIfeiHGN 312
Cdd:smart00757   1 GKIEEALAYARELLAPFAKehEKFLKELEKTMALLAYpdPTEPSPYKE-LLSPSQREKLAEELnsaILELLHGK---SSE 76

                           90       100
                   ....*....|....*....|...
gi 17509663    313 TALATLIQYGLATQKTPSCHNDE 335
Cdd:smart00757  77 SPLEILLSAGLAALKTLLEKGGV 99

U-box domain, a modified RING finger, found in erythroblast macrophage protein (Emp) and similar proteins; Emp, also known as cell proliferation-inducing gene 5 protein or macrophage erythroblast attacher (MAEA), is a key protein which functions in normal differentiation of erythroid cells and macrophages. It is a potential biomarker for hematopoietic evaluation of Hematopoietic stem cell transplantation (HSCT) patients. Emp was initially identified as a heparin-binding protein involved in the association of erythroblasts with macrophages. It promotes erythroid proliferation and maturation. It also plays an important role in erythroblastic island formation. Absence of Emp leads to failure of erythroblast nuclear extrusion. It is required in definitive erythropoiesis and plays a cell intrinsic role in the erythroid lineage. Emp contains a Lissencephaly type-1-like homology (LisH) motif, a C-terminal to LisH (CTLH) domain, and a RING-like U-box domain at the C-terminus.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 17509663 366 SRIFCSLSGKLCDDDkNIPFLFPSGHVIGSAAIERL-KRDDNKLYDPIHKK 415
Cdd:cd16659   1 SRLVCRITGEVMNEH-NPPLALPNGYVYSEKALEEMaEKNDGKVVCPRTGE 50