Rcat domain found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar proteins; ANKIB1 is an RBR-type E3 ubiquitin-protein ligase that may function as part of an E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. It contains N-terminal ankyrin repeats, and 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 ANKIB1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 61656165  509 NCLWLLTNSKPCANCKSPIQKNEGCNHMQCAKCKYDFCWICLEEWKKHSSSTGGYYRCTRYE 570
Cdd:cd20361    1 NCLWLVTNSKPCPNCKSPIQKNEGCNHMKCSKCKYDFCWVCLEEWKKHSSSTGGYFRCNRYE 62

BRcat domain found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar proteins; ANKIB1 is an RBR-type E3 ubiquitin-protein ligase that may function as part of the E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. It contains N-terminal ankyrin repeats, and 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 ANKIB1 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 61656165  410 IKAFVENNPAIKWCPTAGCERAVRLTKQGSNPsgsdtlsfpllRAPAVDCGKGHLFCWECLGEAHEPCDCQTWKNWLQK 488
Cdd:cd20346    1 LRSYVEDNPNLKWCPAPGCGRAVELPGGGSEE-----------GSPEVDCGCGHSFCFNCGEEAHRPVDCETVKKWLKK 68

Ariadne domain; This entry represents the Ariadne domain found in the Ariadne subfamily E3 ubiquitin ligase proteins. The C-terminal Ariadne domain adopts an elongated four-helix bundle consisting of an antiparallel arrangement of seven-to-ten-turn long helices. The Ariadne domain is straddled on one side by the IBR domain, and on the other by the RING2 domain. Notably, the Ariadne domain embraces the surface of RING2 containing the catalytic Cys357. The ariadne Domain Masks the HHARI Catalytic Cys357 and Inhibits Intrinsic E3 Activity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61656165    585 EAEKKHKRFQ-ELDRFMHYYTRYKNHEHSYQLEQRLLKTAKEKmeqLSRaLKETEGGCPDTTFIEDAVHVLLKTRRILKC 663
Cdd:pfam19422    3 DREKKAERAKrDLYRYMHYHNRYKAHTDSFKLESKLKETIQEK---ISI-LEERDSKLRDFSWVTNGLYRLFRSRRVLSY 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 61656165    664 SYPYGFFL------------EPKSTKKEIFELMQTDLEMVTEDLAQKVNRPY 703
Cdd:pfam19422   79 SYPFAFYMfgdelfkdemtkEEREIKQNLFEDQQQQLEANVEKLSKFLEEPF 130

Rcat domain found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar proteins; ANKIB1 is an RBR-type E3 ubiquitin-protein ligase that may function as part of an E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. It contains N-terminal ankyrin repeats, and 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 ANKIB1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 61656165  509 NCLWLLTNSKPCANCKSPIQKNEGCNHMQCAKCKYDFCWICLEEWKKHSSSTGGYYRCTRYE 570
Cdd:cd20361    1 NCLWLVTNSKPCPNCKSPIQKNEGCNHMKCSKCKYDFCWVCLEEWKKHSSSTGGYFRCNRYE 62

BRcat domain found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar proteins; ANKIB1 is an RBR-type E3 ubiquitin-protein ligase that may function as part of the E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. It contains N-terminal ankyrin repeats, and 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 ANKIB1 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 61656165  410 IKAFVENNPAIKWCPTAGCERAVRLTKQGSNPsgsdtlsfpllRAPAVDCGKGHLFCWECLGEAHEPCDCQTWKNWLQK 488
Cdd:cd20346    1 LRSYVEDNPNLKWCPAPGCGRAVELPGGGSEE-----------GSPEVDCGCGHSFCFNCGEEAHRPVDCETVKKWLKK 68

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        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 61656165    403 KRYLQFDIKAFVENNPAIKWCPTAGCERAVRLTKQGSNPSGsdtlsfpllrapaVDCGK-GHLFCWECLGEAHEPCDC 479
Cdd:pfam01485    1 EKYEKLLLKSYVESDPNLKWCPTPDCGYIIELTDGCSNTSH-------------VTCSKcGHEFCFNCKEEWHEGLTC 65

