Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 58037477     63 CLICvspFDGIFKLPKRLDCGHVFCLECLARLSLATAGGgdavaCPMC 110
Cdd:smart00184   1 CPIC---LEEYLKDPVILPCGHTFCRSCIRKWLESGNNT-----CPIC 40

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 58037477  57 PTSPMECLICvspFDGIFKlPKRLDCGHVFCLECLarLSLATAGGGDavACPMCRA 112
Cdd:COG5574 212 PLADYKCFLC---LEEPEV-PSCTPCGHLFCLSCL--LISWTKKKYE--FCPLCRA 259

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        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 58037477  62 ECLICVSPFDGIFKLPKRLDCGHVFCLECLARLsLATAgGGDAVACPMCRA 112
Cdd:cd16587   2 ECPICLESFDEGQLRPKLLHCGHTICEQCLEKL-LASL-SINGVRCPFCRK 50

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 58037477  61 MECLICVSPFDGIFKLPKRLDCGHVFCLECLARLSlATAGGGDAVACPMCRAPTRlAPRRG 121
Cdd:cd16565   1 LDCIICYSAYDLSTRLPRRLYCGHTFCQACLKRLD-TVINEQRWIPCPQCRQNTP-TPRGG 59

RING finger, HC subclass, found in tripartite motif-containing protein 72 (TRIM72) and similar proteins; TRIM72, also known as Mitsugumin-53 (MG53), is a muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at muscle injury sites. It is required in repair of alveolar epithelial cells under plasma membrane stress failure. It interacts with dysferlin to regulate sarcolemmal repair. Upregulation of TRIM72 develops obesity, systemic insulin resistance, dyslipidemia, and hyperglycemia, as well as induces diabetic cardiomyopathy through transcriptional activation of the peroxisome proliferation-activated receptor alpha (PPAR-alpha) signaling pathway. Compensation for the absence of AKT signaling by ERK signaling during TRIM72 overexpression leads to pathological hypertrophy. Moreover, TRIM72 functions as a novel negative feedback regulator of myogenesis by targeting insulin receptor substrate-1 (IRS-1). It is transcriptionally activated by the synergism of myogenin (MyoD) and myocyte enhancer factor 2 (MEF2). TRIM72 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, 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 58037477  63 CLICVSPFDGifklPKRLDCGHVFCLECLARLSLATAGGgdAVACPMCRAPTR 115
Cdd:cd16612   7 CPLCLKLFQS----PVTTECGHTFCQDCLSRVPKEEDGG--STSCPTCQAPTK 53

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        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 58037477  61 MECLICVSPFDGIFKLPKRLDCGHVFCLECLARLSLATAGGGDAVACPMCRAPT 114
Cdd:cd16555   2 LECKICYNRYDLRQRRPKVLECCHRVCAKCLYKIVDLGDSSPSVLVCPFCRFET 55

RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar proteins; TRIM40, also known as probable E3 NEDD8-protein ligase or RING finger protein 35 (RNF35), is highly expressed in the gastrointestinal tract including the stomach, small intestine, and large intestine. It enhances neddylation of inhibitor of nuclear factor kappaB kinase subunit gamma (IKKgamma), inhibits the activity of nuclear factor-kappaB (NF-kappaB)-mediated transcription, and thus prevents inflammation-associated carcinogenesis in the gastrointestinal tract. TRIM40 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        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 58037477  63 CLICVSPFdgifKLPKRLDCGHVFCLECLARlSLATAGGGDAVACPMCRAP 113
Cdd:cd16583   8 CPICQEPL----KEAVSTDCGHLFCRMCLTQ-HAKKASASGVFSCPVCRKP 53

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 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, 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 58037477  63 CLICVspfdGIFKLPKRLDCGHVFCLECLARLSLATAGGGdaVACPMCRAPTRLAPR 119
Cdd:cd16609   6 CSICL----GLYQDPVTLPCQHSFCRACIEDHWRQKDEGS--FSCPECRAPFPEGPT 56

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 finger A1a (RHA1A), A1b (RHA1B) and similar proteins; This subfamily includes Arabidopsis thaliana RHA1A, RHA1B and XERICO. RHA1A is a probable E3 ubiquitin-protein ligase that may possess E3 ubiquitin ligase activity in vitro. RHA1B possesses E3 ubiquitin-protein ligase activity when associated with the E2 enzyme UBC8 in vitro. XERICO functions on abscisic acid homeostasis at post-translational level, probably through ubiquitin/proteasome-dependent substrate-specific degradation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 58037477  62 ECLICVSPFDGIFKLPKRLDCGHVFCLECLARLSLAtagggDAVACPMCRAP 113
Cdd:cd23121   3 CCAICLSDFNSDEKLRQLPKCGHIFHHHCLDRWIRY-----NKITCPLCRAD 49

