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 1335348612 281 SKGVYCLQYDD--QKIVSGLRDNTIKIWDKSTLECKRILTGHTGSVLCLQY--DERVIITGSSDSTVRVWDVNAGEMLNT 356
Cdd:cd00200     9 TGGVTCVAFSPdgKLLATGSGDGTIKVWDLETGELLRTLKGHTGPVRDVAAsaDGTYLASGSSDKTIRLWDLETGECVRT 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 357 LIHHCEAVLHLRF--NNGMMVTCSKDRSIAVWDMASPtdiTLRRVLVGHRAAVNVVDF--DDKYIVSASGDRTIKVWNTS 432
Cdd:cd00200    89 LTGHTSYVSSVAFspDGRILSSSSRDKTIKVWDVETG---KCLTTLRGHTDWVNSVAFspDGTFVASSSQDGTIKLWDLR 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 433 TCEFVRTLNGHKRGIACLQYRD--RLVVSGSSDNTIRLWDIECGACLRVLEGHEELVRCIRFDNKR--IVSGAYDGKIKV 508
Cdd:cd00200   166 TGKCVATLTGHTGEVNSVAFSPdgEKLLSSSSDGTIKLWDLSTGKCLGTLRGHENGVNSVAFSPDGylLASGSEDGTIRV 245

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1335348612 509 WDLMAAldprapagtLCLRTLVEHSGRVFRLQF--DEFQIVSSSHDDTILIWD 559
Cdd:cd00200   246 WDLRTG---------ECVQTLSGHTNSVTSLAWspDGKRLASGSADGTIRIWD 289

D domain of beta-TrCP; This domain is found in eukaryotes, and is approximately 40 amino acids in length. It is found associated with pfam00646, pfam00400. The protein that contains this domain functions as a ubiquitin ligase. Ubiquitination is required to direct proteins towards the proteasome for degradation. This protein is part of the WD40 class of F box proteins. The D domain of these F box proteins is involved in mediating the dimerization of the protein. dimerization is necessary to polyubiquitinate substrates so this D domain is vital in directing substrates towards the proteasome for degradation.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1335348612 117 KYFEQWSESDQVEFVEHLISQMCHYQHGHINSYLKPMLQ 155
Cdd:pfam12125   1 KYFDKWNESDQVDFVEHLLSRMCHYQHGHINSYLKPMLQ 39

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 1335348612 281 SKGVYCLQYDD--QKIVSGLRDNTIKIWDKSTLECKRILTGHTGSVLCLQY--DERVIITGSSDSTVRVWDVNAGEMLNT 356
Cdd:cd00200     9 TGGVTCVAFSPdgKLLATGSGDGTIKVWDLETGELLRTLKGHTGPVRDVAAsaDGTYLASGSSDKTIRLWDLETGECVRT 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 357 LIHHCEAVLHLRF--NNGMMVTCSKDRSIAVWDMASPtdiTLRRVLVGHRAAVNVVDF--DDKYIVSASGDRTIKVWNTS 432
Cdd:cd00200    89 LTGHTSYVSSVAFspDGRILSSSSRDKTIKVWDVETG---KCLTTLRGHTDWVNSVAFspDGTFVASSSQDGTIKLWDLR 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 433 TCEFVRTLNGHKRGIACLQYRD--RLVVSGSSDNTIRLWDIECGACLRVLEGHEELVRCIRFDNKR--IVSGAYDGKIKV 508
Cdd:cd00200   166 TGKCVATLTGHTGEVNSVAFSPdgEKLLSSSSDGTIKLWDLSTGKCLGTLRGHENGVNSVAFSPDGylLASGSEDGTIRV 245

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1335348612 509 WDLMAAldprapagtLCLRTLVEHSGRVFRLQF--DEFQIVSSSHDDTILIWD 559
Cdd:cd00200   246 WDLRTG---------ECVQTLSGHTNSVTSLAWspDGKRLASGSADGTIRIWD 289

