BRcat domain found in an uncharacterized subfamily of RBR proteins; This subfamily contains uncharacterized members of the RBR family, including Arabidopsis thaliana mutator-like transposase, hypothetical protein F9K21.90, and hypothetical protein T16H5.30. The RBR family of RING-type E3 ligases are characterized by containing a 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 corrected as 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 145339149 251 VCDRFHCPNPRCWALMSKTELvESTEDGVRRCCFKCRKAFCINCKVLWHSDLSCKEY 307
Cdd:cd22582    1 VSERVYCPNPDCSALMSKDEL-LEAEDDTPRECPKCRRLFCARCKVPWHAGLSCAEY 56

BRcat (benign-catalytic) and Rcat (required-for-catalysis) domains, part of the RBR (RING1-BRcat-Rcat) domain; The RBR family of RING-type E3 ligases are characterized by containing an RBR (RING1-BRcat-Rcat) 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 RBRs has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis), 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.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 145339149 319 RQCKKCQHMIKLSHKTINVYCRCGYSFCYTCGAQW 353
Cdd:cd22584    3 RRCPQCGHMVELSEGCNHMTCRCGYEFCYLCGAPW 37

BRcat domain found in an uncharacterized subfamily of RBR proteins; This subfamily contains uncharacterized members of the RBR family, including Arabidopsis thaliana mutator-like transposase, hypothetical protein F9K21.90, and hypothetical protein T16H5.30. The RBR family of RING-type E3 ligases are characterized by containing a 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 corrected as 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 145339149 251 VCDRFHCPNPRCWALMSKTELvESTEDGVRRCCFKCRKAFCINCKVLWHSDLSCKEY 307
Cdd:cd22582    1 VSERVYCPNPDCSALMSKDEL-LEAEDDTPRECPKCRRLFCARCKVPWHAGLSCAEY 56

Reverse transcriptase-like; This domain is found in plants and appears to be part of a retrotransposon.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145339149   33 FKGLVREKTSAqlsAGFEVAIFREEDEYLL-FQMKGslhDSTVTVLEAELMALKRGLTEAVSLGINHISICCDRLELYEL 111
Cdd:pfam13456   2 FDGAFKCDSGL---AGAGVVIRDPNGNVLLaGQKKL---GPGASVLEAEAQALIIGLQLAWKLGIRHLIVEGDSATVVQL 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 145339149  112 VMGRlAPEKENIALLMDDVQCIRRELTSSIPVTVTENQAKFAFKLAKES 160
Cdd:pfam13456  76 INGR-SPKQSKLANLLDEIRKLLKRFESVSFEHIPREQNRVADTLAKMA 123

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 145339149  238 EMWEHRIKEEFIPVC-DRFHCPNPRCWALMSKTELVESTedgVRRCCFKCRKAFCINCKVLWHSDLSC 304
Cdd:pfam01485   1 EKYEKLLLKSYVESDpNLKWCPTPDCGYIIELTDGCSNT---SHVTCSKCGHEFCFNCKEEWHEGLTC 65

BRcat domain found in an uncharacterized subfamily of RBR proteins; This subfamily contains uncharacterized members of the RBR family, including Arabidopsis thaliana mutator-like transposase, hypothetical protein F9K21.90, and hypothetical protein T16H5.30. The RBR family of RING-type E3 ligases are characterized by containing a 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 corrected as 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 145339149 251 VCDRFHCPNPRCWALMSKTELvESTEDGVRRCCFKCRKAFCINCKVLWHSDLSCKEY 307
Cdd:cd22582    1 VSERVYCPNPDCSALMSKDEL-LEAEDDTPRECPKCRRLFCARCKVPWHAGLSCAEY 56

Reverse transcriptase-like; This domain is found in plants and appears to be part of a retrotransposon.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145339149   33 FKGLVREKTSAqlsAGFEVAIFREEDEYLL-FQMKGslhDSTVTVLEAELMALKRGLTEAVSLGINHISICCDRLELYEL 111
Cdd:pfam13456   2 FDGAFKCDSGL---AGAGVVIRDPNGNVLLaGQKKL---GPGASVLEAEAQALIIGLQLAWKLGIRHLIVEGDSATVVQL 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 145339149  112 VMGRlAPEKENIALLMDDVQCIRRELTSSIPVTVTENQAKFAFKLAKES 160
Cdd:pfam13456  76 INGR-SPKQSKLANLLDEIRKLLKRFESVSFEHIPREQNRVADTLAKMA 123

