Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1; Roquin-1, also known as RING finger and C3H zinc finger protein 1 (RC3H1), or RING finger protein 198 (RNF198), is a ubiquitously expressed RNA-binding protein essential for degradation of inflammation-related mRNAs and maintenance of immune homeostasis. It is localized in cytoplasmic granules and binds to the 3' untranslated region (3'UTR) of inducible costimulator (Icos) mRNA to post-transcriptionally repress its expression. Roquin-1 interacts with the 3'UTR of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) and tumor-necrosis factor-alpha (TNFalpha), and post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kappaB pathway. Moreover, Roquin-1 shares functions with its paralog Roquin-2 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Roquin-1 contains an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 ubiquitin-ligase function, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger that is involved in RNA recognition, typically contacting AU-rich elements. In addition, both N- and C-terminal to the ROQ domain are combined to form a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain that is highly likely to function as an RNA-binding domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2462505093    6 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 54
Cdd:cd16781      1 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 49

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

                           10        20
                   ....*....|....*....|....*..
gi 2462505093  414 YKTYMCRDMKQRGGCPRGASCTFAHSQ 440
Cdd:pfam00642    1 YKTELCRFFLRTGYCKYGDRCKFAHGQ 27

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1; Roquin-1, also known as RING finger and C3H zinc finger protein 1 (RC3H1), or RING finger protein 198 (RNF198), is a ubiquitously expressed RNA-binding protein essential for degradation of inflammation-related mRNAs and maintenance of immune homeostasis. It is localized in cytoplasmic granules and binds to the 3' untranslated region (3'UTR) of inducible costimulator (Icos) mRNA to post-transcriptionally repress its expression. Roquin-1 interacts with the 3'UTR of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) and tumor-necrosis factor-alpha (TNFalpha), and post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kappaB pathway. Moreover, Roquin-1 shares functions with its paralog Roquin-2 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Roquin-1 contains an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 ubiquitin-ligase function, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger that is involved in RNA recognition, typically contacting AU-rich elements. In addition, both N- and C-terminal to the ROQ domain are combined to form a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain that is highly likely to function as an RNA-binding domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2462505093    6 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 54
Cdd:cd16781      1 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 49

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 2462505093    14 CPICtqtFDETIRKPISLGCGHTVCKMCLNKL---HRKACPF 52
Cdd:smart00184    1 CPIC---LEEYLKDPVILPCGHTFCRSCIRKWlesGNNTCPI 39

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

                           10        20
                   ....*....|....*....|....*..
gi 2462505093  414 YKTYMCRDMKQRGGCPRGASCTFAHSQ 440
Cdd:pfam00642    1 YKTELCRFFLRTGYCKYGDRCKFAHGQ 27

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1; Roquin-1, also known as RING finger and C3H zinc finger protein 1 (RC3H1), or RING finger protein 198 (RNF198), is a ubiquitously expressed RNA-binding protein essential for degradation of inflammation-related mRNAs and maintenance of immune homeostasis. It is localized in cytoplasmic granules and binds to the 3' untranslated region (3'UTR) of inducible costimulator (Icos) mRNA to post-transcriptionally repress its expression. Roquin-1 interacts with the 3'UTR of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) and tumor-necrosis factor-alpha (TNFalpha), and post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kappaB pathway. Moreover, Roquin-1 shares functions with its paralog Roquin-2 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Roquin-1 contains an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 ubiquitin-ligase function, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger that is involved in RNA recognition, typically contacting AU-rich elements. In addition, both N- and C-terminal to the ROQ domain are combined to form a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain that is highly likely to function as an RNA-binding domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2462505093    6 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 54
Cdd:cd16781      1 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 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        40
                   ....*....|....*....|....*....|....*....|....
gi 2462505093   11 FLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 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 2462505093   12 LSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKA------CPF 52
Cdd:cd16587      1 LECPICLESFDEGQLRPKLLHCGHTICEQCLEKLLASLsingvrCPF 47

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 2462505093    14 CPICtqtFDETIRKPISLGCGHTVCKMCLNKL---HRKACPF 52
Cdd:smart00184    1 CPIC---LEEYLKDPVILPCGHTFCRSCIRKWlesGNNTCPI 39

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 2462505093   14 CPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQT 55
Cdd:cd23140      4 CSVCSEGYNEDERVPLLLQCGHTFCKDCLSQMFIRCTDLTLK 45

