RING finger, H2 subclass, found in vacuolar protein sorting-associated protein 11 homolog (Vps11) and similar proteins; Vps11, also known as RING finger protein 108 (RNF108), is a soluble protein involved in regulation of glycolipid degradation and retrograde toxin transport. It is highly expressed in heart and pancreas. Vps11 associates with Vps16, Vps18, and Vps33 to form a Class C Vps core complex that is required for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE)-mediated membrane fusion at the lysosome-like yeast vacuole. The core complex, together with two additional compartment-specific subunits, forms the tethering complexes HOPS (homotypic vacuole fusion and protein sorting) and CORVET (class C core vacuole/endosome transport). CORVET contains the additional Vps3 and Vps8 subunits. It operates at endosomes, controls traffic into late endosomes and interacts with the Rab5/Vps21-GTP form. HOPS contains the additional Vps39 and Vps41 subunits. It operates at the lysosomal vacuole, controls all traffic from late endosomes into the vacuole and interacts with the Rab7/Ypt7-GTP form. Vps11 is a central scaffold protein upon which both HOPS and CORVET assemble. The HOPS and CORVET complexes disassemble in the absence of Vps11, resulting in massive fragmentation of vacuoles. Vps11 contains a clathrin repeat domain and a C-terminal C3H2C3-type RING-H2 finger. This subfamily also includes Vps11 homologs found in fungi, such as Saccharomyces cerevisiae vacuolar membrane protein Pep5p, also known as carboxypeptidase Y-deficient protein 5, vacuolar morphogenesis protein 1, or vacuolar biogenesis protein END1. Pep5p is essential for vacuolar biogenesis. It associates with Pep3p to form a core Pep3p/Pep5p complex that promotes vesicular docking/fusion reactions in conjunction with SNARE proteins at multiple steps in transport routes to the vacuole.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 58037259 820 TKCSICNSALELPSVHFLCGHSFHQHCFESYSESDADCPTCLPE 863
Cdd:cd16688   1 TKCSACGSTLDLPSVHFLCGHSFHQHCLEDYEENDRECPLCAPE 44

Region in Clathrin and VPS; Each region is about 140 amino acids long. The regions are composed of multiple alpha helical repeats. They occur in the arm region of the Clathrin heavy chain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58037259   417 KLEPSYVIRKFLDAQRIHNLTAYLQT-LHRQSLANADHTTLLLNCYTKLKDSSKLEEFIKTKSesevHFDVETAIKVLRQ 495
Cdd:pfam00637   7 PIDVSRVVKLFEKAGLLEELISYLESaLKEDSRENPALQTALIELYAKYDDPEELEEFLKKNN----NYDLEKVAKLCEK 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 58037259   496 AGYYSHALYLaenHAHHEWYLK-IQL-EDIKNYQEALRYIGKL 536
Cdd:pfam00637  83 ADLYEEAVIL---YKKIGNWKEaISLlKKLGDYKDAIEYAVKS 122

RING finger, H2 subclass, found in vacuolar protein sorting-associated protein 11 homolog (Vps11) and similar proteins; Vps11, also known as RING finger protein 108 (RNF108), is a soluble protein involved in regulation of glycolipid degradation and retrograde toxin transport. It is highly expressed in heart and pancreas. Vps11 associates with Vps16, Vps18, and Vps33 to form a Class C Vps core complex that is required for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE)-mediated membrane fusion at the lysosome-like yeast vacuole. The core complex, together with two additional compartment-specific subunits, forms the tethering complexes HOPS (homotypic vacuole fusion and protein sorting) and CORVET (class C core vacuole/endosome transport). CORVET contains the additional Vps3 and Vps8 subunits. It operates at endosomes, controls traffic into late endosomes and interacts with the Rab5/Vps21-GTP form. HOPS contains the additional Vps39 and Vps41 subunits. It operates at the lysosomal vacuole, controls all traffic from late endosomes into the vacuole and interacts with the Rab7/Ypt7-GTP form. Vps11 is a central scaffold protein upon which both HOPS and CORVET assemble. The HOPS and CORVET complexes disassemble in the absence of Vps11, resulting in massive fragmentation of vacuoles. Vps11 contains a clathrin repeat domain and a C-terminal C3H2C3-type RING-H2 finger. This subfamily also includes Vps11 homologs found in fungi, such as Saccharomyces cerevisiae vacuolar membrane protein Pep5p, also known as carboxypeptidase Y-deficient protein 5, vacuolar morphogenesis protein 1, or vacuolar biogenesis protein END1. Pep5p is essential for vacuolar biogenesis. It associates with Pep3p to form a core Pep3p/Pep5p complex that promotes vesicular docking/fusion reactions in conjunction with SNARE proteins at multiple steps in transport routes to the vacuole.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 58037259 820 TKCSICNSALELPSVHFLCGHSFHQHCFESYSESDADCPTCLPE 863
Cdd:cd16688   1 TKCSACGSTLDLPSVHFLCGHSFHQHCLEDYEENDRECPLCAPE 44

