RWD domain of RING finger protein 25 (RNF25) and related proteins; RNF25 (EC 2.3.2.27), also known as AO7, is a putative E3 ubiquitin-protein ligase that was initially identified as an interacting protein of the E2 ubiquitin-conjugating enzyme, Ubc5B. It is ubiquitously expressed in various tissues and is predominantly localized in the nucleus. RNF25 activates nuclear factor (NF)-kappaB-dependent gene expression upon stimulation with interleukin-1 beta (IL-1beta), or tumor necrosis factor (TNF), or overexpression of NF-kappaB-inducing kinase. It interacts with the p65 transactivation domain (TAD) and modulates its transcriptional activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45550424   4 LQDEVESLEAILMDDVCIKRTPsGEVEQIETTVLPLTGEEEEQQYVCVTLQVHPTPGYPEESPTFKLLRPRGLDDARLEA 83
Cdd:cd23818   1 LEEELEALEAIYPDELKVVSED-GAPTELSITLHPATADDESEQYVRLTLVITLPPGYPEEPPKISLRNPRGLSDARLAR 79

                        90       100       110
                ....*....|....*....|....*....|
gi 45550424  84 IRSACNAKIKESIGFPVVFDLIEVVREHLS 113
Cdd:cd23818  80 LLSLLKELAEERAGEPMLFELIELAKEFLT 109

RWD domain of RING finger protein 25 (RNF25) and related proteins; RNF25 (EC 2.3.2.27), also known as AO7, is a putative E3 ubiquitin-protein ligase that was initially identified as an interacting protein of the E2 ubiquitin-conjugating enzyme, Ubc5B. It is ubiquitously expressed in various tissues and is predominantly localized in the nucleus. RNF25 activates nuclear factor (NF)-kappaB-dependent gene expression upon stimulation with interleukin-1 beta (IL-1beta), or tumor necrosis factor (TNF), or overexpression of NF-kappaB-inducing kinase. It interacts with the p65 transactivation domain (TAD) and modulates its transcriptional activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45550424   4 LQDEVESLEAILMDDVCIKRTPsGEVEQIETTVLPLTGEEEEQQYVCVTLQVHPTPGYPEESPTFKLLRPRGLDDARLEA 83
Cdd:cd23818   1 LEEELEALEAIYPDELKVVSED-GAPTELSITLHPATADDESEQYVRLTLVITLPPGYPEEPPKISLRNPRGLSDARLAR 79

                        90       100       110
                ....*....|....*....|....*....|
gi 45550424  84 IRSACNAKIKESIGFPVVFDLIEVVREHLS 113
Cdd:cd23818  80 LLSLLKELAEERAGEPMLFELIELAKEFLT 109

domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily related to the UBCc domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45550424      7 EVESLEAILMDDV-CIKRTPSGEVEQIettVLPLTGEEEEQQYVCVTLQVHPTPGYPEESPTFKLLRPRGLDDARLEAIR 85
Cdd:smart00591   1 ELEALESIYPEDFeVIDEDARIPEITI---KLSPSSDEGEDQYVSLTLQVKLPENYPDEAPPISLLNSEGLSDEQLAELL 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 45550424     86 SACNAKIKESIGFPVVFDLIEVVREHLSGS 115
Cdd:smart00591  78 KKLEEIAEENLGEVMIFELVEKLQEFLSEF 107

Ring finger domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 45550424   121 QCVVCLYGFADGDEFTRTECFHYLHSYCLARHlnaLRRNYQeefdklpawlqktadpfqalCPVCR 186
Cdd:pfam13639   2 ECPICLEEFEEGDKVVVLPCGHHFHRECLDKW---LRSSNT--------------------CPLCR 44

RWD domain of RING finger protein 25 (RNF25) and related proteins; RNF25 (EC 2.3.2.27), also known as AO7, is a putative E3 ubiquitin-protein ligase that was initially identified as an interacting protein of the E2 ubiquitin-conjugating enzyme, Ubc5B. It is ubiquitously expressed in various tissues and is predominantly localized in the nucleus. RNF25 activates nuclear factor (NF)-kappaB-dependent gene expression upon stimulation with interleukin-1 beta (IL-1beta), or tumor necrosis factor (TNF), or overexpression of NF-kappaB-inducing kinase. It interacts with the p65 transactivation domain (TAD) and modulates its transcriptional activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45550424   4 LQDEVESLEAILMDDVCIKRTPsGEVEQIETTVLPLTGEEEEQQYVCVTLQVHPTPGYPEESPTFKLLRPRGLDDARLEA 83
Cdd:cd23818   1 LEEELEALEAIYPDELKVVSED-GAPTELSITLHPATADDESEQYVRLTLVITLPPGYPEEPPKISLRNPRGLSDARLAR 79

