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 1635577135 218 HGKQIRGLAFSsYLRGLLLSASLDNTIKLTSLETNTVVQTY-NAGRPVWSCCWCLDeANYIYAGLANGSILVYDVRNTSS 296
Cdd:cd00200     8 HTGGVTCVAFS-PDGKLLATGSGDGTIKVWDLETGELLRTLkGHTGPVRDVAASAD-GTYLASGSSDKTIRLWDLETGEC 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577135 297 hVQELVAqkARCPLVSLSYMpraasaafPYGGVLAGTLEDAS--FWEqkmdfshwphvlpLEPGGCIDFQTENSSRHCLV 374
Cdd:cd00200    86 -VRTLTG--HTSYVSSVAFS--------PDGRILSSSSRDKTikVWD-------------VETGKCLTTLRGHTDWVNSV 141

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577135 375 TYRPDKnhTTIRSVLMEMSYRLDDTGnpicSCQPVHTFFgGPTCKLltkNAIFQSPENdGNILVCTGDeaaNSALLWDAA 454
Cdd:cd00200   142 AFSPDG--TFVASSSQDGTIKLWDLR----TGKCVATLT-GHTGEV---NSVAFSPDG-EKLLSSSSD---GTIKLWDLS 207

                         250       260       270
                  ....*....|....*....|....*....|.
gi 1635577135 455 SGSLLQDLQT-DQPVLDICpfeVNRNSYLAT 484
Cdd:cd00200   208 TGKCLGTLRGhENGVNSVA---FSPDGYLLA 235

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 1635577135 218 HGKQIRGLAFSsYLRGLLLSASLDNTIKLTSLETNTVVQTY-NAGRPVWSCCWCLDeANYIYAGLANGSILVYDVRNTSS 296
Cdd:cd00200     8 HTGGVTCVAFS-PDGKLLATGSGDGTIKVWDLETGELLRTLkGHTGPVRDVAASAD-GTYLASGSSDKTIRLWDLETGEC 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577135 297 hVQELVAqkARCPLVSLSYMpraasaafPYGGVLAGTLEDAS--FWEqkmdfshwphvlpLEPGGCIDFQTENSSRHCLV 374
Cdd:cd00200    86 -VRTLTG--HTSYVSSVAFS--------PDGRILSSSSRDKTikVWD-------------VETGKCLTTLRGHTDWVNSV 141

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577135 375 TYRPDKnhTTIRSVLMEMSYRLDDTGnpicSCQPVHTFFgGPTCKLltkNAIFQSPENdGNILVCTGDeaaNSALLWDAA 454
Cdd:cd00200   142 AFSPDG--TFVASSSQDGTIKLWDLR----TGKCVATLT-GHTGEV---NSVAFSPDG-EKLLSSSSD---GTIKLWDLS 207

                         250       260       270
                  ....*....|....*....|....*....|.
gi 1635577135 455 SGSLLQDLQT-DQPVLDICpfeVNRNSYLAT 484
Cdd:cd00200   208 TGKCLGTLRGhENGVNSVA---FSPDGYLLA 235

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1635577135   7 DTCTICLEQWTNagDHRLSALRCGHLFGYRCISTWLKgQVRKCPQCN 53
Cdd:pfam13639   1 DECPICLEEFEE--GDKVVVLPCGHHFHRECLDKWLR-SSNTCPLCR 44

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1635577135   6 GDTCTICLEQWTNaGDhRLSALRCGHLFGYRCISTWLKGQVRKCPQCN 53
Cdd:COG5540   323 GVECAICMSNFIK-ND-RLRVLPCDHRFHVGCVDKWLLGYSNKCPVCR 368

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 enable efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1635577135   9 CTICLEQWTNAgdHRLSALRCGHLFGYRCISTWLKGQVRKCPQC 52
Cdd:cd00162     1 CPICREEMNDR--RPVVLLSCGHTFSRSAIARWLEGSKQKCPFC 42

