Vacuolar protein sorting protein 11 C terminal; This domain family is found in eukaryotes, and is approximately 50 amino acids in length. Vps 11 is one of the evolutionarily conserved class C vacuolar protein sorting genes (c-vps: vps11, vps16, vps18, and vps33), whose products physically associate to form the c-vps protein complex required for vesicle docking and fusion.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1804892002 868 NRKVMDMIRAQEQKRDLHDQFQHQLKCSNDSFSVIADYFGRGVF 911
Cdd:pfam12451   1 NETIRELRRAQEESADQHDLFKSALEESTDRFKVIADYFGRGVM 44

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 1804892002 142 VVSCLTVHENLNFMAIGFTDGSVTLnkGDITRDRHSKTQILHKGnyPVTGLAFRQAGKTthLFVVTTEN-VQSYIVSgKD 220
Cdd:cd00200    11 GVTCVAFSPDGKLLATGSGDGTIKV--WDLETGELLRTLKGHTG--PVRDVAASADGTY--LASGSSDKtIRLWDLE-TG 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1804892002 221 YPRVELDTHGCGLRCSALsdpSQDLQFIVAG--DECVYLYQPDERGPCFAFEGHK-----LIAHWFRGYLIIVSRDRKV 292
Cdd:cd00200    84 ECVRTLTGHTSYVSSVAF---SPDGRILSSSsrDKTIKVWDVETGKCLTTLRGHTdwvnsVAFSPDGTFVASSSQDGTI 159

Vacuolar protein sorting protein 11 C terminal; This domain family is found in eukaryotes, and is approximately 50 amino acids in length. Vps 11 is one of the evolutionarily conserved class C vacuolar protein sorting genes (c-vps: vps11, vps16, vps18, and vps33), whose products physically associate to form the c-vps protein complex required for vesicle docking and fusion.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1804892002 868 NRKVMDMIRAQEQKRDLHDQFQHQLKCSNDSFSVIADYFGRGVF 911
Cdd:pfam12451   1 NETIRELRRAQEESADQHDLFKSALEESTDRFKVIADYFGRGVM 44

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1804892002 825 KCSICNSALELPSVHFLCGHSFHQHCFESYSESDADCPTC 864
Cdd:pfam13923   1 MCPICMDMLKDPSTTTPCGHVFCQDCILRALRAGNECPLC 40

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 1804892002  826 CSICNSALELPSVHFLCGHSFHQHCFESYSESDAD-CPTC 864
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNtCPIC 40

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 1804892002 142 VVSCLTVHENLNFMAIGFTDGSVTLnkGDITRDRHSKTQILHKGnyPVTGLAFRQAGKTthLFVVTTEN-VQSYIVSgKD 220
Cdd:cd00200    11 GVTCVAFSPDGKLLATGSGDGTIKV--WDLETGELLRTLKGHTG--PVRDVAASADGTY--LASGSSDKtIRLWDLE-TG 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1804892002 221 YPRVELDTHGCGLRCSALsdpSQDLQFIVAG--DECVYLYQPDERGPCFAFEGHK-----LIAHWFRGYLIIVSRDRKV 292
Cdd:cd00200    84 ECVRTLTGHTSYVSSVAF---SPDGRILSSSsrDKTIKVWDVETGKCLTTLRGHTdwvnsVAFSPDGTFVASSSQDGTI 159

Vacuolar protein sorting protein 11 C terminal; This domain family is found in eukaryotes, and is approximately 50 amino acids in length. Vps 11 is one of the evolutionarily conserved class C vacuolar protein sorting genes (c-vps: vps11, vps16, vps18, and vps33), whose products physically associate to form the c-vps protein complex required for vesicle docking and fusion.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1804892002 868 NRKVMDMIRAQEQKRDLHDQFQHQLKCSNDSFSVIADYFGRGVF 911
Cdd:pfam12451   1 NETIRELRRAQEESADQHDLFKSALEESTDRFKVIADYFGRGVM 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 1804892002 421 KLEPSYVIRKFLDAQRIHNLTAYLQT-LHRQSLANADHTTLLLNCYTKLKDSSKLEEFIKKKSesevHFDVETAIKVLRQ 499
Cdd:pfam00637   7 PIDVSRVVKLFEKAGLLEELISYLESaLKEDSRENPALQTALIELYAKYDDPEELEEFLKKNN----NYDLEKVAKLCEK 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1804892002 500 AGYYSHALYLaenHAHHEWYLK-IQL-EDIKNYQEALRYIGKL 540
Cdd:pfam00637  83 ADLYEEAVIL---YKKIGNWKEaISLlKKLGDYKDAIEYAVKS 122

