Rcat 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 also may 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF14 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 148678141 264 EEMESKDWLEKNSKSCPCCGTPIQKLDGCNKMTCTGCMQYFCWICMGSLSRANPYRHFTDSESPCFNR 331
Cdd:cd20354    1 EEKLSEEWLEKNSKPCPGCGTLIEKIDGCNKMTCTKCRTYFCWLCLKVLSRTNPYSHFSDPNSPCFNR 68

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 148678141 175 LDLMADVVYCPRPCCQLPVMQEPGGTMAICSSCNFAFCTLCRLTYHGLSPCKVTAEK 231
Cdd:cd20341    1 LDSMPDVVYCPRPSCQTPVILEPDENLGICPSCNYAFCTLCRETYHGVSPCKIKEEK 57

Rcat 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 also may 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF14 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 148678141 264 EEMESKDWLEKNSKSCPCCGTPIQKLDGCNKMTCTGCMQYFCWICMGSLSRANPYRHFTDSESPCFNR 331
Cdd:cd20354    1 EEKLSEEWLEKNSKPCPGCGTLIEKIDGCNKMTCTKCRTYFCWLCLKVLSRTNPYSHFSDPNSPCFNR 68

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 148678141 175 LDLMADVVYCPRPCCQLPVMQEPGGTMAICSSCNFAFCTLCRLTYHGLSPCKVTAEK 231
Cdd:cd20341    1 LDSMPDVVYCPRPSCQTPVILEPDENLGICPSCNYAFCTLCRETYHGVSPCKIKEEK 57

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 148678141  165 RYDRLLLQSTLDLMADVVYCPRPCCQLPVMQEPGGT---MAICSSCNFAFCTLCRLTYHGLSPC 225
Cdd:pfam01485   2 KYEKLLLKSYVESDPNLKWCPTPDCGYIIELTDGCSntsHVTCSKCGHEFCFNCKEEWHEGLTC 65

Rcat 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 also may 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF14 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 148678141 264 EEMESKDWLEKNSKSCPCCGTPIQKLDGCNKMTCTGCMQYFCWICMGSLSRANPYRHFTDSESPCFNR 331
Cdd:cd20354    1 EEKLSEEWLEKNSKPCPGCGTLIEKIDGCNKMTCTKCRTYFCWLCLKVLSRTNPYSHFSDPNSPCFNR 68

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        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 148678141 175 LDLMADVVYCPRPCCQLPVMQEPGGTMAICSSCNFAFCTLCRLTYHGLSPCKVTAEK 231
Cdd:cd20341    1 LDSMPDVVYCPRPSCQTPVILEPDENLGICPSCNYAFCTLCRETYHGVSPCKIKEEK 57

Rcat (required-for-catalysis) domain, part of the RBR (RING1-BRcat-Rcat) domain; The RBR family of RING-type E3 ligases are characterized by containing an RBR domain, which was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. It is composed of an extended RING domain (RING1) followed by an in-between RING (IBR) domain and the catalytic domain, which is structurally an IBR domain but is commonly designated RING2. 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, where the IBR and RING2 domains have been renamed as BRcat and Rcat domains, respectively. 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. The Rcat domain contains the catalytic cysteine residue and ubiquitination activity. 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. This model corresponds to the Rcat domain that adopts the same fold as the BRcat domain.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 148678141 275 NSKSCPCCGTPIQKLDGCNKMTCTGCMQYFCWICMG 310
Cdd:cd20336    1 NTKKCPKCKVPIEKNGGCNHMTCSRCGTEFCWLCGK 36

RING finger, HC subclass, found in Saccharomyces cerevisiae translation termination inhibitor protein ITT1 and similar proteins; ITT1 is a protein that modulates the efficiency of translation termination, resulting in the readthrough of all three types of nonsense codons UAA, UAG and UGA. ITT1 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 148678141  92 LFLCSICFCEKLGSDCmYFLECKHVYCKACLKDYFEIQIKDGQVKCLNCPEPQC 145
Cdd:cd23134    4 SYHCGICFEEKKGSDF-IKLPCGHVFCRECLQDYYTIHIQEGEVSSVKCPDPNC 56

Rcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, also called ariadne-2 (ARI-2), protein ariadne-2 homolog, Ariadne RBR E3 ubiquitin protein ligase 2 (ARIH2), or UbcM4-interacting protein 48, is an RBR-type E3 ubiquitin-protein ligase that catalyzes the formation of polyubiquitin chains linked via lysine-48 as well as lysine-63 residues. Its auto-ubiquitylation can be catalyzed 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 hematopoietic 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. This model corresponds to the Rcat domain of TRIAD1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 148678141 275 NSKSCPCCGTPIQKLDGCNKMTCTGCMQYFCWICMGS 311
Cdd:cd20360    2 HTKDCPKCHVCIEKNGGCNHMQCSKCKHEFCWMCLGD 38

