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 1804891968 814 TKCSICNSALELPSVHFLCGHSFHQHCFESYSESDADCPTCLPE 857
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 1804891968 411 KLEPSYVIRKFLDAQRIHNLTAYLQT-LHRQSLANADHTTLLLNCYTKLKDSSKLEEFIKKKSesevHFDVETAIKVLRQ 489
Cdd:pfam00637   7 PIDVSRVVKLFEKAGLLEELISYLESaLKEDSRENPALQTALIELYAKYDDPEELEEFLKKNN----NYDLEKVAKLCEK 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1804891968 490 AGYYSHALYLaenHAHHEWYLK-IQL-EDIKNYQEALRYIGKL 530
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 1804891968 814 TKCSICNSALELPSVHFLCGHSFHQHCFESYSESDADCPTCLPE 857
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 1804891968 411 KLEPSYVIRKFLDAQRIHNLTAYLQT-LHRQSLANADHTTLLLNCYTKLKDSSKLEEFIKKKSesevHFDVETAIKVLRQ 489
Cdd:pfam00637   7 PIDVSRVVKLFEKAGLLEELISYLESaLKEDSRENPALQTALIELYAKYDDPEELEEFLKKNN----NYDLEKVAKLCEK 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1804891968 490 AGYYSHALYLaenHAHHEWYLK-IQL-EDIKNYQEALRYIGKL 530
Cdd:pfam00637  83 ADLYEEAVIL---YKKIGNWKEaISLlKKLGDYKDAIEYAVKS 122

Clathrin heavy chain repeat homology;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804891968  405 YIRTIGKLEPSYVIRKFLDAQRIHNLTAYLQTLHRQSLANADHTTLLLNCYTKlKDSSKLEEFIKKKSEsevHFDVETAI 484
Cdd:smart00299   1 LLEVSDPIDVSEVVELFEKRNLLEELIPYLESALKLNSENPALQTKLIELYAK-YDPQKEIERLDNKSN---HYDIEKVG 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1804891968  485 KVLRQAGYYSHALYLAENHAHHEWYLKIQLEDIKNYQEALRYIGK 529
Cdd:smart00299  77 KLCEKAKLYEEAVELYKKDGNFKDAIVTLIEHLGNYEKAIEYFVK 121

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 1804891968 355 LEMLFKKNLFEMAINLAKSQHLDSDGLAQIFMQYGDHLYSKGNHDGAVQQYIRTIgKLEPSYV------IRKFLDAQRIH 428
Cdd:COG2956   117 AEIYEQEGDWEKAIEVLERLLKLGPENAHAYCELAELYLEQGDYDEAIEALEKAL-KLDPDCArallllAELYLEQGDYE 195

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1804891968 429 NLTAYLQTLHRQSLANADHTTLLLNCYTKLKDSSKLEEFIKKKSESEVHFDVETAI-KVLRQAGYYSHALYLAENH 503
Cdd:COG2956   196 EAIAALERALEQDPDYLPALPRLAELYEKLGDPEEALELLRKALELDPSDDLLLALaDLLERKEGLEAALALLERQ 271

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 1804891968 814 TKCSICNSALELPSVHFLCGHSFHQHCFESYSESDADCPTCLPE 857
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 1804891968 815 KCSICNSAL-------ELPSVHFLCGHSFHQHCFESYSESDADCPTCL 855
Cdd:cd16484     1 KCPICTLPLkesdvgaNSPVVVFFCGHMFHKFCLPELSMTEAACPICL 48

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1804891968 815 KCSICNSALELPSVHFLCGHSFHQHCFESYSESDADCPTC 854
Cdd:pfam13923   1 MCPICMDMLKDPSTTTPCGHVFCQDCILRALRAGNECPLC 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1804891968 816 CSICNSALELPSV--HFLCGHSFHQHCFESYSES-DADCPTC 854
Cdd:cd16448     1 CVICLEEFEEGDVvrLLPCGHVFHLACILRWLESgNNTCPLC 42

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 1804891968 815 KCSICNSALELPSVHFL-CGHSFHQHCFESYSESDADCPTC 854
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 1804891968 815 KCSIC----NSALELPsvhflCGHSFHQHCFESYSESDADCPTC 854
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 1804891968 816 CSICNSALELPSVHFLCGHSFHQHCFESYSESDADCPTC 854
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
                  ....*....|....*....|....*....|....*....|....*....
gi 1804891968 814 TKCSICNSALELPSVHFL--------CGHSFHQHCFESYSESDADCPTC 854
Cdd:cd23117     5 VDCVICMSDIELPSTNSVrrdymvtpCNHIFHTNCLERWMDIKLECPTC 53

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 1804891968 811 FQKTKCSICN-SALELPSVHFL-CGHSFHQHCFESY------SESDADCPTC 854
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 1804891968 816 CSICNSAL--ELPSVHFL-CGHSFHQHCFESYSESDA-DCPTC 854
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 1804891968 809 KIFQKTKCSICNSALELPsVHFLCGHSFHQHC-FESYSESDADCPTC--------LPENRKVMDMIRAQEQK 871
Cdd:cd16596     5 MMWEEVTCPICLDPFVEP-VSIECGHSFCQECiSQVGKGGGSVCPVCrqrfllknLRPNRQLANMVNNLKEI 75

RING finger, H2 subclass, found in TRAF-interacting protein (TRAIP) and similar proteins; TRAIP, also known as RING finger protein 206 (RNF206) or TRIP, is a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation and differentiation. It is found near mitotic chromosomes and functions as a regulator of the spindle assembly checkpoint. TRAIP interacts with tumor necrosis factor (TNF)-receptor-associated factor (TRAF) proteins and inhibits TNF-alpha-mediated nuclear factor (NF)-kappaB activation. It also interacts with two tumor suppressors CYLD and spleen tyrosine kinase (Syk), and DNA polymerase eta, which facilitates translesional synthesis after DNA damage. TRAIP contains an N-terminal C3H2C2-type RING-H2 finger and an extended coiled-coil domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1804891968 816 CSICN----SALELPSVHflCGHSFHQHCFESYSESDADCPTC 854
Cdd:cd16480     2 CTICSdffdNSRDVAAIH--CGHTFHYDCLLQWFDTSRTCPQC 42

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 1804891968 816 CSICnSALELPSVHFLCGHSFHQHCFESYSESDADCPTC 854
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 1804891968 815 KCSICNSALELPSVHFLCGHSFHQHCFESYSE-SDADCPTC 854
Cdd:cd16503     4 TCSICQDLLHDCVSLQPCMHNFCAACYSDWMErSNTECPTC 44