SII-SWORD/CoKE huggingface dataset:
E3 ubiquitin-protein ligase parkin, BRcat domain (BRcat_RBR_parkin)
Type: Domain

This entry represents the BRcat domain found in Parkin and similar proteins from animals. This domain adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity .

E3 ubiquitin-protein ligase 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, catalysing 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 .
E3 ubiquitin-protein ligase parkin, RING finger, HC subclass (RING-HC_RBR_parkin)
Type: Domain

This entry represents the RING domain found in parkin and similar proteins from animals. It is a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination .

E3 ubiquitin-protein ligase 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, catalysing 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 .
E3 ubiquitin-protein ligase parkin, Rcat domain (Rcat_RBR_parkin)
Type: Domain

This entry represents the Rcat domain found in parkin and similar proteins from animals. This domain is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain .

E3 ubiquitin-protein ligase 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, catalysing 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 .
Activating signal cointegrator 1 complex subunit 1, type I KH domain (KH-I_ASCC1)
Type: Domain

This entry represents the type I KH RNA-binding domain of ASCC1 from animals.

ASCC1, also called ASC-1 complex subunit p50, or Trip4 complex subunit p50, plays a role in DNA damage repair as component of the ASCC complex which consists of ASCC1, ASCC2 and ASCC3 subunits (p50, p100 and p200, respectively) . It is part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation . In cells responding to gastrin-activated paracrine signals, it is involved in the induction of SERPINB2 expression by gastrin . ASCC1 may also play a role in the development of neuromuscular junction . This protein has an RNA-binding KH domain fused to a 2H RNA-phosphoesterase and modulates the ASCC3 helicase recruitment to the ASCC complex during alkylation damage.
E3 ubiquitin-protein ligase RNF31, UBA domain (UBA_RNF31)
Type: Domain

This entry represents the UBA domain of RNF31 and similar proteins from vertebrates. This domain is responsible for the interaction with the N-terminal ubiquitin-like domain (UBL) of HOIL-1L .

RING finger protein 31 (RNF31, also known as HOIP, HOIL-1L interacting protein HOIP) is a component of the linear ubiquitin chain assembly complex (LUBAC, also known as E3-ligase complex) . It has been shown that RNF31 interacts with the muscle-specific kinase (MuSK) in mice . In addition, RNF31 can interact with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression .

HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain, an RBR domain, and a C-terminal linear chain determining domain (LDD). 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 (RING1-BRcat-Rcat) 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 .

LUBAC catalyses the formation of linear ubiquitin chains and regulates immune and apoptotic signalling pathways . LUBAC consists of SHARPIN, HOIL-1 (also known as RBCK1) and RNF31 (HOIP) .
E3 ubiquitin-protein ligase RNF31-like, BRcat domain (BRcat_RBR_RNF31-like)
Type: Domain

This entry represents the BRcat domain of RNF31 and similar proteins from animals. This domain adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity .

RING finger protein 31 (RNF31, also known as HOIP, HOIL-1L interacting protein HOIP) is a component of the linear ubiquitin chain assembly complex (LUBAC, also known as E3-ligase complex) . It has been shown that RNF31 interacts with the muscle-specific kinase (MuSK) in mice . In addition, RNF31 can interact with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression .

HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain, an RBR domain, and a C-terminal linear chain determining domain (LDD). 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 (RING1-BRcat-Rcat) 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 .

The fly E3 ubiquitin-protein ligase lubel, which conjugates linear 'Met-1'- and 'Lys-63'-linked polyubiquitin chains to substrates, is also included in this group of proteins. It has been shown to play a role in heat-stress response , as well as being involved in the NF-kappa-B intestinal inflammatory response to oral infection in Drosophila .

LUBAC catalyses the formation of linear ubiquitin chains and regulates immune and apoptotic signalling pathways . LUBAC consists of SHARPIN, HOIL-1 (also known as RBCK1) and RNF31 (HOIP) .
E3 ubiquitin-protein ligase RNF31-like, modified RING finger, HC subclass (RNF31_RBR_mRING-HC-like)
Type: Domain

This entry represents the RING domain of RNF31 and similar proteins from animals. It is a C4C4-type RING finger motif whose overall folding is similar to that of the C3HC4-type RING-HC finger. It is required for RBR-mediated ubiquitination .