Modified RING finger, HC subclass (C3HC3D-type), found in Caenorhabditis elegans putative GTP-binding protein trim-23 homolog (arc-1) and similar proteins; arc-1, also called RING-type E3 ubiquitin transferase arc-1, is an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. arc-1 contains a modified C3HC3D-type RING-HC finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2462505093   11 FLSCPICTQTFDETI--RKP-ISLGCGHTVCKMCLNKLHRK-----ACPFDQT 55
Cdd:cd23124      1 ELECGICQQEYSADDplLIPrILTECGHTICTNCAGTILGQssgsiFCPFDRI 53

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2462505093   14 CPICTQTFDEtirkPIsLGCGHTVCKMCLNKLHRKA-----CP 51
Cdd:pfam13445    1 CPICLELFTD----PV-LPCGHTFCRECLEEMSQKKggkfkCP 38

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        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2462505093   12 LSCPICTqtfdETIRKPISLGCGHTVCKMCLNKL------HRKACPFDQTT 56
Cdd:cd16604      1 LSCPICL----DLLKDPVTLPCGHSFCMGCLGALwgagrgGRASCPLCRQT 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.

                           10        20        30
                   ....*....|....*....|....*....|...
gi 2462505093   12 LSCPICTQTFDEtirkPISLGCGHTVCKMCLNK 44
Cdd:cd16597      6 LTCSICLELFKD----PVTLPCGHNFCGVCIEK 34

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM41, TRIM52 and similar proteins; TRIM41 and TRIM52, two closely related tripartite motif-containing proteins, have dramatically expanded RING domains compared with the rest of the TRIM family proteins. TRIM41 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. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of the TRIM family that contains only RBCC domains. TRIM41, also known as RING finger-interacting protein with C kinase (RINCK), is an E3 ubiquitin-protein ligase that promotes the ubiquitination of protein kinase C (PKC) isozymes in cells. It specifically recognizes the C1 domain of PKC isozymes. It controls the amplitude of PKC signaling by controlling the amount of PKC in the cell. TRIM52, also known as RING finger protein 102 (RNF102), is encoded by a novel, noncanonical antiviral TRIM52 gene in primate genomes with unique specificity determined by the rapidly evolving RING domain.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2462505093   14 CPICTQTFdetiRKPISLGCGHTVCKMCLNKLHRKACP 51
Cdd:cd16602      6 CAICLDYF----KDPVSIGCGHNFCRVCVTQLWGFTCP 39

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462505093   12 LSCPICTQTFdetiRKPISLGCGHTVCKMCLNK----LHRKACPFDQTTINTDIelLPVNSALLQLV 74
Cdd:cd16599      5 LLCPICYEPF----REAVTLRCGHNFCKGCVSRswerQPRAPCPVCKEASSSDD--LRTNHTLNNLV 65

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
                   ....*....|....*....|....*....|....*.
gi 2462505093   10 DFLSCPICTQTFDEtirkPISLGCGHTVCKMCLNKL 45
Cdd:cd16581      1 EELTCSICYNIFDD----PKILPCSHTFCKNCLEKL 32

Modified RING finger, HC subclass (C3HC3D-type), found in uncharacterized proteins similar to tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4); This subfamily corresponds to a group of uncharacterized proteins that shows high sequence similarity with tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4). TRAF4, also known as cysteine-rich domain associated with RING and Traf domains protein 1, or metastatic lymph node gene 62 protein (MLN 62), or RING finger protein 83 (RNF83), is a member of TRAF protein family, which mainly function in the immune system, where they mediate signaling through tumor necrosis factor receptors (TNFRs) and interleukin-1/Toll-like receptors (IL-1/TLRs). It also plays a critical role in the nervous system, as well as in carcinogenesis. Like TRAF4, members of this subfamily contain a modified C3HC3D-type RING-HC finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2462505093   14 CPICtqtfDETIRKPISLG-CGHTVCKMCLNKLHRKA--CPFDQTTINTD 60
Cdd:cd23126      7 CPVC----CQVLRYPVQFEeCGHRVCSSCLPELLRVEprCPIDQGPIDRD 52

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 2462505093   10 DFLSCPICTQTFdetiRKPISLGCGHTVCKMCLNKLHRKA-------CP 51
Cdd:cd16579      3 KFLRCPGCKAEY----KCPKLLPCLHTVCSGCLEALAEQAsettefqCP 47

