Rcat domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1 is also called RBCK1, HOIL-1L, RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, Hepatitis B virus X-associated protein 4, RING finger protein 54 (RNF54), ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28). Together with the E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), it forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has an RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of HOIL1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 617385749 633 LVQSGEAMHCPQCGIIVQKRDGCDWLRCTVCHTEICWVTRGPRWGPKGPGDTSGGCRCNVNNQKCHPKCQNCH 705
Cdd:cd20358    1 LVKSGEAMHCPQCQVIVQKKDGCDWIRCSMCKTEICWVTKGPRWGPGGPGDTSGGCRCRVNGQKCHPNCQNCH 73

BRcat 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 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 BRcat domain of HOIL1 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 617385749 556 AESRCEGSYHCATPDCLGWCVYEDTVNVFHCPVCRKHNCLICKAIHEGMNCKQYQDNLAARAIND 620
Cdd:cd20345    1 AESRSPNSFHCKTPDCPGWCFYEDDVNEFLCPVCKHTNCLTCKAIHEGMNCKEYQDDLRLRANND 65

Zinc finger domain; Zinc finger domain in Ran-binding proteins (RanBPs), and other proteins. In RanBPs, this domain binds RanGDP.

                           10        20
                   ....*....|....*....|..
gi 617385749   392 WSCPSCTYINKPTRPGCEICST 413
Cdd:smart00547   3 WECPACTFLNFASRSKCFACGA 24

Rcat domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1 is also called RBCK1, HOIL-1L, RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, Hepatitis B virus X-associated protein 4, RING finger protein 54 (RNF54), ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28). Together with the E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), it forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has an RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of HOIL1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 617385749 633 LVQSGEAMHCPQCGIIVQKRDGCDWLRCTVCHTEICWVTRGPRWGPKGPGDTSGGCRCNVNNQKCHPKCQNCH 705
Cdd:cd20358    1 LVKSGEAMHCPQCQVIVQKKDGCDWIRCSMCKTEICWVTKGPRWGPGGPGDTSGGCRCRVNGQKCHPNCQNCH 73

ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also termed RBCK1, or HOIL-1L, or RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, or Hepatitis B virus X-associated protein 4, or RING finger protein 54 (RNF54), or ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28), together with E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), 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 a RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 617385749 221 TEINLAVIVED-SSSSCCITVKVFPHMTTASLKQQMFLEYGFHPRVQRWVIGQCLCTDLRTLASYGVRQDGDTAFLYLLS 299
Cdd:cd01799    1 TEISIKVYVEDkSSSSGPITLKVRPHTTIASLKRQIFLEYGFPPSVQRWIIGKRLATDDETLLSYGIKDSGDPAFLYLVS 80

                 .
gi 617385749 300 A 300
Cdd:cd01799   81 A 81

Modified RING finger, HC subclass (C3HC3D-type), found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also known as 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 E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), form 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 the 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 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 modified C3HC3D-type RING-HC finger required for RBR-mediated ubiquitination.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 617385749 468 LVPNPEPVDCKICFVDLQSGEGVLLRECLHCFCKECLRSIIMLCEEPEVSCPYRDD 523
Cdd:cd16633    1 LVPNQEPFECPICFDDVPPGEGVVLRECLHSFCRECLRGAIQNSEEAEVKCPFRDD 56

Zn-finger in Ran binding protein and others;

                          10        20
                  ....*....|....*....|....*
gi 617385749  392 WSCPSCTYINKPTRPGCEICSTNRP 416
Cdd:pfam00641   5 WDCSKCLVQNFATSTKCVACQAPKP 29

Rcat domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1 is also called RBCK1, HOIL-1L, RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, Hepatitis B virus X-associated protein 4, RING finger protein 54 (RNF54), ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28). Together with the E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), it forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has an RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of HOIL1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 617385749 633 LVQSGEAMHCPQCGIIVQKRDGCDWLRCTVCHTEICWVTRGPRWGPKGPGDTSGGCRCNVNNQKCHPKCQNCH 705
Cdd:cd20358    1 LVKSGEAMHCPQCQVIVQKKDGCDWIRCSMCKTEICWVTKGPRWGPGGPGDTSGGCRCRVNGQKCHPNCQNCH 73

ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also termed RBCK1, or HOIL-1L, or RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, or Hepatitis B virus X-associated protein 4, or RING finger protein 54 (RNF54), or ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28), together with E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), 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 a RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 617385749 221 TEINLAVIVED-SSSSCCITVKVFPHMTTASLKQQMFLEYGFHPRVQRWVIGQCLCTDLRTLASYGVRQDGDTAFLYLLS 299
Cdd:cd01799    1 TEISIKVYVEDkSSSSGPITLKVRPHTTIASLKRQIFLEYGFPPSVQRWIIGKRLATDDETLLSYGIKDSGDPAFLYLVS 80