RING finger, HC subclass, found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, also known as ariadne-2 (ARI-2), protein ariadne-2 homolog, Ariadne RBR E3 ubiquitin protein ligase 2 (ARIH2), or UbcM4-interacting protein 48, is an RBR-type E3 ubiquitin-protein ligase that catalyzes the formation of polyubiquitin chains linked via lysine-48, as well as lysine-63 residues. Its auto-ubiquitylation can be catalyzed 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 hematopoietic 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 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. This model corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 148678141  93 FLCSICFCEKLGSDcMYFLECKHVYCKACLKDYFEIQIKDGQVKCLNCPEPQCPS 147
Cdd:cd16773    1 VTCGVCCEDVPKDE-LFSLACGHYFCNDCWKQYLTVKIKDGVSTGIECMAPDCKV 54

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
                 ....*....|....*....|....*....|....*....|..
gi 148678141 271 WLEKNSKSCPCCGTPIQKLDGCNKMTC--TGCMQYFCWICMG 310
Cdd:cd20356    1 WIAANTKECPKCHVTIEKNGGCNHMVCrnQNCKYEFCWVCLG 42

Rcat domain found in E3 ubiquitin-protein ligase ARI7 and similar proteins; This subfamily contains probable RBR-type E3 ubiquitin-protein ligases (EC 2.3.2.31) including Arabidopsis thaliana ARI5, ARI6, ARI7, and ARI8, as well as Dictyostelium discoideum RbrA (also called Ariadne-like ubiquitin ligase). They may function as part of E3 complexes, which accept ubiquitin from E2 ubiquitin-conjugating enzymes and then transfer it to substrates. RbrA may be required for normal cell-type proportioning and cell sorting during multicellular development, and is also necessary for spore cell viability. Members of this subfamily contain 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 ARI7-like proteins that are essential for RBR E3 ligase activity and adopt the same fold as the BRcat domain.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 148678141 275 NSKSCPCCGTPIQKLDGCNKMTCTG-CMQYFCWICMG 310
Cdd:cd22583    1 NTKPCPKCKRPIEKNQGCMHMTCSPpCKHEFCWLCLG 37

Rcat domain found in RING finger protein 144B (RNF144B); RNF144B, also called PIR2, IBR domain-containing protein 2 (IBRDC2), or p53-inducible RING finger protein (p53RFP), is a transmembrane (TM) domain-containing RBR E3 ubiquitin-protein ligase that induces p53-dependent but caspase-independent apoptosis. It interacts with E2 ubiquitin-conjugating enzymes UbcH7 and UbcH8, but not with UbcH5. It is involved in ubiquitination and degradation of p21, a p53 downstream protein promoting growth arrest and antagonizing apoptosis, suggesting a role in switching a cell from p53-mediated growth arrest to apoptosis. Moreover, RNF144B regulates the levels of Bax, a pro-apoptotic protein from the Bcl-2 family, and protects cells from unprompted Bax activation and cell death. It also regulates epithelial homeostasis by mediating degradation of p21WAF1 and p63. RNF144B contains an RBR domain followed by a potential single-TM 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF144B that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 148678141 277 KSCPCCGTPIQKLDGCNKMTCTGCMQYFCWICMGSLSRANPYRHFtdSESPCFNRLFHA 335
Cdd:cd20369    7 KQCPVCRVYIERNEGCAQMMCKNCKHTFCWYCLQNLDNDIFLRHY--DKGPCRNKLGHS 63

Rcat domain found in cullin-9 (CUL-9) and similar proteins; 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 tumor 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. This model corresponds to the Rcat domain of CUL-9 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 148678141 276 SKSCPCCGTPIQKLDGCNKMTCTGCMQYFCWICMGS 311
Cdd:cd20359    7 SKRCPSCQAQIEKNEGCLHMTCAKCNHGFCWRCLKP 42

Rcat domain found in RING finger protein 144A (RNF144A); RNF144A, also called UbcM4-interacting protein 4 (UIP4), or ubiquitin-conjugating enzyme 7-interacting protein 4, is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that targets DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and thus promotes DNA damage-induced cell apoptosis. It is transcriptionally repressed by metastasis-associated protein 1 (MTA1) and inhibits MTA1-driven cancer cell migration and invasion. RNF144A contains an RBR domain followed by a potential single-TM 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 functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF144A that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 148678141 277 KSCPCCGTPIQKLDGCNKMTCTGCMQYFCWICMGSLSRANPYRHFtdSESPCFNRLFHA 335
Cdd:cd20368    7 KRCPKCKVYIERDEGCAQMMCKNCKHAFCWYCLESLDDDFLLIHY--DKGPCRNKLGHS 63