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 2462505093   14 CPICTQTFDetirKPISLGCGHTVCKMCLNKLHRKA------CP 51
Cdd:pfam15227    1 CPICLDYLE----KPVSIECGHSFCLSCINSLQKEPdgesllCP 40

RING finger, HC subclass, found in tripartite motif-containing protein 68 (TRIM68) and similar proteins; TRIM68, also known as RING finger protein 137 (RNF137) or SSA protein SS-56 (SS-56), is an E3 ubiquitin-protein ligase that negatively regulates Toll-like receptor (TLR)- and RIG-I-like receptor (RLR)-driven type I interferon production by degrading TRK fused gene (TFG), a novel driver of IFN-beta downstream of anti-viral detection systems. It also functions as a cofactor for androgen receptor-mediated transcription by regulating ligand-dependent transcription of androgen receptor in prostate cancer cells. Moreover, TRIM68 is a cellular target of autoantibody responses in Sjogre's syndrome (SS), as well as systemic lupus erythematosus (SLE). It is also an auto-antigen for T cells in SS and SLE. TRIM68 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.

                           10        20        30
                   ....*....|....*....|....*....|....
gi 2462505093   12 LSCPICtQTFdetIRKPISLGCGHTVCKMCLNKL 45
Cdd:cd16610      2 VACPIC-MTF---LREPVSIDCGHSFCHSCLSGL 31

RING finger, HC subclass, found in constitutive photomorphogenesis protein 1 (COP1) and similar proteins; COP1, also known as RING finger and WD repeat domain protein 2 (RFWD2) or RING finger protein 200 (RNF200), is a central regulator of photomorphogenic development in plants, which targets key transcription factors for proteasome-dependent degradation. It is localized predominantly in the nucleus, but may also be present in the cytosol. Mammalian COP1 functions as an E3 ubiquitin-protein ligase that interacts with Jun transcription factors and modulates their transcriptional activity. It also interacts with and negatively regulates the tumor-suppressor protein p53. Moreover, COP1 associates with COP9 signalosome subunit 6 (CSN6), and is involved in 14-3-3sigma ubiquitin-mediated degradation. The CSN6-COP1 link enhances ubiquitin-mediated degradation of p27(Kip1), a critical CDK inhibitor involved in cell cycle regulation, to promote cancer cell growth. Furthermore, COP1 functions as the negative regulator of ETV1 and influences prognosis in triple-negative breast cancer. COP1 contains an N-terminal extension, a C3HC4-type RING-HC finger, a coiled coil domain, and seven WD40 repeats. In human COP1, a classic leucine-rich NES, and a novel bipartite NLS is bridged by the RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2462505093   12 LSCPICTQTFDEtirkPISLGCGHTVCKMCLNK--LHRKACP 51
Cdd:cd16504      3 FLCPICFDIIKE----AFVTKCGHSFCYKCIVKhlEQKNRCP 40

RING finger, HC subclass, found in tripartite motif-containing protein 62 (TRIM62) and similar proteins; TRIM62, also known as Ductal Epithelium Associated Ring Chromosome 1 (DEAR1), is a cytoplasmic E3 ubiquitin-protein ligase that was identified as a dominant regulator of acinar morphogenesis in the mammary gland. It is implicated in the inflammatory response of immune cells by regulating the Toll-like receptor 4 (TLR4) signaling pathway, leading to increased activity of the activator protein 1 (AP-1) transcription factor in primary macrophages. It is also involved in muscular protein homeostasis, especially during inflammation-induced atrophy, and may play a role in the pathogenesis of ICU-acquired weakness (ICUAW) by activating and maintaining inflammation in myocytes. Moreover, TRIM62 facilitates K27-linked poly-ubiquitination of CARD9 and also regulates CARD9-mediated anti-fungal immunity and intestinal inflammation. It also functions as a chromosome 1p35 tumor suppressor and negatively regulates transforming growth factor beta (TGFbeta)-driven epithelial-mesenchymal transition (EMT) by binding to and promoting the ubiquitination of SMAD3, a major effector of TGFbeta-mediated EMT. TRIM62 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
                   ....*....|....*....|....*....|....*
gi 2462505093    9 TDFLSCPICTQTFdetiRKPISLGCGHTVCKMCLN 43
Cdd:cd16608      4 KDELLCSICLSIY----QDPVSLGCEHYFCRQCIT 34