RING finger, HC subclass, found in tripartite motif-containing protein TRIM58 and similar proteins; TRIM58, also known as protein BIA2, is an erythroid E3 ubiquitin-protein ligase induced during late erythropoiesis. It binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. It may participate in the erythroblast enucleation process through regulation of nuclear polarization. TRIM58 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.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 58037477  77 PKRLDCGHVFCLECLARLSLATAGGGDAV-ACPMCRAP 113
Cdd:cd16606  15 PVSVDCGHSFCLRCISEFCEKSDSAQGGVyACPQCRGP 52

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 58037477  63 CLICVspfdGIFKLPKRLDCGHVFCLECLARlSLATAGGGDAvACPMCRAPTRLAPR 119
Cdd:cd16597   8 CSICL----ELFKDPVTLPCGHNFCGVCIEK-TWDSQHGSEY-SCPQCRATFPRRPE 58

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        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 58037477  62 ECLICVSPFDGIFKLPKRLDCGHVFCLECLARLSLATAggGDAVACPMCRAPT 114
Cdd:cd23140   3 ECSVCSEGYNEDERVPLLLQCGHTFCKDCLSQMFIRCT--DLTLKCPRCRQSV 53

RING finger, HC subclass, found in Saccharomyces cerevisiae translation termination inhibitor protein ITT1 and similar proteins; ITT1 is a protein that modulates the efficiency of translation termination, resulting in the readthrough of all three types of nonsense codons UAA, UAG and UGA. ITT1 contains a typical C3HC4-type RING-HC finger.

                        10        20        30
                ....*....|....*....|....*....|
gi 58037477  62 ECLICVSPFDGIFKLpkRLDCGHVFCLECL 91
Cdd:cd23134   6 HCGICFEEKKGSDFI--KLPCGHVFCRECL 33

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 58037477    63 CLICVSPFDgifklPKRLDCGHVFCLECLARLSlatAGGGDAVACP 108
Cdd:pfam13445   1 CPICLELFT-----DPVLPCGHTFCRECLEEMS---QKKGGKFKCP 38

RING finger, HC subclass, found in Arabidopsis thaliana proteolysis 1 protein (PRT1) and similar proteins; PRT1, also called RING-type E3 ubiquitin transferase PRT1, is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It functions in the N-end rule pathway of protein degradation, where it specifically recognizes and ubiquitinates proteins with an N-terminal bulky aromatic amino acid (Phe). It does not act on aliphatic hydrophobic and basic N-terminal residues (Arg or Leu) containing proteins. PRT1 contains a typical C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 58037477  62 ECLICVspfDGIFKlPKRLDCGHVFCLECLARlslaTAGGGDAVACPMCRAP 113
Cdd:cd23132   4 LCCICL---DLLYK-PVVLECGHVFCFWCVHR----CMNGYDESHCPLCRRP 47

RING finger, HC subclass, found in malin and similar proteins; Malin ("mal" for seizure in French), also known as NHL repeat-containing protein 1 (NHLRC1), or EPM2B, is a nuclear E3 ubiquitin-protein ligase that ubiquitinates and promotes the degradation of laforin (EPM2A encoding protein phosphatase). Malin and laforin operate as a functional complex that play key roles in regulating cellular functions such as glycogen metabolism, unfolded cellular stress response, and proteolytic processes. They act as pro-survival factors that negatively regulate the Hipk2-p53 cell death pathway. They also negatively regulate cellular glucose uptake by preventing plasma membrane targeting of glucose transporters. Moreover, they degrade polyglucosan bodies in concert with glycogen debranching enzyme and brain isoform glycogen phosphorylase. Furthermore, they, together with Hsp70, form a new functional complex that suppress the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system. Defects in either malin or laforin may cause Lafora disease (LD), a fatal form of teenage-onset autosomal recessive progressive myoclonus epilepsy. In addition, malin may have function, independent of laforin, in lysosomal biogenesis and/or lysosomal glycogen disposal. Malin contains six NHL-repeat protein-protein interaction domains and a C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 58037477  61 MECLICVSPFDGIFK-LPKRLDCGHVFCLECLARLSlatAGGGDAVACPMCR 111
Cdd:cd16516   1 LECKVCFEKYSHQQEhRPRNLPCGHVLCRECVTALA---HPRRSKLECPFCR 49

RING finger, HC subclass, found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 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, 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. This subfamily also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins that may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by N-terminal RBCC domains only.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 58037477  61 MECLICVSpfdgIFKLPKRLDCGHVFCLECLARLSLATAGggdAVACPMCR 111
Cdd:cd16605   1 LLCPICLE----VFKEPLMLQCGHSYCKSCLVSLSGELDG---QLLCPVCR 44