RING finger protein 31 (RNF31, also known as HOIP, HOIL-1L interacting protein HOIP) is a component of the linear ubiquitin chain assembly complex (LUBAC, also known as E3-ligase complex) . It has been shown that RNF31 interacts with the muscle-specific kinase (MuSK) in mice . In addition, RNF31 can interact with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression .

HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain, an RBR domain, and a C-terminal linear chain determining domain (LDD). 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 (RING1-BRcat-Rcat) 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 .

LUBAC catalyses the formation of linear ubiquitin chains and regulates immune and apoptotic signalling pathways . LUBAC consists of SHARPIN, HOIL-1 (also known as RBCK1) and RNF31 (HOIP) .

The fly E3 ubiquitin-protein ligase lubel, which conjugates linear 'Met-1'- and 'Lys-63'-linked polyubiquitin chains to substrates, is also included in this group of proteins. It has been shown to play a role in heat-stress response , as well as being involved in the NF-kappa-B intestinal inflammatory response to oral infection in Drosophila .
E3 ubiquitin-protein ligase RNF31-like, Rcat domain (Rcat_RBR_RNF31-like)
Type: Domain

This entry represents the Rcat domain found in RNF31 and similar proteins from animals. This domain is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain .

RING finger protein 31 (RNF31, also known as HOIP, HOIL-1L interacting protein HOIP) is a component of the linear ubiquitin chain assembly complex (LUBAC, also known as E3-ligase complex) . It has been shown that RNF31 interacts with the muscle-specific kinase (MuSK) in mice . In addition, RNF31 can interact with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression .

HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain, an RBR domain, and a C-terminal linear chain determining domain (LDD). 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 (RING1-BRcat-Rcat) 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 .

LUBAC catalyses the formation of linear ubiquitin chains and regulates immune and apoptotic signalling pathways . LUBAC consists of SHARPIN, HOIL-1 (also known as RBCK1) and RNF31 (HOIP) .

The fly E3 ubiquitin-protein ligase lubel, which conjugates linear 'Met-1'- and 'Lys-63'-linked polyubiquitin chains to substrates, is also included in this group of proteins. It has been shown to play a role in heat-stress response , as well as being involved in the NF-kappa-B intestinal inflammatory response to oral infection in Drosophila .
E3 ubiquitin-protein ligase RNF31-like, Bbox1 zinc finger (Bbox1_RNF31-like)
Type: Domain

This entry represents the type 1 B-box (Bbox1) zinc finger of RNF31 and similar proteins from animals. It is characterised by a C6H2 zinc-binding consensus motif. It shows high sequence similarity with B-Box-type 1 zinc finger found in tripartite motif-containing proteins (TRIMs).

RING finger protein 31 (RNF31, also known as HOIP, HOIL-1L interacting protein HOIP) is a component of the linear ubiquitin chain assembly complex (LUBAC, also known as E3-ligase complex) . It has been shown that RNF31 interacts with the muscle-specific kinase (MuSK) in mice . In addition, RNF31 can interact with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression .

HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain, an RBR domain, and a C-terminal linear chain determining domain (LDD). 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 (RING1-BRcat-Rcat) 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 .

LUBAC catalyses the formation of linear ubiquitin chains and regulates immune and apoptotic signalling pathways . LUBAC consists of SHARPIN, HOIL-1 (also known as RBCK1) and RNF31 (HOIP) .

The fly E3 ubiquitin-protein ligase lubel, which conjugates linear 'Met-1'- and 'Lys-63'-linked polyubiquitin chains to substrates, is also included in this group of proteins. It has been shown to play a role in heat-stress response , as well as being involved in the NF-kappa-B intestinal inflammatory response to oral infection in Drosophila .
E3 ubiquitin-protein ligase RNF216, RING finger, HC subclass (RING-HC_RBR_RNF216)
Type: Domain

This entry represents the RING domain of RNF216 and similar proteins from animals and fungi. It is a C3HC4-type RING-HC finger motif required for RBR-mediated ubiquitination.