Region in Clathrin and VPS; Each region is about 140 amino acids long. The regions are composed of multiple alpha helical repeats. They occur in the arm region of the Clathrin heavy chain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58037259   417 KLEPSYVIRKFLDAQRIHNLTAYLQT-LHRQSLANADHTTLLLNCYTKLKDSSKLEEFIKTKSesevHFDVETAIKVLRQ 495
Cdd:pfam00637   7 PIDVSRVVKLFEKAGLLEELISYLESaLKEDSRENPALQTALIELYAKYDDPEELEEFLKKNN----NYDLEKVAKLCEK 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 58037259   496 AGYYSHALYLaenHAHHEWYLK-IQL-EDIKNYQEALRYIGKL 536
Cdd:pfam00637  83 ADLYEEAVIL---YKKIGNWKEaISLlKKLGDYKDAIEYAVKS 122

Clathrin heavy chain repeat homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58037259    411 YIRTIGKLEPSYVIRKFLDAQRIHNLTAYLQTLHRQSLANADHTTLLLNCYTKlKDSSKLEEFIKTKSEsevHFDVETAI 490
Cdd:smart00299   1 LLEVSDPIDVSEVVELFEKRNLLEELIPYLESALKLNSENPALQTKLIELYAK-YDPQKEIERLDNKSN---HYDIEKVG 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 58037259    491 KVLRQAGYYSHALYLAENHAHHEWYLKIQLEDIKNYQEALRYIGK 535
Cdd:smart00299  77 KLCEKAKLYEEAVELYKKDGNFKDAIVTLIEHLGNYEKAIEYFVK 121

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58037259 142 VVSCLTVHENLNFMAIGFTDGSVTLnkGDITRDRHSKTQILHKGnyPVTGLAFRQAGKTthLFVVTTEN-VQSYIVSgKD 220
Cdd:cd00200  11 GVTCVAFSPDGKLLATGSGDGTIKV--WDLETGELLRTLKGHTG--PVRDVAASADGTY--LASGSSDKtIRLWDLE-TG 83

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 58037259 221 YPRVELDTHGCGLRCSALsdpSQDLQFIVAG--DECVYLYQPDERGPCFAFEGHK-----LIVHWFRGYLVIVSRDRKV 292
Cdd:cd00200  84 ECVRTLTGHTSYVSSVAF---SPDGRILSSSsrDKTIKVWDVETGKCLTTLRGHTdwvnsVAFSPDGTFVASSSQDGTI 159