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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 145339149 253 DRFHCPNPRCwalmSKTELVESTEDGVRRCCFKCRKAFCINCKVLWHSDLSCKEY 307
Cdd:cd20335    3 NLRWCPTPDC----GGVIRVEEPGDGPRVTCPSCGTSFCFKCKEEWHEGLTCEEY 53

Ribonuclease H-like superfamily, including RNase H, HI, HII, HIII, and RNase-like domain IV of spliceosomal protein Prp8; Ribonuclease H (RNase H) enzymes are divided into two major families, Type 1 and Type 2, based on amino acid sequence similarities and biochemical properties. RNase H is an endonuclease that cleaves the RNA strand of an RNA/DNA hybrid in a sequence non-specific manner in the presence of divalent cations. It is widely present in various organisms, including bacteria, archaea, and eukaryotes. Most prokaryotic and eukaryotic genomes contain multiple RNase H genes. Despite the lack of amino acid sequence homology, type 1 and type 2 RNase H share a main-chain fold and steric configurations of the four acidic active-site residues and have the same catalytic mechanism and functions in cells. RNase H is involved in DNA replication, repair and transcription. An important RNase H function is to remove Okazaki fragments during DNA replication. RNase H inhibitors have been explored as anti-HIV drug targets since RNase H inactivation inhibits reverse transcription. This model also includes the Prp8 domain IV, which adopts the RNase fold but shows low sequence homology; domain IV is implicated in key spliceosomal interactions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145339149  52 AIFReeDEYLLFQMKGSLHDSTVTVLEAELMALKRGLTEAVSLGINHISICCDRLELYELVMGRLAPEKENIALLMDdvq 131
Cdd:cd06222   18 GVLR--DHEGGWLGGFALKIGAPTALEAELLALLLALELALDLGYLKVIIESDSKYVVDLINSGSFKWSPNILLIED--- 92

                         90       100       110
                 ....*....|....*....|....*....|..
gi 145339149 132 cIRRELTSSIPVTVT-----ENQAkfAFKLAK 158
Cdd:cd06222   93 -ILLLLSRFWSVKIShvpreGNQV--ADALAK 121

BRcat 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 BRcat domain of the RNF144 protein subfamily that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 145339149 257 CPNPRCWALMSKTELVESTE-DGVRRCCFKCRKAFCINCKVLWHSDLSCKEYK 308
Cdd:cd20349   11 CPRAGCETVCHVCPPSGSAPvTAVPVQCPKCGLTFCSICKAAWHAGQSCDENM 63

non-LTR RNase HI domain of reverse transcriptases; Ribonuclease H (RNase H) is classified into two families, type 1 (prokaryotic RNase HI, eukaryotic RNase H1 and viral RNase H) and type 2 (prokaryotic RNase HII and HIII, and eukaryotic RNase H2). Ribonuclease HI (RNase HI) is an endonuclease that cleaves the RNA strand of an RNA/DNA hybrid in a sequence non-specific manner. RNase H is widely present in various organisms, including bacteria, archaea and eukaryotes. RNase HI has also been observed as an adjunct domain to the reverse transcriptase gene in retroviruses, long-term repeat (LTR)-bearing retrotransposons and non-LTR retrotransposons. RNase HI in LTR retrotransposons perform degradation of the original RNA template, generation of a polypurine tract (the primer for plus-strand DNA synthesis), and final removal of RNA primers from newly synthesized minus and plus strands. The catalytic residues for RNase H enzymatic activity, three aspartatic acids and one glutamic acid residue (DEDD), are unvaried across all RNase H domains. The position of the RNase domain of non-LTR and LTR transposons is at the carboxyl terminal of the reverse transcriptase (RT) domain and their RNase domains group together, indicating a common evolutionary origin. Many non-LTR transposons have lost the RNase domain because their activity is at the nucleus and cellular RNase may suffice; however LTR retrotransposons always encode their own RNase domain because it requires RNase activity in RNA-protein particles in the cytoplasm. RNase H inhibitors have been explored as an anti-HIV drug target because RNase H inactivation inhibits reverse transcription.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 145339149  46 SAGFEVAIFREedeYLLFQMKGSLHDSTvTVLEAELMALKRGLTEAVSLG--INHISICCD 104
Cdd:cd09276   12 SVGAGFVIYRG---GEVISRSYRLGTHA-SVFDAELEAILEALELALATArrARKVTIFTD 68