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 15224815    72 GLGLSLCDSHDYTKQEINKALRNqklAAHPEAAELAAIIHGLKWALELGIERIQFFCDDSNILAYVTRKaAPNESIVAKL 151
Cdd:pfam13456  14 GAGVVIRDPNGNVLLAGQKKLGP---GASVLEAEAQALIIGLQLAWKLGIRHLIVEGDSATVVQLINGR-SPKQSKLANL 89

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 15224815   152 LEHVSLLQTRFTSCQaLATVSRDDIVSVIKLAKDA 186
Cdd:pfam13456  90 LDEIRKLLKRFESVS-FEHIPREQNRVADTLAKMA 123

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
                ....*....|....*....|....
gi 15224815 367 GWKKCSQCQSIVQHGGGCQQMTCR 390
Cdd:cd22584   1 GWRRCPQCGHMVELSEGCNHMTCR 24

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 15224815    72 GLGLSLCDSHDYTKQEINKALRNqklAAHPEAAELAAIIHGLKWALELGIERIQFFCDDSNILAYVTRKaAPNESIVAKL 151
Cdd:pfam13456  14 GAGVVIRDPNGNVLLAGQKKLGP---GASVLEAEAQALIIGLQLAWKLGIRHLIVEGDSATVVQLINGR-SPKQSKLANL 89

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 15224815   152 LEHVSLLQTRFTSCQaLATVSRDDIVSVIKLAKDA 186
Cdd:pfam13456  90 LDEIRKLLKRFESVS-FEHIPREQNRVADTLAKMA 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 15224815   285 KDRVYCPNPSCSFLMsdldlirhISKNPRHSEEARKCMECGLSFCKKCHVPWHYKKTC 342
Cdd:pfam01485  16 PNLKWCPTPDCGYII--------ELTDGCSNTSHVTCSKCGHEFCFNCKEEWHEGLTC 65

RNAse HI family that includes archaeal, some bacterial as well as plant RNase HI; Ribonuclease H (RNase H) is classified into two evolutionarily unrelated 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). RNase H is an endonuclease that cleaves the RNA strand of an RNA/DNA hybrid in a sequence non-specific manner. RNase H is involved in DNA replication, repair and transcription. RNase H is widely present in various organisms, including bacteria, archaea and eukaryotes and 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 (DEDD) residues and have the same catalytic mechanism and functions in cells. One of the important functions of RNase H is to remove Okazaki fragments during DNA replication. Most archaeal genomes contain only type 2 RNase H (RNase HII); however, a few contain RNase HI as well. Although archaeal RNase HI sequences conserve the DEDD active-site motif, they lack other common features important for catalytic function, such as the basic protrusion region. Archaeal RNase HI homologs are more closely related to retroviral RNase HI than bacterial and eukaryotic type I RNase H in enzymatic properties.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15224815 104 AELAAIIHGLKWALELGIERIQFFCdDSNILAY-VTRKAAPNESIVAKLLEHVSLLQTRFTSCQaLATVSRDDIVSVIKL 182
Cdd:cd09279  45 AEYEALIAGLELALELGAEKLEIYG-DSQLVVNqLNGEYKVKNERLKPLLEKVLELLAKFELVE-LKWIPREQNKEADAL 122

                ....*
gi 15224815 183 AKDAI 187
Cdd:cd09279 123 ANQAL 127

RING finger, HC subclass, found in RNA polymerase II transcription factor B subunit 3 (TFB3) from fungi; TFB3, also known as RNA polymerase II transcription factor B 38 kDa subunit, RNA polymerase II transcription factor B p38 subunit, or Rig2, is a component of the general transcription and DNA repair factor IIH (TFIIH or factor B), which is essential for both basal and activated transcription and is involved in nucleotide excision repair (NER) of damaged DNA. TFIIH has CTD kinase and DNA-dependent ATPase activities, and is essential for polymerase II transcription in vitro. TFB3 is a homolog of MAT1 of higher eukaryotes which forms a ternary complex with MO15 (cdk7) and cyclin H. It physically interacts with Ubc4 and the Nedd8-conjugating enzyme Ubc12 as well as the Hrt1/Rtt101 complex. It targets the yeast Cul4-type cullin Rtt101 for its neddylation and ubiquitylation, and regulates neddylation and activity of cullin-3, but not Cdc53. TFB3 contains an N-terminal C3HC4-type RING-HC finger and a C-terminal MAT1 domain responsible for the interaction with the transcription factor TFIIH.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15224815 201 ESCPVCYA--YVSPNDKFEVQG-CFHRICVTCMRKPFSSEQilrgntAICPYPDC 252
Cdd:cd16573   2 EKCPVCKSdrYLNPDMKFLINPeCYHKMCESCVDRIFTLGP------AQCPYKGC 50