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

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 61656165     403 KRYLQFDIKAFVENNPAIKWCPTAGCERAVRLTKQGSNPSgsdtlsfpllrapaVDCGK-GHLFCWECLGEAHEPCDC 479
Cdd:smart00647    1 EKYERLLLESYVESNPDLKWCPAPDCSAAIIVTEEEGCNR--------------VTCPKcGFSFCFRCKVPWHSPVSC 64

Ankyrin repeats (3 copies);

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61656165     50 LHYAARHGMNRILgTFLFGRDGNPNKRNVHNETSMHLLCMGpqimisegtlhprlarpveddfRRADCLQMILqwkgakl 129
Cdd:pfam12796    1 LHLAAKNGNLELV-KLLLENGADANLQDKNGRTALHLAAKN----------------------GHLEIVKLLL------- 50

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 61656165    130 dqgeyERAAIDAVDNKKnTPLHYAAASGMKACVELLVKHGGDLFAEN 176
Cdd:pfam12796   51 -----EHADVNLKDNGR-TALHYAARSGHLEIVKLLLEKGADINVKD 91

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.

                            10        20
                    ....*....|....*....|....*...
gi 61656165     147 NTPLHYAAASGMKACVELLVKHGGDLFA 174
Cdd:smart00248    3 RTPLHLAAENGNLEVVKLLLDKGADINA 30

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 61656165  329 LDTSL-CDICMCSISVfedPVDMPCGHDFCRGCWEAFLNlkiqegeaHNIFCPAY---ECFQLVP 389
Cdd:COG5432   22 LDSMLrCRICDCRISI---PCETTCGHTFCSLCIRRHLG--------TQPFCPVCredPCESRLR 75

Rcat domain found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar proteins; ANKIB1 is an RBR-type E3 ubiquitin-protein ligase that may function as part of an E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. It contains N-terminal ankyrin repeats, and 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 ANKIB1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 61656165  509 NCLWLLTNSKPCANCKSPIQKNEGCNHMQCAKCKYDFCWICLEEWKKHSSSTGGYYRCTRYE 570
Cdd:cd20361    1 NCLWLVTNSKPCPNCKSPIQKNEGCNHMKCSKCKYDFCWVCLEEWKKHSSSTGGYFRCNRYE 62

BRcat domain found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar proteins; ANKIB1 is an RBR-type E3 ubiquitin-protein ligase that may function as part of the E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. It contains N-terminal ankyrin repeats, and 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 ANKIB1 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 61656165  410 IKAFVENNPAIKWCPTAGCERAVRLTKQGSNPsgsdtlsfpllRAPAVDCGKGHLFCWECLGEAHEPCDCQTWKNWLQK 488
Cdd:cd20346    1 LRSYVEDNPNLKWCPAPGCGRAVELPGGGSEE-----------GSPEVDCGCGHSFCFNCGEEAHRPVDCETVKKWLKK 68

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        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 61656165  515 TNSKPCANCKSPIQKNEGCNHMQCAKCKYDFCWICLEEWKKHSSStggYYRCTRYE 570
Cdd:cd20360    1 AHTKDCPKCHVCIEKNGGCNHMQCSKCKHEFCWMCLGDWKTHGSE---YYECSRYK 53

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 61656165  516 NSKPCANCKSPIQKNEGCNHMQCAKCKYDFCWICLEEW 553
Cdd:cd20336    1 NTKKCPKCKVPIEKNGGCNHMTCSRCGTEFCWLCGKPW 38

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 61656165  517 SKPCANCKSPIQKNEGCNHMQC--AKCKYDFCWICLEEWK 554
Cdd:cd20357    7 TKPCPKCKVPTEKNGGCMHMKCprPQCGLEWCWICGCEWN 46

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        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 61656165  517 SKPCANCKSPIQKNEGCNHMQCAKCKYDFCWICLEEWKkhsSSTGGYYRCT 567
Cdd:cd20359    7 SKRCPSCQAQIEKNEGCLHMTCAKCNHGFCWRCLKPWK---PTHKDYYNCS 54