                        90       100       110
                ....*....|....*....|....*....|
gi 45550424  84 IRSACNAKIKESIGFPVVFDLIEVVREHLS 113
Cdd:cd23818  80 LLSLLKELAEERAGEPMLFELIELAKEFLT 109

domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily related to the UBCc domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45550424      7 EVESLEAILMDDV-CIKRTPSGEVEQIettVLPLTGEEEEQQYVCVTLQVHPTPGYPEESPTFKLLRPRGLDDARLEAIR 85
Cdd:smart00591   1 ELEALESIYPEDFeVIDEDARIPEITI---KLSPSSDEGEDQYVSLTLQVKLPENYPDEAPPISLLNSEGLSDEQLAELL 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 45550424     86 SACNAKIKESIGFPVVFDLIEVVREHLSGS 115
Cdd:smart00591  78 KKLEEIAEENLGEVMIFELVEKLQEFLSEF 107

RWD domain of eIF-2-alpha kinase GCN2 and related proteins; GCN2 (EC 2.7.11.1), also called eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4), acts as a metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability. It also plays a role in modulating the adaptive immune response to yellow fever virus infection and promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45550424   5 QDEVESLEAILMDDV-CIKRTPSGEVE-QIETTVLPLTGEEEEQqYVCVTLQVHPTPGYPEESPTFKLLRPRGLDDARLE 82
Cdd:cd23823   5 EEELEALQSIYGDDFeDLSSKKAVWSPpEFRIRLRPQEGESEEN-HVSVDLHVKFPPTYPDVPPEIELENVKGLSDEQLE 83

                        90       100       110
                ....*....|....*....|....*....|.
gi 45550424  83 AIRSACNAKIKESIGFPVVFDLIEVVREHLS 113
Cdd:cd23823  84 ELLKELEELAKELLGEEMIFELAEAVQEFLE 114

RWD, DRWD, and ELF domain family; The family includes the RWD, double-RWD (DRWD), and ELF domains. They belong to the ubiquitin-conjugating (UBC) superfamily that represents a structural domain with an alpha-beta(4)-alpha(3) core fold. The RWD domain (named after three major RWD-containing proteins: RING finger, WD-repeat-containing proteins and DEXD-like helicases) mediates protein-protein interactions in a variety of pathways in eukaryotes. The DRWD domain is responsible for substrate binding. It is involved in interactions with other kinetochore proteins. The ELF (N-terminal E2-like fold) domain is found in all Fanconi anemia group L protein (FANCL) homologs. It is required to promote efficient DNA damage-induced FANCD2 (Fanconi anemia group D2 protein) monoubiquitination in vertebrate cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45550424  10 SLEAILMDDVCIKRTPSGEVEQIETTvlpltgEEEEQQYVCVTLQVHPTPGY-PEESPTFKLLRPRGLDDARLEAIRSAC 88
Cdd:cd11605   1 ALESIYGDELEVLSDDSPLRFSIRLS------PEEEEDDPPLELEFTLPPGYpPEEPPLITLRSPKLSSAERLSLLKLEL 74

                        90       100
                ....*....|....*....|
gi 45550424  89 NAKIKESIGFPVVFDLIEVV 108
Cdd:cd11605  75 EEAAEENLGEPMLFDLVEAL 94

RWD domain of RWD domain-containing protein 1 (RWDD1) and related proteins; RWDD1, also called DRG family-regulatory protein 2 (DFRP2), or PTD013, interacts with DRG2 and protects DRG2 from proteolytic degradation. It is an androgen receptor-interacting protein that functions as a coactivator of androgen-dependent transcription.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45550424   5 QDEVESLEAILMDDVCIKRTPSGEVEQIETTVlplTGEEEEQQYVCVTLQVHPTPGYPEESPTFKLLRPRGLDDARLEAI 84
Cdd:cd23816   6 RNELEALESIYPDEFTVLSEEPPISFTITVTS---EEEENEDETVSVTLKFTYTEKYPDEAPLIEIISHENLEDEDIEDL 82

                        90       100
                ....*....|....*....|....*...
gi 45550424  85 RSACNAKIKESIGFPVVFDLIEVVREHL 112
Cdd:cd23816  83 LELLEQQAEENLGMVMVFTIVSAVQEKL 110

H2 subclass of RING (RING-H2) fingers 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 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). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger 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 serves as a scaffold 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 45550424 122 CVVCLYGFADGDEFTRTECFHYLHSYCLARhlnalrrnyqeefdklpaWLQKTadpfQALCPVCR 186
Cdd:cd16448   1 CVICLEEFEEGDVVRLLPCGHVFHLACILR------------------WLESG----NNTCPLCR 43

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 45550424 117 LPSGQCVVCLYGFADGDEFTRTECFHYLHSYCLArhlnalrrnyqeefdklpAWLQKTadpfQALCPVCRE 187
Cdd:cd16473   2 LECEECAICLENYQNGDLLRGLPCGHVFHQNCID------------------VWLERD----NHCCPVCRW 50

RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and similar proteins; This family includes two highly similar E3 ubiquitin-protein ligases, Praja-1 and Praja-2. Praja-1, also known as RING finger protein 70, is a RING-H2 finger ubiquitin ligase encoded by gene PJA1, a novel human X chromosome gene abundantly expressed in the brain. It has been implicated in bone and liver development, as well as memory formation and X-linked mental retardation (MRX). Praja-1 interacts with and activates the ubiquitin-conjugating enzyme UbcH5B, and shows E2-dependent E3 ubiquitin ligase activity. It is a 3-deazaneplanocin A (DZNep)-induced ubiquitin ligase that directly ubiquitinates individual polycomb repressive complex 2 (PRC2) subunits in a cell free system, which leads to their proteasomal degradation. It also plays an important role in neuronal plasticity, which is the basis for learning and memory. Moreover, Praja-1 ubiquitinates embryonic liver fodrin (ELF) and Smad3, but not Smad4, in a transforming growth factor-beta (TGF-beta)-dependent manner. It controls ELF abundance through ubiquitin-mediated degradation, and further regulates TGF-beta signaling, which plays a key role in the suppression of gastric carcinoma. Praja-1 also regulates the transcription function of the homeodomain protein Dlx5 by controlling the stability of Dlxin-1, via a ubiquitin-dependent degradation pathway. Praja-2, also known as RING finger protein 131, NEURODAP1, or KIAA0438, is an E2-dependent E3 ubiquitin ligase that interacts with and activates the ubiquitin-conjugating enzyme UbcH5B. It functions as an A-kinase anchoring protein (AKAP)-like E3 ubiquitin ligase that plays a critical role in controlling cyclic AMP (cAMP)-dependent PKA activity and pro-survival signaling, and further promotes cell proliferation and growth. Praja-2 is also involved in protein sorting at the postsynaptic density region of axosomatic synapses and possibly plays a role in synaptic communication and plasticity. Together with the AMPK-related kinase SIK2 and the CDK5 activator CDK5R1/p35, it forms a SIK2-p35-PJA2 complex that plays an essential role for glucose homeostasis in pancreatic beta cell functional compensation. Praja-2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumor-suppressor Hippo signaling. Both Praja-1 and Praja-2 contain a potential nuclear localization signal (NLS) and a C-terminal C3H2C3-type RING-H2 motif.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 45550424 121 QCVVCLYGFADGDEFTRTECFHYLHSYCLArhlnalrrnyqeefdklpAWLQKTADpfqalCPVCREHI 189
Cdd:cd16465   1 CCPICCSEYVKDEIATELPCHHLFHKPCIT------------------AWLQKSGT-----CPVCRHVL 46

RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; This subfamily includes RING finger proteins RNF38, RNF44, and similar proteins. RNF38 is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 is an uncharacterized RING finger protein that shows high sequence similarity to RNF38. Both RNF38 and RNF44 contain a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C3-type RING-H2 finger. In addition, RNF38 harbors two potential nuclear localization signals.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 45550424 119 SGQCVVCLYGFADGDEFTRTECFHYLHSYCLARhlnalrrnyqeefdklpaWLQKTADpfqalCPVCR 186
Cdd:cd16472   2 QTQCVVCMCDYEKRQLLRVLPCSHEFHAKCIDK------------------WLKTNRT-----CPICR 46

RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; The family includes RING finger proteins RNF111, RNF165, and similar proteins. RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It also interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. The N-terminal half of RNF111 harbors three SUMO-interacting motifs (SIMs). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. Both RNF165 and RNF111 contain a C-terminal C3H2C3-type RING-H2 finger.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 45550424 122 CVVCLYGFADGDEFTRTECFHYLHSYCLARhlnalrrnyqeefdklpaWLQKtadpfQALCPVCREH 188
Cdd:cd16474   3 CTICLSDFEEGEDVRRLPCMHLFHQECVDQ------------------WLST-----NKRCPICRVD 46

RWD domain of RWD domain-containing protein 4 (RWDD4) and related proteins; RWDD4, also called protein FAM28A, is a target of the tumor suppressor MicroRNA (MiR)-506 in bladder cancer cells. Downregulation of RWDD4 suppresses bladder cancer cell proliferation, migration and invasion. RWDD4 has also been identified as a modifier of metastasis in human prostate cancer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45550424   5 QDEVESLEAILMDDVCIKrtpsgeveQI-ETTVLPLTGEEEEQQyvCVTLQVHPTPGYPEESPTFKL-------LrprgL 76
Cdd:cd23817   1 EEELEVLLSIYEGDENFK--------QIsDTTFQYKYGEDGDPK--SFLLEISWPENYPEEPPIINLdafynkhI----S 66

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 45550424  77 DDARlEAIRSACNAKIKESIGFPVVFDLIEVVREHL 112
Cdd:cd23817  67 SSVK-EKIVSKLNEEAEQNLGSAMTYTLFEWAKENA 101