RWD domain of RING finger protein 14 (RNF14) and related proteins; RNF14, also called androgen receptor (AR)-associated protein 54 (ARA54), HFB30, or Triad2 protein, is an RBR-type E3 ubiquitin-protein ligase (EC 2.3.2.31) that is highly expressed in the testis and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3). Its differential localization may play an important role in testicular development and spermatogenesis in humans. RNF14 functions as a transcriptional regulator of mitochondrial and immune function in muscles. It is a ligand-dependent AR co-activator that enhances AR-dependent transcriptional activation. It also may participate in enhancing cell cycle progression and cell proliferation via induction of cyclin D1. Moreover, RNF14 is crucial for colon cancer cell survival. It acts as a new enhancer of Wnt-dependent transcriptional outputs that act at the level of the T-cell factor/lymphoid enhancer factor (TCF/LEF)-beta-catenin complex.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57226170  18 QEDELTVLESIYPGQIKIHPNpnnRPGRILTLTLPVKLSSPTKVSIStaSNNGESSIPSLTLSHLPALSLCVALPETYPL 97
Cdd:cd23820   1 QEDELEALEAIYPDDLVVDSD---SSSGRGSLEIPVELEPPLSVVLS--SDGSDEGERTLKVSHLPPITLRFSLPPGYPS 75

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 57226170  98 LVPPApISLRAplfkghddklgSWLFQNDLREIESRLRRMWDDdkeawDQGQGVLWRWWDWVVNGDF 164
Cdd:cd23820  76 TSPPE-FTLEC-----------SWLSPEQLSALCERLDELWEE-----NGGDVVLFSWIDFLQDEAL 125

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 57226170 206 EQTAFPCSICWENRKGGRCVEMPgCGCVFCTECLGECWTLAISEGTLEAVACPSVACVKQR 266
Cdd:cd23134   1 LRSSYHCGICFEEKKGSDFIKLP-CGHVFCRECLQDYYTIHIQEGEVSSVKCPDPNCGKEI 60

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57226170    294 ERWEVFKDRRIVEIDPSFCICPQPKCQAAVppptpsgtcgnssapkairladltkpssgSLHVPADVPRgsgqsvplted 373
Cdd:smart00647   1 EKYERLLLESYVESNPDLKWCPAPDCSAAI-----------------------------IVTEEEGCNR----------- 40

                           90       100
                   ....*....|....*....|....*.
gi 57226170    374 rwaayRLCPKCNFSFCLYCSSTWHGP 399
Cdd:smart00647  41 -----VTCPKCGFSFCFRCKVPWHSP 61

RWD domain of RING finger protein 14 (RNF14) and related proteins; RNF14, also called androgen receptor (AR)-associated protein 54 (ARA54), HFB30, or Triad2 protein, is an RBR-type E3 ubiquitin-protein ligase (EC 2.3.2.31) that is highly expressed in the testis and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3). Its differential localization may play an important role in testicular development and spermatogenesis in humans. RNF14 functions as a transcriptional regulator of mitochondrial and immune function in muscles. It is a ligand-dependent AR co-activator that enhances AR-dependent transcriptional activation. It also may participate in enhancing cell cycle progression and cell proliferation via induction of cyclin D1. Moreover, RNF14 is crucial for colon cancer cell survival. It acts as a new enhancer of Wnt-dependent transcriptional outputs that act at the level of the T-cell factor/lymphoid enhancer factor (TCF/LEF)-beta-catenin complex.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57226170  18 QEDELTVLESIYPGQIKIHPNpnnRPGRILTLTLPVKLSSPTKVSIStaSNNGESSIPSLTLSHLPALSLCVALPETYPL 97
Cdd:cd23820   1 QEDELEALEAIYPDDLVVDSD---SSSGRGSLEIPVELEPPLSVVLS--SDGSDEGERTLKVSHLPPITLRFSLPPGYPS 75

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 57226170  98 LVPPApISLRAplfkghddklgSWLFQNDLREIESRLRRMWDDdkeawDQGQGVLWRWWDWVVNGDF 164
Cdd:cd23820  76 TSPPE-FTLEC-----------SWLSPEQLSALCERLDELWEE-----NGGDVVLFSWIDFLQDEAL 125

RWD domain; This domain was identified in WD40 repeat proteins and Ring finger domain proteins. The function of this domain is unknown. GCN2 is the alpha-subunit of the only translation initiation factor (eIF2 alpha) kinase that appears in all eukaryotes. Its function requires an interaction with GCN1 via the domain at its N-terminus, which is termed the RWD domain after three major RWD-containing proteins: RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases. The structure forms an alpha + beta sandwich fold consisting of two layers: a four-stranded antiparallel beta-sheet, and three side-by-side alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57226170    17 MQEDELTVLESIYPGQIKIhpnPNNRPGRILTLTLPVKLSSPTKVSistasnngessipsltlSHLPALSLCVALPETYP 96
Cdd:pfam05773   2 EQEEELEALESIYPDEFEV---ISDSPYESLEIEIKLSLDSDESDS-----------------SHLPPLVLKFTLPEDYP 61