Modified RING finger, HC subclass (C4C4-type), found in RNF144 proteins; This group includes RNF144A and RNF144B, both of which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF144A, also known as UbcM4-interacting protein 4 (UIP4) or ubiquitin-conjugating enzyme 7-interacting protein 4, targets DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and thus promote DNA damage-induced cell apoptosis. It is transcriptionally repressed by metastasis-associated protein 1 (MTA1) and inhibits MTA1-driven cancer cell migration and invasion. RNF144B, also known as PIR2, IBR domain-containing protein 2 (IBRDC2), or p53-inducible RING finger protein (p53RFP), induces p53-dependent but caspase-independent apoptosis. It interacts with E2 ubiquitin-conjugating enzymes UbcH7 and UbcH8, but not with UbcH5. It is involved in ubiquitination and degradation of p21, a p53 downstream protein promoting growth arrest and antagonizing apoptosis, suggesting a role in switching a cell from p53-mediated growth arrest to apoptosis. Moreover, RNF144B regulates the levels of Bax, a pro-apoptotic protein from the Bcl-2 family, and protects cells from unprompted Bax activation and cell death. It also regulates epithelial homeostasis by mediating degradation of p21WAF1 and p63. Both RNF144A and RNF144B contain an RBR domain followed by a potential single-TM 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 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. This model corresponds to the RING domain, a 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.

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 148678141  93 FLCSICFCEKLGSDCMYFLECKHVYCKACLKDYFEIQIKDGQVKCLNCPEPQC 145
Cdd:cd16632    1 ITCKLCLEEVPLREMYTLQSCGCIFCLQCLKQYVEVLIREGNVSSITCPDAAC 53

Rcat domain found in RING finger protein 216 (RNF216); RNF216, also called Triad domain-containing protein 3 (Triad3A), ubiquitin-conjugating enzyme 7-interacting protein 1, or zinc finger protein inhibiting NF-kappa-B (ZIN), is an RBR-type E3 ubiquitin-protein ligase that interacts with several components of the Toll-like receptor (TLR) signaling and promotes their proteolytic degradation. It negatively regulates the RIG-I RNA sensing pathway through Lys48-linked, ubiquitin-mediated degradation of the tumor 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 tumor necrosis factor receptor-1 (TNF-R1)-induced NF-kappa B activation, following disruption of Hsp90 binding. Moreover, RNF216 is involved in inflammatory diseases by 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 2DL4/KIR2DL4 (killer cell Ig-like receptor with two Ig-like domains and a long cytoplasmic domain 4)-mediated NF-kappaB signaling from internalized 2DL4, which functions by promoting ubiquitylation and degradation of endocytosed receptor from early endosomes. Furthermore, RNF216 interacts with human immunodeficiency virus type 1 (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 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. The family corresponds to the Rcat domain of RNF216 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

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                 ....*....|....*....|....*....|....*....|...
gi 148678141 279 CPCCGTPIQKLDGCNKMTCtGCMQYFCWICMGSLsraNPYRHF 321
Cdd:cd20353   12 CPKCKTKFIKSEGCNKMTC-RCGAKMCYICRKPI---KGYDHF 50

RING finger, HC subclass, found in Saccharomyces cerevisiae histone E3 ligase 2 (HEL2) and similar proteins; HEL2 is an E3 ubiquitin-protein ligase that interacts with the E2 ubiquitin-conjugating enzyme UBC4 and histones H3 and H4. It plays an important role in regulating histone protein levels and also likely to contribute to the maintenance of genomic stability in the budding yeast. HEL2 can be phosphorylated by the DNA damage checkpoint kinase and histone protein regulator Rad53. This subfamily also includes Schizosaccharomyces pombe histone E3 ligase 1 (HEL1), also known as DNA-break-localizing protein 4 (dbl4), and Dictyostelium discoideum Ariadne-like ubiquitin ligase (RbrA). RbrA may act as an E3 ubiquitin-protein ligase that appears to be required for normal cell-type proportioning and cell sorting during multicellular development, and is also necessary for spore cell viability. Members of this subfamily contain 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 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. This model corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.

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                 ....*....|....*....|....*....|....*....|....*....|....
gi 148678141  93 FLCSICFCEklGSDCMYFLECKHVYCKACLKDYFEIQIKDGQVKCL-NCPEPQC 145
Cdd:cd16625    1 FECPICCDD--GELETFSLECGHEFCVDCYSQYLTSKIKEEGEGCRiTCPGEKC 52

RING finger, HC subclass, found in Schizosaccharomyces pombe DNA repair protein Rad8 (SpRad8) and similar proteins; SpRad8 is a conserved protein homologous to Saccharomyces cerevisiae DNA repair protein Rad5 and human helicase-like transcription factor (HLTF) that is required for error-free postreplication repair by contributing to polyubiquitylation of PCNA. SpRad8 contains a C3HC4-type RING-HC finger responsible for the E3 ubiquitin ligase activity, a SNF2-family helicase domain including an ATP binding site, and a family-specific HIRAN domain (HIP116, Rad5p N-terminal domain) that contributes to nuclear localization.

