Roquin II domain; The ROQ domain is composed of three subdomains, I, II and III. This entry describes the second domain, ROQ II. Structural analysis reveals similarity of domain II to the helix-turn-helix (HTH) fold. Mutagenesis and biochemical studies show that that the HTH fold in domain II contributes to binding dsRNA at the 5'arm.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 157822509   268 EEFRSYEALRREHDAQIVHIAMEAGLRISPEQWSSLLYGDLAHKSHMQSIIDKLQS 323
Cdd:pfam18386    1 DEFRSYEALRREHDAQIVQIAFEYGLRISPEQWSALLYGDQAHRSHMQSIIDKLQS 56

104 kDa microneme/rhoptry antigen; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822509  523 KVGKVGTNGQNAGPSAESvsenkigSPPKTPVsnAAATSAGPSNFGTELNSLPPKSS--PFLTRVPVYPQHSENIQYFQD 600
Cdd:PTZ00449  550 GETKEGEVGKKPGPAKEH-------KPSKIPT--LSKKPEFPKDPKHPKDPEEPKKPkrPRSAQRPTRPKSPKLPELLDI 620

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822509  601 PRTQIPFEVPQYPQTgyyPPPPTVPAGvtpcvPRFVRSNNVPESSLPPAS--MPYA--------DHYSTFSPRDRMNSSP 670
Cdd:PTZ00449  621 PKSPKRPESPKSPKR---PPPPQRPSS-----PERPEGPKIIKSPKPPKSpkPPFDpkfkekfyDDYLDAAAKSKETKTT 692

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822509  671 YQPPPPQQYGPVPPVPSGMYAPVYDSRRIwrPAMYQRDDiiRSNSLPPMDVMHSSVYQTSLRERYNSLDGYYSVTCQPPN 750
Cdd:PTZ00449  693 VVLDESFESILKETLPETPGTPFTTPRPL--PPKLPRDE--EFPFEPIGDPDAEQPDDIEFFTPPEEERTFFHETPADTP 768

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 157822509  751 DPRTTVPLPREPCGHLKSSCEEQLRRKPDQWTQYHTQKTPVSSTLP 796
Cdd:PTZ00449  769 LPDILAEEFKEEDIHAETGEPDEAMKRPDSPSEHEDKPPGDHPSLP 814

CCCH-type Zn-finger protein [General function prediction only];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157822509  393 QNYSRKGHETPQPQPNSKYKTSMCRDLRQQGGCPRGTNCTFAHSQEELEKYRLRNKKMSATVRTF 457
Cdd:COG5063    95 QNYPWSPRGSNANKPYGLYKTEMLRSSTEIPYCRYPDKNPFAHSKAISSLAQTHPKYKTESLEVF 159

Roquin II domain; The ROQ domain is composed of three subdomains, I, II and III. This entry describes the second domain, ROQ II. Structural analysis reveals similarity of domain II to the helix-turn-helix (HTH) fold. Mutagenesis and biochemical studies show that that the HTH fold in domain II contributes to binding dsRNA at the 5'arm.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 157822509   268 EEFRSYEALRREHDAQIVHIAMEAGLRISPEQWSSLLYGDLAHKSHMQSIIDKLQS 323
Cdd:pfam18386    1 DEFRSYEALRREHDAQIVQIAFEYGLRISPEQWSALLYGDQAHRSHMQSIIDKLQS 56

zinc-RING finger domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 157822509    14 CPICYNEFDENvHKPISLGCSHTVCKTCLNKLHRKA-CPFDQT 55
Cdd:pfam14634    2 CNKCFKELSKT-RPFYLTSCGHIFCEECLTRLLQERqCPICKK 43

104 kDa microneme/rhoptry antigen; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822509  523 KVGKVGTNGQNAGPSAESvsenkigSPPKTPVsnAAATSAGPSNFGTELNSLPPKSS--PFLTRVPVYPQHSENIQYFQD 600
Cdd:PTZ00449  550 GETKEGEVGKKPGPAKEH-------KPSKIPT--LSKKPEFPKDPKHPKDPEEPKKPkrPRSAQRPTRPKSPKLPELLDI 620

