WD40 repeat [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 521 RGHQDSVTGLAV--GGGFLFSSSYDRTILIWSLKDFSHVHTFKGHQDKVMALI------HIegtepvcVSGDGGGGIFVW 592
Cdd:COG2319  117 TGHTGAVRSVAFspDGKTLASGSADGTVRLWDLATGKLLRTLTGHSGAVTSVAfspdgkLL-------ASGSDDGTVRLW 189

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 593 STTfplEEQPLRKWYEPKDWrytgIHALAYSEYGH-VYTGSGDNTIKAWSLQDGSLLCTMSGHKSVVSTLVV-VNG-VLY 669
Cdd:COG2319  190 DLA---TGKLLRTLTGHTGA----VRSVAFSPDGKlLASGSADGTVRLWDLATGKLLRTLTGHSGSVRSVAFsPDGrLLA 262

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 670 SGSWDGTVRLWSLSDNSLLTVLGEETpGIVRSIlSLAADDQTLVAAYQNGDIQIW--RDDTLMKSMKIQNGAILSIAV-- 745
Cdd:COG2319  263 SGSADGTVRLWDLATGELLRTLTGHS-GGVNSV-AFSPDGKLLASGSDDGTVRLWdlATGKLLRTLTGHTGAVRSVAFsp 340

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 186478734 746 NGKWLFTGGWDKTINVQELSGDEIsvncahVGSIPG-SSVITSLLYW-EGKLFA-GFADKTIKVY 807
Cdd:COG2319  341 DGKTLASGSDDGTVRLWDLATGEL------LRTLTGhTGAVTSVAFSpDGRTLAsGSADGTVRLW 399

WD40 repeat [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 521 RGHQDSVTGLAV--GGGFLFSSSYDRTILIWSLKDFSHVHTFKGHQDKVMALI------HIegtepvcVSGDGGGGIFVW 592
Cdd:COG2319  117 TGHTGAVRSVAFspDGKTLASGSADGTVRLWDLATGKLLRTLTGHSGAVTSVAfspdgkLL-------ASGSDDGTVRLW 189

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 593 STTfplEEQPLRKWYEPKDWrytgIHALAYSEYGH-VYTGSGDNTIKAWSLQDGSLLCTMSGHKSVVSTLVV-VNG-VLY 669
Cdd:COG2319  190 DLA---TGKLLRTLTGHTGA----VRSVAFSPDGKlLASGSADGTVRLWDLATGKLLRTLTGHSGSVRSVAFsPDGrLLA 262

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 670 SGSWDGTVRLWSLSDNSLLTVLGEETpGIVRSIlSLAADDQTLVAAYQNGDIQIW--RDDTLMKSMKIQNGAILSIAV-- 745
Cdd:COG2319  263 SGSADGTVRLWDLATGELLRTLTGHS-GGVNSV-AFSPDGKLLASGSDDGTVRLWdlATGKLLRTLTGHTGAVRSVAFsp 340

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 186478734 746 NGKWLFTGGWDKTINVQELSGDEIsvncahVGSIPG-SSVITSLLYW-EGKLFA-GFADKTIKVY 807
Cdd:COG2319  341 DGKTLASGSDDGTVRLWDLATGEL------LRTLTGhTGAVTSVAFSpDGRTLAsGSADGTVRLW 399

