Modified RING finger, H2 subclass (C3H3C2-type), found in WD repeat-containing protein mio and simialr proteins; This family contains Mio,its counterpart Sea4 from yeast, and other homologs. Mio/Sea4 is a component of the GATOR2 complex, which also includes another four subunits, Seh1, Sec13, Sea2/WDR24, and Sea3/WDR59. GATOR2 and GATOR1, which is composed of three subunits, DEPDC5, Nprl2, and Nprl3, form the Rag-interacting complex GATOR (GAP Activity Towards Rags). Inhibition of GATOR1 subunits makes mTORC1 signaling resistant to amino acid deprivation. In contrast, inhibition of GATOR2 subunits suppresses mTORC1 signaling and GATOR2 negatively regulates DEPDC5. Mio interacts with endogenous RagA and RagC, and plays an essential role in the activation of mTOR Complex 1 (mTORC1) by amino acids. In GATOR2, Mio and Seh1 localize to lysosomes and autolysosomes, and form a heterodimer that is required to oppose the TORC1 inhibitory activity of the Iml1/GATOR1 complex to prevent the constitutive down-regulation of TORC1 activity in later stages of oogenesis. A tissue-specific requirement is necessary for Mio to be involved in cell growth in the female germ line. Mio contains an N-terminal WD40 domain and a C-terminal RING-H2 finger with an unusual arrangement of zinc-coordinating residues. The cysteines and histidines in the RING-H2 finger are arranged as a modified C3H3C2-type, rather than the canonical C3H2C3-type.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 109150419 782 LPRCALCLINMGTPVSSCPGGTKSDekVDLSKDKKLAQFNNWFTWCHNCRHGGHAGHMLSWFRDHAECPVSACTCKC 858
Cdd:cd16691    1 LPRCSLCLIPMGTPSSSLPGATASD--VDLSSDKKLAPFSSWFTWCQTCRHGGHAGHLQEWFRDHSECPVSGCDCKC 75

Modified RING finger, H2 subclass (C3H3C2-type), found in WD repeat-containing protein mio and simialr proteins; This family contains Mio,its counterpart Sea4 from yeast, and other homologs. Mio/Sea4 is a component of the GATOR2 complex, which also includes another four subunits, Seh1, Sec13, Sea2/WDR24, and Sea3/WDR59. GATOR2 and GATOR1, which is composed of three subunits, DEPDC5, Nprl2, and Nprl3, form the Rag-interacting complex GATOR (GAP Activity Towards Rags). Inhibition of GATOR1 subunits makes mTORC1 signaling resistant to amino acid deprivation. In contrast, inhibition of GATOR2 subunits suppresses mTORC1 signaling and GATOR2 negatively regulates DEPDC5. Mio interacts with endogenous RagA and RagC, and plays an essential role in the activation of mTOR Complex 1 (mTORC1) by amino acids. In GATOR2, Mio and Seh1 localize to lysosomes and autolysosomes, and form a heterodimer that is required to oppose the TORC1 inhibitory activity of the Iml1/GATOR1 complex to prevent the constitutive down-regulation of TORC1 activity in later stages of oogenesis. A tissue-specific requirement is necessary for Mio to be involved in cell growth in the female germ line. Mio contains an N-terminal WD40 domain and a C-terminal RING-H2 finger with an unusual arrangement of zinc-coordinating residues. The cysteines and histidines in the RING-H2 finger are arranged as a modified C3H3C2-type, rather than the canonical C3H2C3-type.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 109150419 782 LPRCALCLINMGTPVSSCPGGTKSDekVDLSKDKKLAQFNNWFTWCHNCRHGGHAGHMLSWFRDHAECPVSACTCKC 858
Cdd:cd16691    1 LPRCSLCLIPMGTPSSSLPGATASD--VDLSSDKKLAPFSSWFTWCQTCRHGGHAGHLQEWFRDHSECPVSGCDCKC 75

