BRcat domain found in F-box only protein 43 (FBXO43); FBXO43, also called FBX43 or endogenous meiotic inhibitor 2 (EMI2), plays a key role during the meiotic cell cycle. It is required to establish and maintain the arrest of oocytes at the second meiotic metaphase until fertilization. It probably acts by inhibiting the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. It may recognize and bind to some phosphorylated proteins and promotes their ubiquitination and degradation. FBXO43 contains an F-box domain, and the first half of the RBR domain that 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat (benign-catalytic) domain that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 767952881 643 DEALKPCPRCQSPAKYQPYKKRGLCSRTACGFDFCVLCLCAYHGSEECSRG 693
Cdd:cd20365    1 DEALKPCPRCQSPAKYQPVKKRGLCSREACGFDFCVLCLCAFHGSKECTSG 51

BRcat domain found in F-box only protein 43 (FBXO43); FBXO43, also called FBX43 or endogenous meiotic inhibitor 2 (EMI2), plays a key role during the meiotic cell cycle. It is required to establish and maintain the arrest of oocytes at the second meiotic metaphase until fertilization. It probably acts by inhibiting the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. It may recognize and bind to some phosphorylated proteins and promotes their ubiquitination and degradation. FBXO43 contains an F-box domain, and the first half of the RBR domain that 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat (benign-catalytic) domain that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767952881 643 DEALKPCPRCQSPAKYQPYKKRGLCSRTACGFDFCVLCLCAYHGSEECSRG 693
Cdd:cd20365    1 DEALKPCPRCQSPAKYQPVKKRGLCSREACGFDFCVLCLCAFHGSKECTSG 51

IBR domain, a half RING-finger domain; The IBR (In Between Ring fingers) domain is often found to occur between pairs of ring fingers (pfam00097). This domain has also been called the C6HC domain and DRIL (for double RING finger linked) domain. Proteins that contain two Ring fingers and an IBR domain (these proteins are also termed RBR family proteins) are thought to exist in all eukaryotic organizms. RBR family members play roles in protein quality control and can indirectly regulate transcription. Evidence suggests that RBR proteins are often parts of cullin-containing ubiquitin ligase complexes. The ubiquitin ligase Parkin is an RBR family protein whose mutations are involved in forms of familial Parkinson's disease.

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 767952881  638 KTLFTDEALKPCPR--CQSPAKYQPYKKRGLCSR-TACGFDFCVLCLCAYHGSEEC 690
Cdd:pfam01485  10 SYVESDPNLKWCPTpdCGYIIELTDGCSNTSHVTcSKCGHEFCFNCKEEWHEGLTC 65

BRcat domain found in F-box only protein 43 (FBXO43); FBXO43, also called FBX43 or endogenous meiotic inhibitor 2 (EMI2), plays a key role during the meiotic cell cycle. It is required to establish and maintain the arrest of oocytes at the second meiotic metaphase until fertilization. It probably acts by inhibiting the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. It may recognize and bind to some phosphorylated proteins and promotes their ubiquitination and degradation. FBXO43 contains an F-box domain, and the first half of the RBR domain that 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat (benign-catalytic) domain that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 767952881 643 DEALKPCPRCQSPAKYQPYKKRGLCSRTACGFDFCVLCLCAYHGSEECSRG 693
Cdd:cd20365    1 DEALKPCPRCQSPAKYQPVKKRGLCSREACGFDFCVLCLCAFHGSKECTSG 51

F-box domain found in F-box only protein 43 (FBXO43) and similar proteins; FBXO43, also called FBX43, or endogenous meiotic inhibitor 2 (EMI2), plays a key role during the meiotic cell cycle. It is required to establish and maintain the arrest of oocytes at the second meiotic metaphase until fertilization. It probably acts by inhibiting the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. It may recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767952881 465 TELKYRNLKHILAMVLESLTAESLCrtirrqdpwecrgnegekscgtgflqddgyggacgklvslfldSVWKVSRNWREI 544
Cdd:cd22171    1 AELKNRNLKHILAIILDLLTAESIC-------------------------------------------SFWKVSKNWRDI 37