F-box domain found in F-box/WD repeat-containing protein 1A (FBXW1A) and similar proteins; FBXW1A, also called E3RSIkappaB, epididymis tissue protein Li 2a, F-box and WD repeats protein beta-TrCP, or pIkappaBalpha-E3 receptor subunit, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as CTNNB1, NFKBIA, NFKBIB and NFKBIE, as well as phosphorylated NFKB1, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 153 MLQRDFITALPARGLDHIAENILSYLDAKSLCAAELVCKEWYRVTSDGMLWKKLIERMVR 212
Cdd:cd22182     1 MLQRDFITALPARGLDHIAENILSYLDAKSLCAAELVCKEWYRVTSDGMLWKKLIERMVR 60

D domain of beta-TrCP; This domain is found in eukaryotes, and is approximately 40 amino acids in length. It is found associated with F-box domain, WD domain. The protein that contains this domain functions as a ubiquitin ligase. Ubiquitination is required to direct proteins towards the proteasome for degradation. This protein is part of the WD40 class of F box proteins. The D domain of these F box proteins is involved in mediating the dimerisation of the protein. Dimerisation is necessary to polyubiquitinate substrates so this D domain is vital in directing substrates towards the proteasome for degradation.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1335348612  116 VKYFEQWSESDQVEFVEHLISQMCHYQHGHINSYLKPMLQ 155
Cdd:smart01028   1 VKYFEKWSESDQVDFVEHLISRMCHYQHGHINSYLKPMLQ 40

F-box-like; This is an F-box-like family.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1335348612 159 ITALParglDHIAENILSYLDAKSLCAAELVCKEWYRVTSDGMLWKKL 206
Cdd:pfam12937   1 LSSLP----DEILLQIFSYLDPKDLLRLALVCRRWRELASDDSLWRRL 44

WD domain, G-beta repeat;

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1335348612 474 GACLRVLEGHEELVRCIRF--DNKRIVSGAYDGKIKVWD 510
Cdd:pfam00400   1 GKLLKTLEGHTGSVTSLAFspDGKLLASGSDDGTVKVWD 39

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 1335348612 281 SKGVYCLQYDD--QKIVSGLRDNTIKIWDKSTLECKRILTGHTGSVLCLQY--DERVIITGSSDSTVRVWDVNAGEMLNT 356
Cdd:cd00200     9 TGGVTCVAFSPdgKLLATGSGDGTIKVWDLETGELLRTLKGHTGPVRDVAAsaDGTYLASGSSDKTIRLWDLETGECVRT 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 357 LIHHCEAVLHLRF--NNGMMVTCSKDRSIAVWDMASPtdiTLRRVLVGHRAAVNVVDF--DDKYIVSASGDRTIKVWNTS 432
Cdd:cd00200    89 LTGHTSYVSSVAFspDGRILSSSSRDKTIKVWDVETG---KCLTTLRGHTDWVNSVAFspDGTFVASSSQDGTIKLWDLR 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 433 TCEFVRTLNGHKRGIACLQYRD--RLVVSGSSDNTIRLWDIECGACLRVLEGHEELVRCIRFDNKR--IVSGAYDGKIKV 508
Cdd:cd00200   166 TGKCVATLTGHTGEVNSVAFSPdgEKLLSSSSDGTIKLWDLSTGKCLGTLRGHENGVNSVAFSPDGylLASGSEDGTIRV 245

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1335348612 509 WDLMAAldprapagtLCLRTLVEHSGRVFRLQF--DEFQIVSSSHDDTILIWD 559
Cdd:cd00200   246 WDLRTG---------ECVQTLSGHTNSVTSLAWspDGKRLASGSADGTIRIWD 289

WD40 repeat [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 281 SKGVYCLQY--DDQKIVSGLRDNTIKIWDKSTLECKRILTGHTGSVLCLQY--DERVIITGSSDSTVRVWDVNAGEMLNT 356
Cdd:COG2319   162 SGAVTSVAFspDGKLLASGSDDGTVRLWDLATGKLLRTLTGHTGAVRSVAFspDGKLLASGSADGTVRLWDLATGKLLRT 241

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 357 LIHHCEAVLHLRFN-NG-MMVTCSKDRSIAVWDMASPTditLRRVLVGHRAAVNVVDF--DDKYIVSASGDRTIKVWNTS 432
Cdd:COG2319   242 LTGHSGSVRSVAFSpDGrLLASGSADGTVRLWDLATGE---LLRTLTGHSGGVNSVAFspDGKLLASGSDDGTVRLWDLA 318