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822509  601 PRTQIPFEVPQYPQTgyyPPPPTVPAGvtpcvPRFVRSNNVPESSLPPAS--MPYA--------DHYSTFSPRDRMNSSP 670
Cdd:PTZ00449  621 PKSPKRPESPKSPKR---PPPPQRPSS-----PERPEGPKIIKSPKPPKSpkPPFDpkfkekfyDDYLDAAAKSKETKTT 692

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822509  671 YQPPPPQQYGPVPPVPSGMYAPVYDSRRIwrPAMYQRDDiiRSNSLPPMDVMHSSVYQTSLRERYNSLDGYYSVTCQPPN 750
Cdd:PTZ00449  693 VVLDESFESILKETLPETPGTPFTTPRPL--PPKLPRDE--EFPFEPIGDPDAEQPDDIEFFTPPEEERTFFHETPADTP 768

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 157822509  751 DPRTTVPLPREPCGHLKSSCEEQLRRKPDQWTQYHTQKTPVSSTLP 796
Cdd:PTZ00449  769 LPDILAEEFKEEDIHAETGEPDEAMKRPDSPSEHEDKPPGDHPSLP 814

CCCH-type Zn-finger protein [General function prediction only];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157822509  393 QNYSRKGHETPQPQPNSKYKTSMCRDLRQQGGCPRGTNCTFAHSQEELEKYRLRNKKMSATVRTF 457
Cdd:COG5063    95 QNYPWSPRGSNANKPYGLYKTEMLRSSTEIPYCRYPDKNPFAHSKAISSLAQTHPKYKTESLEVF 159

Roquin II domain; The ROQ domain is composed of three subdomains, I, II and III. This entry describes the second domain, ROQ II. Structural analysis reveals similarity of domain II to the helix-turn-helix (HTH) fold. Mutagenesis and biochemical studies show that that the HTH fold in domain II contributes to binding dsRNA at the 5'arm.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 157822509   268 EEFRSYEALRREHDAQIVHIAMEAGLRISPEQWSSLLYGDLAHKSHMQSIIDKLQS 323
Cdd:pfam18386    1 DEFRSYEALRREHDAQIVQIAFEYGLRISPEQWSALLYGDQAHRSHMQSIIDKLQS 56

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1, Roquin-2, and similar proteins; The ROQUIN family includes Roquin-1, Roquin-2, and similar proteins, which localize to the cytoplasm and upon stress, are concentrated in stress granules. They may play essential roles in preventing T-cell-mediated autoimmune disease and in microRNA-mediated repression of inducible costimulator (Icos) mRNA. They function as E3 ubiquitin ligases consisting of an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 activity, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger involved in RNA recognition.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 157822509   11 FLSCPICYNEFDENVHKPISLGCSHTVCKTCLNKLHRKACPFDQ 54
Cdd:cd16638     1 FLSCPVCTNEFDGTQRKPISLGCGHTVCKTCLSKLHRKQCPFDQ 44