WD40 repeat [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150419  84 NGRVVLTSlGQDHNSKFKDLIGKEFV---PKHARQCNTLAWNPlDSNWLAAGLDkhraDFSVLIWDicskytpdivpmek 160
Cdd:COG2319  131 DGKTLASG-SADGTVRLWDLATGKLLrtlTGHSGAVTSVAFSP-DGKLLASGSD----DGTVRLWD-------------- 190

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150419 161 vkLSAGETETTLLvtkplyelGQNDACLSLCWLPRDQKLLLAGMHRNLAIFDLRNTSQKMFVN--TKAVQGVTVDPyfhD 238
Cdd:COG2319  191 --LATGKLLRTLT--------GHTGAVRSVAFSPDGKLLASGSADGTVRLWDLATGKLLRTLTghSGSVRSVAFSP---D 257

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150419 239 --RVAS-FYEGQVAIWDLRKfEKPVLTLTEQPKPLTKVAWCPTRTgLLATLTRDsNIIRLYDMQhTPTPIGDETEPTIIE 315
Cdd:COG2319  258 grLLASgSADGTVRLWDLAT-GELLRTLTGHSGGVNSVAFSPDGK-LLASGSDD-GTVRLWDLA-TGKLLRTLTGHTGAV 333

                        250
                 ....*....|....
gi 109150419 316 RSVQ--PCDNYIAS 327
Cdd:COG2319  334 RSVAfsPDGKTLAS 347

Modified RING finger, H2 subclass (C3H3C2-type), found in WD repeat-containing protein mio and simialr proteins; This family contains Mio,its counterpart Sea4 from yeast, and other homologs. Mio/Sea4 is a component of the GATOR2 complex, which also includes another four subunits, Seh1, Sec13, Sea2/WDR24, and Sea3/WDR59. GATOR2 and GATOR1, which is composed of three subunits, DEPDC5, Nprl2, and Nprl3, form the Rag-interacting complex GATOR (GAP Activity Towards Rags). Inhibition of GATOR1 subunits makes mTORC1 signaling resistant to amino acid deprivation. In contrast, inhibition of GATOR2 subunits suppresses mTORC1 signaling and GATOR2 negatively regulates DEPDC5. Mio interacts with endogenous RagA and RagC, and plays an essential role in the activation of mTOR Complex 1 (mTORC1) by amino acids. In GATOR2, Mio and Seh1 localize to lysosomes and autolysosomes, and form a heterodimer that is required to oppose the TORC1 inhibitory activity of the Iml1/GATOR1 complex to prevent the constitutive down-regulation of TORC1 activity in later stages of oogenesis. A tissue-specific requirement is necessary for Mio to be involved in cell growth in the female germ line. Mio contains an N-terminal WD40 domain and a C-terminal RING-H2 finger with an unusual arrangement of zinc-coordinating residues. The cysteines and histidines in the RING-H2 finger are arranged as a modified C3H3C2-type, rather than the canonical C3H2C3-type.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 109150419 782 LPRCALCLINMGTPVSSCPGGTKSDekVDLSKDKKLAQFNNWFTWCHNCRHGGHAGHMLSWFRDHAECPVSACTCKC 858
Cdd:cd16691    1 LPRCSLCLIPMGTPSSSLPGATASD--VDLSSDKKLAPFSSWFTWCQTCRHGGHAGHLQEWFRDHSECPVSGCDCKC 75

Modified RING finger, H2 subclass (C3H3C2-type), found in WD repeat-containing protein mio and its homologs; This subfamily contains Mio, WDR24, WDR59, and their counterparts Sea4, Sea2, and Sea3 from yeast, respectively. Mio/Sea4, Sea2/WDR24, and Sea3/WDR59 are components of the GATOR2 complex, which also includes another two subunits, Seh1and Sec13. GATOR2 and GATOR1, which is composed of three subunits, DEPDC5, Nprl2, and Nprl3, form the Rag-interacting complex GATOR (GAP Activity Towards Rags). Inhibition of GATOR1 subunits makes mTORC1 signaling resistant to amino acid deprivation. In contrast, inhibition of GATOR2 subunits suppresses mTORC1 signaling and GATOR2 negatively regulates DEPDC5. All subfamily members contain an N-terminal WD40 domain and a C-terminal RING-H2 finger with an unusual arrangement of zinc-coordinating residues. The cysteines and histidines in the RING-H2 finger are arranged as a modified C3H3C2-type, rather than the canonical C3H2C3-type.