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                 ....*....|....*....|....*....|....*....|....*....|
gi 148678141  95 CSICfCEKLGSDCmYFLECKHVYCKACLKDYFEIQIKDGQV-KCLNCPEP 143
Cdd:cd16572    7 CPIC-AEEPISEL-ALTRCWHSACKDCLLDHIEFQKSKNEVpLCPTCRQP 54

RING finger, HC subclass, 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 a novel ubiquitin-conjugating enzyme, UbcD10. HHARI, also known as 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 1, 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 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. This model corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 148678141  94 LCSICFCEkLGSDCMYFLECKHVYCKACLKDYFEIQIKD-GQVKCLNCPEPQC 145
Cdd:cd16626    2 PCDICYLN-YPNSYMTGLECGHKFCMQCWKEYLTTKIMEeGMGQTISCPAHGC 53

zinc-RING finger domain;

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                  ....*....|....*....|....*....|....*.
gi 148678141   95 CSICFCEKLGSDCMYFLECKHVYCKACLKDYFEIQI 130
Cdd:pfam14634   2 CNKCFKELSKTRPFYLTSCGHIFCEECLTRLLQERQ 37

BRcat domain found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, also called ariadne-2 (ARI-2), protein ariadne-2 homolog, Ariadne RBR E3 ubiquitin protein ligase 2 (ARIH2), or UbcM4-interacting protein 48, is an RBR-type E3 ubiquitin-protein ligase that catalyzes the formation of polyubiquitin chains linked via lysine-48 as well as lysine-63 residues. Its auto-ubiquitylation can be catalyzed 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 hematopoietic 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. This model corresponds to the BRcat domain of TRIAD1 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

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                 ....*....|....*....|....*....|....*....|....*.
gi 148678141 183 YCPRPCCQLPVM-QEPGGTMAICSSCNFAFCTLCRLTYHGLSPCKV 227
Cdd:cd20344   11 FCPGPDCPVVIRaLEPKAKRVQCKRCKTSFCFKCGEDYHAPTDCET 56

Rcat domain found in RING finger protein 19A (RNF19A); RNF19A, also called double ring-finger protein (Dorfin), or p38, is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that localizes to the ubiquitylated inclusions in Parkinson's disease (PD), dementia with Lewy bodies (LBs), multiple system atrophy, and amyotrophic lateral sclerosis (ALS). It interacts with Psmc3, a protein component of the 19S regulatory cap of the 26S proteasome, and further participates in the ubiquitin-proteasome system in acrosome biogenesis, spermatid head shaping, and development of the head-tail coupling apparatus and tail. It modulates the ubiquitination and degradation of calcium-sensing receptor (CaR), which may contribute to a general mechanism for CaR quality control during biosynthesis. Moreover, RNF19A can also ubiquitylate mutant superoxide dismutase 1 (SOD1), the causative gene of familial ALS. It may associate with endoplasmic reticulum-associated degradation (ERAD) pathway, which is related to the pathogenesis of neurodegenerative disorders, such as PD or Alzheimer's disease. It is also involved in the pathogenic process of PD and LB formation by ubiquitylation of synphilin-1. RNF19A contains an RBR domain followed by three 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 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 RNF19A that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

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                 ....*....|....*....|....*....|....*....
gi 148678141 277 KSCPCCGTPIQKLD--GCNKMTCTGCMQYFCWICMGSLS 313
Cdd:cd20370   10 KPCPRCAAYIIKMNdgSCNHMTCAVCGCEFCWLCMKEIS 48

Ring finger domain;

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                  ....*....|....*....|....*....|....*
gi 148678141   95 CSICFCEKLGSDCMYFLECKHVYCKACLKDYFEIQ 129
Cdd:pfam13639   3 CPICLEEFEEGDKVVVLPCGHHFHRECLDKWLRSS 37

Modified RING finger, HC subclass (C4C4-type), found in HOIL-1-interacting protein (HOIP) and similar proteins; HOIP, also known as RING finger protein 31 (RNF31) or zinc in-between-RING-finger ubiquitin-associated domain protein, together with HOIL-1 and SHARPIN, forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis. It also interacts 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 responsible for the interaction with the N-terminal ubiquitin-like domain (UBL) of HOIL-1L, 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 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. This model corresponds to the RING domain, 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.

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                 ....*....|....*....|....*....|....*....|....*..
gi 148678141  95 CSICFCEKLGSDCMYFLECKHVYCKACLKDYFEIQIKDGQVKCLNCP 141
Cdd:cd16631    3 CPICFNSFPRNKMVSLTSCECKICPDCFKQYFTVVIKEKHIRDLVCP 49