                 .
gi 617385749 300 A 300
Cdd:cd01799   81 A 81

Modified RING finger, HC subclass (C3HC3D-type), found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also known as 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 E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), form 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 the 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 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 modified C3HC3D-type RING-HC finger required for RBR-mediated ubiquitination.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 617385749 468 LVPNPEPVDCKICFVDLQSGEGVLLRECLHCFCKECLRSIIMLCEEPEVSCPYRDD 523
Cdd:cd16633    1 LVPNQEPFECPICFDDVPPGEGVVLRECLHSFCRECLRGAIQNSEEAEVKCPFRDD 56

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
                 ....*....|....*....|....*....
gi 617385749 642 CPQCGIIVQKRDGCDWLRCTVCHTEICWV 670
Cdd:cd22585    5 CPKCKSLIEKIDGCNHVTCTRCGTHICWV 33

Rcat 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 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 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 RNF14 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                         10        20
                 ....*....|....*....|....*....
gi 617385749 642 CPQCGIIVQKRDGCDWLRCTVCHTEICWV 670
Cdd:cd20354   16 CPGCGTLIEKIDGCNKMTCTKCRTYFCWL 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 617385749 639 AMHCPQCGIIVQKRDGCDWLRCTVCHTEICW 669
Cdd:cd20350    5 AQKCPKCKVYIQRSEGCDHMTCSQCNTNFCY 35

Rcat domain found in E3 ubiquitin-protein ligase ARI7 and similar proteins; This subfamily contains probable RBR-type E3 ubiquitin-protein ligases (EC 2.3.2.31) including Arabidopsis thaliana ARI5, ARI6, ARI7, and ARI8, as well as Dictyostelium discoideum RbrA (also called Ariadne-like ubiquitin ligase). They may function as part of E3 complexes, which accept ubiquitin from E2 ubiquitin-conjugating enzymes and then transfer it to substrates. RbrA may be required for normal cell-type proportioning and cell sorting during multicellular development, and is also necessary for spore cell viability. Members of this subfamily 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 of ARI7-like proteins that are essential for RBR E3 ligase activity and adopt the same fold as the BRcat domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 617385749 641 HCPQCGIIVQKRDGCDWLRCTV-CHTEICWVTRGPrWGPKGpGDTSGGCRCNV 692
Cdd:cd22583    4 PCPKCKRPIEKNQGCMHMTCSPpCKHEFCWLCLGP-WSEHG-ERTGGFYACNR 54

Zn-finger in Ran binding protein and others;

                          10        20
                  ....*....|....*....|....*
gi 617385749  392 WSCPSCTYINKPTRPGCEICSTNRP 416
Cdd:pfam00641   5 WDCSKCLVQNFATSTKCVACQAPKP 29

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
                 ....*....|....*....|....*....|
gi 617385749 477 CKICFVDLQSGEGVLLRECLHCFCKECLRS 506
Cdd:cd16628    8 CNICFLDKLGSECMYFKDCGHVYCKECLKE 37

Rcat domain found in human homolog of Drosophila Ariadne (HHARI) and similar proteins; This subfamily includes Drosophila melanogaster protein ariadne-1 (ARI-1), and its eukaryotic homologs, such as HHARI. ARI-1 is a widely expressed Drosophila RING-finger protein that localizes mainly in the cytoplasm, and is required for neural development. It interacts with the ubiquitin-conjugating enzyme, UbcD10. HHARI is also called H7-AP2, monocyte protein 6 (MOP-6), protein ariadne-1 homolog, Ariadne RBR E3 ubiquitin protein ligase 1 (ARIH1), ariadne-1 (ARI-1), UbcH7-binding protein, UbcM4-interacting protein, or ubiquitin-conjugating enzyme E2-binding protein. It is an RBR-type E3 ubiquitin-protein ligase highly expressed in nuclei, where it is co-localized with nuclear bodies including Cajal, PML, and Lewy bodies. It interacts with the E2 conjugating enzymes UbcH7, UbcH8, UbcM4 and UbcD10 in human, mouse and fly, and modulates the ubiquitylation of substrate proteins including single-minded 2 (SIM2) and translation initiation factor 4E homologous protein (4EHP). It functions as a potent mediator of DNA damage-induced translation arrest, which protects stem and cancer cells against genotoxic stress by initiating a 4EHP-mediated mRNA translation arrest. HHARI contains an RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been 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 HHARI and similar proteins that are essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

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gi 617385749 642 CPQCGIIVQKRDGCDWLRC--TVCHTEICWVTRGPrWGPKG 680
Cdd:cd20356    9 CPKCHVTIEKNGGCNHMVCrnQNCKYEFCWVCLGP-WEPHG 48