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        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 61656165    403 KRYLQFDIKAFVENNPAIKWCPTAGCERAVRLTKQGSNPSGsdtlsfpllrapaVDCGK-GHLFCWECLGEAHEPCDC 479
Cdd:pfam01485    1 EKYEKLLLKSYVESDPNLKWCPTPDCGYIIELTDGCSNTSH-------------VTCSKcGHEFCFNCKEEWHEGLTC 65

Ariadne domain; This entry represents the Ariadne domain found in the Ariadne subfamily E3 ubiquitin ligase proteins. The C-terminal Ariadne domain adopts an elongated four-helix bundle consisting of an antiparallel arrangement of seven-to-ten-turn long helices. The Ariadne domain is straddled on one side by the IBR domain, and on the other by the RING2 domain. Notably, the Ariadne domain embraces the surface of RING2 containing the catalytic Cys357. The ariadne Domain Masks the HHARI Catalytic Cys357 and Inhibits Intrinsic E3 Activity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61656165    585 EAEKKHKRFQ-ELDRFMHYYTRYKNHEHSYQLEQRLLKTAKEKmeqLSRaLKETEGGCPDTTFIEDAVHVLLKTRRILKC 663
Cdd:pfam19422    3 DREKKAERAKrDLYRYMHYHNRYKAHTDSFKLESKLKETIQEK---ISI-LEERDSKLRDFSWVTNGLYRLFRSRRVLSY 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 61656165    664 SYPYGFFL------------EPKSTKKEIFELMQTDLEMVTEDLAQKVNRPY 703
Cdd:pfam19422   79 SYPFAFYMfgdelfkdemtkEEREIKQNLFEDQQQQLEANVEKLSKFLEEPF 130

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 61656165  334 CDICMCsisvfEDPVD----MPCGHDFCRGCWEAFLNLKIQEGEAHNIFCPAYEC 384
Cdd:cd16773    3 CGVCCE-----DVPKDelfsLACGHYFCNDCWKQYLTVKIKDGVSTGIECMAPDC 52

Ankyrin repeat [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61656165   14 NGDENLACQIYENNPQLKESL-----DPNISYGEpyqHNTPLHYAARHGMNRILgTFLFGRDGNPNKRNVHNETSMHLLC 88
Cdd:COG0666  119 DGETPLHLAAYNGNLEIVKLLleagaDVNAQDND---GNTPLHLAAANGNLEIV-KLLLEAGADVNARDNDGETPLHLAA 194

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61656165   89 MgpqimisegtlhprlarpveddFRRADCLQMILQwKGAKldqgeyeraaIDAVDNKKNTPLHYAAASGMKACVELLVKH 168
Cdd:COG0666  195 E----------------------NGHLEIVKLLLE-AGAD----------VNAKDNDGKTALDLAAENGNLEIVKLLLEA 241

                        170       180       190
                 ....*....|....*....|....*....|
gi 61656165  169 GGDLFAENENRDTPCDCAEKQQHKDLALSL 198
Cdd:COG0666  242 GADLNAKDKDGLTALLLAAAAGAALIVKLL 271

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 61656165  333 LCDICMCSISVFEdPVDMPCGHDFCRGCWEAFLNLKIQ-EGEAHNIFCPAYECFQLV 388
Cdd:cd16626    2 PCDICYLNYPNSY-MTGLECGHKFCMQCWKEYLTTKIMeEGMGQTISCPAHGCDILV 57

Rcat domain found in the RNF144 protein subfamily; The RNF144 subfamily includes RNF144A and RNF144B, which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF144A, also called UbcM4-interacting protein 4 (UIP4), or ubiquitin-conjugating enzyme 7-interacting protein 4, 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. RNF144B, also called 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 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 the RNF144 protein subfamily that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 61656165  518 KPCANCKSPIQKNEGCNHMQCAKCKYDFCWICLE 551
Cdd:cd20352    6 KRCPMCHVPIERDEGCAQMMCKNCKHVFCWYCLA 39

Rcat domain found in RING finger protein 217 (RNF217); RNF217, also called IBR domain-containing protein 1 (IBRDC1), is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase, with different splice variants, that is mainly expressed in testis and skeletal muscle. 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 an 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 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 RNF217 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 61656165  516 NSKPCANCKSPIQKNEGCNHMQCAKCKYDFCWICLEEWK 554
Cdd:cd20350    4 NAQKCPKCKVYIQRSEGCDHMTCSQCNTNFCYRCGERYR 42

