SII-SWORD/CoKE huggingface dataset:
E3 ubiquitin-protein ligase RNF216, Rcat domain (Rcat_RBR_RNF216)
Type: Domain

This entry represents the Rcat domain of RNF216 and similar proteins from animals and fungi. It is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

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 RNF14, Rcat domain (Rcat_RBR_RNF14)
Type: Domain

This entry represents the Rcat domain of RNF14 and similar eukaryotic proteins. This domain is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

Ring Finger Protein 14 (RNF14, ARA54, Triad2) belongs to the ring between ring fingers (RBR) family. It is an E3 ubiquitin ligase that acts on unknown substrates and has autoubiquitination activity . It is an enhancer of the Wnt-dependent transcriptional outputs acting at the level of the TCF/LEF-beta-catenin complex , crucial for colon cancer cell survival. 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. It may function as an AR (androgen receptor) coactivators to induce AR target gene expression . RNF14 may play a regulatory role in mitochondrial and immune gene expression .

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.

E3 ubiquitin-protein ligase itt1, the homologue of RNF14 in yeast, is also included in this group. It modulates the efficiency of translation termination, resulting in the readthrough of all three types of nonsense codons UAA, UAG and UGA .
BICC1, first type I KH domain (BICC1_KH-I_rpt1)
Type: Domain

This entry represents the first type I KH RNA-binding domain of BICC/BICC1.

Bicaudal-C from Drosophila melanogaster (BICC) and its homologues from vertebrates BICC1, are RNA-binding proteins with translational repression function; they regulate gene expression and modulate cell proliferation and apoptosis . BICC1 is a negative regulator of Wnt signalling . These proteins are involved in the regulation of embryonic differentiation and play a role in the regulation of Dvl (Dishevelled) signalling, particularly in the correct cilia orientation and nodal flow generation . In Drosophila, disruption of BICC can disturb the normal migration direction of the anterior follicle cell of oocytes . In mammals, mutations in this gene are associated with polycystic kidney disease and it was suggested that the BICC1 protein can indirectly interact with ANKS6 protein (ANKS6 is also associated with polycystic kidney disease) through some protein and RNA intermediates .

BICC1 contains N-terminal K homology (KH) RNA-binding vigilin-like repeats and a C-terminal SAM domain.
E3 ubiquitin-protein ligase RNF217, variant RING finger, HC subclass (RNF217_RBR_vRING-HC)
Type: Domain

This entry represents the RING domain of RNF217 and similar proteins from vertebrates. It is a variant C4C4-type RING finger whose overall folding is similar to that of the C3HC4-type RING-HC finger. It is required for RBR-mediated ubiquitination.

E3 ubiquitin-protein ligase RNF217, also known as IBR domain-containing protein 1 (IBRDC1), is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase mainly expressed in testis and skeletal muscle, as different splice variants. It interacts with the anti-apoptotic protein HAX1, and is adjacent to a translocation breakpoint involving ETV6 in childhood acute lymphoblastic leukemia (ALL). RNF217 contains a RBR domain followed by TMs. 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 corrected as RING-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 function to facilitate the ubiquitination reaction .
E3 ubiquitin-protein ligase RNF217, BRcat domain (BRcat_RBR_RNF217)
Type: Domain

This entry represents the BRcat (benign-catalytic) domain of RNF217 and similar proteins from animals. It adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

E3 ubiquitin-protein ligase RNF217, also known as IBR domain-containing protein 1 (IBRDC1), is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase mainly expressed in testis and skeletal muscle, as different splice variants. It interacts with the anti-apoptotic protein HAX1, and is adjacent to a translocation breakpoint involving ETV6 in childhood acute lymphoblastic leukemia (ALL). RNF217 contains a RBR domain followed by TMs. 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 corrected as RING-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 function to facilitate the ubiquitination reaction .
E3 ubiquitin-protein ligase RNF217, Rcat domain (Rcat_RBR_RNF217)
Type: Domain

This entry represents the Rcat domain of RNF217 and similar proteins from animals. It is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

