HOIP UBA domain pair; HOIP-UB is a binding domain on E3 ubiquitin-protein ligase RNF31 like proteins. E3 ubiquitin-protein ligase RNF31 is often referred to as HOIL-1L binding partner. The interaction of HOIL-1L and HOIP is thus via the UBL-UBA interaction. this interaction is important in E3 complex formation and the subsequent activation of NF-kappaB. This family contains two UBA-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2068670006 1392 MKKQGLELVQVLRDAEDAGYTSEDVSIALTHCGDKNPLEWLKENWRHMVDTVSTLATNYGQERRVNDIGSITGAEARLAL 1471
Cdd:pfam16678    2 MREEGLELVHLIREAEKYGFSPEEVYAALRYSGGSNPLQWLKTEWPHLLDTVAALAASEGKELKENTVGVLSRAEARLAL 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2068670006 1472 RVHKGNIWAAVTECVEERQKKFNEIYARGKFTREAVVRSLEKHDGDADAAFLELNKFQLQPFMMKIWG 1539
Cdd:pfam16678   82 LEAGGDVEKAVKECVRDRRKKVKELMSLGFFDREDCVQALRQSGGDVEGALVLLQRPLLEPFHQRIWE 149

BRcat domain found in HOIL-1-interacting protein (HOIP) and similar proteins; HOIP, also called RING finger protein 31 (RNF31) or zinc in-between-RING-finger ubiquitin-associated domain protein, together with HOIL-1 and SHARPIN, forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis. It also interacts with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression. HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain responsible for interaction with the N-terminal ubiquitin-like domain (UBL) of HOIL-1L, an RBR domain, and a C-terminal linear chain determining domain (LDD). The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been 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 HOIP and similar proteins that adopt the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2068670006 2756 ETHELFQRKLRDWTLMKDPNFRWCNKCSSGFIANARARKLICPDCKDVTCAHCRAPWEAAHEGISCEAFTRWKTDND 2832
Cdd:cd20337      2 DVYELFQKKLRDRNLMKDPNFRWCAHCSFGFIYEPEQLKMQCPQCGKVTCFKCKKPWEDQHEGISCEQFQEWKREND 78

Modified RING finger, HC subclass (C4C4-type), found in HOIL-1-interacting protein (HOIP) and similar proteins; HOIP, also known as RING finger protein 31 (RNF31) or zinc in-between-RING-finger ubiquitin-associated domain protein, together with HOIL-1 and SHARPIN, forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis. It also interacts with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression. HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain responsible for the interaction with the N-terminal ubiquitin-like domain (UBL) of HOIL-1L, an RBR domain, and a C-terminal linear chain determining domain (LDD). The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a C4C4-type RING finger motif whose overall folding is similar to that of the C3HC4-type RING-HC finger. It is required for RBR-mediated ubiquitination.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2068670006 2676 QECELCAEKHPMRRMVSMLQCIHRCCSDCAKTYFTFQIKTKNLREVRCPFCNEP 2729
Cdd:cd16631      1 QECPICFNSFPRNKMVSLTSCECKICPDCFKQYFTVVIKEKHIRDLVCPACGLP 54

HOIP UBA domain pair; HOIP-UB is a binding domain on E3 ubiquitin-protein ligase RNF31 like proteins. E3 ubiquitin-protein ligase RNF31 is often referred to as HOIL-1L binding partner. The interaction of HOIL-1L and HOIP is thus via the UBL-UBA interaction. this interaction is important in E3 complex formation and the subsequent activation of NF-kappaB. This family contains two UBA-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2068670006 1392 MKKQGLELVQVLRDAEDAGYTSEDVSIALTHCGDKNPLEWLKENWRHMVDTVSTLATNYGQERRVNDIGSITGAEARLAL 1471
Cdd:pfam16678    2 MREEGLELVHLIREAEKYGFSPEEVYAALRYSGGSNPLQWLKTEWPHLLDTVAALAASEGKELKENTVGVLSRAEARLAL 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2068670006 1472 RVHKGNIWAAVTECVEERQKKFNEIYARGKFTREAVVRSLEKHDGDADAAFLELNKFQLQPFMMKIWG 1539
Cdd:pfam16678   82 LEAGGDVEKAVKECVRDRRKKVKELMSLGFFDREDCVQALRQSGGDVEGALVLLQRPLLEPFHQRIWE 149