RING finger, HC subclass, found in tripartite motif-containing protein 32 (TRIM32) and similar proteins; TRIM32, also known as 72 kDa Tat-interacting protein, zinc finger protein HT2A, or BBS11, is an E3 ubiquitin-protein ligase that promotes degradation of several targets, including actin, PIASgamma, Abl interactor 2, dysbindin, X-linked inhibitor of apoptosis (XIAP), p73 transcription factor, thin filaments and Z-bands during fasting. It plays important roles in neuronal differentiation of neural progenitor cells, as well as in controlling cell fate in skeletal muscle progenitor cells. It reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin-PI3K dissociation. It also functions as a pluripotency-reprogramming roadblock that facilitates cellular transition towards differentiation by modulating the levels of Oct4 and cMyc. Moreover, TRIM32 is an intrinsic influenza A virus (IAV) restriction factor which senses and targets the polymerase basic protein 1 (PB1) for ubiquitination and protein degradation. It also plays a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo, binds specifically to the activation domain of HIV-1 Tat, and can also interact with the HIV-2 and EIAV Tat proteins in vivo. Furthermore, TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2 (N-myc downstream-regulated gene). It negatively regulates tumor suppressor p53 to promote tumorigenesis. It also facilitates degradation of MYCN on spindle poles and induces asymmetric cell division in human neuroblastoma cells. In addition, TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress. It also plays a role in regeneration by affecting satellite cell cycle progression via modulation of the SUMO ligase PIASy (PIAS4). Defects in TRIM32 leads to limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and Bardet-Biedl syndrome. TRIM32 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain. The NHL domain mediates the interaction with Argonaute proteins and consequently allows TRIM32 to modulate the activity of certain miRNAs.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 186478734   4 PECPVCLQSYDGESTVPRVLACGHTACEECLTNLPKK-FPDTIRCPACTVL 53
Cdd:cd16587    1 LECPICLESFDEGQLRPKLLHCGHTICEQCLEKLLASlSINGVRCPFCRKV 51

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 186478734     6 CPVCLQSYdgeSTVPRVLACGHTACEECLTNLPKKfpDTIRCPAC 50
Cdd:smart00184   1 CPICLEEY---LKDPVILPCGHTFCRSCIRKWLES--GNNTCPIC 40

PQQ-like domain; This domain contains several repeats of the PQQ repeat.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734  618 HALAYSEyGHVYTGSGDNTIKAWSLQDGSLLCTMSGHKSVVSTLVVVNGVLYSGSWDGTVRLWSLSDNSLL-TVLGEETP 696
Cdd:pfam13360  27 GGVAVDG-GRLFVATGGGQLVALDAATGKLLWRQTLSGEVLGAPLVAGGRVFVVAGDGSLIALDAADGRRLwSYQRSGEP 105

                          90       100
                  ....*....|....*....|....*
gi 186478734  697 GIVRSILSLAADDQTLVAAYQNGDI 721
Cdd:pfam13360 106 LALRSSGSPAVVGDTVVAGFSSGKL 130

WD40 repeat [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 521 RGHQDSVTGLAV--GGGFLFSSSYDRTILIWSLKDFSHVHTFKGHQDKVMALI------HIegtepvcVSGDGGGGIFVW 592
Cdd:COG2319  117 TGHTGAVRSVAFspDGKTLASGSADGTVRLWDLATGKLLRTLTGHSGAVTSVAfspdgkLL-------ASGSDDGTVRLW 189

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 593 STTfplEEQPLRKWYEPKDWrytgIHALAYSEYGH-VYTGSGDNTIKAWSLQDGSLLCTMSGHKSVVSTLVV-VNG-VLY 669
Cdd:COG2319  190 DLA---TGKLLRTLTGHTGA----VRSVAFSPDGKlLASGSADGTVRLWDLATGKLLRTLTGHSGSVRSVAFsPDGrLLA 262

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 670 SGSWDGTVRLWSLSDNSLLTVLGEETpGIVRSIlSLAADDQTLVAAYQNGDIQIW--RDDTLMKSMKIQNGAILSIAV-- 745
Cdd:COG2319  263 SGSADGTVRLWDLATGELLRTLTGHS-GGVNSV-AFSPDGKLLASGSDDGTVRLWdlATGKLLRTLTGHTGAVRSVAFsp 340

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 186478734 746 NGKWLFTGGWDKTINVQELSGDEIsvncahVGSIPG-SSVITSLLYW-EGKLFA-GFADKTIKVY 807
Cdd:COG2319  341 DGKTLASGSDDGTVRLWDLATGEL------LRTLTGhTGAVTSVAFSpDGRTLAsGSADGTVRLW 399