E3 ubiquitin-protein ligase RNF217, also known as IBR domain-containing protein 1 (IBRDC1), is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase mainly expressed in testis and skeletal muscle, as different splice variants. It interacts with the anti-apoptotic protein HAX1, and is adjacent to a translocation breakpoint involving ETV6 in childhood acute lymphoblastic leukemia (ALL). RNF217 contains a RBR domain followed by TMs. 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 corrected as RING-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 function to facilitate the ubiquitination reaction .
BICC1, third type I KH domain (BICC1_KH-I_rpt3)
Type: Domain

This entry represents the third type I KH RNA-binding domain of BICC/BICC1.

Bicaudal-C from Drosophila melanogaster (BICC) and its homologues from vertebrates BICC1, are RNA-binding proteins with translational repression function; they regulate gene expression and modulate cell proliferation and apoptosis . BICC1 is a negative regulator of Wnt signalling . These proteins are involved in the regulation of embryonic differentiation and play a role in the regulation of Dvl (Dishevelled) signalling, particularly in the correct cilia orientation and nodal flow generation . In Drosophila, disruption of BICC can disturb the normal migration direction of the anterior follicle cell of oocytes . In mammals, mutations in this gene are associated with polycystic kidney disease and it was suggested that the BICC1 protein can indirectly interact with ANKS6 protein (ANKS6 is also associated with polycystic kidney disease) through some protein and RNA intermediates .

BICC1 contains N-terminal K homology (KH) RNA-binding vigilin-like repeats and a C-terminal SAM domain.
BICC1, second type I KH (BICC1_KH-I_rpt2)
Type: Domain

This entry represents the second type I KH RNA-binding domain of BICC/BICC1.

Bicaudal-C from Drosophila melanogaster (BICC) and its homologues from vertebrates BICC1, are RNA-binding proteins with translational repression function; they regulate gene expression and modulate cell proliferation and apoptosis . BICC1 is a negative regulator of Wnt signalling . These proteins are involved in the regulation of embryonic differentiation and play a role in the regulation of Dvl (Dishevelled) signalling, particularly in the correct cilia orientation and nodal flow generation . In Drosophila, disruption of BICC can disturb the normal migration direction of the anterior follicle cell of oocytes . In mammals, mutations in this gene are associated with polycystic kidney disease and it was suggested that the BICC1 protein can indirectly interact with ANKS6 protein (ANKS6 is also associated with polycystic kidney disease) through some protein and RNA intermediates .

BICC1 contains N-terminal K homology (KH) RNA-binding vigilin-like repeats and a C-terminal SAM domain.
E3 ubiquitin-protein ligase ARIH2, BRcat domain (BRcat_RBR_TRIAD1)
Type: Domain

This entry represents the BRcat (benign-catalytic) domain of TRIAD1 and similar proteins from animals. It adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

E3 ubiquitin-protein ligase ARIH2 (ARI2), also called TRIAD1 and ariadne-2 (ARI-2), is an RBR-type E3 ubiquitin-protein ligase that catalyses the formation of polyubiquitin chains linked via lysine-48 as well as lysine-63 residues. Its auto-ubiquitylation can be catalysed by the E2 conjugating enzyme UBCH7. TRIAD1 has been implicated in hematopoiesis, specifically in myelopoiesis, as well as in embryogenesis. It functions as a regulator of endosomal transport, and is required for the proper function of multivesicular bodies. It also acts as a novel ubiquitination target for proteasome-dependent degradation by murine double minute 2 (MDM2). As a proapoptotic protein, TRIAD1 promotes p53 activation, and inhibits MDM2-mediated p53 ubiquitination and degradation. Furthermore, TRIAD1 can inhibit the ubiquitination and proteasomal degradation of growth factor independence 1 (Gfi1), a transcriptional repressor essential for the function and development of many different haematopoietic lineages. TRIAD1 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 .
E3 ubiquitin-protein ligase TRIAD1, Rcat domain (Rcat_RBR_TRIAD1)
Type: Domain