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 57226170    97 lLVPPaPISLRAPLFkghddklgswLFQNDLREIESRLRRMWDDDKeawdqGQGVLWRWWDWV 159
Cdd:pfam05773  62 -DEPP-KISLSSPWN----------LSDEQVLSLLEELEELAEENL-----GEVMIFELIEWL 107

BRcat domain found in RING finger protein 14 (RNF14); RNF14, also called androgen receptor (AR)-associated protein 54 (ARA54), HFB30, or Triad2 protein, is an RBR-type E3 ubiquitin-protein ligase that is highly expressed in the testis and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3). Its differential localization may play an important role in testicular development and spermatogenesis in humans. RNF14 functions as a transcriptional regulator of mitochondrial and immune function in muscles. It is a ligand-dependent AR co-activator that enhances AR-dependent transcriptional activation. It may also participate in enhancing cell cycle progression and cell proliferation via induction of cyclin D1. Moreover, RNF14 is crucial for colon cancer cell survival. It acts as a new enhancer of the Wnt-dependent transcriptional outputs that acts at the level of the T-cell factor/lymphoid enhancer factor (TCF/LEF)-beta-catenin complex. RNF14 contains an N-terminal RWD domain, and a C-terminal RBR domain. The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of RNF14 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 57226170 361 PRGSGQSvPLTEDRWAAYRLCPKCNFSFCLYCSSTWHGPHTvCSLP 406
Cdd:cd20341  11 PRPSCQT-PVILEPDENLGICPSCNYAFCTLCRETYHGVSP-CKIK 54

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 57226170    438 ERMVSKWREDEMNTQWlhsrtkaCPS--CS--VRVEKSVGCNHMQCGRCSAHFCYLCGQ 492
Cdd:smart00647   5 RLLLESYVESNPDLKW-------CPApdCSaaIIVTEEEGCNRVTCPKCGFSFCFRCKV 56

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57226170   294 ERWEVFKDRRIVEIDPSFCICPQPKCQAAVPPPTPSGTCGNSSapkairladltkpssgslhvpadvprgsgqsvplted 373
Cdd:pfam01485   1 EKYEKLLLKSYVESDPNLKWCPTPDCGYIIELTDGCSNTSHVT------------------------------------- 43

                          90       100
                  ....*....|....*....|....*...
gi 57226170   374 rwaayrlCPKCNFSFCLYCSSTWHGPHT 401
Cdd:pfam01485  44 -------CSKCGHEFCFNCKEEWHEGLT 64

RWD domain of RING finger protein 14 (RNF14) and related proteins; RNF14, also called androgen receptor (AR)-associated protein 54 (ARA54), HFB30, or Triad2 protein, is an RBR-type E3 ubiquitin-protein ligase (EC 2.3.2.31) that is highly expressed in the testis and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3). Its differential localization may play an important role in testicular development and spermatogenesis in humans. RNF14 functions as a transcriptional regulator of mitochondrial and immune function in muscles. It is a ligand-dependent AR co-activator that enhances AR-dependent transcriptional activation. It also may participate in enhancing cell cycle progression and cell proliferation via induction of cyclin D1. Moreover, RNF14 is crucial for colon cancer cell survival. It acts as a new enhancer of Wnt-dependent transcriptional outputs that act at the level of the T-cell factor/lymphoid enhancer factor (TCF/LEF)-beta-catenin complex.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57226170  18 QEDELTVLESIYPGQIKIHPNpnnRPGRILTLTLPVKLSSPTKVSIStaSNNGESSIPSLTLSHLPALSLCVALPETYPL 97
Cdd:cd23820   1 QEDELEALEAIYPDDLVVDSD---SSSGRGSLEIPVELEPPLSVVLS--SDGSDEGERTLKVSHLPPITLRFSLPPGYPS 75

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 57226170  98 LVPPApISLRAplfkghddklgSWLFQNDLREIESRLRRMWDDdkeawDQGQGVLWRWWDWVVNGDF 164
Cdd:cd23820  76 TSPPE-FTLEC-----------SWLSPEQLSALCERLDELWEE-----NGGDVVLFSWIDFLQDEAL 125

Rcat (required-for-catalysis) 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 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 Rcat domain contains 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. This model corresponds to the Rcat domain that adopts the same fold as the BRcat domain.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 57226170 458 TKACPSCSVRVEKSVGCNHMQCGRCSAHFCYLCGQSI 494
Cdd:cd20336   2 TKKCPKCKVPIEKNGGCNHMTCSRCGTEFCWLCGKPW 38