RING finger, HC subclass, found in tripartite motif-containing protein 32 (TRIM32) and similar proteins; TRIM32, also known as 72 kDa Tat-interacting protein, zinc finger protein HT2A, or BBS11, is an E3 ubiquitin-protein ligase that promotes degradation of several targets, including actin, PIASgamma, Abl interactor 2, dysbindin, X-linked inhibitor of apoptosis (XIAP), p73 transcription factor, thin filaments and Z-bands during fasting. It plays important roles in neuronal differentiation of neural progenitor cells, as well as in controlling cell fate in skeletal muscle progenitor cells. It reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin-PI3K dissociation. It also functions as a pluripotency-reprogramming roadblock that facilitates cellular transition towards differentiation by modulating the levels of Oct4 and cMyc. Moreover, TRIM32 is an intrinsic influenza A virus (IAV) restriction factor which senses and targets the polymerase basic protein 1 (PB1) for ubiquitination and protein degradation. It also plays a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo, binds specifically to the activation domain of HIV-1 Tat, and can also interact with the HIV-2 and EIAV Tat proteins in vivo. Furthermore, TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2 (N-myc downstream-regulated gene). It negatively regulates tumor suppressor p53 to promote tumorigenesis. It also facilitates degradation of MYCN on spindle poles and induces asymmetric cell division in human neuroblastoma cells. In addition, TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress. It also plays a role in regeneration by affecting satellite cell cycle progression via modulation of the SUMO ligase PIASy (PIAS4). Defects in TRIM32 leads to limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and Bardet-Biedl syndrome. TRIM32 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain. The NHL domain mediates the interaction with Argonaute proteins and consequently allows TRIM32 to modulate the activity of certain miRNAs.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 157822509   12 LSCPICYNEFDENVHKPISLGCSHTVCKTCLNKLHRKA------CPF 52
Cdd:cd16587     1 LECPICLESFDEGQLRPKLLHCGHTICEQCLEKLLASLsingvrCPF 47

RING finger, HC subclass, found in RING finger protein 182 (RNF182) and similar proteins; RNF182 is a brain-enriched E3 ubiquitin-protein ligase that stimulates E2-dependent polyubiquitination in vitro. It is upregulated in Alzheimer"s disease (AD) brains and neuronal cells exposed to injurious insults. It interacts with ATP6V0C and promotes its degradation by the ubiquitin-proteosome pathway, suggesting a very specific role in controlling the turnover of an essential component of the neurotransmitter release machinery. RNF182 contains an N-terminal C3HC4-type RING-HC finger, and a C-terminal transmembrane domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 157822509   12 LSCPICYNEFDENVHKPISLGCSHTVCKTCLNKLH--------RKACPF 52
Cdd:cd16555     2 LECKICYNRYDLRQRRPKVLECCHRVCAKCLYKIVdlgdsspsVLVCPF 50

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 157822509   12 LSCPICYNEFDEnvhkPISLGCSHTVCKTCLNKL---HRKACPFD 53
Cdd:cd16449     1 LECPICLERLKD----PVLLPCGHVFCRECIRRLlesGSIKCPIC 41

104 kDa microneme/rhoptry antigen; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822509  523 KVGKVGTNGQNAGPSAESvsenkigSPPKTPVsnAAATSAGPSNFGTELNSLPPKSS--PFLTRVPVYPQHSENIQYFQD 600
Cdd:PTZ00449  550 GETKEGEVGKKPGPAKEH-------KPSKIPT--LSKKPEFPKDPKHPKDPEEPKKPkrPRSAQRPTRPKSPKLPELLDI 620

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822509  601 PRTQIPFEVPQYPQTgyyPPPPTVPAGvtpcvPRFVRSNNVPESSLPPAS--MPYA--------DHYSTFSPRDRMNSSP 670
Cdd:PTZ00449  621 PKSPKRPESPKSPKR---PPPPQRPSS-----PERPEGPKIIKSPKPPKSpkPPFDpkfkekfyDDYLDAAAKSKETKTT 692

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822509  671 YQPPPPQQYGPVPPVPSGMYAPVYDSRRIwrPAMYQRDDiiRSNSLPPMDVMHSSVYQTSLRERYNSLDGYYSVTCQPPN 750
Cdd:PTZ00449  693 VVLDESFESILKETLPETPGTPFTTPRPL--PPKLPRDE--EFPFEPIGDPDAEQPDDIEFFTPPEEERTFFHETPADTP 768

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 157822509  751 DPRTTVPLPREPCGHLKSSCEEQLRRKPDQWTQYHTQKTPVSSTLP 796
Cdd:PTZ00449  769 LPDILAEEFKEEDIHAETGEPDEAMKRPDSPSEHEDKPPGDHPSLP 814

Zinc finger C-x8-C-x5-C-x3-H type (and similar);

                           10        20
                   ....*....|....*....|....*..
gi 157822509   411 YKTSMCRDLRQQGGCPRGTNCTFAHSQ 437
Cdd:pfam00642    1 YKTELCRFFLRTGYCKYGDRCKFAHGQ 27