E3 ubiquitin-protein ligase RNF216, also known as Triad domain-containing protein 3 (Triad3A), is a RBR-type E3 ubiquitin-protein ligase that interacts with several components of Toll-like receptor (TLR) signalling and promotes their proteolytic degradation. It negatively regulates the RIG-I RNA sensing pathway through Lys48-linked, ubiquitin-mediated degradation of the tumour necrosis factor receptor-associated factor 3 (TRAF3) adapter following RNA virus infection. It also controls ubiquitination and proteasomal degradation of receptor-interacting protein 1 (RIP1), a serine/threonine protein kinase that is critically involved in tumour necrosis factor receptor-1 (TNF-R1)-induced NF-kappa B activation, following disruption of Hsp90 binding. Moreover, RNF216 is involved in inflammatory diseases through strongly inhibiting autophagy in macrophages. It interacts with and ubiquitinates BECN1, a key regulator in autophagy, thereby contributing to BECN1 degradation. It regulates synaptic strength by ubiquitination of Arc, resulting in its rapid proteasomal degradation. It is also a key negative regulator of sustained Killer cell Ig-like receptor (KIR) with two Ig-like domains and a long cytoplasmic domain 4 (2DL4)-mediated NF-kappaB signalling from internalized 2DL4, which functions by promoting ubiquitylation and degradation of endocytosed receptor from early endosomes . Furthermore, RNF216 interacts with HIV-1 Virion infectivity factor (Vif) protein, which is essential for the productive infection of primary human CD4 T lymphocytes and macrophages . Mutations in RNF216 may result in Gordon Holmes syndrome, a condition defined by hypogonadotropic hypogonadism and cerebellar ataxia, as well as in autosomal recessive Huntington-like disorder .

RNF216 contains a 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 corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use 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.
E3 ubiquitin-protein ligase RNF216, BRcat domain (BRcat_RBR_RNF216)
Type: Domain

This entry represents the BRcat domain of RNF216 and similar proteins from animals and fungi. This domain adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

E3 ubiquitin-protein ligase RNF216, also known as Triad domain-containing protein 3 (Triad3A), is a RBR-type E3 ubiquitin-protein ligase that interacts with several components of Toll-like receptor (TLR) signalling and promotes their proteolytic degradation. It negatively regulates the RIG-I RNA sensing pathway through Lys48-linked, ubiquitin-mediated degradation of the tumour necrosis factor receptor-associated factor 3 (TRAF3) adapter following RNA virus infection. It also controls ubiquitination and proteasomal degradation of receptor-interacting protein 1 (RIP1), a serine/threonine protein kinase that is critically involved in tumour necrosis factor receptor-1 (TNF-R1)-induced NF-kappa B activation, following disruption of Hsp90 binding. Moreover, RNF216 is involved in inflammatory diseases through strongly inhibiting autophagy in macrophages. It interacts with and ubiquitinates BECN1, a key regulator in autophagy, thereby contributing to BECN1 degradation. It regulates synaptic strength by ubiquitination of Arc, resulting in its rapid proteasomal degradation. It is also a key negative regulator of sustained Killer cell Ig-like receptor (KIR) with two Ig-like domains and a long cytoplasmic domain 4 (2DL4)-mediated NF-kappaB signalling from internalized 2DL4, which functions by promoting ubiquitylation and degradation of endocytosed receptor from early endosomes . Furthermore, RNF216 interacts with HIV-1 Virion infectivity factor (Vif) protein, which is essential for the productive infection of primary human CD4 T lymphocytes and macrophages . Mutations in RNF216 may result in Gordon Holmes syndrome, a condition defined by hypogonadotropic hypogonadism and cerebellar ataxia, as well as in autosomal recessive Huntington-like disorder .

RNF216 contains a 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 corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use 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.