RING finger, HC subclass, found in RING finger protein 222 (RNF222) and similar proteins; RNF222 is an uncharacterized C3HC4-type RING-HC finger-containing protein. It may function as an E3 ubiquitin-protein ligase.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2462505093   13 SCPICTQTFDetiRKPISLGCGHTVCKMCLNKL---HRKACP 51
Cdd:cd16564      2 ECPVCYEDFD---DAPRILSCGHSFCEDCLVKQlvsMTISCP 40

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
                   ....*....|....*....|....*....|....*....|....*....
gi 2462505093   12 LSCPICTQTFDETIRK-PISLGCGHTVCKMCLNKLHRKA----CPFDQT 55
Cdd:cd16645      2 LECGVCEDVFSLQGDKvPRLLLCGHTVCHDCLTRLPLHGravrCPFDRQ 50

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.

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                   ....*....|....*....|....*....|....
gi 2462505093   12 LSCPICTQTFDEtirkPISLGCGHTVCKMCLNKL 45
Cdd:cd16605      1 LLCPICLEVFKE----PLMLQCGHSYCKSCLVSL 30

RING finger, HC subclass, found in RING finger protein 186 (RNF186) and similar proteins; RNF186 is an E3 ubiquitin-protein ligase with an N-terminal C3HC4-type RING-HC finger and two putative C-terminal transmembrane domains which enable it to localize in a certain organelle. It regulates RING-dependent self-ubiquitination, as well as endoplasmic reticulum (ER) stress-mediated apoptosis through interaction with the Bcl-2 family protein BNip1.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 2462505093   12 LSCPICTQTFDETIRKPISLGCGHTVCKMCL 42
Cdd:cd16557      2 LECLVCRNPYSCFVRKPKLLACQHAFCAICL 32

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
                   ....*....|....*....|....*....|....*....|....*
gi 2462505093   14 CPICTqtfdETIRKPISLGCGHTVCKMCLNKLHRKA-------CP 51
Cdd:cd16583      8 CPICQ----EPLKEAVSTDCGHLFCRMCLTQHAKKAsasgvfsCP 48

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, 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, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                           10        20        30
                   ....*....|....*....|....*....|.
gi 2462505093   12 LSCPICTQTFdetiRKPISLGCGHTVCKMCL 42
Cdd:cd16594      6 LTCPICLDYF----TDPVTLDCGHSFCRACI 32

RING finger, HC subclass, found in RING finger protein 146 (RNF146) and similar proteins; RNF146, also known as dactylidin, or iduna, is a cytoplasmic E3 ubiquitin-protein ligase that is responsible for PARylation-dependent ubiquitination (PARdU). It displays neuroprotective property due to its inhibition of Parthanatos, a PAR dependent cell death, via binding with Poly(ADP-ribose) (PAR). It also modulates PAR polymerase-1 (PARP-1)-mediated oxidative cell injury in cardiac myocytes. Moreover, RNF146 mediates tankyrase-dependent degradation of axin, thereby positively regulating Wnt signaling. It also facilitates DNA repair and protects against cell death induced by DNA damaging agents or gamma-irradiation by translocating to the nucleus after cellular injury and promoting the ubiquitination and degradation of various nuclear proteins involved in DNA damage repair. Furthermore, RNF146 is implicated in neurodegenerative disease and cancer development. It regulates the development and progression of non-small cell lung cancer (NSCLC) by enhancing cell growth, invasion, and survival. RNF146 contains an N-terminal C3HC4-type RING-HC finger followed by a WWE domain with a poly(ADP-ribose) (PAR) binding motif at the tail.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2462505093   12 LSCPICTQtfdeTIRKPISLGCGHTVCKMCLN--KLHRKACPFDQTTINTD 60
Cdd:cd16546      1 PECPICLQ----TCIHPVKLPCGHIFCYLCVKgvAWQSKRCALCRQEIPED 47