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 186478734 521 RGHQDSVTGLAV--GGGFLFSSSYDRTILIWSLKDFSHVHTFKGHQDKVMALIHI-EGTEPVCVSGDggGGIFVWSTTFP 597
Cdd:cd00200    6 KGHTGGVTCVAFspDGKLLATGSGDGTIKVWDLETGELLRTLKGHTGPVRDVAASaDGTYLASGSSD--KTIRLWDLETG 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 598 leeQPLRKWYEPKDWrytgIHALAYSEYGH-VYTGSGDNTIKAWSLQDGSLLCTMSGHKSVVSTLVV--VNGVLYSGSWD 674
Cdd:cd00200   84 ---ECVRTLTGHTSY----VSSVAFSPDGRiLSSSSRDKTIKVWDVETGKCLTTLRGHTDWVNSVAFspDGTFVASSSQD 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 675 GTVRLWSLSDNSLLTVLGEETpGIVRSIlSLAADDQTLVAAYQNGDIQIW--RDDTLMKSMKIQNGAILSIAV--NGKWL 750
Cdd:cd00200  157 GTIKLWDLRTGKCVATLTGHT-GEVNSV-AFSPDGEKLLSSSSDGTIKLWdlSTGKCLGTLRGHENGVNSVAFspDGYLL 234

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 186478734 751 FTGGWDKTINV---------QELSGDEISVNCahVGSIPGSSVitsllywegkLFAGFADKTIKVY 807
Cdd:cd00200  235 ASGSEDGTIRVwdlrtgecvQTLSGHTNSVTS--LAWSPDGKR----------LASGSADGTIRIW 288

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 186478734 520 MRGHQDSVTGLAV--GGGFLFSSSYDRTILIWSLKDFSHVHTFKGHQDKVMAlIHIEGTEPVCVSGDGGGGIFVWSttfp 597
Cdd:cd00200  131 LRGHTDWVNSVAFspDGTFVASSSQDGTIKLWDLRTGKCVATLTGHTGEVNS-VAFSPDGEKLLSSSSDGTIKLWD---- 205

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734 598 LEEQPLRKWYEPKDwryTGIHALAYSEYGH-VYTGSGDNTIKAWSLQDGSLLCTMSGHKSVVSTLVVVN--GVLYSGSWD 674
Cdd:cd00200  206 LSTGKCLGTLRGHE---NGVNSVAFSPDGYlLASGSEDGTIRVWDLRTGECVQTLSGHTNSVTSLAWSPdgKRLASGSAD 282

                 ....*..
gi 186478734 675 GTVRLWS 681
Cdd:cd00200  283 GTIRIWD 289

RING finger, HC subclass, found in tripartite motif-containing protein 32 (TRIM32) and similar proteins; TRIM32, also known as 72 kDa Tat-interacting protein, zinc finger protein HT2A, or BBS11, is an E3 ubiquitin-protein ligase that promotes degradation of several targets, including actin, PIASgamma, Abl interactor 2, dysbindin, X-linked inhibitor of apoptosis (XIAP), p73 transcription factor, thin filaments and Z-bands during fasting. It plays important roles in neuronal differentiation of neural progenitor cells, as well as in controlling cell fate in skeletal muscle progenitor cells. It reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin-PI3K dissociation. It also functions as a pluripotency-reprogramming roadblock that facilitates cellular transition towards differentiation by modulating the levels of Oct4 and cMyc. Moreover, TRIM32 is an intrinsic influenza A virus (IAV) restriction factor which senses and targets the polymerase basic protein 1 (PB1) for ubiquitination and protein degradation. It also plays a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo, binds specifically to the activation domain of HIV-1 Tat, and can also interact with the HIV-2 and EIAV Tat proteins in vivo. Furthermore, TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2 (N-myc downstream-regulated gene). It negatively regulates tumor suppressor p53 to promote tumorigenesis. It also facilitates degradation of MYCN on spindle poles and induces asymmetric cell division in human neuroblastoma cells. In addition, TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress. It also plays a role in regeneration by affecting satellite cell cycle progression via modulation of the SUMO ligase PIASy (PIAS4). Defects in TRIM32 leads to limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and Bardet-Biedl syndrome. TRIM32 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain. The NHL domain mediates the interaction with Argonaute proteins and consequently allows TRIM32 to modulate the activity of certain miRNAs.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 186478734   4 PECPVCLQSYDGESTVPRVLACGHTACEECLTNLPKK-FPDTIRCPACTVL 53
Cdd:cd16587    1 LECPICLESFDEGQLRPKLLHCGHTICEQCLEKLLASlSINGVRCPFCRKV 51