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 1635577135   9 CTICLEQWTNAGDhrLSALRCGHLFGYRCISTWLKgQVRKCPQC 52
Cdd:cd16480     2 CTICSDFFDNSRD--VAAIHCGHTFHYDCLLQWFD-TSRTCPQC 42

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 1635577135 201 VKMLSTANMKSSQYIPMHGKQIRGLAFSSyLRGLLLSASLDNTIKLTSLETNTVVQTYNA-GRPVWSCCWCLDEaNYIYA 279
Cdd:cd00200   159 IKLWDLRTGKCVATLTGHTGEVNSVAFSP-DGEKLLSSSSDGTIKLWDLSTGKCLGTLRGhENGVNSVAFSPDG-YLLAS 236

                          90       100
                  ....*....|....*....|....*....
gi 1635577135 280 GLANGSILVYDVRnTSSHVQELVAQKARC 308
Cdd:cd00200   237 GSEDGTIRVWDLR-TGECVQTLSGHTNSV 264

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 1635577135 201 VKMLSTANMKSSQYIPMHGKQIRGLAFSSYLRgLLLSASLDNTIKLTSLETNTVVQTYNA-GRPVWSCCWCLDEaNYIYA 279
Cdd:cd00200    75 IRLWDLETGECVRTLTGHTSYVSSVAFSPDGR-ILSSSSRDKTIKVWDVETGKCLTTLRGhTDWVNSVAFSPDG-TFVAS 152

                          90
                  ....*....|....
gi 1635577135 280 GLANGSILVYDVRN 293
Cdd:cd00200   153 SSQDGTIKLWDLRT 166

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1635577135   7 DTCTICLEQWTNagDHRLSALRCGHLFGYRCISTWLKgQVRKCPQCN 53
Cdd:pfam13639   1 DECPICLEEFEE--GDKVVVLPCGHHFHRECLDKWLR-SSNTCPLCR 44

RING finger, H2 subclass, found in 43 kDa receptor-associated protein of the synapse (Rapsyn) and similar proteins; Rapsyn, also known as acetylcholine receptor (AChR)-associated 43 kDa protein or RING finger protein 205 (RNF205), is a 43 kDa postsynaptic protein that plays an essential role in the clustering and maintenance of AChR in the postsynaptic membrane of the motor endplate. AChRs enable the transport of rapsyn from the Golgi complex to the plasma membrane through a molecule-specific interaction. Rapsyn also mediates subsynaptic anchoring of protein kinase A (PKA) type I in close proximity to the postsynaptic membrane, which is essential for synapse maintenance. Its mutations in humans cause endplate AChR deficiency and myasthenic syndrome. Rapsyn contains an N-terminal myristoylation signal required for membrane association, seven tetratricopeptide repeats (TPRs) that subserve rapsyn self-association, a coiled-coil domain responsible for the binding of determinants within the long cytoplasmic loop of each AChR subunit, a C3H2C3-type RING-H2 finger that binds to the cytoplasmic domain of beta-dystroglycan and to S-NRAP and links rapsyn to the subsynaptic cytoskeleton, and a serine phosphorylation site.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1635577135  21 DHRLSALRCGHLFGYRCISTWLKGQVRKCPQCNK 54
Cdd:cd16478    15 NEQLQALPCSHIFHLKCLQTNLRGGTRGCPNCRR 48

WD40 repeat [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577135 180 ALSCLVISQPSPQASFLPGFGVKMLSTANMKSSQYIPMHGKQIRGLAFSSylRG-LLLSASLDNTIKLTSLETNTVVQTY 258
Cdd:COG2319    81 VLSVAFSPDGRLLASASADGTVRLWDLATGLLLRTLTGHTGAVRSVAFSP--DGkTLASGSADGTVRLWDLATGKLLRTL 158

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577135 259 NA-GRPVWSCCWCLDEaNYIYAGLANGSILVYDVRnTSSHVQELVAQKArcPLVSLSYMP---RAASAAF--------PY 326
Cdd:COG2319   159 TGhSGAVTSVAFSPDG-KLLASGSDDGTVRLWDLA-TGKLLRTLTGHTG--AVRSVAFSPdgkLLASGSAdgtvrlwdLA 234