BRcat domain found in HOIL-1-interacting protein (HOIP) and similar proteins; HOIP, also called RING finger protein 31 (RNF31) or zinc in-between-RING-finger ubiquitin-associated domain protein, together with HOIL-1 and SHARPIN, forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis. It also interacts with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression. HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain responsible for interaction with the N-terminal ubiquitin-like domain (UBL) of HOIL-1L, an RBR domain, and a C-terminal linear chain determining domain (LDD). The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been 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 HOIP and similar proteins that adopt the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2068670006 2756 ETHELFQRKLRDWTLMKDPNFRWCNKCSSGFIANARARKLICPDCKDVTCAHCRAPWEAAHEGISCEAFTRWKTDND 2832
Cdd:cd20337      2 DVYELFQKKLRDRNLMKDPNFRWCAHCSFGFIYEPEQLKMQCPQCGKVTCFKCKKPWEDQHEGISCEQFQEWKREND 78

Modified RING finger, HC subclass (C4C4-type), found in HOIL-1-interacting protein (HOIP) and similar proteins; HOIP, also known as RING finger protein 31 (RNF31) or zinc in-between-RING-finger ubiquitin-associated domain protein, together with HOIL-1 and SHARPIN, forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis. It also interacts with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression. HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain responsible for the interaction with the N-terminal ubiquitin-like domain (UBL) of HOIL-1L, an RBR domain, and a C-terminal linear chain determining domain (LDD). The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a C4C4-type RING finger motif whose overall folding is similar to that of the C3HC4-type RING-HC finger. It is required for RBR-mediated ubiquitination.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2068670006 2676 QECELCAEKHPMRRMVSMLQCIHRCCSDCAKTYFTFQIKTKNLREVRCPFCNEP 2729
Cdd:cd16631      1 QECPICFNSFPRNKMVSLTSCECKICPDCFKQYFTVVIKEKHIRDLVCPACGLP 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2068670006 2759 ELFQRKLRDWTLMKDPNFRWC--NKCSSGFIAN---ARARKLICPDCKDVTCAHCRAPWeaaHEGISC 2821
Cdd:pfam01485    1 EKYEKLLLKSYVESDPNLKWCptPDCGYIIELTdgcSNTSHVTCSKCGHEFCFNCKEEW---HEGLTC 65

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
                   ....*....|....*....|....*....|....*....|....*
gi 2068670006 2851 CP--KCKFTYSLAKGG--CMHFTCTQCKFEFCSGCSQPFRQGSRC 2891
Cdd:pfam01485   21 CPtpDCGYIIELTDGCsnTSHVTCSKCGHEFCFNCKEEWHEGLTC 65

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....
gi 2068670006  2851 CP--KCKFTYSLAKG-GCMHFTCTQCKFEFCSGCSQPFRQGSRC 2891
Cdd:smart00647   21 CPapDCSAAIIVTEEeGCNRVTCPKCGFSFCFRCKVPWHSPVSC 64

HOIP UBA domain pair; HOIP-UB is a binding domain on E3 ubiquitin-protein ligase RNF31 like proteins. E3 ubiquitin-protein ligase RNF31 is often referred to as HOIL-1L binding partner. The interaction of HOIL-1L and HOIP is thus via the UBL-UBA interaction. this interaction is important in E3 complex formation and the subsequent activation of NF-kappaB. This family contains two UBA-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2068670006 1392 MKKQGLELVQVLRDAEDAGYTSEDVSIALTHCGDKNPLEWLKENWRHMVDTVSTLATNYGQERRVNDIGSITGAEARLAL 1471
Cdd:pfam16678    2 MREEGLELVHLIREAEKYGFSPEEVYAALRYSGGSNPLQWLKTEWPHLLDTVAALAASEGKELKENTVGVLSRAEARLAL 81

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2068670006 1472 RVHKGNIWAAVTECVEERQKKFNEIYARGKFTREAVVRSLEKHDGDADAAFLELNKFQLQPFMMKIWG 1539
Cdd:pfam16678   82 LEAGGDVEKAVKECVRDRRKKVKELMSLGFFDREDCVQALRQSGGDVEGALVLLQRPLLEPFHQRIWE 149