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
                 ....*....|....*....|....*....|....*....|....*....
gi 186478734   3 EPECPVCLQSY--DGESTVPRVLA-CGHTACEECLTNLPKKFPDTIRCP 48
Cdd:cd23124    1 ELECGICQQEYsaDDPLLIPRILTeCGHTICTNCAGTILGQSSGSIFCP 49

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 186478734    6 CPVCLQSYdgesTVPrVLACGHTACEECLTNLPKKFPDTIRCP 48
Cdd:pfam13445   1 CPICLELF----TDP-VLPCGHTFCRECLEEMSQKKGGKFKCP 38

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 186478734   4 PECPVCLQSYDgesTVPRVLACGHTACEECLTNLpkKFPDTIRCPAC 50
Cdd:cd16564    1 SECPVCYEDFD---DAPRILSCGHSFCEDCLVKQ--LVSMTISCPIC 42

RING finger, HC subclass, found in RING finger protein RNF224 and similar proteins; RNF224 is uncharacterized C3HC4-type RING-HC finger-containing proteins. It may function as an E3 ubiquitin-protein ligase.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 186478734   5 ECPVCLQSYDGESTVPRVLACGHTACEECLTNLPKKFPDT--IRCPAC 50
Cdd:cd16565    2 DCIICYSAYDLSTRLPRRLYCGHTFCQACLKRLDTVINEQrwIPCPQC 49

HC subclass of RING (RING-HC) finger 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 a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers 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 serve as scaffolds 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 186478734   5 ECPVCLQSYDgestVPRVLACGHTACEECLTNLPKKfpDTIRCPAC 50
Cdd:cd16449    2 ECPICLERLK----DPVLLPCGHVFCRECIRRLLES--GSIKCPIC 41

zinc-RING finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 186478734    5 ECPVCLQSYDGEStVPRVLACGHTACEECLTNLPKKfpdtIRCPAC 50
Cdd:pfam14634   1 HCNKCFKELSKTR-PFYLTSCGHIFCEECLTRLLQE----RQCPIC 41

RING finger, HC subclass, found in Caenorhabditis elegans RING finger protein NHL-1 and similar proteins; NHL-1 functions as an E3 ubiquitin-protein ligase in the presence of both UBC-13 and UBC-1 within the ubiquitin pathway of Caenorhabditis elegans. It acts in chemosensory neurons to promote stress resistance in distal tissues by the transcription factor DAF-16 activation but is dispensable for the activation of heat shock factor 1 (HSF-1). NHL-1 belongs to the TRIM (tripartite motif)-NHL 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 domain, as well as an 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 186478734   6 CPVCLQSYdgesTVPRVLACGHTACEE-CLTNLPKKFPDTIRCPAC 50
Cdd:cd16524    8 CPICLDRY----RRPKLLPCQHTFCLSpCLEGLVDYVTRKLKCPEC 49

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 186478734   4 PECPVCLQSY-DGESTVPRVLACGHTACEECLTNLPKKFPDTIRCPAC 50
Cdd:cd16516    1 LECKVCFEKYsHQQEHRPRNLPCGHVLCRECVTALAHPRRSKLECPFC 48

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and similar proteins; TRIM13 and TRIM59, two closely related tripartite motif-containing proteins, belong to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, followed by a C-terminal transmembrane domain. TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts with proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 186478734   2 EEPECPVCLQSYDGestvPRVLACGHTACEECLTNL----PKKFPDTIRCPAC 50
Cdd:cd16581    1 EELTCSICYNIFDD----PKILPCSHTFCKNCLEKLlaasGYYLLASLKCPTC 49

RING finger, HC subclass, found in RING finger protein 182 (RNF182) and similar proteins; RNF182 is a brain-enriched E3 ubiquitin-protein ligase that stimulates E2-dependent polyubiquitination in vitro. It is upregulated in Alzheimer"s disease (AD) brains and neuronal cells exposed to injurious insults. It interacts with ATP6V0C and promotes its degradation by the ubiquitin-proteosome pathway, suggesting a very specific role in controlling the turnover of an essential component of the neurotransmitter release machinery. RNF182 contains an N-terminal C3HC4-type RING-HC finger, and a C-terminal transmembrane domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 186478734   3 EPECPVCLQSYDGESTVPRVLACGHTACEECL---TNLPKKFPDTIRCPAC 50
Cdd:cd16555    1 ELECKICYNRYDLRQRRPKVLECCHRVCAKCLykiVDLGDSSPSVLVCPFC 51