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and similar proteins; TRIM13 and TRIM59, two closely related tripartite motif-containing proteins, belong 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, followed by a C-terminal transmembrane domain. 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). 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 58037477  63 CLICVSpfdgIFKLPKRLDCGHVFCLECLARLSLATAGGGDA-VACPMCR 111
Cdd:cd16581   5 CSICYN----IFDDPKILPCSHTFCKNCLEKLLAASGYYLLAsLKCPTCR 50

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 58037477  61 MECLICvspfDGIF-----KLPKRLDCGHVFCLECLARLSLAtaggGDAVACPMCR 111
Cdd:cd16645   2 LECGVC----EDVFslqgdKVPRLLLCGHTVCHDCLTRLPLH----GRAVRCPFDR 49

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
                ....*....|....*....|....*....|...
gi 58037477  63 CLICVSPFDGIFKLPKRLDCGHVFCLECLARLS 95
Cdd:cd16638   4 CPVCTNEFDGTQRKPISLGCGHTVCKTCLSKLH 36

RING finger, HC subclass, found in RING finger protein 170 (RNF170) and similar proteins; RNF170, also known as putative LAG1-interacting protein, is an endoplasmic reticulum (ER) membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination-dependent degradation of type-I inositol 1,4,5-trisphosphate (IP3) receptors (ITPR1) via the endoplasmic-reticulum-associated protein degradation (ERAD) pathway. A point mutation (arginine to cysteine at position 199) in the RNF170 gene is linked with autosomal-dominant sensory ataxia (ADSA), a disease characterized by neurodegeneration in the posterior columns of the spinal cord. RNF170 contains a C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 58037477  60 PMECLICVSPFdgifKLPKRLDCGHVFCLECLaRLSLATAGGGDAVACPMCR 111
Cdd:cd16553   1 DMECPICLQDA----RFPVETNCGHLFCGPCI-ITYWRHGSWLGAVSCPVCR 47

RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar proteins; HLTF, also known as DNA-binding protein/plasminogen activator inhibitor 1 regulator, HIP116, RING finger protein 80, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3, or sucrose nonfermenting protein 2-like 3, is a yeast RAD5 homolog found in mammals. It has both E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. It is involved in Lys-63-linked poly-ubiquitination of proliferating cell nuclear antigen (PCNA) at Lys-164 and in the regulation of DNA damage tolerance. It shows double-stranded DNA translocase activity with 3'-5' polarity, thereby facilitating regression of the replication fork. HLTF contains an N-terminal HIRAN (HIP116 and RAD5 N-terminal) domain, a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 58037477  62 ECLICVSPFdgifKLPKRLDCGHVFCLECLARlSLATagggDAVACPMCRAP 113
Cdd:cd16509   5 ECAICLDSL----TNPVITPCAHVFCRRCICE-VIQR----EKAKCPMCRAP 47

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3), Deltex-3-like (DTX3L) and similar proteins; This subfamily contains Deltex3 (DTX3) and Deltex-3-like (DTX3L), both of which are E3 ubiquitin-protein ligases belonging to the Deltex (DTX) family. DTX3, also known as RING finger protein 154 (RNF154), has a biological function that remains unclear. DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. In contrast to other DTXs, both DTX3 and DTX3L contain a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N termini and further enhance self-ubiquitination.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 58037477  62 ECLICVSPFdgifKLPKRLD-CGHVFCLECLAR-LSLATagggdavACPMCR 111
Cdd:cd16506   2 TCPICLDEI----QNKKTLEkCKHSFCEDCIDRaLQVKP-------VCPVCG 42

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein RNFT1, RNFT2, and similar proteins; Both RNFT1 and RNFT2 are multi-pass membrane proteins containing a C3HC4-type RING-HC finger. Their biological roles remain unclear.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 58037477  63 CLICVSPFdgifKLPKRLDCGHVFCLECLA------RlslatagggdavACPMCR 111
Cdd:cd16532   3 CPICQDEF----KDPVVLRCKHIFCEDCVSewfereR------------TCPLCR 41

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.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 58037477  63 CLICVspfdGIFKLPKRLDCGHVFCLECLARLSLATAGGgdAVACPMCRAP 113
Cdd:cd16604   3 CPICL----DLLKDPVTLPCGHSFCMGCLGALWGAGRGG--RASCPLCRQT 47

RING finger, HC subclass, found in tripartite motif-containing protein 26 (TRIM26) and similar proteins; TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM26 belongs 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.