BRcat domain found in HOIL-1-interacting protein (HOIP) and similar proteins; HOIP, also called RING finger protein 31 (RNF31) or zinc in-between-RING-finger ubiquitin-associated domain protein, together with HOIL-1 and SHARPIN, forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis. It also interacts with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression. HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain responsible for interaction with the N-terminal ubiquitin-like domain (UBL) of HOIL-1L, an RBR domain, and a C-terminal linear chain determining domain (LDD). The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been 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 HOIP and similar proteins that adopt the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2068670006 2756 ETHELFQRKLRDWTLMKDPNFRWCNKCSSGFIANARARKLICPDCKDVTCAHCRAPWEAAHEGISCEAFTRWKTDND 2832
Cdd:cd20337      2 DVYELFQKKLRDRNLMKDPNFRWCAHCSFGFIYEPEQLKMQCPQCGKVTCFKCKKPWEDQHEGISCEQFQEWKREND 78

Modified RING finger, HC subclass (C4C4-type), found in HOIL-1-interacting protein (HOIP) and similar proteins; HOIP, also known as RING finger protein 31 (RNF31) or zinc in-between-RING-finger ubiquitin-associated domain protein, together with HOIL-1 and SHARPIN, forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis. It also interacts with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression. HOIP contains three Npl4 zinc fingers, a central ubiquitin-associated (UBA) domain responsible for the interaction with the N-terminal ubiquitin-like domain (UBL) of HOIL-1L, an RBR domain, and a C-terminal linear chain determining domain (LDD). The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a C4C4-type RING finger motif whose overall folding is similar to that of the C3HC4-type RING-HC finger. It is required for RBR-mediated ubiquitination.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2068670006 2676 QECELCAEKHPMRRMVSMLQCIHRCCSDCAKTYFTFQIKTKNLREVRCPFCNEP 2729
Cdd:cd16631      1 QECPICFNSFPRNKMVSLTSCECKICPDCFKQYFTVVIKEKHIRDLVCPACGLP 54

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 2068670006 2848 GITCPKCKFTYSLAkGGCMHFTCTQCKFEFCSGCSQP 2884
Cdd:cd14799      2 TKWCPKCHFGFEKE-RGCMHATCPQCRQEFCWRCKRQ 37

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

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2068670006  2759 ELFQRK-LRDWtLMKDPNFRWC--NKCSSGFIA--NARARKLICPDCKDVTCAHCRAPWeaaHEGISC 2821
Cdd:smart00647    1 EKYERLlLESY-VESNPDLKWCpaPDCSAAIIVteEEGCNRVTCPKCGFSFCFRCKVPW---HSPVSC 64

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 2068670006 2773 DPNFRWC--NKCSSGFIA--NARARKLICPDCKDVTCAHCRAPWeaaHEGISCEAF 2824
Cdd:cd20335      1 NPNLRWCptPDCGGVIRVeePGDGPRVTCPSCGTSFCFKCKEEW---HEGLTCEEY 53

B-box-type 1 zinc finger (Bbox1); The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain, in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, the B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2). This family corresponds to the type 1 B-box (Bbox1).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2068670006   74 CDLCGSAPAAVRCDRCGsQAFCLSCDDMYHRHPR-RSTHQRKAV 116
Cdd:cd19757      2 CDECEEREATVYCLECE-EFLCDDCSDAIHRRGKlTRSHKLVPL 44

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 2068670006 2851 CPKCKfTYSLAKGGCMHFTCTQCKFEFCSGCSQPFRQ 2887
Cdd:cd20350      8 CPKCK-VYIQRSEGCDHMTCSQCNTNFCYRCGERYRQ 43

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
                   ....*....|....*....|....*....|....*....|....*..
gi 2068670006 2851 CPKCKFTysLAK-GGCMHFTCTQCKFEFCSGCSQPFRQ-GS---RCS 2892
Cdd:cd20360      6 CPKCHVC--IEKnGGCNHMQCSKCKHEFCWMCLGDWKThGSeyyECS 50

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 2068670006 2773 DPNFRWCNK---------CSSGFIANARARKLICPDCKDVTCAHCRAPWeaaHEGISCEAFTR 2826
Cdd:cd20349      5 DPNRTWCPRagcetvchvCPPSGSAPVTAVPVQCPKCGLTFCSICKAAW---HAGQSCDENMK 64

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.

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gi 2068670006 2851 CPKCKfTYSLAKGGCMHFTCT--QCKFEFCSGC 2881
Cdd:cd20357     10 CPKCK-VPTEKNGGCMHMKCPrpQCGLEWCWIC 41

RING finger, HC subclass, found in RING finger protein 19A (RNF19A) and similar proteins; RNF19A, also known as 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, 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. 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 corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.