                         90
                 ....*....|..
gi 767952881 545 VVQDKNANRRRK 556
Cdd:cd22171   38 IVQDKSAYQRRK 49

BRcat domain found in RING finger protein 14 (RNF14); RNF14, also called androgen receptor (AR)-associated protein 54 (ARA54), HFB30, or Triad2 protein, is an RBR-type E3 ubiquitin-protein ligase that is highly expressed in the testis and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3). Its differential localization may play an important role in testicular development and spermatogenesis in humans. RNF14 functions as a transcriptional regulator of mitochondrial and immune function in muscles. It is a ligand-dependent AR co-activator that enhances AR-dependent transcriptional activation. It may also participate in enhancing cell cycle progression and cell proliferation via induction of cyclin D1. Moreover, RNF14 is crucial for colon cancer cell survival. It acts as a new enhancer of the Wnt-dependent transcriptional outputs that acts at the level of the T-cell factor/lymphoid enhancer factor (TCF/LEF)-beta-catenin complex. RNF14 contains an N-terminal RWD domain, and a C-terminal RBR domain. 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 BRcat domain of RNF14 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 767952881 649 CPR--CQSPAKYQPYKKRGLCSrtACGFDFCVLCLCAYHGSEEC 690
Cdd:cd20341   10 CPRpsCQTPVILEPDENLGICP--SCNYAFCTLCRETYHGVSPC 51

Rcat domain found in parkin and similar proteins; Parkin, also called Parkinson juvenile disease protein 2, is an RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746, and AIMP2. It mediates monoubiquitination as well as Lys6-, Lys11-, Lys48- and Lys63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like domain and a C-terminal RBR domain that 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of parkin that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 767952881 647 KPCPRCQSPAKyqpykKRG-----LCSRTACGFDFCVLCLCAYhgSEEC 690
Cdd:cd20357    8 KPCPKCKVPTE-----KNGgcmhmKCPRPQCGLEWCWICGCEW--NRDC 49

Rcat domain found in human homolog of Drosophila Ariadne (HHARI) and similar proteins; This subfamily includes Drosophila melanogaster protein ariadne-1 (ARI-1), and its eukaryotic homologs, such as HHARI. ARI-1 is a widely expressed Drosophila RING-finger protein that localizes mainly in the cytoplasm, and is required for neural development. It interacts with the ubiquitin-conjugating enzyme, UbcD10. HHARI is also called H7-AP2, monocyte protein 6 (MOP-6), protein ariadne-1 homolog, Ariadne RBR E3 ubiquitin protein ligase 1 (ARIH1), ariadne-1 (ARI-1), UbcH7-binding protein, UbcM4-interacting protein, or ubiquitin-conjugating enzyme E2-binding protein. It is an RBR-type E3 ubiquitin-protein ligase highly expressed in nuclei, where it is co-localized with nuclear bodies including Cajal, PML, and Lewy bodies. It interacts with the E2 conjugating enzymes UbcH7, UbcH8, UbcM4 and UbcD10 in human, mouse and fly, and modulates the ubiquitylation of substrate proteins including single-minded 2 (SIM2) and translation initiation factor 4E homologous protein (4EHP). It functions as a potent mediator of DNA damage-induced translation arrest, which protects stem and cancer cells against genotoxic stress by initiating a 4EHP-mediated mRNA translation arrest. HHARI contains an RBR domain that 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 changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of HHARI and similar proteins that are essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767952881 647 KPCPRCQSPAKyqpykKRG-----LCSRTACGFDFCVLCLCAY--HGSE--ECSR 692
Cdd:cd20356    7 KECPKCHVTIE-----KNGgcnhmVCRNQNCKYEFCWVCLGPWepHGSSwyNCNR 56

In Between Ring fingers; the domains occurs between pairs og RING fingers

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 767952881   646 LKPCPR--CQSPAKYQ--PYKKRGLCSrtACGFDFCVLCLCAYHGSEEC 690
Cdd:smart00647  18 LKWCPApdCSAAIIVTeeEGCNRVTCP--KCGFSFCFRCKVPWHSPVSC 64