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                ....*....|....*....|....*....|....*....|....
gi 58037477  77 PKRLDCGHVFCLECLARLSlATAGGGDAVACPMCRAPTRLAPRR 120
Cdd:cd16598  17 PVTIDCGHNFCRSCITDYC-PISGGHERPVCPLCRKPFKKENIR 59

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

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                  ....*....|....*....|....*....|....*....|....*...
gi 58037477    63 CLICVSPFDGIFKLpkrLDCGHVFCLECLARLSLATagggdAVACPMC 110
Cdd:pfam00097   1 CPICLEEPKDPVTL---LPCGHLFCSKCIRSWLESG-----NVTCPLC 40

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.

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                ....*....|....*....|....*....|....*....|....*....|..
gi 58037477  63 CLICVSPF---DGIFKLPkrldCGHVFCLECLARLsLATAGGgdavACPMCR 111
Cdd:cd16448   1 CVICLEEFeegDVVRLLP----CGHVFHLACILRW-LESGNN----TCPLCR 43

RING finger, HC subclass, found in RING finger protein 208 (RNF208) and similar proteins; RNF208 is an E3 ubiquitin-protein ligase whose activity can be modulated by S-nitrosylation. It contains a C3HC4-type RING-HC finger.

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                ....*....|....*....|....*....|....*....|....*....|....*..
gi 58037477  60 PMECLICVSPFDGIFKLPKRLDCGHVFCLECLARLsLATAGGGDAVACPMCRAPTRL 116
Cdd:cd16559   1 PLLCPTCGHSYNFTNKRPRILSCLHSVCEECLQIL-YESCPKYKFISCPTCKRETVL 56

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.

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                ....*....|....*....|....*....|....*....|....*....|..
gi 58037477  62 ECLICVspfdGIFKLPKRLDCGHVFCLECLARlSLATAGggdavACPMCRAP 113
Cdd:cd16514   3 ECSLCL----RLLYEPVTTPCGHTFCRACLER-CLDHSP-----KCPLCRTS 44

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 58037477  63 CLICVSPFdgifKLPKRLDCGHVFCLECLARLSLATAgggdavACPMCR 111
Cdd:cd23135   6 CSICFSEI----RSGAILKCGHFFCLSCIASWLREKS------TCPLCK 44

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

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                ....*....|....*....|....*....|....*....|....*....|....*.
gi 58037477  57 PTSPMECLICvspFDGIFKlPKRLDCGHVFCLECLarLSLATAGGGDavACPMCRA 112
Cdd:COG5574 212 PLADYKCFLC---LEEPEV-PSCTPCGHLFCLSCL--LISWTKKKYE--FCPLCRA 259

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.

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                ....*....|....*....|....*....|....*....|
gi 58037477  74 FKLPKRLDCGHVFCLECLARLSlATAGGGDAVACPMCRAP 113
Cdd:cd16579  14 YKCPKLLPCLHTVCSGCLEALA-EQASETTEFQCPICKAS 52

RING finger, HC subclass, found in peroxin-2 (PEX2) and similar proteins; PEX2, also known as peroxisome biogenesis factor 2, 35 kDa peroxisomal membrane protein, peroxisomal membrane protein 3, peroxisome assembly factor 1 (PAF-1), or RING finger protein 72 (RNF72), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It may be involved in the biogenesis of peroxisomes, as well as in peroxisomal matrix protein import. Mutations in the PEX2 gene are the primary defect in a subset of patients with Zellweger syndrome and related peroxisome biogenesis disorders. Moreover, PEX2 functions as an E3-ubiquitin ligase that mediates the UBC4-dependent polyubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation.

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                ....*....|....*....|....*....|....*....|....*....|....*.
gi 58037477  61 MECLIC-VSPFdgifKLPKRLDCGHVFCLECLArlslATAGGGDAVACPMCRAPTR 115
Cdd:cd16526   2 TECAICgEWPT----NNPYSTGCGHVYCYYCIK----SNLLADDSFTCPRCGSPVS 49

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 58037477  61 MECLICVSpfdgIFKLPKRLDCGHVFCLECLARlslATAGGGDAVACPMCRAPTRLAPRR 120
Cdd:cd16590   7 LTCPICLD----YFQDPVSIECGHNFCRGCLHR---NWAPGGGPFPCPECRHPSAPAALR 59

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 58037477  63 CLICVSpfdgIFKLPKRLDCGHVFCLECLARLSLATAGGGDAVACPMCR---APTRLAPRRGL 122
Cdd:cd16591   9 CPICLE----LLTEPLSLDCGHSFCQACITANHKESVNQEGESSCPVCRtsyQPENLRPNRHL 67