RING finger, HC subclass, found in RING finger protein RNF183, RNF223, RNF225 and similar proteins; RNF183 is an E3 ubiquitin-protein ligase that is upregulated during intestinal inflammation and is negatively regulated by miR-7. It promotes intestinal inflammation by increasing the ubiquitination and degradation of inhibitor of kappa B, thereby resulting in secondary activation of the Nuclear factor-kappaB (NF-kB) pathway. The interaction between RNF183-mediated ubiquitination and miRNA may be an important novel epigenetic mechanism in the pathogenesis of inflammatory bowel disease (IBD). The biological function of RNF223 and RNF225 remains unclear. Members of this family contain an N-terminal C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 157822509   12 LSCPICYNEFDENVHKPISLGCSHTVCKTCLNKL--------HRKACPF 52
Cdd:cd16556     1 LECSICFSSYDNTFKTPKLLDCGHTFCLECLARLslasppqaERVPCPL 49

RING finger, HC subclass, found in tripartite motif-containing protein 59 (TRIM59) and similar proteins; TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis. It is upregulated in gastric cancer and promotes gastric carcinogenesis by interacting with and targeting the P53 tumor suppressor for its ubiquitination and degradation. It also acts as a novel accessory molecule involved in cytotoxicity of BCG-activated macrophages (BAM). Moreover, TRIM59 may serve as a multifunctional regulator for innate immune signaling pathways. It interacts with ECSIT and negatively regulates nuclear factor-kappaB (NF- kappa B) and interferon regulatory factor (IRF)-3/7-mediated signal pathways. TRIM59 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region. In addition, TRIM59 contains a C-terminal transmembrane domain.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 157822509   10 EFLSCPICYNEFDEnvhkPISLGCSHTVCKTCLNKL 45
Cdd:cd16763     2 EDLTCSVCYSLFED----PRVLPCSHTFCRNCLENI 33

RING finger, HC subclass, found in promyelocytic leukemia protein (PML) and similar proteins; Protein PML, also known as RING finger protein 71 (RNF71) or tripartite motif-containing protein 19 (TRIM19), is predominantly a nuclear protein with a broad intrinsic antiviral activity. It is the eponymous component of PML nuclear bodies (PML NBs) and has been implicated in a wide variety of cell processes, including DNA damage signaling, apoptosis, and transcription. PML interferes with the replication of many unrelated viruses, including human immunodeficiency virus 1 (HIV-1), human foamy virus (HFV), poliovirus, influenza virus, rabies virus, EMCV, adeno-associated virus (AAV), and vesicular stomatitis virus (VSV). It also selectively interacts with misfolded proteins through distinct substrate recognition sites and conjugates these proteins with the small ubiquitin-like modifiers (SUMOs) through its SUMO ligase activity. PML belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 157822509   11 FLSCPICYNEFdenvHKPISLGCSHTVCKTCLNKLHRKA-------CP 51
Cdd:cd16579     4 FLRCPGCKAEY----KCPKLLPCLHTVCSGCLEALAEQAsettefqCP 47

RING finger, HC subclass, found in Arabidopsis thaliana protein KEEP ON GOING (KEG) and similar proteins; KEG, also called RING-type E3 ubiquitin transferase KEG, is a RING E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. It is essential for Arabidopsis growth and development. It acts as a negative regulator of abscisic acid signaling. It is required for ABSCISIC ACID-INSENSITIVE5 (ABI5) degradation, by mediating its ubiquitination. Together with EDR1, KEG may regulate endocytic trafficking and/or the formation of signaling complexes on trans-Golgi network (TGN)/ early endosome (EE) vesicles during stress responses. KEG is a multidomain protein that includes a C3HC4-type RING-HC finger, a kinase domain, ankyrin repeats, and 12 HERC2-like (for HECT and RCC1-like) repeats.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 157822509   14 CPICYNEFDENVHKPISLGCSHTVCKTCLNKLHRKACPFDQT 55
Cdd:cd23140     4 CSVCSEGYNEDERVPLLLQCGHTFCKDCLSQMFIRCTDLTLK 45

