RWD domain of RING finger protein 14 (RNF14) and related proteins; RNF14, also called androgen receptor (AR)-associated protein 54 (ARA54), HFB30, or Triad2 protein, is an RBR-type E3 ubiquitin-protein ligase (EC 2.3.2.31) 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 Wnt-dependent transcriptional outputs that act at the level of the T-cell factor/lymphoid enhancer factor (TCF/LEF)-beta-catenin complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831510536  12 ELEALESVLRENkLTRISDWADKNAEIRgiIEVGFDTLSdpKVTIEGTSDSSDHFSIPLDILPPIRLKFHLPNDYPSVSS 91
Cdd:cd23820     4 ELEALEAIYPDD-LVVDSDSSSGRGSLE--IPVELEPPL--SVVLSSDGSDEGERTLKVSHLPPITLRFSLPPGYPSTSP 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1831510536  92 PKLELESYWMNQEQMTSCETELARICEENQMMEVLFMCYQTIID 135
Cdd:cd23820    79 PEFTLECSWLSPEQLSALCERLDELWEENGGDVVLFSWIDFLQD 122

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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 different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 enable efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1831510536 179 FVNTLFDCEVCYDSQMGQHCIKFQPCSHVFCKQCTFDYYRT 219
Cdd:cd16628     1 FNSKIFTCNICFLDKLGSECMYFKDCGHVYCKECLKEYFEV 41

RWD domain of RING finger protein 14 (RNF14) and related proteins; RNF14, also called androgen receptor (AR)-associated protein 54 (ARA54), HFB30, or Triad2 protein, is an RBR-type E3 ubiquitin-protein ligase (EC 2.3.2.31) 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 Wnt-dependent transcriptional outputs that act at the level of the T-cell factor/lymphoid enhancer factor (TCF/LEF)-beta-catenin complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831510536  12 ELEALESVLRENkLTRISDWADKNAEIRgiIEVGFDTLSdpKVTIEGTSDSSDHFSIPLDILPPIRLKFHLPNDYPSVSS 91
Cdd:cd23820     4 ELEALEAIYPDD-LVVDSDSSSGRGSLE--IPVELEPPL--SVVLSSDGSDEGERTLKVSHLPPITLRFSLPPGYPSTSP 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1831510536  92 PKLELESYWMNQEQMTSCETELARICEENQMMEVLFMCYQTIID 135
Cdd:cd23820    79 PEFTLECSWLSPEQLSALCERLDELWEENGGDVVLFSWIDFLQD 122

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 1831510536 266 IREMEDTVECPRENCQKVAYVtDRQRFLAECSYCNFSFCNLCKQTFHGIERCKWKKGD 323
Cdd:cd20341     1 LDSMPDVVYCPRPSCQTPVIL-EPDENLGICPSCNYAFCTLCRETYHGVSPCKIKEEK 57

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1831510536  255 AKYETIMLEKAIREMEDTVECPRENCQKVAYVT-DRQRFLAECSYCNFSFCNLCKQTFHGIERC 317
Cdd:smart00647   1 EKYERLLLESYVESNPDLKWCPAPDCSAAIIVTeEEGCNRVTCPKCGFSFCFRCKVPWHSPVSC 64

RING finger, HC subclass, found in RING finger protein 14 (RNF14) and similar proteins; RNF14, also known as androgen receptor-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 muscle. It is a ligand-dependent androgen receptor (AR) co-activator and may 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 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
                  ....*....|....*....|....*....|....*....|.
gi 1831510536 179 FVNTLFDCEVCYDSQMGQHCIKFQPCSHVFCKQCTFDYYRT 219
Cdd:cd16628     1 FNSKIFTCNICFLDKLGSECMYFKDCGHVYCKECLKEYFEV 41

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1831510536 357 ERFLNEEWLDSNSK----PCPKCSVSIEKNEGCHK---MHCTKCDTYFCWLC 401
Cdd:pfam01485   4 EKLLLKSYVESDPNlkwcPTPDCGYIIELTDGCSNtshVTCSKCGHEFCFNC 55

RWD domain of RING finger protein 14 (RNF14) and related proteins; RNF14, also called androgen receptor (AR)-associated protein 54 (ARA54), HFB30, or Triad2 protein, is an RBR-type E3 ubiquitin-protein ligase (EC 2.3.2.31) 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 Wnt-dependent transcriptional outputs that act at the level of the T-cell factor/lymphoid enhancer factor (TCF/LEF)-beta-catenin complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831510536  12 ELEALESVLRENkLTRISDWADKNAEIRgiIEVGFDTLSdpKVTIEGTSDSSDHFSIPLDILPPIRLKFHLPNDYPSVSS 91
Cdd:cd23820     4 ELEALEAIYPDD-LVVDSDSSSGRGSLE--IPVELEPPL--SVVLSSDGSDEGERTLKVSHLPPITLRFSLPPGYPSTSP 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1831510536  92 PKLELESYWMNQEQMTSCETELARICEENQMMEVLFMCYQTIID 135
Cdd:cd23820    79 PEFTLECSWLSPEQLSALCERLDELWEENGGDVVLFSWIDFLQD 122