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
                ....*....|....*....|....*....|....*
gi 57226170 456 SRTKACPSCSVRVEKSVGCNHMQCGRCSAHFCYLC 490
Cdd:cd20360   1 AHTKDCPKCHVCIEKNGGCNHMQCSKCKHEFCWMC 35

Rcat domain found in ankyrin repeat and IBR domain-containing protein 1 (ANKIB1) and similar proteins; ANKIB1 is an RBR-type E3 ubiquitin-protein ligase that may function as part of an E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. It contains N-terminal ankyrin repeats, and an RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of ANKIB1 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 57226170 450 NTQWLHSRTKACPSCSVRVEKSVGCNHMQCGRCSAHFCYLC 490
Cdd:cd20361   1 NCLWLVTNSKPCPNCKSPIQKNEGCNHMKCSKCKYDFCWVC 41

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 57226170 461 CPSCSVRVEKSVGCNHMQCGRCSAHFCYLCGQ 492
Cdd:cd20350   8 CPKCKVYIQRSEGCDHMTCSQCNTNFCYRCGE 39

Rcat domain of ATP-dependent RNA helicase DEAH12 and similar proteins; This group includes Arabidopsis thaliana ATP-dependent RNA helicases DEAH11 and DEAH12, which may be bifunctional proteins that function as DEAD-box RNA helicases (EC 3.6.4.13) and RBR-type E3 ubiquitin-protein ligases (EC 2.3.2.31). As RNA helicases, they may utilize the energy from ATP hydrolysis to unwind RNA (or DNA). DEAD-box RNA helicases participate in every aspect of RNA metabolism. As E3 ubiquitin-protein ligase, they may function as part of E3 complexes, which accept ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfer it to substrates. Other members of this group may not have an RNA helicase domain. All members contain an RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                        10        20        30
                ....*....|....*....|....*....|..
gi 57226170 459 KACPSCSVRVEKSVGCNHMQCGRCSAHFCYLC 490
Cdd:cd22585   3 KRCPKCKSLIEKIDGCNHVTCTRCGTHICWVC 34

Rcat domain found in cullin-9 (CUL-9) and similar proteins; CUL-9, also called UbcH7-associated protein 1 (H7-AP1), p53-associated parkin-like cytoplasmic protein, or PARC, is a cytoplasmic RBR-type E3 ubiquitin-protein ligase that function as a tumor suppressor and promotes p53-dependent apoptosis. It mediates the ubiquitination and degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells. It is also a critical downstream effector of the 3M complex in the maintenance of microtubules and genome integrity. Moreover, CUL-9, together with CUL-7, forms homodimers and heterodimers, as well as some atypical cullin RING ligase complexes, which may exhibit ubiquitin ligase activity. CUL-9 contains a CPH domain (conserved in Cul7, PARC, and HERC2 proteins), a DOC (DOC1/APC10) domain, cullin homology domains linked with E3 ligase function, and a C-terminal RBR domain previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of CUL-9 that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 57226170 458 TKACPSCSVRVEKSVGCNHMQCGRCSAHFCYLCGQSIKPT 497
Cdd:cd20359   7 SKRCPSCQAQIEKNEGCLHMTCAKCNHGFCWRCLKPWKPT 46

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57226170  19 EDELTVLESIYPGQIKIHPNPNnrpgRILTLTLPVKLSsptkvsistasnngessipsltlsHLPALSLCVALPETYPLL 98
Cdd:cd23821   1 AEEIEALEAIYGEDFVVIDESA----RSFVIRIELDGP------------------------HLPPLVLRVHLPPDYPSH 52

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 57226170  99 VPPaPISLRAPlfkghddklgsWLFQNDLREIESRLRRMWDDDKeawdqGQGVLWRWWDWV 159
Cdd:cd23821  53 SPP-IFELSAP-----------WLSGEERSELCAELDEIWEENA-----GEPVLFQWVEWL 96

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
                ....*....|....*....|....*....|....
gi 57226170 458 TKACPSCSVRVEKSVGCNHMQC-GRCSAHFCYLC 490
Cdd:cd22583   2 TKPCPKCKRPIEKNQGCMHMTCsPPCKHEFCWLC 35

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 57226170 459 KACPSCSVRVEKSVGCNHMQCGRCSAHFCYLCGQSIKPTDPYKHFNTpgQPCYGKL 514
Cdd:cd20352   6 KRCPMCHVPIERDEGCAQMMCKNCKHVFCWYCLASLDDDFLLRHYDK--GPCKNKL 59

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 57226170 212 CSICWENRKGGRCVEMPGCGCVFCTECLGECWTLAISEGTLEAVACPSVAC 262
Cdd:cd16632   3 CKLCLEEVPLREMYTLQSCGCIFCLQCLKQYVEVLIREGNVSSITCPDAAC 53