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 186478734   1 MEEPECPVCLQSYDGestvPRVLACGHTACEECLTNLPKKFPDTIRCPACTVLVK 55
Cdd:cd16611    2 TEELHCPLCLDFFRD----PVMLSCGHNFCQSCITGFWELQAEDTTCPECRELCQ 52

RING finger, HC subclass, found in tripartite motif-containing protein 3 (TRIM3); TRIM3, also known as brain-expressed RING finger protein (BERP), RING finger protein 97 (RNF97), or RING finger protein 22 (RNF22), is an E3 ubiquitin-protein ligase involved in the pathogenesis of various cancers. It functions as a tumor suppressor that regulates asymmetric cell division in glioblastoma. It binds to the cdk inhibitor p21(WAF1/CIP1) and regulates its availability that promotes cyclin D1-cdk4 nuclear accumulation. Moreover, TRIM3 plays an important role in the central nervous system (CNS). It is encoded by the gene BERP (brain-expressed RING finger protein), a unique p53-regulated gene that modulates seizure susceptibility and GABAAR cell surface expression. Furthermore, TRIM3 mediates activity-dependent turnover of postsynaptic density (PSD) scaffold proteins GKAP/SAPAP1 and is a negative regulator of dendritic spine morphology. In addition, TRIM3 may be involved in vesicular trafficking via its association with the cytoskeleton-associated-recycling or transport (CART) complex that is necessary for efficient transferrin receptor recycling, but not for epidermal growth factor receptor (EGFR) degradation. It also regulates the motility of the kinesin superfamily protein KIF21B. TRIM3 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 186478734   6 CPVCLQSYDgestVPRVLACGHTACEECLTNLPKKFPDTIRCPAC 50
Cdd:cd16768    7 CSICLDRYH----NPKVLPCLHTFCERCLQNYIPPQSLTLSCPVC 47

RING finger, HC subclass, found in tripartite motif-containing protein 13 (TRIM13) and similar proteins; 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). It also targets the known ER proteolytic substrate CD3-delta, but not the N-end rule substrate Ub-R-YFP (yellow fluorescent protein) for degradation. Moreover, TRIM13 regulates ubiquitination and degradation of NEMO to suppress tumor necrosis factor (TNF) induced nuclear factor-kappaB (NF- kappa B) activation. It is also involved in NF-kappaB p65 activation and nuclear factor of activated T-cells (NFAT)-dependent activation of c-Rel upon T-cell receptor engagement. Furthermore, TRIM13 negatively regulates melanoma differentiation-associated gene 5 (MDA5)-mediated type I interferon production. It also regulates caspase-8 ubiquitination, translocation to autophagosomes, and activation during ER stress induced cell death. Meanwhile, TRIM13 enhances ionizing radiation-induced apoptosis by increasing p53 stability and decreasing AKT kinase activity through MDM2 and AKT degradation. TRIM13 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. In addition, TRIM13 contains a C-terminal transmembrane domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 186478734   2 EEPECPVCLQSYDGestvPRVLACGHTACEECL------TNLPKKFPDTIRCPAC 50
Cdd:cd16762    2 EDLTCPICCCLFDD----PRVLPCSHNFCKKCLegilegNVRTMLWRPPFKCPTC 52