                         10        20        30
                 ....*....|....*....|....*....|...
gi 109150419 824 FTWCHNCRHGGHAGHMLSWFRDHAECPVSaCTC 856
Cdd:cd16488   13 SSFCLNCGHGGHAECIREWFEDHTECPTG-CGC 44

Modified RING finger, H2 subclass (C3H3C2-type), found in WD repeat-containing protein 24 (WDR24) and similar proteins; WDR24 is a component of the GATOR2 complex, which also includes another four subunits, Seh1, Sec13, Sea3/WDR59, and Mio/Sea4. GATOR2 and GATOR1, which is composed of three subunits, DEPDC5, Nprl2, and Nprl3, form the Rag-interacting complex GATOR (GAP Activity Towards Rags). Inhibition of GATOR1 subunits makes mTORC1 signaling resistant to amino acid deprivation. In contrast, inhibition of GATOR2 subunits suppresses mTORC1 signaling and GATOR2 negatively regulates DEPDC5. WDR24 contains an N-terminal WD40 domain and a C-terminal RING-H2 finger with an unusual arrangement of zinc-coordinating residues. The cysteines and histidines in the RING-H2 finger are arranged as a modified C3H3C2-type, rather than the canonical C3H2C3-type. Sea2 is the yeast counterpart of WDR24. It is not included in this subfamily.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 109150419 824 FTWCHNCRHGGHAGHMLSWFRDHAECPvSACTCKC 858
Cdd:cd16693   13 YVWCQGCGHGGHLEHMKEWFSTNSHCP-AGCGHLC 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 109150419 112 HARQCNTLAWNPlDSNWLAAGLdkhrADFSVLIWDICS-----KYTPDIVPMEKVKLSAGeteTTLLVT----------- 175
Cdd:cd00200    8 HTGGVTCVAFSP-DGKLLATGS----GDGTIKVWDLETgellrTLKGHTGPVRDVAASAD---GTYLASgssdktirlwd 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150419 176 ----KPLYEL-GQNDACLSLCWLPRDQKLLLAGMHRNLAIFDLRNTSQKMFVN--TKAVQGVTVDPyFHDRVASF-YEGQ 247
Cdd:cd00200   80 letgECVRTLtGHTSYVSSVAFSPDGRILSSSSRDKTIKVWDVETGKCLTTLRghTDWVNSVAFSP-DGTFVASSsQDGT 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 109150419 248 VAIWDLRKFeKPVLTLTEQPKPLTKVAWCPTRTGLLATlTRDSNiIRLYDMQ 299
Cdd:cd00200  159 IKLWDLRTG-KCVATLTGHTGEVNSVAFSPDGEKLLSS-SSDGT-IKLWDLS 207

WD40 repeat [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150419  84 NGRVVLTSlGQDHNSKFKDLIGKEFV---PKHARQCNTLAWNPlDSNWLAAGldkhRADFSVLIWDicskytpdivpmek 160
Cdd:COG2319  215 DGKLLASG-SADGTVRLWDLATGKLLrtlTGHSGSVRSVAFSP-DGRLLASG----SADGTVRLWD-------------- 274

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109150419 161 vkLSAGETETTLLvtkplyelGQNDACLSLCWLPRDQKLLLAGMHRNLAIFDLrNTSQKMFV---NTKAVQGVTVDPyFH 237
Cdd:COG2319  275 --LATGELLRTLT--------GHSGGVNSVAFSPDGKLLASGSDDGTVRLWDL-ATGKLLRTltgHTGAVRSVAFSP-DG 342

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 109150419 238 DRVAS-FYEGQVAIWDLRKfEKPVLTLTEQPKPLTKVAWCPTRTgLLATLTRDsNIIRLYDMQ 299
Cdd:COG2319  343 KTLASgSDDGTVRLWDLAT-GELLRTLTGHTGAVTSVAFSPDGR-TLASGSAD-GTVRLWDLA 402