RING finger, HC subclass, found in tripartite motif-containing protein 39 (TRIM39) and similar proteins; TRIM39, also known as RING finger protein 23 (RNF23) or testis-abundant finger protein, is an E3 ubiquitin-protein ligase that plays a role in controlling DNA damage-induced apoptosis through inhibition of the anaphase promoting complex (APC/C), a multiprotein ubiquitin ligase that controls multiple cell cycle regulators, including cyclins, geminin, and others. TRIM39 also functions as a regulator of several key processes in the proliferative cycle. It directly regulates p53 stability. It modulates cell cycle progression and DNA damage responses via stabilizing p21. Moreover, TRIM39 negatively regulates the nuclear factor kappaB (NFkappaB)-mediated signaling pathway through stabilization of Cactin, an inhibitor of NFkappaB- and Toll-like receptor (TLR)-mediated transcription, which is induced by inflammatory stimulants such as tumor necrosis factor alpha. Furthermore, TRIM39 is a MOAP-1-binding protein that can promote apoptosis signaling through stabilization of MOAP-1 via the inhibition of its poly-ubiquitination process. TRIM39 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
                   ....*....|....*....|....*....|..
gi 2462505093   12 LSCPICTqtfdETIRKPISLGCGHTVCKMCLN 43
Cdd:cd16601      2 ASCSLCK----EYLKDPVIIECGHNFCRACIT 29

Modified RING finger, HC subclass (C3HC3D-type), found in PHD and RING finger domain-containing protein 1 (PHRF1) and similar proteins; PHRF1, also known as KIAA1542, or CTD-binding SR-like protein rA9, is a ubiquitin ligase which induces the ubiquitination of TGIF (TG-interacting factor) at lysine 130. It acts as a tumor suppressor that promotes the transforming growth factor (TGF)-beta cytostatic program through selective release of TGIF-driven promyelocytic leukemia protein (PML) inactivation. PHRF1 contains a plant homeodomain (PHD) finger and a modified C3HC3D-type RING-HC finger.

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                   ....*....|....*....|....*....|....*....|....*..
gi 2462505093   13 SCPICTQTF-DETIRKPISlgCGHTVCKMCLNKLHRKA--CPFDQTT 56
Cdd:cd16635      6 SCPICLNTFrDQAVGTPES--CDHIFCLDCILEWSKNAntCPVDRIV 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
                   ....*....|....*....|....*....|....
gi 2462505093   12 LSCPICTQTFDETIRKPISLGCGHTVCKMCLNKL 45
Cdd:cd16565      1 LDCIICYSAYDLSTRLPRRLYCGHTFCQACLKRL 34

Variant RING finger, HC subclass (C4C4-type), found in Ret finger protein-like (RFPL) family; The RFPL family, also known as the RING-B30 family, represents a group of RFPL gene products, RFPL1, RFPL2, RFPL3, and RFPL4A, which are characterized by containing an N-terminal RFPL1, 2, 3-specifying helix (RSH), a C4C4- or a variant C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger, an RFPL-defining motif (RDM), and C-terminal PRY/SPRY-forming B30.2 domain. RFPL1, also known as RING finger protein 78 (RNF78), is expressed during cell differentiation. RFPL2, also known as RING finger protein 79 (RNF79), shows high sequence similarity with other RFPL gene products. Its biological role remains unclear. RFPL3 interacts directly with CREB binding protein (CBP) in the nucleus of lung cancer cells. RFPL3 and CBP synergistically upregulate TERT activity and promote lung cancer growth. Moreover, RFPL3 acts as a novel E3 ubiquitin ligase modulating the integration activity of human immunodeficiency virus, type 1 (HIV-1) preintegration complex. RFPL4A, also known as RING finger protein 210 (RNF210), is a novel factor that increases the G1 population and decreases sensitivity to chemotherapy in human colorectal cancer cells. This model corresponds to the C4C4-type RING finger. RFPL4A lacks the fourth conserved zinc-binding residue, cysteine, and the eighth zinc-binding residue, cysteine; in RFPL2, it is replaced by serine.

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                   ....*....|....*....|....*....|....*.
gi 2462505093   13 SCPICTQTFDEtirkPISLGCGHTVCKMCLNKLHRK 48
Cdd:cd16621      2 SCPVCSDYLEK----PVSLECGYACCLQCLNSLQKE 33

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.