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 1804892002 826 CSICNSALELPSV--HFLCGHSFHQHCFESYSES-DADCPTC 864
Cdd:cd16448     1 CVICLEEFEEGDVvrLLPCGHVFHLACILRWLESgNNTCPLC 42

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1804892002 826 CSICNSALELPS--VHFLCGHSFHQHCFESYSESDADCPTC 864
Cdd:pfam13639   3 CPICLEEFEEGDkvVVLPCGHHFHRECLDKWLRSSNTCPLC 43

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 1804892002  826 CSICNSALELPSVHFLCGHSFHQHCFESYSESDAD-CPTC 864
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNtCPIC 40

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1804892002 822 QKTKCSICNSALELPSVhFLCGHSFHQHCFESYSESDADCPTC 864
Cdd:cd23135     2 QKLSCSICFSEIRSGAI-LKCGHFFCLSCIASWLREKSTCPLC 43

RING-H2 zinc finger domain; There are 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding. The protein, of which this domain is the conserved region, participates in diverse functions relevant to chromosome metabolism and cell cycle control.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1804892002 826 CSICNSALE-------------LPSVHFLCGHSFHQHCFESYSESDADCPTC 864
Cdd:pfam12678   3 CAICRNPFMepcpecqapgddeCPVVWGECGHAFHLHCISRWLKTNNTCPLC 54

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 1804892002 821 FQKTKCSICN-SALELPSVHFL-CGHSFHQHCFESY------SESDADCPTC 864
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 1804892002 826 CSICNSAL--ELPSVHFL-CGHSFHQHCFESYSESDA-DCPTC 864
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 1804892002 819 KIFQKTKCSICNSALELPsVHFLCGHSFHQHC-FESYSESDADCPTC--------LPENRKVMDMIRAQEQK 881
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 1804892002 361 LEMLFKKNLFEMAINLAKSQHLDSDGLAQIFMQYGDHLYSKGNHDGAVQQYIRSVwrtigKLEPSYV------IRKFLDA 434
Cdd:COG2956   117 AEIYEQEGDWEKAIEVLERLLKLGPENAHAYCELAELYLEQGDYDEAIEALEKAL-----KLDPDCArallllAELYLEQ 191

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1804892002 435 QRIHNLTAYLQTLHRQSLANADHTTLLLNCYTKLKDSSKLEEFIKKKSESEVHFDVETAI-KVLRQAGYYSHALYLAENH 513
Cdd:COG2956   192 GDYEEAIAALERALEQDPDYLPALPRLAELYEKLGDPEEALELLRKALELDPSDDLLLALaDLLERKEGLEAALALLERQ 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 1804892002 826 CSICnSALELPSVHFLCGHSFHQHCFESYSESDADCPTC 864
Cdd:cd16535     4 CSIC-SELFIEAVTLNCSHSFCSYCITEWMKRKKECPIC 41

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        40
                  ....*....|....*....|....*....|....*....|.
gi 1804892002 826 CSICNSALELPsVHFLCGHSFHQHCF-ESYSESDA-DCPTC 864
Cdd:cd16608     9 CSICLSIYQDP-VSLGCEHYFCRQCItEHWSRSEHrDCPEC 48

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1804892002 826 CSICNSALELPSVHFLCGHSFHQHCFESYSESDA-DCPTC 864
Cdd:pfam00097   1 CPICLEEPKDPVTLLPCGHLFCSKCIRSWLESGNvTCPLC 40

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1804892002 826 CSICNSALELPsVHFLCGHSFHQHCFESYSESD----ADCPTC 864
Cdd:cd16604     3 CPICLDLLKDP-VTLPCGHSFCMGCLGALWGAGrggrASCPLC 44

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1804892002 825 KCSICNSALE-------LPsvhflCGHSFHQHCFESYSESDADCPTC 864
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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1804892002 825 KCSICNSALE-------LPsvhflCGHSFHQHCFESYSESDADCPTC 864
Cdd:cd16681    12 KCTICLSILEegedvrrLP-----CMHLFHQVCVDQWLITNKKCPIC 53