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 15224815    72 GLGLSLCDSHDYTKQEINKALRNqklAAHPEAAELAAIIHGLKWALELGIERIQFFCDDSNILAYVTRKaAPNESIVAKL 151
Cdd:pfam13456  14 GAGVVIRDPNGNVLLAGQKKLGP---GASVLEAEAQALIIGLQLAWKLGIRHLIVEGDSATVVQLINGR-SPKQSKLANL 89

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 15224815   152 LEHVSLLQTRFTSCQaLATVSRDDIVSVIKLAKDA 186
Cdd:pfam13456  90 LDEIRKLLKRFESVS-FEHIPREQNRVADTLAKMA 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15224815 285 KDRVYCPNPSCSFLmsdldlirhISKNPRHSEEARKCMECGLSFCKKCHVPWHYKKTCDEF 345
Cdd:cd20335   2 PNLRWCPTPDCGGV---------IRVEEPGDGPRVTCPSCGTSFCFKCKEEWHEGLTCEEY 53

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 15224815   285 KDRVYCPNPSCSFLMsdldlirhISKNPRHSEEARKCMECGLSFCKKCHVPWHYKKTC 342
Cdd:pfam01485  16 PNLKWCPTPDCGYII--------ELTDGCSNTSHVTCSKCGHEFCFNCKEEWHEGLTC 65

RNAse HI family that includes archaeal, some bacterial as well as plant RNase HI; Ribonuclease H (RNase H) is classified into two evolutionarily unrelated 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). RNase H is an endonuclease that cleaves the RNA strand of an RNA/DNA hybrid in a sequence non-specific manner. RNase H is involved in DNA replication, repair and transcription. RNase H is widely present in various organisms, including bacteria, archaea and eukaryotes and 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 (DEDD) residues and have the same catalytic mechanism and functions in cells. One of the important functions of RNase H is to remove Okazaki fragments during DNA replication. Most archaeal genomes contain only type 2 RNase H (RNase HII); however, a few contain RNase HI as well. Although archaeal RNase HI sequences conserve the DEDD active-site motif, they lack other common features important for catalytic function, such as the basic protrusion region. Archaeal RNase HI homologs are more closely related to retroviral RNase HI than bacterial and eukaryotic type I RNase H in enzymatic properties.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15224815 104 AELAAIIHGLKWALELGIERIQFFCdDSNILAY-VTRKAAPNESIVAKLLEHVSLLQTRFTSCQaLATVSRDDIVSVIKL 182
Cdd:cd09279  45 AEYEALIAGLELALELGAEKLEIYG-DSQLVVNqLNGEYKVKNERLKPLLEKVLELLAKFELVE-LKWIPREQNKEADAL 122

                ....*
gi 15224815 183 AKDAI 187
Cdd:cd09279 123 ANQAL 127

Rcat domain found in an uncharacterized subfamily of RBR proteins; This subfamily contains uncharacterized members of the RBR family, including Arabidopsis thaliana mutator-like transposase and hypothetical protein At2g19610/F3P11.21. 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. 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 is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                        10        20
                ....*....|....*....|....
gi 15224815 367 GWKKCSQCQSIVQHGGGCQQMTCR 390
Cdd:cd22584   1 GWRRCPQCGHMVELSEGCNHMTCR 24

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15224815 287 RVYCPNPSCSFLMSDLDLIRHISKNPRhseeARKCMECGLSFCKKCHVPWHYKKTCDEFKK 347
Cdd:cd20349   8 RTWCPRAGCETVCHVCPPSGSAPVTAV----PVQCPKCGLTFCSICKAAWHAGQSCDENMK 64

Ribonuclease HI [Replication, recombination and repair];

                        10        20
                ....*....|....*....|....*.
gi 15224815 104 AELAAIIHGLKWALELGIERIQFFCD 129
Cdd:COG0328  45 AELTALIAALEALKELGPCEVEIYTD 70