RING finger, H2 subclass, found in vacuolar protein sorting-associated protein 11 homolog (Vps11) and similar proteins; Vps11, also known as RING finger protein 108 (RNF108), is a soluble protein involved in regulation of glycolipid degradation and retrograde toxin transport. It is highly expressed in heart and pancreas. Vps11 associates with Vps16, Vps18, and Vps33 to form a Class C Vps core complex that is required for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE)-mediated membrane fusion at the lysosome-like yeast vacuole. The core complex, together with two additional compartment-specific subunits, forms the tethering complexes HOPS (homotypic vacuole fusion and protein sorting) and CORVET (class C core vacuole/endosome transport). CORVET contains the additional Vps3 and Vps8 subunits. It operates at endosomes, controls traffic into late endosomes and interacts with the Rab5/Vps21-GTP form. HOPS contains the additional Vps39 and Vps41 subunits. It operates at the lysosomal vacuole, controls all traffic from late endosomes into the vacuole and interacts with the Rab7/Ypt7-GTP form. Vps11 is a central scaffold protein upon which both HOPS and CORVET assemble. The HOPS and CORVET complexes disassemble in the absence of Vps11, resulting in massive fragmentation of vacuoles. Vps11 contains a clathrin repeat domain and a C-terminal C3H2C3-type RING-H2 finger. This subfamily also includes Vps11 homologs found in fungi, such as Saccharomyces cerevisiae vacuolar membrane protein Pep5p, also known as carboxypeptidase Y-deficient protein 5, vacuolar morphogenesis protein 1, or vacuolar biogenesis protein END1. Pep5p is essential for vacuolar biogenesis. It associates with Pep3p to form a core Pep3p/Pep5p complex that promotes vesicular docking/fusion reactions in conjunction with SNARE proteins at multiple steps in transport routes to the vacuole.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 58037259 820 TKCSICNSALELPSVHFLCGHSFHQHCFESYSESDADCPTCLPE 863
Cdd:cd16688   1 TKCSACGSTLDLPSVHFLCGHSFHQHCLEDYEENDRECPLCAPE 44

RING finger, H2 subclass, found in vacuolar protein sorting-associated proteins Vps8, Vps11, Vps18, Vps41, and similar proteins; This subfamily corresponds to a group of vacuolar protein sorting-associated proteins containing a C-terminal C3H2C3-type RING-H2 finger, which includes Vps8, Vps11, Vps18, and Vps41. Vps11 and Vps18 associate with Vps16 and Vps33 to form a Class C Vps core complex that is required for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE)-mediated membrane fusion at the lysosome-like yeast vacuole. The core complex, together with two additional compartment-specific subunits, forms the tethering complexes HOPS (homotypic vacuole fusion and protein sorting) and CORVET (class C core vacuole/endosome transport). CORVET contains the additional Vps3 and Vps8 subunits. It operates at endosomes, controls traffic into late endosomes and interacts with the Rab5/Vps21-GTP form. HOPS contains the additional Vps39 and Vps41 subunits. It operates at the lysosomal vacuole, controls all traffic from late endosomes into the vacuole and interacts with the Rab7/Ypt7-GTP form.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 58037259 821 KCSICNSAL-------ELPSVHFLCGHSFHQHCFESYSESDADCPTCL 861
Cdd:cd16484   1 KCPICTLPLkesdvgaNSPVVVFFCGHMFHKFCLPELSMTEAACPICL 48

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 58037259   821 KCSICNSALELPSVHFLCGHSFHQHCFESYSESDADCPTC 860
Cdd:pfam13923   1 MCPICMDMLKDPSTTTPCGHVFCQDCILRALRAGNECPLC 40

Clathrin heavy chain repeat homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58037259    411 YIRTIGKLEPSYVIRKFLDAQRIHNLTAYLQTLHRQSLANADHTTLLLNCYTKlKDSSKLEEFIKTKSEsevHFDVETAI 490
Cdd:smart00299   1 LLEVSDPIDVSEVVELFEKRNLLEELIPYLESALKLNSENPALQTKLIELYAK-YDPQKEIERLDNKSN---HYDIEKVG 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 58037259    491 KVLRQAGYYSHALYLAENHAHHEWYLKIQLEDIKNYQEALRYIGK 535
Cdd:smart00299  77 KLCEKAKLYEEAVELYKKDGNFKDAIVTLIEHLGNYEKAIEYFVK 121

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 58037259 821 KCSICNSALELPSVHFL-CGHSFHQHCFESYSESDADCPTC 860
Cdd:cd16481   1 PCIICHDDLKPDQLAKLeCGHIFHKECIKQWLKEQSTCPTC 41

RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar proteins; AMFR, also known as AMF receptor, or RING finger protein 45, or ER-protein gp78, is an internalizing cell surface glycoprotein localized in both plasma membrane caveolae and the endoplasmic reticulum (ER). It is involved in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. AMFR also functions as a RING finger-dependent ubiquitin protein ligase (E3) implicated in the degradation from the ER. AMFR contains an N-terminal RING-H2 finger and a C-terminal ubiquitin-associated (UBA)-like CUE domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 58037259 821 KCSIC----NSALELPsvhflCGHSFHQHCFESYSESDADCPTC 860
Cdd:cd16455   2 DCAICwesmQSARKLP-----CGHLFHNSCLRSWLEQDTSCPTC 40

RING finger, H2 subclass, found in synoviolin and similar proteins; Synoviolin, also known as synovial apoptosis inhibitor 1 (Syvn1), Hrd1, or Der3, is an endoplasmic reticulum (ER)-anchoring E3 ubiquitin ligase that functions as a suppressor of ER stress-induced apoptosis and plays a role in homeostasis maintenance. It also targets tumor suppressor gene p53 for proteasomal degradation, suggesting crosstalk between ER associated degradation (ERAD) and p53 mediated apoptotic pathway under ER stress. Moreover, synoviolin controls body weight and mitochondrial biogenesis through negative regulation of the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1beta. It upregulates amyloid beta production by targeting a negative regulator of gamma-secretase, Retention in endoplasmic reticulum 1 (Rer1), for degradation. It is also involved in the degradation of endogenous immature nicastrin, and affects amyloid beta-protein generation. Moreover, synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of rheumatoid arthritis (RA). It functions as an anti-apoptotic factor that is responsible for the outgrowth of synovial cells during the development of RA. It promotes inositol-requiring enzyme 1 (IRE1) ubiquitination and degradation in synovial fibroblasts with collagen-induced arthritis. Furthermore, the upregulation of synoviolin may represent a protective response against neurodegeneration in Parkinson's disease (PD). In addition, synoviolin is involved in liver fibrogenesis. Synoviolin contains a C3H2C2-type RING-H2 finger.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 58037259 822 CSICNSALELPSVHFLCGHSFHQHCFESYSESDADCPTC 860
Cdd:cd16479   4 CIICREEMTVGAKKLPCGHIFHLSCLRSWLQRQQTCPTC 42

RING finger, H2 subclass, found in Saccharomyces cerevisiae transmembrane E3 ubiquitin-protein ligase 1 (TUL1) and similar proteins; This subfamily includes Saccharomyces cerevisiae TUL1, Schizosaccharomyces pombe DSC E3 ubiquitin ligase complex subunit 1 (DSC1), and Arabidopsis thaliana protein FLYING SAUCER 2 (FLY2). TUL1 is the catalytic component of DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes and function in protein homeostasis under non-stress conditions, and support a role in protein quality control. It mediates ubiquitination of vacuolar proteins such as CPS1, PPN1, PEP12 and other proteins containing exposed hydrophilic residues within their transmembrane domains, leading to their sorting into internal vesicles in late endosomes. TUL1 also targets the unpalmitoylated endosomal SNARE TLG1 to the multivesicular body (MVB) pathway. DSC1, also known as defective for SREBP cleavage protein 1, is the catalytic component of the DSC E3 ubiquitin ligase complex required for the sre1 transcriptional activator proteolytic cleavage to release the soluble transcription factor from the membrane in low oxygen or sterol conditions. FLY2 acts as an E3 ubiquitin-protein ligase that may be involved in xylem development. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 58037259 820 TKCSICNSALELPSVHFL--------CGHSFHQHCFESYSESDADCPTC---LP 862
Cdd:cd23117   5 VDCVICMSDIELPSTNSVrrdymvtpCNHIFHTNCLERWMDIKLECPTCrrpLP 58