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577135 327 GGVLAGTLEDASFWEQKMDFShwphvlplePGGCIdfqtenssrhcLVTYRPDKnhtTIRsvLmemsYRLdDTGNPIcsc 406
Cdd:COG2319   235 TGKLLRTLTGHSGSVRSVAFS---------PDGRL-----------LASGSADG---TVR--L----WDL-ATGELL--- 281

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1635577135 407 qpvhTFFGGPTCKLLTknAIFqSPenDGNILVCTGDEaaNSALLWDAASGSLLQDLQ 463
Cdd:COG2319   282 ----RTLTGHSGGVNS--VAF-SP--DGKLLASGSDD--GTVRLWDLATGKLLRTLT 327

WD40 repeat [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577135 218 HGKQIRGLAFSSylRG-LLLSASLDNTIKLTSLETNTVVQTYNA-GRPVWSCCWCLDeANYIYAGLANGSILVYDVrNTS 295
Cdd:COG2319   203 HTGAVRSVAFSP--DGkLLASGSADGTVRLWDLATGKLLRTLTGhSGSVRSVAFSPD-GRLLASGSADGTVRLWDL-ATG 278

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577135 296 SHVQELVAQKArcplvslsympRAASAAF-PYGGVLAGTLED--ASFWEqkmdfshwphvlpLEPGGCIDFQTENSSRHC 372
Cdd:COG2319   279 ELLRTLTGHSG-----------GVNSVAFsPDGKLLASGSDDgtVRLWD-------------LATGKLLRTLTGHTGAVR 334

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577135 373 LVTYRPDKNH-------TTIrsvlmemsyRLDDTGNPicscQPVHTFFGGPTckllTKNAIFQSPenDGNILVCTGDEaa 445
Cdd:COG2319   335 SVAFSPDGKTlasgsddGTV---------RLWDLATG----ELLRTLTGHTG----AVTSVAFSP--DGRTLASGSAD-- 393

                         250
                  ....*....|
gi 1635577135 446 NSALLWDAAS 455
Cdd:COG2319   394 GTVRLWDLAT 403

RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; This subfamily includes RNF24, RNF122, and similar proteins. RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. Both RNF24 and RNF122 contain an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1635577135   7 DTCTICLEQWTNagDHRLSALRCGHLFGYRCISTWLkgQVRK-CPQCNKKA 56
Cdd:cd16469     1 DTCAVCLEEFKL--KEELGVCPCGHAFHTKCLKKWL--EVRNsCPICKSPV 47

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1635577135    9 CTICLEQWTnagdHRLSALRCGHLFGYRCISTWLKGQVRKCPQC 52
Cdd:smart00184   1 CPICLEEYL----KDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40

RING finger, H2 subclass, found in RING finger protein 13 (RNF13) and similar proteins; RNF13 is a widely expressed membrane-associated E3 ubiquitin-protein ligase that is functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. Its expression is developmentally regulated during myogenesis and is upregulated in various tumors. RNF13 negatively regulates cell proliferation through its E3 ligase activity. It functions as an important regulator of inositol-requiring transmembrane kinase/endonuclease IRE1alpha, mediating endoplasmic reticulum (ER) stress-induced apoptosis through the activation of the IRE1alpha-TRAF2-JNK signaling pathway. Moreover, RNF13 is involved in the regulation of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex via the ubiquitination of snapin, a SNAP25-interacting protein, which thereby controls synaptic function. In addition, RNF13 participates in regulating the function of satellite cells by modulating cytokine composition. RNF13 is evolutionarily conserved among many metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1635577135   4 EEGDTCTICLEQWTNaGDhRLSALRCGHLFGYRCISTWLKGQVRKCPQCNKKARHS 59
Cdd:cd16796     6 DEYDVCAICLDEYEE-GD-KLRILPCSHAYHCKCVDPWLTKTKKTCPVCKQKVVPS 59