RING finger, HC subclass, found in postreplication repair protein RAD18 and similar proteins; RAD18, also known as HR18 or RING finger protein 73 (RNF73), is an E3 ubiquitin-protein ligase involved in post replication repair of UV-damaged DNA via its recruitment to stalled replication forks. It associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on K164. It also interacts with another E2 ubiquitin conjugating enzyme RAD6 to form a complex that monoubiquitinates proliferating cell nuclear antigen at stalled replication forks in DNA translesion synthesis. Moreover, Rad18 is a key factor in double-strand break DNA damage response (DDR) pathways via its association with K63-linked polyubiquitylated chromatin proteins. It can function as a mediator for DNA damage response signals to activate the G2/M checkpoint in order to maintain genome integrity and cell survival after ionizing radiation (IR) exposure. RAD18 contains a C3HC4-type RING-HC finger, a ubiquitin-binding zinc finger domain (UBZ), a SAP (SAF-A/B, Acinus and PIAS) domain, and a RAD6-binding domain (R6BD).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 157822509    9 TEFLSCPICYNEFDenvHKPISLGCSHTVCKTCLNK--LHRKACP 51
Cdd:cd16529     2 DDLLRCPICFEYFN---TAMMITQCSHNYCSLCIRRflSYKTQCP 43

RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar proteins; TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. It plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. This subfamily also includes RING finger protein 135 (RNF135). RNF135, also known as RIG-I E3 ubiquitin ligase (REUL) or Riplet, is a widely expressed E3 ubiquitin-protein ligase that consists of an N-terminal C3HC4-type RING-HC finger and C-terminal B30.2/SPRY and PRY motifs, but lacks the B-box and coiled-coil domains that are also typically present in TRIM proteins. RNF135 serves as a specific retinoic acid-inducible gene-I (RIG-I)-interacting protein that ubiquitinates RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity to produce antiviral type-I interferon (IFN) during the early phase of viral infection. It also has been identified as a bio-marker and therapy target of glioblastoma. It associates with the ERK signal transduction pathway and plays a role in glioblastoma cell proliferation, migration and cell cycle.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 157822509   12 LSCPICYNEFDEnvhkPISLGCSHTVCKTCLNKL------HRKACP 51
Cdd:cd16604     1 LSCPICLDLLKD----PVTLPCGHSFCMGCLGALwgagrgGRASCP 42

zinc finger of C3HC4-type, RING; This is a family of primate-specific Ret finger protein-like (RFPL) zinc-fingers of the C3HC4 type. Ret finger protein-like proteins are primate-specific target genes of Pax6, a key transcription factor for pancreas, eye and neocortex development. This domain is likely to be DNA-binding. This zinc-finger domain together with the RDM domain, pfam11002, forms a large zinc-finger structure of the RING/U-Box superfamily. RING-containing proteins are known to exert an E3 ubiquitin protein ligase activity with the zinc-finger structure being mandatory for binding to the E2 ubiquitin-conjugating enzyme.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 157822509    14 CPICYNEFDenvhKPISLGCSHTVCKTCLNKLHRKA------CP 51
Cdd:pfam15227    1 CPICLDYLE----KPVSIECGHSFCLSCINSLQKEPdgesllCP 40

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 157822509   12 LSCPICYNEFDENVhkpiSLGCSHTVCKTCLN--KLHRKACPFDQTAINTDIDVL 64
Cdd:cd16535     2 LQCSICSELFIEAV----TLNCSHSFCSYCITewMKRKKECPICRKPITSKTRSL 52

second RING finger, HC subclass, found in the LON peptidase N-terminal domain and RING finger protein family; The LON peptidase N-terminal domain and RING finger protein family includes LONRF1 (also known as RING finger protein 191 or RNF191), LONRF2 (also known as RING finger protein 192, RNF192, or neuroblastoma apoptosis-related protease), LONRF3 (also known as RING finger protein 127 or RNF127), which are characterized by containing two C3HC4-type RING-HC fingers, four tetratricopeptide (TPR) repeats, and an ATP-dependent protease La (LON) substrate-binding domain at the C-terminus. Their biological functions remain unclear. This model corresponds to the second RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 157822509   12 LSCPICYNEFdenvHKPISLGCSHTVCKTCLNKL--HRKACP 51
Cdd:cd16514     2 LECSLCLRLL----YEPVTTPCGHTFCRACLERCldHSPKCP 39

RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; RNF168 is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. It, together with RNF8, functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates, such as H2A and H2AX with H2AK13/15 ubiquitylation, facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. Moreover, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. RNF168 contains an N-terminal C3HC4-type RING-HC finger that catalyzes H2A-K15ub and interacts with H2A, and two MIU (motif interacting with ubiquitin) domains responsible for the interaction with K63 linked poly-ubiquitin.

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gi 157822509   14 CPICYNEFDEnvhkPISLGCSHTVCKTCLNKLHRKA---CPFDQTAINT 59
Cdd:cd16550     3 CPICLEILVE----PVTLPCNHTLCMPCFQSTVEKAslcCPLCRLRISS 47

RING finger, HC subclass, found in tripartite motif-containing protein TRIM25 and similar proteins; TRIM25, also known as estrogen-responsive finger protein (EFP), RING finger protein 147 (RNF147), or RING-type E3 ubiquitin transferase, is an E3 ubiquitin/ISG15 ligase that is induced by estrogen and is therefore particularly abundant in placenta and uterus. TRIM25 regulates various cellular processes through E3 ubiquitin ligase activity, transferring ubiquitin and ISG15 to target proteins. It mediates K63-linked polyubiquitination of retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. It is also required for melanoma differentiation-associated gene 5 (MDA5) and mitochondrial antiviral signaling (MAVS, also known as IPS-1, VISA, Cardiff) mediated activation of nuclear factor-kappaB (NF-kappaB) and interferon production. Upon UV irradiation, TRIM25 interacts with mono-ubiquitinated PCNA and promotes its ISG15 modification (ISGylation), suggesting a crucial role in termination of error-prone translesion DNA synthesis. TRIM25 also functions as a novel regulator of p53 and Mdm2. It enhances p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26S proteasomes. Meanwhile, it inhibits p53's transcriptional activity and dampens the response to DNA damage, and is essential for medaka development and this dependence is rescued by silencing of p53. Moreover, TRIM25 is involved in the host cellular innate immune response against retroviral infection. It interferes with the late stage of feline leukemia virus (FeLV) replication. Furthermore, TRIM25 acts as an oncogene in gastric cancer. Its blockade by RNA interference inhibits migration and invasion of gastric cancer cells through transforming growth factor-beta (TGF-beta) signaling, suggesting it presents a novel target for the detection and treatment of gastric cancer. In addition, TRIM25 acts as an RNA-specific activator for Lin28a/TuT4-mediated uridylation. TRIM25 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

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gi 157822509   12 LSCPICYNEFDEnvhkPISLGCSHTVCKTCLNK 44
Cdd:cd16597     6 LTCSICLELFKD----PVTLPCGHNFCGVCIEK 34

RING finger, HC subclass, found in tripartite motif-containing protein 13 (TRIM13) and similar proteins; TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts with proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). It also targets the known ER proteolytic substrate CD3-delta, but not the N-end rule substrate Ub-R-YFP (yellow fluorescent protein) for degradation. Moreover, TRIM13 regulates ubiquitination and degradation of NEMO to suppress tumor necrosis factor (TNF) induced nuclear factor-kappaB (NF- kappa B) activation. It is also involved in NF-kappaB p65 activation and nuclear factor of activated T-cells (NFAT)-dependent activation of c-Rel upon T-cell receptor engagement. Furthermore, TRIM13 negatively regulates melanoma differentiation-associated gene 5 (MDA5)-mediated type I interferon production. It also regulates caspase-8 ubiquitination, translocation to autophagosomes, and activation during ER stress induced cell death. Meanwhile, TRIM13 enhances ionizing radiation-induced apoptosis by increasing p53 stability and decreasing AKT kinase activity through MDM2 and AKT degradation. TRIM13 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region. In addition, TRIM13 contains a C-terminal transmembrane domain.