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 1831510536 266 IREMEDTVECPRENCQKVAYVtDRQRFLAECSYCNFSFCNLCKQTFHGIERCKWKKGD 323
Cdd:cd20341     1 LDSMPDVVYCPRPSCQTPVIL-EPDENLGICPSCNYAFCTLCRETYHGVSPCKIKEEK 57

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
                  ....*....|....*....|....*....|....*....|....*..
gi 1831510536 361 NEEWLDSNSKPCPKCSVSIEKNEGCHKMHCTKCDTYFCWLCSETLDK 407
Cdd:cd20361     1 NCLWLVTNSKPCPNCKSPIQKNEGCNHMKCSKCKYDFCWVCLEEWKK 47

RWD domain of protein IMPACT and related proteins; IMPACT, also imprinted and ancient gene protein homolog, acts as a translational regulator that ensures constant high levels of translation upon a variety of stress conditions, such as amino acid starvation, UV-C irradiation, proteasome inhibitor treatment, and glucose deprivation. It plays a role as a negative regulator of EIF2AK4/GCN2 kinase activity. It impairs GCN1-mediated EIF2AK4/GCN2 activation, and hence EIF2AK4/GCN2-mediated eIF-2-alpha phosphorylation and subsequent down-regulation of protein synthesis. IMPACT may be required to regulate translation in specific neuronal cells under amino acid starvation conditions by preventing GCN2 activation and therefore ATF4 synthesis. Through its inhibitory action on EIF2AK4/GCN2, IMPACT plays a role in differentiation of neuronal cells by stimulating neurite outgrowth.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1831510536  60 SDSSDHFSI----PLDILPPIRLKFHLPNDYPSVSSPKLELESYWMNQEQMTSCETELARICEENQMMEVLFMC 129
Cdd:cd23821    19 DESARSFVIrielDGPHLPPLVLRVHLPPDYPSHSPPIFELSAPWLSGEERSELCAELDEIWEENAGEPVLFQW 92

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1831510536 366 DSNSKPCPKCSVSIEKNEGCHKMHCTKCDTYFCWLCSETLDKEDPYKHFQgDGSCSGRL 424
Cdd:cd20352     2 DAPIKRCPMCHVPIERDEGCAQMMCKNCKHVFCWYCLASLDDDFLLRHYD-KGPCKNKL 59

Rcat domain of ATP-dependent RNA helicase DEAH12 and similar proteins; This group includes Arabidopsis thaliana ATP-dependent RNA helicases DEAH11 and DEAH12, which may be bifunctional proteins that function as DEAD-box RNA helicases (EC 3.6.4.13) and RBR-type E3 ubiquitin-protein ligases (EC 2.3.2.31). As RNA helicases, they may utilize the energy from ATP hydrolysis to unwind RNA (or DNA). DEAD-box RNA helicases participate in every aspect of RNA metabolism. As E3 ubiquitin-protein ligase, they may function as part of E3 complexes, which accept ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfer it to substrates. Other members of this group may not have an RNA helicase domain. All members 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 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1831510536 368 NSKPCPKCSVSIEKNEGCHKMHCTKCDTYFCWLCSETLDKEDP-YKH 413
Cdd:cd22585     1 DVKRCPKCKSLIEKIDGCNHVTCTRCGTHICWVCLKVFETSSEcYAH 47

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1831510536  255 AKYETIMLEKAIREMEDTVECPRENCQKVAYVT-DRQRFLAECSYCNFSFCNLCKQTFHGIERC 317
Cdd:smart00647   1 EKYERLLLESYVESNPDLKWCPAPDCSAAIIVTeEEGCNRVTCPKCGFSFCFRCKVPWHSPVSC 64

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 1831510536 256 KYETIMLEKAIREMEDTVECPRENCQKVAYVTD--RQRFLAECSYCNFSFCNLCKQTFHGIERC 317
Cdd:pfam01485   2 KYEKLLLKSYVESDPNLKWCPTPDCGYIIELTDgcSNTSHVTCSKCGHEFCFNCKEEWHEGLTC 65

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 1831510536 367 SNSKPCPKCSVSIEKNEGCHKMHCTKCDTYFCWLCSE 403
Cdd:cd20350     3 RNAQKCPKCKVYIQRSEGCDHMTCSQCNTNFCYRCGE 39