RING finger, HC subclass, found in radiation sensitivity protein 5 (RAD5) and similar proteins; RAD5, also known as revertibility protein 2 (REV2), or DNA repair protein RAD5, is a probable helicase, and a member of the UBC2/RAD6 epistasis group. It functions with the DNA repair protein RAD18 in error-free postreplication DNA repair. It is involved in the maintenance of wild-type rates of instability of simple repetitive sequences such as poly(GT) repeats. It may also be involved in maintaining a balance which acts in favor of error-prone non-homologous joining during DNA double-strand breaks repairs. It recruits the UBC13-MMS2 dimer to chromatin for DNA repair. RAD5 contains a typical C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 58037259 817 FQKTKCSICN-SALELPSVHFL-CGHSFHQHCFESY------SESDADCPTC 860
Cdd:cd23131   1 LIEVECSICTqEPIEVGEVVFTeCGHSFCEDCLLEYiefqnkKKLDLKCPNC 52

RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; Pirh2, also known as RING finger and CHY zinc finger domain-containing protein 1 (Rchy1), androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, RING finger protein 199 (RNF199), or zinc finger protein 363 (ZNF363), is a p53 inducible E3 ubiquitin-protein ligase that functions as a negative regulator of p53. It preferably ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting a role of Pirh2 in downregulating the transcriptionally active form of p53 in the cell. Moreover, Pirh2 inhibits the transcriptional activity of p73, a homolog of the tumor suppressor p53, by promoting its ubiquitination. It also monoubiquitinates DNA polymerase eta (PolH) to suppress translesion DNA synthesis. Furthermore, Pirh2 functions as a negative regulator of the cyclin-dependent kinase inhibitor p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. Pirh2 enhances androgen receptor (AR) signaling through inhibition of histone deacetylase 1 (HDAC1) and is overexpressed in prostate cancer. It interacts with TIP60 and this association may regulate Pirh2 stability. In addition, the oncoprotein pleomorphic adenoma gene like 2 (PLAGL2) can bind to the Pirh2 dimer and therefore control the stability of Pirh2. Pirh2 contains a total of nine zinc-binding sites with six located at the N-terminal region, two in the C3H2C3-type RING-H2 domain, and one in the C-terminal region. Nine zinc binding sites comprise three different zinc coordination schemes, including RING type cross-brace zinc coordination, C4 zinc finger, and a novel left-handed beta-spiral zinc-binding motif formed by three recurrent CCHC sequence motifs. This subfamily also includes Drosophila melanogaster Deltex, a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 58037259 822 CSICNSAL--ELPSVHFL-CGHSFHQHCFESYSESDA-DCPTC 860
Cdd:cd16464   2 CPVCLEDLftSREPVHVLpCGHLMHSTCFEEYLKSGNyRCPLC 44

RING finger, HC subclass, found in tripartite motif-containing protein TRIM21 and similar proteins; TRIM21, also known as 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, Ro(SS-A), RING finger protein 81 (RNF81), or Sjoegren syndrome type A antigen (SS-A), is a ubiquitously expressed E3 ubiquitin-protein ligase and a high affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. As a cytosolic Fc receptor, TRIM21 binds the Fc of virus-associated antibodies and targets the complex in the cytosol for proteasomal degradation in a process known as antibody-dependent intracellular neutralization (ADIN), and provides an intracellular immune response to protect host defense against pathogen infection. It shows remarkably broad isotype specificity as it does not only bind IgG, but also IgM and IgA. Moreover, TRIM21 promotes the cytosolic DNA sensor cGAS and the cytosolic RNA sensor RIG-I sensing of viral genomes during infection by antibody-opsonized virus. It stimulates inflammatory signaling and activates innate transcription factors, such as nuclear factor-kappaB (NF-kappaB). TRIM21 also plays an essential role in p62-regulated redox homeostasis, suggesting it may be a viable target for treating pathological conditions resulting from oxidative damage. Furthermore, TRIM21 may have implications for various autoimmune diseases associated with uncontrolled antiviral signaling through the regulation of Nmi-IFI35 complex-mediated inhibition of innate antiviral response. TRIM21 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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 58037259 815 KIFQKTKCSICNSALELPsVHFLCGHSFHQHC-FESYSESDADCPTC--------LPENRKVMDMIRAQEQK 877
Cdd:cd16596   5 MMWEEVTCPICLDPFVEP-VSIECGHSFCQECiSQVGKGGGSVCPVCrqrfllknLRPNRQLANMVNNLKEI 75