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gi 157822509   10 EFLSCPICYNEFDEnvhkPISLGCSHTVCKTCL 42
Cdd:cd16762     2 EDLTCPICCCLFDD----PRVLPCSHNFCKKCL 30

RING finger, HC subclass, found in RING finger protein RNF224 and similar proteins; RNF224 is uncharacterized C3HC4-type RING-HC finger-containing proteins. It may function as an E3 ubiquitin-protein ligase.

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gi 157822509   12 LSCPICYNEFDENVHKPISLGCSHTVCKTCLNKL 45
Cdd:cd16565     1 LDCIICYSAYDLSTRLPRRLYCGHTFCQACLKRL 34

RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation, but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal C3HC4-type RING-HC finger.

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gi 157822509   14 CPICynefDENVHKPISLGCSHTVCKTCL 42
Cdd:cd16613     3 CICC----QELVYKPITTPCKHNICKSCL 27

RING finger, HC subclass, found in Arabidopsis thaliana protein BENZOIC ACID HYPERSENSITIVE 1 (BAH1) and similar proteins; This subfamily includes Arabidopsis thaliana BAH1 and BAH1-like. BAH1, also known as protein NITROGEN LIMITATION ADAPTATION (NLA), or RING-type E3 ubiquitin transferase BAH1, acts as an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. It plays a role in salicylic acid-mediated negative feedback regulation of salicylic acid (SA) accumulation. It may be involved in the overall regulation of SA, benzoic acid and phenylpropanoid biosynthesis. It controls the adaptability to nitrogen limitation by channeling the phenylpropanoid metabolic flux to the induced anthocyanin synthesis. BAH1-like, also known as RING finger protein 178, or RING-type E3 ubiquitin transferase BAH1-like, is a probable E3 ubiquitin-protein ligase. Members of this subfamily contain a typical C3HC4-type RING-HC finger.

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gi 157822509   12 LSCPICYnefdENVHKPISLGCSHTVCKTC 41
Cdd:cd23127     9 LTCSICL----DTVFDPVALGCGHLFCNSC 34

RING finger, HC subclass, found in tripartite motif-containing protein TRIM4 and similar proteins; TRIM4 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that has recently evolved and is present only in higher mammals. It transiently interacts with mitochondria, induces mitochondrial aggregation and sensitizes the cells to hydrogen peroxide (H2O2) induced death. Its interaction with peroxiredoxin 1 (PRX1) is critical for the regulation of H2O2 induced cell death. Moreover, TRIM4 functions as a positive regulator of RIG-I-mediated type I interferon induction. It regulates the K63-linked ubiquitination of RIG-1 and assembly of antiviral signaling complex at the mitochondria.

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gi 157822509   10 EFLSCPICYNEFDEnvhkPISLGCSHTVCKTClnkLHRKACP 51
Cdd:cd16590     5 EELTCPICLDYFQD----PVSIECGHNFCRGC---LHRNWAP 39

Modified RING finger, HC subclass (C3HC3D-type), found in tripartite motif-containing protein 23 (TRIM23) and similar proteins; TRIM23, also known as ADP-ribosylation factor domain-containing protein 1, GTP-binding protein ARD-1, or RING finger protein 46 (RNF46), is an E3 ubiquitin-protein ligase belonging to the C-IX subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a modified C3HC3D-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as C-terminal ADP ribosylation factor (ARF) domains. TRIM23 is involved in nuclear factor (NF)-kappaB activation. It mediates atypical lysine 27 (K27)-linked polyubiquitin conjugation to NF-kappaB essential modulator NEMO, also known as IKKgamma, which plays an important role in the NF-kappaB pathway, and this conjugation is essential for TLR3- and RIG-I/MDA5-mediated antiviral innate and inflammatory responses. It also regulates adipocyte differentiation via stabilization of the adipogenic activator peroxisome proliferator-activated receptor gamma (PPARgamma) through atypical ubiquitin conjugation to PPARgamma. Moreover, TRIM23 interacts with and polyubiquitinates yellow fever virus (YFV) NS5 to promote its binding to STAT2 and trigger type I interferon (IFN-I) signaling inhibition.