BRcat (benign-catalytic) 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 as 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 BRcat domain adopts the same fold as the Rcat domain while lacking 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. The model corresponds to the BRcat domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 61656165  417 NPAIKWCPTAGCERAVRLTKQGSNPSgsdtlsfpllrapaVDCGK-GHLFCWECLGEAHEPCDCQTW 482
Cdd:cd20335    1 NPNLRWCPTPDCGGVIRVEEPGDGPR--------------VTCPScGTSFCFKCKEEWHEGLTCEEY 53

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
                 ....*....|....*....|....*....|....
gi 61656165  518 KPCANCKSPIQKNEGCNHMQCAKCKYDFCWICLE 551
Cdd:cd20369    7 KQCPVCRVYIERNEGCAQMMCKNCKHTFCWYCLQ 40

Ankyrin repeats (3 copies);

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61656165     50 LHYAARHGMNRILgTFLFGRDGNPNKRNVHNETSMHLLCMGpqimisegtlhprlarpveddfRRADCLQMILqwkgakl 129
Cdd:pfam12796    1 LHLAAKNGNLELV-KLLLENGADANLQDKNGRTALHLAAKN----------------------GHLEIVKLLL------- 50

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 61656165    130 dqgeyERAAIDAVDNKKnTPLHYAAASGMKACVELLVKHGGDLFAEN 176
Cdd:pfam12796   51 -----EHADVNLKDNGR-TALHYAARSGHLEIVKLLLEKGADINVKD 91

RING finger, HC subclass, found in Arabidopsis thaliana protein ariadne homolog 6 (ARI6) and similar proteins; This subfamily includes ARI6 and ARI11. They might act as E3 ubiquitin-protein ligases, or as part of E3 complexes, which accept ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfer it to substrates. Members of this subfamily contain a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 61656165  334 CDICMCSISVfEDPVDMPCGHDFCRGCWEAFLNLKIQEGEA-HNIFCPAYECFQLVPVDV 392
Cdd:cd23141    4 CGICFESFPV-EEMRAASCGHYFCKTCWTGYIHTAISDGPGcLDLRCPDPSCPAAVGEDM 62

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 61656165  413 FVENNPAIKWCPTAGCERAVRLTKQgsnpsgsdtlsfpllRAPAVDCGKGHL-FCWECLGEAHEPCDCQTWKNWLQK 488
Cdd:cd20344    2 YVKSHPQLRFCPGPDCPVVIRALEP---------------KAKRVQCKRCKTsFCFKCGEDYHAPTDCETIKKWLTK 63

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.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 61656165  518 KPCANCKSPIQK-NEG-CNHMQCAKCKYDFCWICLEE 552
Cdd:cd20370   10 KPCPRCAAYIIKmNDGsCNHMTCAVCGCEFCWLCMKE 46

Rcat domain found in RING finger protein 19B (RNF19B); RNF19B, also called IBR domain-containing protein 3, or natural killer (NK) lytic-associated molecule (NKLAM), is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that plays a role in controlling tumor dissemination and metastasis. It is involved in the cytolytic function of NK cells and cytotoxic T lymphocytes (CTLs). It interacts with ubiquitin conjugates UbcH7 and UbcH8, and ubiquitinates uridine kinase like-1 protein, targeting it for degradation. Moreover, RNF19B is a novel component of macrophage phagosomes and plays a role in macrophage anti-bacterial activity. It functions as a novel modulator of macrophage inducible nitric oxide synthase (iNOS) expression. RNF19B 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 RNF19B that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 61656165  518 KPCANCKSPIQK-NEG-CNHMQCAKCKYDFCWICLEE 552
Cdd:cd20371    5 KPCPRCSAYIIKmNDGsCNHMTCAVCGCEFCWLCMKE 41

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 61656165  334 CDICMcsiSVFEDPVDMPCGHDFCRGCWEAFLnlkiqegEAHNIFCP 380
Cdd:cd16449    3 CPICL---ERLKDPVLLPCGHVFCRECIRRLL-------ESGSIKCP 39

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.