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gi 2068670006 2677 ECELCAEKHPMRRMVSMLQCIHRCCSDCAKTYFTFQIkTKNLREVRCPFCNE 2728
Cdd:cd16775      2 ECPLCLLRHSKDRFPDIMTCHHRSCADCLRQYLRIEI-SESRVNISCPECSE 52

RING finger, HC subclass, found in radiation sensitivity protein 5 (RAD5) and similar proteins; RAD5, also known as revertibility protein 2 (REV2), or DNA repair protein RAD5, is a probable helicase, and a member of the UBC2/RAD6 epistasis group. It functions with the DNA repair protein RAD18 in error-free postreplication DNA repair. It is involved in the maintenance of wild-type rates of instability of simple repetitive sequences such as poly(GT) repeats. It may also be involved in maintaining a balance which acts in favor of error-prone non-homologous joining during DNA double-strand breaks repairs. It recruits the UBC13-MMS2 dimer to chromatin for DNA repair. RAD5 contains a typical C3HC4-type RING-HC finger.

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gi 2068670006 2677 ECELCAEKhPMRRM-VSMLQCIHRCCSDCAKTYFTFQIKTKNlrEVRCPFCNEP 2729
Cdd:cd23131      5 ECSICTQE-PIEVGeVVFTECGHSFCEDCLLEYIEFQNKKKL--DLKCPNCREP 55

B-box-type 1 zinc finger found in B-box (BBX) family of plant transcription factors and similar proteins; The BBX family includes a group of zinc finger transcription factors that contain one or two B-box motifs, and sometimes also feature a CCT (CONSTANS, CO-like, and TOC1) domain. They play important roles in plant growth and development, including seedling photomorphogenesis, photoperiodic regulation of flowering, shade avoidance, and responses to biotic and abiotic stresses. Their B-box motifs show high sequence similarity with B-Box-type 1 zinc finger found in tripartite motif-containing proteins (TRIMs) and are involved in mediating transcriptional regulation and protein-protein interaction in plant signaling. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif; this family contains a modified motif, C3XC2H2, where X can be D, E, C or H.

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gi 2068670006   74 CDLCGSAPAAVRCDRCGSQaFCLSCDDMYH---RHPRRstHQR 113
Cdd:cd19821      2 CDSCESAPAVVYCRADRAS-LCRACDAKVHsanKLASR--HQR 41

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

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gi 2068670006 2674 LQQECELCAEKhPMRRMvSMLQCIHRCCSDCAKTYFTFQiKTKNlREVRCPFCNEP 2729
Cdd:cd16572      3 AENECPICAEE-PISEL-ALTRCWHSACKDCLLDHIEFQ-KSKN-EVPLCPTCRQP 54

Double zinc ribbon; This family consists of a pair of zinc ribbon domains.

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gi 2068670006   66 ENRRDGKNCDLCGSAPAAVRCDRCGSQA-----FCLSC 98
Cdd:pfam12773    7 PNPPGAKFCPACGTPLKPDRCPNCGAPVppnarFCPYC 44

UBA domain found in E3 ubiquitin-protein ligase RING finger protein 31 and similar proteins; RNF31, also called HOIL-1-interacting protein (HOIP), or zinc in-between-RING-finger ubiquitin-associated domain protein, together with HOIL-1 and SHARPIN, forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis. RNF31 contains a central ubiquitin-associated (UBA) domain that is responsible for the interaction with the N-terminal ubiquitin-like domain (UBL) of HOIL-1L. In addition, RNF31 can interact with the atypical mammalian orphan receptor DAX-1, trigger DAX-1 ubiquitination and stabilization, and participate in repressing steroidogenic gene expression.

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gi 2068670006 1484 ECVEERQKKFNEIYARGKFTREAVVRSLEKHDGDADAAFLELNKFQLQPFMMKIW 1538
Cdd:cd14325      1 QCLRDRRVKVKELGSLGFGDATRCLQALRQSGGDVRGALVLLQRQLLEPFHQRLW 55

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.