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 finger A1a (RHA1A), A1b (RHA1B) and similar proteins; This subfamily includes Arabidopsis thaliana RHA1A, RHA1B and XERICO. RHA1A is a probable E3 ubiquitin-protein ligase that may possess E3 ubiquitin ligase activity in vitro. RHA1B possesses E3 ubiquitin-protein ligase activity when associated with the E2 enzyme UBC8 in vitro. XERICO functions on abscisic acid homeostasis at post-translational level, probably through ubiquitin/proteasome-dependent substrate-specific degradation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1635577135   7 DTCTICLEQWtNAGDHRLSALRCGHLFGYRCISTWLKGQVRKCPQC 52
Cdd:cd23121     2 DCCAICLSDF-NSDEKLRQLPKCGHIFHHHCLDRWIRYNKITCPLC 46

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 1635577135 201 VKMLSTANMKSSQYIPMHGKQIRGLAFSSYlRGLLLSASLDNTIKLTSLETNTVVQTYNAGR-PVWSCCWClDEANYIYA 279
Cdd:cd00200   201 IKLWDLSTGKCLGTLRGHENGVNSVAFSPD-GYLLASGSEDGTIRVWDLRTGECVQTLSGHTnSVTSLAWS-PDGKRLAS 278

                          90
                  ....*....|.
gi 1635577135 280 GLANGSILVYD 290
Cdd:cd00200   279 GSADGTIRIWD 289

WD40 repeat [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577135 201 VKMLSTANMKSSQYIPMHGKQIRGLAFSSYLRgLLLSASLDNTIKLTSLETNTVVQTYNA-GRPVWSCCWCLDEaNYIYA 279
Cdd:COG2319   270 VRLWDLATGELLRTLTGHSGGVNSVAFSPDGK-LLASGSDDGTVRLWDLATGKLLRTLTGhTGAVRSVAFSPDG-KTLAS 347

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1635577135 280 GLANGSILVYDVrNTSSHVQELVAQKArcPLVSLSYMP---RAASAAF 324
Cdd:COG2319   348 GSDDGTVRLWDL-ATGELLRTLTGHTG--AVTSVAFSPdgrTLASGSA 392

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 1635577135   9 CTICLEQWTnaGDHRLSALRCGHLFGYRCISTWLKGQVRKCPQCN 53
Cdd:cd16448     1 CVICLEEFE--EGDVVRLLPCGHVFHLACILRWLESGNNTCPLCR 43

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        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1635577135   3 EEEGDT---CTICLEQWTNAGDHRlsALRCGHLFGYRCISTWLkGQVRKCPQC 52
Cdd:cd16682     1 GEESDTdekCTICLSMLEDGEDVR--RLPCMHLFHQLCVDQWL-AMSKKCPIC 50

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1635577135   6 GDTCTICLEQWTNaGDhRLSALRCGHLFGYRCISTWLKGQVRKCPQCN 53
Cdd:COG5540   323 GVECAICMSNFIK-ND-RLRVLPCDHRFHVGCVDKWLLGYSNKCPVCR 368

RING finger, H2 subclass, found in DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3) and similar proteins; DZIP3, also known as RNA-binding ubiquitin ligase of 138 kDa (RUL138) or 2A-HUB protein, is an RNA-binding E3 ubiquitin-protein ligase that interacts with coactivator-associated arginine methyltransferase 1 (CARM1) and acts as a transcriptional coactivator of estrogen receptor (ER) alpha. It is also a histone H2A ubiquitin ligase that catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatorial component of the repression machinery required for repressing a specific chemokine gene expression program, critically modulating migratory responses to Toll-like receptors (TLR) activation. DZIP3 contains a C3H2C3-type RING-H2 finger at the C-terminus.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1635577135   9 CTICLEqWTNAGDhRLSALRCGHLFGYRCISTWLKGQvRKCPQC 52
Cdd:cd16460     3 CVICHE-AFSDGD-RLLVLPCAHKFHTQCIGPWLDGQ-QTCPTC 43

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.