                            10        20
                    ....*....|....*....|....*...
gi 61656165     147 NTPLHYAAASGMKACVELLVKHGGDLFA 174
Cdd:smart00248    3 RTPLHLAAENGNLEVVKLLLDKGADINA 30

RING finger, HC subclass, found in tripartite motif-containing protein 8 (TRIM8) and similar proteins; TRIM8, also known as glioblastoma-expressed RING finger protein (GERP) or RING finger protein 27 (RNF27), is a probable E3 ubiquitin-protein ligase that may promote proteasomal degradation of suppressor of cytokine signaling 1 (SOCS1) and further regulate interferon-gamma signaling. It functions as a new p53 modulator that stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation. TRIM8 deficit dramatically impairs p53 stabilization and activation in response to chemotherapeutic drugs. TRIM8 also modulates tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta)-triggered nuclear factor-kappaB (NF- kappa B) activation by targeting transforming growth factor beta (TGFbeta) activated kinase 1 (TAK1) for K63-linked polyubiquitination. Moreover, TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90beta and consequently regulates transcription of Nanog in embryonic stem cells. It also interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL-6-dependent activation of STAT3. TRIM8 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The coiled coil domain is required for homodimerization and the region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1.

                         10        20
                 ....*....|....*....|....*...
gi 61656165  333 LCDICMcsiSVFEDPVDMPCGHDFCRGC 360
Cdd:cd16580   13 ICPICL---HVFVEPVQLPCKHNFCRGC 37

RING finger, HC subclass, found in tripartite motif-containing protein TRIM17 and similar proteins; TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (Terf), is a crucial E3 ubiquitin ligase that is necessary and sufficient for neuronal apoptosis and contributes to Mcl-1 ubiquitination in cerebellar granule neurons (CGNs). It interacts in a SUMO-dependent manner with nuclear factor of activated T cell NFATc3 transcription factor, and thus inhibits the activity of NFATc3 by preventing its nuclear localization. In contrast, it binds to and inhibits NFATc4 transcription factor in a SUMO-independent manner. Moreover, TRIM17 stimulates degradation of kinetochore protein ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM17 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 61656165  330 DTSLCDICMcsiSVFEDPVDMPCGHDFCRGC----WEAFLNLKIQEGEAHNIFCPayECFQLVP 389
Cdd:cd16595    4 EEATCSICL---DYFTDPVMTTCGHNFCRACiqlsWEKARGKKGRRKQKGSFPCP--ECREMSP 62

Ankyrin repeats (many copies);

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 61656165    147 NTPLHYAAASGMKACVELLVKHGGDLFAENENRDTPCDCAEKQQHKDLA 195
Cdd:pfam13637    2 LTALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFAASNGNVEVL 50

Rcat domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1 is also called RBCK1, HOIL-1L, RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, Hepatitis B virus X-associated protein 4, RING finger protein 54 (RNF54), ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28). 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 recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-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. This model corresponds to the Rcat domain of HOIL1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20
                 ....*....|....*....|....*....
gi 61656165  520 CANCKSPIQKNEGCNHMQCAKCKYDFCWI 548
Cdd:cd20358   10 CPQCQVIVQKKDGCDWIRCSMCKTEICWV 38

Ring finger domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 61656165    334 CDICMCSISVFEDPVDMPCGHDFCRGCWEAFLnlkiqegeAHNIFCP 380
Cdd:pfam13639    3 CPICLEEFEEGDKVVVLPCGHHFHRECLDKWL--------RSSNTCP 41

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 61656165    334 CDICMCsisVFEDPVdMPCGHDFCRGCweafLNLKiQEGEAHNIFCP 380
Cdd:pfam13445    1 CPICLE---LFTDPV-LPCGHTFCREC----LEEM-SQKKGGKFKCP 38

RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar proteins; TRIM77 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including two consecutive zinc-binding domains, a C3HC4-type RING-HC finger and Bbox2, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

                         10        20
                 ....*....|....*....|....*...
gi 61656165  335 DICMCSI--SVFEDPVDMPCGHDFCRGC 360
Cdd:cd16543    2 DQLTCSIclDLLKDPVTIPCGHSFCMNC 29

RING finger, HC subclass, found in tripartite motif-containing protein TRIM4 and similar proteins; TRIM4 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that has recently evolved and is present only in higher mammals. It transiently interacts with mitochondria, induces mitochondrial aggregation and sensitizes the cells to hydrogen peroxide (H2O2) induced death. Its interaction with peroxiredoxin 1 (PRX1) is critical for the regulation of H2O2 induced cell death. Moreover, TRIM4 functions as a positive regulator of RIG-I-mediated type I interferon induction. It regulates the K63-linked ubiquitination of RIG-1 and assembly of antiviral signaling complex at the mitochondria.