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gi 2068670006 2677 ECELCAEkhpMRRMVSMLQCIHRCCSDCAKTYFTfqiktknLREVRCPFC 2726
Cdd:cd16449      2 ECPICLE---RLKDPVLLPCGHVFCRECIRRLLE-------SGSIKCPIC 41

B-box-type 1 zinc finger found in tumor suppressor cylindromatosis (CYLD) and similar proteins; CYLD, also termed ubiquitin carboxyl-terminal hydrolase CYLD, or deubiquitinating enzyme CYLD, or ubiquitin thioesterase CYLD, or ubiquitin-specific-processing protease CYLD, is a microtubule-associated deubiquitinase that specifically cleaves Lys-63-linked polyubiquitin chains. It plays a pivotal role in a wide range of cellular activities, including innate immunity, cell division, and ciliogenesis. CYLD antagonizes NF-kappaB and JNK signaling by disassembly of Lys63-linked ubiquitin chains synthesized in response to cytokine stimulation. Structural characterization reveals a small zinc-binding B-box inserted within the ubiquitin specific protease (USP) domain of CYLD. The B-box motif shows high sequence similarity with B-Box-type 1 zinc finger found in tripartite motif-containing proteins (TRIMs) and is responsible for its intermolecular interaction and cytoplasmic localization. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

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gi 2068670006   72 KNCDLCGSaPAAVRCDRC--------GSQAFCLSCDDMYHRHPRRSTHQRKAVD 117
Cdd:cd19816      2 RECIICGG-LAEYECRDCyldpgiggKIKAFCKKCNKQTHLHPKRQNHKPRPLS 54

Modified RING finger, HC subclass (C4C4-type), found in RNF144 proteins; This group includes RNF144A and RNF144B, both of which are transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligases. RNF144A, also known as UbcM4-interacting protein 4 (UIP4) or ubiquitin-conjugating enzyme 7-interacting protein 4, targets DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and thus promote DNA damage-induced cell apoptosis. It is transcriptionally repressed by metastasis-associated protein 1 (MTA1) and inhibits MTA1-driven cancer cell migration and invasion. RNF144B, also known as PIR2, IBR domain-containing protein 2 (IBRDC2), or p53-inducible RING finger protein (p53RFP), induces p53-dependent but caspase-independent apoptosis. It interacts with E2 ubiquitin-conjugating enzymes UbcH7 and UbcH8, but not with UbcH5. It is involved in ubiquitination and degradation of p21, a p53 downstream protein promoting growth arrest and antagonizing apoptosis, suggesting a role in switching a cell from p53-mediated growth arrest to apoptosis. Moreover, RNF144B regulates the levels of Bax, a pro-apoptotic protein from the Bcl-2 family, and protects cells from unprompted Bax activation and cell death. It also regulates epithelial homeostasis by mediating degradation of p21WAF1 and p63. Both RNF144A and RNF144B contain an RBR domain followed by a potential single-TM domain. The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a C4C4-type RING finger whose overall folding is similar to that of the C3HC4-type RING-HC finger. It is required for RBR-mediated ubiquitination.

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gi 2068670006 2678 CELCAEKHPMRRMVSMLQCihRC--CSDCAKTYFTFQIKTKNLREVRCP 2724
Cdd:cd16632      3 CKLCLEEVPLREMYTLQSC--GCifCLQCLKQYVEVLIREGNVSSITCP 49

BRcat 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 pathway 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 (TNF) 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 TNF receptor-1-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. This model corresponds to the BRcat domain of RNF216 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

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gi 2068670006 2779 CNKCS-SGFIANARARKLIC--PDCKDVTCAHCRAPWeaaHEGISCEAFTR 2826
Cdd:cd20339      7 CPFCNyAAILDPTEVKVFRCpnPECRKESCRKCKKEW---HIPLTCEEVEK 54

Modified RING finger, HC subclass (C4C4-type), found in RING finger protein 144B (RNF144B); RNF144B, also known as PIR2, IBR domain-containing protein 2 (IBRDC2), or p53-inducible RING finger protein (p53RFP), is a transmembrane (TM) domain-containing RBR (RING1-IBR-RING2) 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 corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a C4C4-type RING finger whose overall folding is similar to that of the C3HC4-type RING-HC finger. It is required for RBR-mediated ubiquitination.

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gi 2068670006 2678 CELCAEKHPMRRMVSMLQCIHRCCSDCAKTYFTFQIKTKNLREVRCP 2724
Cdd:cd16778      3 CKLCLCEHPFDAMTTLQECDCVFCTPCLKQYVQLAIREGCGSPITCP 49

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 2068670006 2851 CPKCK-FTYSLAKGGCMHFTCTQCKFEFCSGC 2881
Cdd:cd20355      7 CPRCGaLIIKMDDGSCNHMTCAVCGAEFCWLC 38