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                   ....*....|....*....|....*....|....*....|....*..
gi 2462505093   12 LSCPICTQTFDETI-RKPISLGCGHTVCKMCLNKLHRKA-----CPF 52
Cdd:cd16516      1 LECKVCFEKYSHQQeHRPRNLPCGHVLCRECVTALAHPRrskleCPF 47

zinc finger;

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                    ....*....|....*....|....*..
gi 2462505093   413 KYKTYMCRDMKqRGGCPRGASCTFAHS 439
Cdd:smart00356    1 KYKTELCKFFK-RGYCPRGDRCKFAHP 26

RING finger, HC subclass, found in Drosophila melanogaster protein Seven-in-Absentia (sina) and its homologs; This subfamily includes the Drosophila melanogaster protein Seven-in-Absentia (sina), its mammalian orthologs, SIAH1 and SIAH2, plant SINA-related proteins, and similar proteins. Sina plays an important role in the phyllopod-dependent degradation of the transcriptional repressor tramtrack to allow the formation of the R7 photoreceptor in the developing eye of Drosophila melanogaster. Both SIAH1 and SIAH2 are E3 ubiquitin-protein ligases, mediating the ubiquitinylation and subsequent proteasomal degradation of biologically important target proteins that regulate general functions, such as cell cycle control, apoptosis, and DNA repair. They are inducible by the tumor suppressor and transcription factor p53. SIAH2 can also be regulated by sex hormones and cytokine signaling. Moreover, they share high sequence similarity, but possess contrary roles in cancer, with SIAH1 more often acting as a tumor suppressor while SIAH2 functions as a proto-oncogene. Plant SINAT1-5 are putative E3 ubiquitin ligases involved in the regulation of stress responses. All subfamily members possess two characteristic domains, an N-terminal C3HC4-type RING-HC finger and a C-terminal tumor necrosis factor (TNF) receptor associated factor (TRAF)-like substrate-binding domain (SBD).

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                   ....*....|....*....|....*....|....*....|..
gi 2462505093   12 LSCPICTqtfdETIRKPIsLGC--GHTVCKMCLNKLHRKaCP 51
Cdd:cd16571      1 LECPVCF----EPLLPPI-YQCsnGHLLCSSCRSKLTNK-CP 36

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 2462505093   12 LSCPICTQTFDEtirkPISLGCGHTVCKMClnkLHRKACP 51
Cdd:cd16590      7 LTCPICLDYFQD----PVSIECGHNFCRGC---LHRNWAP 39

RING finger, HC subclass, found in yeast Bre1 and its homologs from eukaryotes; Bre1 is an E3 ubiquitin-protein ligase that catalyzes monoubiquitination of histone H2B in concert with the E2 ubiquitin-conjugating enzyme, Rad6. The Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks (DSBs) during meiosis in yeast. it is also required, indirectly, for the methylation of histone 3 on lysine 4 (H3K4) and 79. RNF20, also known as BRE1A and RNF40, also known as BRE1B, are the mammalian homologs of Bre1. They work together to form a heterodimeric Bre1 complex that facilitate the K120 monoubiquitination of histone H2B (H2Bub1), a DNA damage-induced histone modification that is crucial for recruitment of the chromatin remodeler SNF2h to DNA double-strand break (DSB) damage sites. Moreover, the Bre1 complex acts as a tumor suppressor, augmenting expression of select tumor suppressor genes and suppressing select oncogenes. Deficiency in the mammalian histone H2B ubiquitin ligase Bre1 leads to replication stress and chromosomal instability. All subfamily members contain a C3HC4-type RING-HC finger at its C-terminus.

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                   ....*....|....*....|....*....|....*....|....
gi 2462505093   12 LSCPICTQTFDETIrkpISLgCGHTVCKMCLNKL----HRKaCP 51
Cdd:cd16499      7 LKCSVCNDRFKDVI---ITK-CGHVFCNECVQKRletrQRK-CP 45

RING finger, HC subclass, found in RING finger protein 166 (RNF166) and similar proteins; RNF166 is encoded by the gene RNF166 targeted by thyroid hormone receptor alpha1 (TRalpha1), which is important in brain development. It plays an important role in RNA virus-induced interferon-beta production by enhancing the ubiquitination of TRAF3 and TRAF6. RNF166, together with three closely related proteins: RNF114, RNF125 and RNF138, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                           10        20        30
                   ....*....|....*....|....*....|..
gi 2462505093   12 LSCPICTQTFdetiRKPISLG-CGHTVCKMCL 42
Cdd:cd16549      2 FSCPICLEVY----HKPVVITsCGHTFCGECL 29