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gi 157822509   12 LSCPICYNEFDENVHK-PISLGCSHTVCKTCLNKLHRKA----CPFDQT 55
Cdd:cd16645     2 LECGVCEDVFSLQGDKvPRLLLCGHTVCHDCLTRLPLHGravrCPFDRQ 50

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.

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gi 157822509   12 LSCPICYnEFDENvhkPISLGCSHTVCKTCLNK-LHRKA----CPFDQTAIN 58
Cdd:cd16498    17 LECPICL-ELLKE---PVSTKCDHQFCRFCILKlLQKKKkpapCPLCKKSVT 64

RING finger, HC subclass, found in Saccharomyces cerevisiae increased recombination centers protein 20 (IRC20) and similar proteins; IRC20 is an uncharacterized ATP-dependent helicase that is probably involved in a pathway contributing to genomic integrity. IRC20 contains a typical C3HC4-type RING-HC finger.

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gi 157822509   12 LSCPICYNEFdenvHKPISLGCSHTVCKTCLNKL--HRKACP 51
Cdd:cd23135     4 LSCSICFSEI----RSGAILKCGHFFCLSCIASWlrEKSTCP 41

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four closely related tripartite motif-containing proteins, belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

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gi 157822509   10 EFLSCPICYnefdENVHKPISLGCSHTVCKTCLNKLHRKA 49
Cdd:cd16591     5 EEVTCPICL----ELLTEPLSLDCGHSFCQACITANHKES 40

RING finger, HC subclass, found in tripartite motif-containing protein 8 (TRIM8) and similar proteins; TRIM8, also known as glioblastoma-expressed RING finger protein (GERP) or RING finger protein 27 (RNF27), is a probable E3 ubiquitin-protein ligase that may promote proteasomal degradation of suppressor of cytokine signaling 1 (SOCS1) and further regulate interferon-gamma signaling. It functions as a new p53 modulator that stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation. TRIM8 deficit dramatically impairs p53 stabilization and activation in response to chemotherapeutic drugs. TRIM8 also modulates tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta)-triggered nuclear factor-kappaB (NF- kappa B) activation by targeting transforming growth factor beta (TGFbeta) activated kinase 1 (TAK1) for K63-linked polyubiquitination. Moreover, TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90beta and consequently regulates transcription of Nanog in embryonic stem cells. It also interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL-6-dependent activation of STAT3. TRIM8 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The coiled coil domain is required for homodimerization and the region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1.

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gi 157822509   10 EFLSCPICYNEFDEnvhkPISLGCSHTVCKTCLNK 44
Cdd:cd16580    10 EELICPICLHVFVE----PVQLPCKHNFCRGCIGE 40

RING finger, HC subclass, found in RING finger protein 152 (RNF152) and similar proteins; RNF152 is a lysosome-anchored E3 ubiquitin-protein ligase involved in apoptosis. It is polyubiquitinated through K48 linkage. It negatively regulates the activation of the mTORC1 pathway by targeting RagA GTPase for K63-linked ubiquitination. It interacts with and ubiquitinates RagA in an amino-acid-sensitive manner. The ubiquitination of RagA recruits its inhibitor GATOR1, a GAP complex for Rag GTPases, to the Rag complex, thereby inactivating mTORC1 signaling. RNF152 contains an N-terminal C3HC4-type RING-HC finger and a C-terminal transmembrane domain, both of which are responsible for its E3 ligase activity.

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gi 157822509   12 LSCPICYNEFDENvHKPISLGCSHTVCKTCLNKL 45
Cdd:cd16548     1 LECQICFNYYSPR-RRPKLLDCKHTCCSVCLQQM 33