RING finger, HC subclass, found in SH3 domain-containing RING finger protein 1 (SH3RF1) and similar proteins; SH3RF1, also known as plenty of SH3s (POSH), RING finger protein 142 (RNF142), or SH3 multiple domains protein 2 (SH3MD2), is a trans-Golgi network-associated pro-apoptotic scaffold protein with E3 ubiquitin-protein ligase activity. It also plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and c-Jun N-terminal kinase (JNK) mediated apoptosis, linking Rac1 to downstream components. SH3RF1 also enhances the ubiquitination of ROMK1 potassium channel resulting in its increased endocytosis. Moreover, SH3RF1 assembles an inhibitory complex with the actomyosin regulatory protein Shroom3, which links to the actin-myosin network to regulate neuronal process outgrowth. It also forms a complex with apoptosis-linked gene-2 (ALG-2) and ALG-2-interacting protein (ALIX/AIP1) in a calcium-dependent manner to play a role in the regulation of the JNK pathway. Furthermore, direct interaction of SH3RF1 and another molecular scaffold JNK-interacting protein (JIP) is required for apoptotic activation of JNKs. Interaction of SH3RF1 and E3 ubiquitin-protein isopeptide ligases, Siah proteins, further promotes JNK activation and apoptosis. In addition, SH3RF1 binds to and degrades TAK1, a crucial activator of both the JNK and the Relish signaling pathways. SH3RF1 contains an N-terminal C3HC4-type RING-HC finger responsible for the E3 ligase activity and four Src Homology 3 (SH3) domains, which are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 186478734   5 ECPVCLQSYDGEStvpRVLACGHTACEECLTNLPKKfPDTIRCPACTVL 53
Cdd:cd16748    4 ECPVCLERLDATA---KVLPCQHTFCRRCLLGIVGS-RSELRCPECRTL 48

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 186478734   2 EEPECPVCLQSYDgestVPRVLACGHTACEECLTnlpKKFPDTIRCPACTVLVK 55
Cdd:cd16561    1 GEQECSICLEDLN----DPVKLPCDHVFCEECIR---QWLPGQMSCPLCRTELP 47

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        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 186478734   3 EPECPVCLQSYDGESTVPRVLACGHTACEECLTNLPKKFPDT--IRCPAC 50
Cdd:cd16557    1 DLECLVCRNPYSCFVRKPKLLACQHAFCAICLKLILCEQDGTwsVTCPLC 50

RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar proteins; TRIM77 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 two consecutive zinc-binding domains, a C3HC4-type RING-HC finger and Bbox2, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 186478734   6 CPVCLQSYDGESTVPrvlaCGHTACEECLTNLPKKFPDTIRCPACtvLVKFPP 58
Cdd:cd16543    6 CSICLDLLKDPVTIP----CGHSFCMNCITLLWDRKQGVPSCPQC--RESFPP 52

RING finger, HC subclass, found in SH3 domain-containing RING finger proteins SH3RF1, SH3RF2, SH3RF3, and similar proteins; SH3RF1, also known as plenty of SH3s (POSH), RING finger protein 142 (RNF142), or SH3 multiple domains protein 2 (SH3MD2), is a trans-Golgi network-associated pro-apoptotic scaffold protein with E3 ubiquitin-protein ligase activity. SH3RF2, also known as heart protein phosphatase 1-binding protein (HEPP1), plenty of SH3s (POSH)-eliminating RING protein (POSHER), protein phosphatase 1 regulatory subunit 39, or RING finger protein 158 (RNF158), is a putative E3 ubiquitin-protein ligase that acts as an anti-apoptotic regulator for the c-Jun N-terminal kinase (JNK) pathway by binding to and promoting the proteasomal degradation of SH3RF1 (or POSH) that is required for pro-apoptotic JNK activation. SH3RF3, also known as plenty of SH3s 2 (POSH2) or SH3 multiple domains protein 4 (SH3MD4), is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2) and may play a role in regulating c-Jun N-terminal kinase (JNK) mediated apoptosis in certain conditions. Members of this subfamily contain an N-terminal C3HC4-type RING-HC finger responsible for the E3 ligase activity and four Src Homology 3 (SH3) domains, which are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 186478734   5 ECPVCLQSYDGEStvpRVLACGHTACEECLTNLPKKfPDTIRCPAC 50
Cdd:cd16570    2 ECPVCLERLDVSA---KVLPCQHTFCKRCLQIIVAS-RGELRCPEC 43