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 1831510536 369 SKPCPKCSVSIEKNEGCHKMHCTKCDTYFCWLC 401
Cdd:cd20359     7 SKRCPSCQAQIEKNEGCLHMTCAKCNHGFCWRC 39

RWD, DRWD, and ELF domain family; The family includes the RWD, double-RWD (DRWD), and ELF domains. They belong to the ubiquitin-conjugating (UBC) superfamily that represents a structural domain with an alpha-beta(4)-alpha(3) core fold. The RWD domain (named after three major RWD-containing proteins: RING finger, WD-repeat-containing proteins and DEXD-like helicases) mediates protein-protein interactions in a variety of pathways in eukaryotes. The DRWD domain is responsible for substrate binding. It is involved in interactions with other kinetochore proteins. The ELF (N-terminal E2-like fold) domain is found in all Fanconi anemia group L protein (FANCL) homologs. It is required to promote efficient DNA damage-induced FANCD2 (Fanconi anemia group D2 protein) monoubiquitination in vertebrate cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1831510536  60 SDSSDHFSIPL-----DILPPIRLKFHLPNDYPSVSSPKLELESYW-MNQEQMTSCETELARICEENQMMEVLFMCYQTI 133
Cdd:cd11605    15 DDSPLRFSIRLspeeeEDDPPLELEFTLPPGYPPEEPPLITLRSPKlSSAERLSLLKLELEEAAEENLGEPMLFDLVEAL 94

RING finger, HC subclass, found in RING finger protein 14 (RNF14) and similar proteins; RNF14, also known as androgen receptor-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 muscle. It is a ligand-dependent androgen receptor (AR) co-activator and may 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 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
                  ....*....|....*....|....*....|....*....|.
gi 1831510536 179 FVNTLFDCEVCYDSQMGQHCIKFQPCSHVFCKQCTFDYYRT 219
Cdd:cd16628     1 FNSKIFTCNICFLDKLGSECMYFKDCGHVYCKECLKEYFEV 41

Rcat domain found in the RING finger protein 19 (RNF19) subfamily; This subfamily includes RING finger protein RNF19A and RNF19B, which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF19A, also called double ring-finger protein (Dorfin) or p38, 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 the 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. RNF19B, also called IBR domain-containing protein 3, or natural killer (NK) lytic-associated molecule (NKLAM), 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. 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 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 RNF19 subfamily that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

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gi 1831510536 370 KPCPKCSVSIEK-NEG-CHKMHCTKCDTYFCWLC 401
Cdd:cd20355     5 KPCPRCGALIIKmDDGsCNHMTCAVCGAEFCWLC 38

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.

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gi 1831510536 372 CPKCSVSIEKNEGCHKMHCTKCDTYFCW 399
Cdd:cd20358    10 CPQCQVIVQKKDGCDWIRCSMCKTEICW 37

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 1831510536 372 CPKCSVSIEKNEGCHKMHCtKCDTYFCWLCSETLdkeDPYKHF 414
Cdd:cd20353    12 CPKCKTKFIKSEGCNKMTC-RCGAKMCYICRKPI---KGYDHF 50

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.

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gi 1831510536 270 EDTVECPRENCQKVAYVTDRQR-FLAECSYCNFSFCNLCKQTFHGIERCK 318
Cdd:cd20335     2 PNLRWCPTPDCGGVIRVEEPGDgPRVTCPSCGTSFCFKCKEEWHEGLTCE 51

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 1831510536 370 KPCPKCSVSIEK-NEG-CHKMHCTKCDTYFCWLC 401
Cdd:cd20370    10 KPCPRCAAYIIKmNDGsCNHMTCAVCGCEFCWLC 43

BRcat domain found in the RING finger protein 19 (RNF19) subfamily; This subfamily includes RING finger protein RNF19A and RNF19B, both of which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF19A, also called double ring-finger protein (Dorfin), or p38, 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 the 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. RNF19B, also called IBR domain-containing protein 3 or natural killer (NK) lytic-associated molecule (NKLAM), 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 (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 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 the RNF19 subfamily that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

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gi 1831510536 253 LYAKYETIMLEKAIREMEDTVECPRENCQKVAYVTDRqrflAECSY-------CNFSFCNLCKQTFHGIERCK 318
Cdd:cd20338     1 LLEKYEEFMLRRVLVRDPDARWCPAPDCGYAVIATGC----ASCPKltcqrpgCGTEFCYHCKQPWHPNQTCD 69

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

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gi 1831510536 357 ERFLNEEWLDSNSK----PCPKCSVSIEKNEGCHK---MHCTKCDTYFCWLC 401
Cdd:pfam01485   4 EKLLLKSYVESDPNlkwcPTPDCGYIIELTDGCSNtshVTCSKCGHEFCFNC 55