Lipopolysaccharide biosynthesis regulator YciM/LapB, contains six TPR domains and a C-terminal metal-binding domain [Cell wall/membrane/envelope biogenesis];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58037259 361 LEMLFKKNLFEMAINLAKSQHLDSDGLAQIFMQYGDHLYSKGNHDGAVQQYIRTIgKLEPSYV------IRKFLDAQRIH 434
Cdd:COG2956 117 AEIYEQEGDWEKAIEVLERLLKLGPENAHAYCELAELYLEQGDYDEAIEALEKAL-KLDPDCArallllAELYLEQGDYE 195

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 58037259 435 NLTAYLQTLHRQSLANADHTTLLLNCYTKLKDSSKLEEFIKTKSESEVHFDVETAI-KVLRQAGYYSHALYLAENH 509
Cdd:COG2956 196 EAIAALERALEQDPDYLPALPRLAELYEKLGDPEEALELLRKALELDPSDDLLLALaDLLERKEGLEAALALLERQ 271

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

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 58037259 822 CSICnSALELPSVHFLCGHSFHQHCFESYSESDADCPTC 860
Cdd:cd16535   4 CSIC-SELFIEAVTLNCSHSFCSYCITEWMKRKKECPIC 41

RING finger, HC subclass, found in checkpoint with forkhead and RING finger domains protein (CHFR); CHFR, also known as RING finger protein 196 (RNF196), is a checkpoint protein that delays entry into mitosis in response to stress. It functions as an E3 ubiquitin ligase that ubiquitinates and degrades its target proteins, such as Aurora-A, Plk1, Kif22, and PARP-1, which are critical for proper mitotic transitions. It also plays an important role in cell cycle progression and tumor suppression, and is negatively regulated by SUMOylation-mediated proteasomal ubiquitylation. Moreover, CHFR is involved in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation. CHFR contains a fork head associated (FHA) domain and a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 58037259 821 KCSICNSALELPSVHFLCGHSFHQHCFESYSE-SDADCPTC 860
Cdd:cd16503   4 TCSICQDLLHDCVSLQPCMHNFCAACYSDWMErSNTECPTC 44

RING finger, HC subclass, found in Saccharomyces cerevisiae radiation sensitivity protein 18 (RAD18) and similar proteins; RAD18, also called RING-type E3 ubiquitin transferase RAD18, acts as a postreplication repair E3 ubiquitin-protein ligase that associates with the E2 ubiquitin conjugating enzyme UBC2/RAD6 to form the UBC2-RAD18 ubiquitin ligase complex involved in postreplicative repair (PRR) of damaged DNA. The UBC2-RAD18 complex cooperates with RAD5 and the UBC13-MMS2 dimer to attach mono-ubiquitin chains on 'Lys-164' of POL30, which is necessary for PRR. The UBC2-RAD18 complex is also involved in prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine. RAD18 is an E3 RING-finger protein belonging to the UBC2/RAD6 epistasis group. It contains a typical C3HC4-type RING-HC finger.

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gi 58037259 821 KCSICNSALELPsVHFLCGHSFHQHCFESYSESDADCPTCLPENRK 866
Cdd:cd23148   5 RCHICKDLLKAP-MRTPCNHTFCSFCIRTHLNNDARCPLCKAEVTE 49

RING finger, H2 subclass, found in RING finger protein 165 (RNF165) and similar proteins; RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. RNF165 contains two serine rich domains, a nuclear localization signal, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is responsible for the enhancement of BMP-Smad1/5/8 signaling in the spinal cord.

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gi 58037259 821 KCSICNSALE-------LPsvhflCGHSFHQHCFESYSESDADCPTC 860
Cdd:cd16682   9 KCTICLSMLEdgedvrrLP-----CMHLFHQLCVDQWLAMSKKCPIC 50

RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. RNF111 also regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.

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gi 58037259 821 KCSICNSALE-------LPsvhflCGHSFHQHCFESYSESDADCPTC 860
Cdd:cd16681  12 KCTICLSILEegedvrrLP-----CMHLFHQVCVDQWLITNKKCPIC 53