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                  ....*....|....*....|....*....|....*....|....*
gi 1635577135   8 TCTICLEQwtnagDHRLSALRCGHLFGYRCISTWLKGQVRKCPQC 52
Cdd:cd16449     2 ECPICLER-----LKDPVLLPCGHVFCRECIRRLLESGSIKCPIC 41

RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; The family includes RING finger proteins RNF111, RNF165, 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 also 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. The N-terminal half of RNF111 harbors three SUMO-interacting motifs (SIMs). 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). 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. Both RNF165 and RNF111 contain a C-terminal C3H2C3-type RING-H2 finger.

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                  ....*....|....*....|....*....|....*....|....
gi 1635577135   9 CTICLEQWTNAGDHRlsALRCGHLFGYRCISTWLKGQvRKCPQC 52
Cdd:cd16474     3 CTICLSDFEEGEDVR--RLPCMHLFHQECVDQWLSTN-KRCPIC 43

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1635577135   4 EEGDTCTICLEQWTnagdhRLSALRCGHLFGYRCISTWLK---GQVRKCPQCNKKARH 58
Cdd:cd16609     1 EEELTCSICLGLYQ-----DPVTLPCQHSFCRACIEDHWRqkdEGSFSCPECRAPFPE 53

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        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1635577135   7 DTCTICLEQWTNAGdhrlSALRCGHLFGYRCISTWLKGQvRKCPQC 52
Cdd:cd16479     2 NTCIICREEMTVGA----KKLPCGHIFHLSCLRSWLQRQ-QTCPTC 42

RING finger, HC subclass, found in RING finger protein RNF5, RNF185 and similar proteins; RNF5 and RNF185 are E3 ubiquitin-protein ligases that are anchored to the outer membrane of the endoplasmic reticulum (ER). RNF5 acts at early stages of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) biosynthesis, and functions as a target for therapeutic modalities to antagonize mutant CFTR proteins in CF patients carrying the F508del allele. RNF185 controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical endoplasmic reticulum-associated degradation (ERAD) model substrates. Moreover, both RNF5 and RNF185 play important roles in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) are also included in this family. They possess E3 ubiquitin-protein ligase activity and may play a role in the growth and development of Arabidopsis. All members of this family contain a C3HC4-type RING-HC finger.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1635577135   9 CTICLEQWTNAgdhrlSALRCGHLFGYRCISTWL--KGQVRKCPQCN 53
Cdd:cd16534     3 CNICLDTASDP-----VVTMCGHLFCWPCLYQWLetRPDRQTCPVCK 44

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.

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                  ....*....|....*....|....*....|....*....|....
gi 1635577135   9 CTICLEQWtnagdHRLSALRCGHLFGYRCISTWLKGQvRKCPQC 52
Cdd:cd16561     5 CSICLEDL-----NDPVKLPCDHVFCEECIRQWLPGQ-MSCPLC 42

RING finger, H2 subclass, found in RING finger protein 43 (RNF43) and similar proteins; RNF43 is a transmembrane E3 ubiquitin-protein ligase that plays an important role in frizzled (FZD)-dependent regulation of the Wnt/beta-catenin pathway. It functions as a tumor suppressor that inhibits Wnt/beta-catenin signaling by ubiquitinating FZD receptor and targeting it to the lysosomal pathway for degradation. miR-550a-5p directly targeted the 3'-UTR of gene RNF43 and regulated its expression. Moreover, RNF43 interacts with NEDD-4-like ubiquitin-protein ligase-1 (NEDL1) and regulates p53-mediated transcription. It may also be involved in cell growth control through the interaction with HAP95, a chromatin-associated protein interfacing the nuclear envelope. Mutations of RNF43 have been identified in various tumors, including colorectal cancer (CRC), endometrial cancer, mucinous ovarian tumors, gastric adenocarcinoma, pancreatic ductal adenocarcinoma, liver fluke-associated cholangiocarcinoma, hepatocellular carcinoma, and glioma. RNF43 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region.