This entry represents the Rcat domain of TRIAD1 and similar proteins from animals. It is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

E3 ubiquitin-protein ligase ARIH2 (ARI2), also called TRIAD1 and ariadne-2 (ARI-2), is an RBR-type E3 ubiquitin-protein ligase that catalyses the formation of polyubiquitin chains linked via lysine-48 as well as lysine-63 residues. Its auto-ubiquitylation can be catalysed by the E2 conjugating enzyme UBCH7. TRIAD1 has been implicated in hematopoiesis, specifically in myelopoiesis, as well as in embryogenesis. It functions as a regulator of endosomal transport, and is required for the proper function of multivesicular bodies. It also acts as a novel ubiquitination target for proteasome-dependent degradation by murine double minute 2 (MDM2). As a proapoptotic protein, TRIAD1 promotes p53 activation, and inhibits MDM2-mediated p53 ubiquitination and degradation. Furthermore, TRIAD1 can inhibit the ubiquitination and proteasomal degradation of growth factor independence 1 (Gfi1), a transcriptional repressor essential for the function and development of many different haematopoietic lineages. TRIAD1 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 .
Heme-oxidized IRP2 ubiquitin ligase 1, Rcat domain (Rcat_RBR_HOIL1)
Type: Domain

This entry represents the Rcat domain of HOIL1 and similar proteins from animals. It is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

Heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) is also called RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4 and RING finger protein 54 (RNF54). Together with the E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), it forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognise heme-oxidised IRP2 (iron regulatory protein 2) and is thought to affect the turnover of oxidatively damaged proteins .

HOIL-1 contains an N-terminal ubiquitin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has 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.
Heme-oxidized IRP2 ubiquitin ligase 1, BRcat domain (BRcat_RBR_HOIL1)
Type: Domain

This entry represents the BRcat domain of HOIL1 and similar proteins from animals. It adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

Heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) is also called RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4 and RING finger protein 54 (RNF54). Together with the E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), it forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognise heme-oxidised IRP2 (iron regulatory protein 2) and is thought to affect the turnover of oxidatively damaged proteins .

HOIL-1 contains an N-terminal ubiquitin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has 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.
Heme-oxidized IRP2 ubiquitin ligase 1, modified RING finger, HC subclass (HOIL1_RBR_mRING-HC-C3HC3D)
Type: Domain

This entry represents the RING domain of HOIL1 and similar proteins from animals. It is a modified C3HC3D-type RING-HC finger required for RBR-mediated ubiquitination.

Heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) is also called RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4 and RING finger protein 54 (RNF54). Together with the E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), it forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognise heme-oxidised IRP2 (iron regulatory protein 2) and is thought to affect the turnover of oxidatively damaged proteins .

HOIL-1 contains an N-terminal ubiquitin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has 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.
Cullin-9, Rcat domain (Rcat_RBR_CUL9)
Type: Domain

This entry represents the Rcat domain of Cullin-9 and similar proteins from vertebrates. It is essential for RBR E3 ligase activity. This domain adopts the same fold as the BRcat domain and similarly coordinates two zinc atoms that are essential for its folding.

Cullin-9 (CUL-9), also called UbcH7-associated protein 1 (H7-AP1), p53-associated parkin-like cytoplasmic protein, or PARC, is a cytoplasmic RBR-type E3 ubiquitin-protein ligase that function as a tumour suppressor and promotes p53-dependent apoptosis. It mediates the ubiquitination and degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells. It is also a critical downstream effector of the 3M complex in the maintenance of microtubules and genome integrity. Moreover, CUL-9, together with CUL-7, forms homodimers and heterodimers, as well as some atypical Cullin RING ligase complexes, which may exhibit ubiquitin ligase activity. CUL-9 contains a CPH domain (conserved in Cul7, PARC, and HERC2 proteins), a DOC (DOC1/APC10) domain, cullin homology domains linked with E3 ligase function, and a C-terminal RBR domain 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 .