RING finger, HC subclass, found in tripartite motif-containing protein 9 (TRIM9) and similar proteins; TRIM9, human ortholog of rat Spring, also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. TRIM9 plays an important role in the regulation of neuronal functions and participates in the neurodegenerative disorders through its ligase activity. It interacts with the WD repeat region of beta-transducin repeat-containing protein (beta-TrCP) through its N-terminal degron motif depending on the phosphorylation status, and thus negatively regulates nuclear factor-kappaB (NF-kappaB) activation in the NF-kappaB pro-inflammatory signaling pathway. Moreover, TRIM9 acts as a critical catalytic link between Netrin-1 and the exocytic soluble NSF attachment receptor protein (SNARE) machinery in murine cortical neurons. It promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. TRIM9 belongs to the C-I 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 COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 186478734   2 EEPECPVCLQSYDGestvPRVLACGHTACEECLTNLPKKFPDT------IRCPAC 50
Cdd:cd16755    2 EELKCPVCGSFYRE----PIILPCSHNLCLACARNILVQTPEAespqscLTCPQC 52

RING finger, HC subclass, found in Schizosaccharomyces pombe DNA repair protein Rad8 (SpRad8) and similar proteins; SpRad8 is a conserved protein homologous to Saccharomyces cerevisiae DNA repair protein Rad5 and human helicase-like transcription factor (HLTF) that is required for error-free postreplication repair by contributing to polyubiquitylation of PCNA. SpRad8 contains a C3HC4-type RING-HC finger responsible for the E3 ubiquitin ligase activity, a SNF2-family helicase domain including an ATP binding site, and a family-specific HIRAN domain (HIP116, Rad5p N-terminal domain) that contributes to nuclear localization.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 186478734   3 EPECPVCLQSYDGESTVPRvlaCGHTACEECLTN---LPKKFPDTIRCPAC 50
Cdd:cd16572    4 ENECPICAEEPISELALTR---CWHSACKDCLLDhieFQKSKNEVPLCPTC 51

RING finger, HC subclass, found in tripartite motif-containing protein 45 (TRIM45) and similar proteins; TRIM45, also known as RING finger protein 99 (RNF99), is a novel receptor for activated C-kinase (RACK1)-interacting protein that suppresses transcriptional activities of Elk-1 and AP-1 and downregulates mitogen-activated protein kinase (MAPK) signal transduction through inhibiting RACK1/PKC (protein kinase C) complex formation. It also negatively regulates tumor necrosis factor alpha (TNFalpha)-induced nuclear factor-kappaB (NF-kappa B)-mediated transcription and suppresses cell proliferation. TRIM45 belongs to the C-VII subclass of the TRIM (tripartite motif) 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 region, as well as a filamin-type immunoglobulin (IG-FLMN) domain and NHL repeats positioned C-terminal to the RBCC domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478734   4 PECPVCLQSYdgesTVPRVLACGHTACEECLTNL-PKKFPD------------TIRCPAC 50
Cdd:cd16588    1 TRCPVCGKLF----QEPRLLPCLHTLCSPCLRQLePFSVCGlrggdrseksnySVLCPVC 56

RING finger, HC subclass, found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. This subfamily also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins that may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by N-terminal RBCC domains only.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 186478734   6 CPVCLQSYDGestvPRVLACGHTACEECLTNLPKKFPDTIRCPAC 50
Cdd:cd16605    3 CPICLEVFKE----PLMLQCGHSYCKSCLVSLSGELDGQLLCPVC 43

RING finger, HC subclass, found in SH3 domain-containing RING finger protein 3 (SH3RF3) and similar proteins; SH3RF3, also known as plenty of SH3s 2 (POSH2) or SH3 multiple domains protein 4 (SH3MD4), is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in a screen for interacting partners of p21-activated kinase 2 (PAK2). It may play a role in regulating c-Jun N-terminal kinase (JNK) mediated apoptosis in certain conditions. It also interacts with GTP-loaded Rac1. SH3RF3 is highly homologous to SH3RF1. Both contain an N-terminal C3HC4-type RING-HC finger responsible for the E3 ligase activity and four Src Homology 3 (SH3) domains, which are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 186478734   5 ECPVCLQSYDGEStvpRVLACGHTACEECLTNLPKKfPDTIRCPAC 50
Cdd:cd16750    4 ECSVCLERLDTTS---KVLPCQHTFCRRCLESIVSS-RKELRCPEC 45