                         10        20
                 ....*....|....*....|....*..
gi 61656165  334 CDICMcsiSVFEDPVDMPCGHDFCRGC 360
Cdd:cd16590    9 CPICL---DYFQDPVSIECGHNFCRGC 32

RING finger, HC subclass, found in the family of RING finger proteins RNF19A, RNF19B and similar proteins; The family includes RING finger protein RNF19A and RNF19B, both of which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF19A, also known as double ring-finger protein (Dorfin) or p38, localizes to the ubiquitylated inclusions in Parkinson's disease (PD), dementia with Lewy bodies, 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. RNF19B, also known as IBR domain-containing protein 3 or natural killer lytic-associated molecule (NKLAM), plays a role in controlling tumor dissemination and metastasis. It is involved in the cytolytic function of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). It interacts with ubiquitin conjugates UbcH7 and UbcH8, and ubiquitinates uridine kinase like-1 (URKL-1) protein, targeting it for degradation. Moreover, RNF19B is a novel component of macrophage phagosomes and plays a role in macrophage anti-bacterial activity. It functions as a novel modulator of macrophage inducible nitric oxide synthase (iNOS) expression. Both RNF19A and RNF19B contain 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 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 61656165  334 CDICMCSISVFEDPVDMPCGHDFCRGCWEAFLNLKIQEGEAhNIFCPayEC 384
Cdd:cd16629    3 CPLCLDDLSPEFFPILLSCEHRSCRDCLRQYLTIEISESRV-NISCP--EC 50

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of Numb protein LNX1, LNX2, and similar proteins; The ligand of Numb protein X (LNX) family, also known as PDZ and RING (PDZRN) family, includes LNX1-5, which can interact with Numb, a key regulator of neurogenesis and neuronal differentiation. LNX5 (also known as PDZK4 or PDZRN4L) shows high sequence homology to LNX3 and LNX4, but it lacks the RING domain. LNX1-4 proteins function as E3 ubiquitin ligases and have a unique domain architecture consisting of an N-terminal RING-HC finger for E3 ubiquitin ligase activity and either two or four PDZ domains necessary for substrate-binding. LNX1/LNX2-like proteins contain a modified C3HC3D-type RING-HC finger and four PDZ domains. This model corresponds to the RING finger.

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gi 61656165  333 LCDICmcsISVFEDPVDMPCGHDFCRGCWEAFlnLKIQEgeahniFCP 380
Cdd:cd16637    3 TCHIC---LQPLVEPLDTPCGHTFCYKCLTNY--LKIQQ------CCP 39

RING finger, HC subclass, found in tripartite motif-containing protein 39 (TRIM39) and similar proteins; TRIM39, also known as RING finger protein 23 (RNF23) or testis-abundant finger protein, is an E3 ubiquitin-protein ligase that plays a role in controlling DNA damage-induced apoptosis through inhibition of the anaphase promoting complex (APC/C), a multiprotein ubiquitin ligase that controls multiple cell cycle regulators, including cyclins, geminin, and others. TRIM39 also functions as a regulator of several key processes in the proliferative cycle. It directly regulates p53 stability. It modulates cell cycle progression and DNA damage responses via stabilizing p21. Moreover, TRIM39 negatively regulates the nuclear factor kappaB (NFkappaB)-mediated signaling pathway through stabilization of Cactin, an inhibitor of NFkappaB- and Toll-like receptor (TLR)-mediated transcription, which is induced by inflammatory stimulants such as tumor necrosis factor alpha. Furthermore, TRIM39 is a MOAP-1-binding protein that can promote apoptosis signaling through stabilization of MOAP-1 via the inhibition of its poly-ubiquitination process. TRIM39 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.