Rcat domain found in RING finger protein 144B (RNF144B); RNF144B, also called PIR2, IBR domain-containing protein 2 (IBRDC2), or p53-inducible RING finger protein (p53RFP), is a transmembrane (TM) domain-containing RBR 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 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 RNF144B that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 57226170 459 KACPSCSVRVEKSVGCNHMQCGRCSAHFCYLCGQSIKPTDPYKHFNTpgQPCYGKL 514
Cdd:cd20369   7 KQCPVCRVYIERNEGCAQMMCKNCKHTFCWYCLQNLDNDIFLRHYDK--GPCRNKL 60

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 57226170 212 CSICWENRKGGRCVEMPGCGCVFCTECLGECWTLAISEGTLEAVACPSVACVKQ 265
Cdd:cd16778   3 CKLCLCEHPFDAMTTLQECDCVFCTPCLKQYVQLAIREGCGSPITCPDMACTKT 56

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 57226170 455 HSRTKACPSCSVRVEK--SVGCNHMQCGRCSAHFCYLCGQSI 494
Cdd:cd20355   1 ADDIKPCPRCGALIIKmdDGSCNHMTCAVCGAEFCWLCMKEI 42

Rcat domain found in RING finger protein 144A (RNF144A); RNF144A, also called UbcM4-interacting protein 4 (UIP4), or ubiquitin-conjugating enzyme 7-interacting protein 4, is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that 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. RNF144A 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 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 RNF144A that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 57226170 459 KACPSCSVRVEKSVGCNHMQCGRCSAHFCYLCGQSIKPTDPYKHFNTpgQPCYGKL 514
Cdd:cd20368   7 KRCPKCKVYIERDEGCAQMMCKNCKHAFCWYCLESLDDDFLLIHYDK--GPCRNKL 60

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57226170    294 ERWEVFKDRRIVEIDPSFCICPQPKCQAAVppptpsgtcgnssapkairladltkpssgSLHVPADVPRgsgqsvplted 373
Cdd:smart00647   1 EKYERLLLESYVESNPDLKWCPAPDCSAAI-----------------------------IVTEEEGCNR----------- 40

                           90       100
                   ....*....|....*....|....*.
gi 57226170    374 rwaayRLCPKCNFSFCLYCSSTWHGP 399
Cdd:smart00647  41 -----VTCPKCGFSFCFRCKVPWHSP 61

RWD domain of Saccharomyces cerevisiae genetically interacts with ribosomal genes protein 2 (GIR2) and related proteins; GIR2, also called DRG family-regulatory protein 2, acts as a negative regulator of GCN2 kinase activity by interacting with GCN1 and disrupting the GCN1-GCN2 interaction in amino acid-starved cells. It also interacts with RBG1. The RBG1-GIR2 complex is responsible for efficient cell growth under conditions of amino acid depletion and binds the activator GCN1. Critical mutations in the RWD domain of GIR2 abolishes its interaction with GCN1. GIR2 may interact with ribosomes through GCN1, which binds directly to ribosomes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 57226170  18 QEDELTVLESIYPGQIkihpnpnnrpgRILTLTLP-VKLssptKVSISTASNNGESSIPSLTLSHLpaLSLCVALPETYP 96
Cdd:cd23824   5 QEQELEVLESIYPDEL-----------TVLNDEYPnIQF----EVDLKLELDPLDDTADSLSKEHT--LVVDFQLPENYP 67

                        90       100
                ....*....|....*....|....
gi 57226170  97 LLVPpaPISLRA---PLFKGHDDK 117
Cdd:cd23824  68 DEAP--IISIEPqevSLKDEDEEE 89

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

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 57226170 461 CPSCSVRVEKSVG-CNHMQCGRCSAHFCYLCGQSIKPTD 498
Cdd:cd20351  19 CPKCKFRYALAKGgCMHFTCTQCRHEFCSGCYNPFKAGN 57

Rcat domain found in RING finger protein 19B (RNF19B); RNF19B, also called IBR domain-containing protein 3, or natural killer (NK) lytic-associated molecule (NKLAM), is a transmembrane (TM) domain-containing RBR-type E3 ubiquitin-protein ligase that 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. Moreover, RNF19B is a novel component of macrophage phagosomes and plays a role in macrophage anti-bacterial activity. It functions as a novel modulator of macrophage inducible nitric oxide synthase (iNOS) expression. RNF19B contains an RBR domain followed by three TMs. The RBR domain was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction. This model corresponds to the Rcat domain of RNF19B that is essential for RBR E3 ligase activity and adopts the same fold as the BRcat domain.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 57226170 459 KACPSCSVRVEK--SVGCNHMQCGRCSAHFCYLCGQSI 494
Cdd:cd20371   5 KPCPRCSAYIIKmnDGSCNHMTCAVCGCEFCWLCMKEI 42