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                  ....*....|....*....|....*....|....*....|....
gi 1635577135   9 CTICLEQWTNAGDHRLsaLRCGHLFGYRCISTWLKgQVRKCPQC 52
Cdd:cd16798     6 CAICLEEFSEGQELRI--ISCSHEFHRECVDPWLH-QHRTCPLC 46

RING finger, HC subclass, found in RING finger protein 185 (RNF185) and similar proteins; RNF185 is an E3 ubiquitin-protein ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR). It controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical ERAD model substrates. It also negatively regulates osteogenic differentiation by targeting dishevelled2 (Dvl2), a key mediator of the Wnt signaling pathway, for degradation. Moreover, RNF185 regulates selective mitochondrial autophagy through interaction with the Bcl-2 family protein BNIP1. It also plays an important role in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. RNF185 contains a C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1635577135   9 CTICLEqwtNAGDHRLSAlrCGHLFGYRCISTWLKGQVRK--CPQCNKKARHSDIVVLY 65
Cdd:cd16744     3 CNICLD---TAKDAVVSL--CGHLFCWPCLHQWLETRPNRqvCPVCKAGISRDKVIPLY 56

RING finger, H2 subclass, found in RING finger proteins RNF43, ZNRF3, and similar proteins; RNF43 and ZNRF3 (also known as RNF203) are transmembrane E3 ubiquitin-protein ligases that belong to the PA-TM-RING ubiquitin ligase family, characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region. Both RNF43 and RNF203 function as tumor suppressors involved in the regulation of Wnt/beta-catenin signaling. They negatively regulate Wnt signaling by interacting with complexes of frizzled (FZD) receptors and low-density lipoprotein receptor-related protein (LRP) 5/6, which leads to ubiquitination of FZD and endocytosis of the Wnt receptor. Dishevelled (DVL), a positive Wnt regulator, is required for ZNRF3/RNF43-mediated ubiquitination and degradation of FZD. They also associate with R-spondin 1 (RSPO1). This interaction may block FZD ubiquitination and enhances Wnt signaling.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1635577135   9 CTICLEQWTNAGDHRLsaLRCGHLFGYRCISTWLKgQVRKCPQCN 53
Cdd:cd16666     2 CAICLEEYEEGQELRV--LPCQHEFHRKCVDPWLL-QNHTCPLCL 43

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1635577135   9 CTICLEQWTNAgdhrlsALRCGHLFGYRCI--STWLKGQVRKCP 50
Cdd:pfam13445   1 CPICLELFTDP------VLPCGHTFCRECLeeMSQKKGGKFKCP 38

RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; This subfamily includes RING finger proteins RNF38, RNF44, and similar proteins. RNF38 is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 is an uncharacterized RING finger protein that shows high sequence similarity to RNF38. Both RNF38 and RNF44 contain a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C3-type RING-H2 finger. In addition, RNF38 harbors two potential nuclear localization signals.

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                  ....*....|....*....|....*....|....*....|....
gi 1635577135   9 CTICLEQWTNagDHRLSALRCGHLFGYRCISTWLKGQvRKCPQC 52
Cdd:cd16472     5 CVVCMCDYEK--RQLLRVLPCSHEFHAKCIDKWLKTN-RTCPIC 45

RING finger, H2 subclass, found in RING finger protein 126 (RNF126) and similar proteins; RNF126 is a Bag6-dependent E3 ubiquitin ligase that is involved in the mislocalized protein (MLP) pathway of quality control. It regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR). Moreover, RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation, and could be a novel therapeutic target in breast and prostate cancers. It is also able to ubiquitylate cytidine deaminase (AID), a poorly soluble protein that is essential for antibody diversification. In addition, RNF126 and the related protein, RNF115 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. RNF126 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1635577135   9 CTICLEQWTNAGDHRlsALRCGHLFGYRCISTWLKgQVRKCPQCNK 54
Cdd:cd16801     2 CPVCKEDYTVGENVR--QLPCNHLFHNDCIVPWLE-QHDTCPVCRK 44