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 433 TCEFVRTLNGHKRGIACLQYR--DRLVVSGSSDNTIRLWDIECGACLRVLEGHEELVRCIRF--DNKRIVSGAYDGKIKV 508
Cdd:COG2319   319 TGKLLRTLTGHTGAVRSVAFSpdGKTLASGSDDGTVRLWDLATGELLRTLTGHTGAVTSVAFspDGRTLASGSADGTVRL 398

                  ...
gi 1335348612 509 WDL 511
Cdd:COG2319   399 WDL 401

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 1335348612 313 CKRILTGHTGSVLCLQY--DERVIITGSSDSTVRVWDVNAGEMLntlihhceavlhlrfnngmmvtcskdrsiavwdmas 390
Cdd:cd00200     1 LRRTLKGHTGGVTCVAFspDGKLLATGSGDGTIKVWDLETGELL------------------------------------ 44

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 391 ptditlrRVLVGHRAAVNVVDF--DDKYIVSASGDRTIKVWNTSTCEFVRTLNGHKRGIACLQYR--DRLVVSGSSDNTI 466
Cdd:cd00200    45 -------RTLKGHTGPVRDVAAsaDGTYLASGSSDKTIRLWDLETGECVRTLTGHTSYVSSVAFSpdGRILSSSSRDKTI 117

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 467 RLWDIECGACLRVLEGHEELVRCIRF--DNKRIVSGAYDGKIKVWDLmaaldprapAGTLCLRTLVEHSGRVFRLQF--D 542
Cdd:cd00200   118 KVWDVETGKCLTTLRGHTDWVNSVAFspDGTFVASSSQDGTIKLWDL---------RTGKCVATLTGHTGEVNSVAFspD 188

                         250
                  ....*....|....*...
gi 1335348612 543 EFQIVSSSHDDTILIWDF 560
Cdd:cd00200   189 GEKLLSSSSDGTIKLWDL 206

WD40 repeat [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 272 QRIHCRSETSKGVYCLQY--DDQKIVSGLRDNTIKIWDKSTLECKRILTGHTGSVLCLQY--DERVIITGSSDSTVRVWD 347
Cdd:COG2319   237 KLLRTLTGHSGSVRSVAFspDGRLLASGSADGTVRLWDLATGELLRTLTGHSGGVNSVAFspDGKLLASGSDDGTVRLWD 316

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 348 VNAGEMLNTLIHHCEAVLHLRF--NNGMMVTCSKDRSIAVWDMASPTditLRRVLVGHRAAVNVVDF--DDKYIVSASGD 423
Cdd:COG2319   317 LATGKLLRTLTGHTGAVRSVAFspDGKTLASGSDDGTVRLWDLATGE---LLRTLTGHTGAVTSVAFspDGRTLASGSAD 393

                         170
                  ....*....|
gi 1335348612 424 RTIKVWNTST 433
Cdd:COG2319   394 GTVRLWDLAT 403

F-box domain found in F-box/WD repeat-containing proteins, FBXW1A, FBXW1B and similar proteins; FBXW1A, also called E3RSIkappaB, epididymis tissue protein Li 2a, F-box and WD repeats protein beta-TrCP, or pIkappaBalpha-E3 receptor subunit, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as CTNNB1, NFKBIA, NFKBIB and NFKBIE, as well as phosphorylated NFKB1, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2. FBXW1B, also called F-box/WD repeat-containing protein 11 (FBXW11), F-box and WD repeats protein beta-TrCP2, or homologous to Slimb protein (HOS), is the substrate-recognition component of an SCF E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as IFNAR1, CEP68 and CDC25A, as well as phosphorylated CTNNB1, NFKBIA, PER1 and PER2. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1335348612 155 QRDFITALPARGLDHIAENILSYLDAKSLCAAELVCKEWYRVTSDGMLWKK 205
Cdd:cd22130     1 QRDFISALPAKGLDHIAENILSYLDAKSLCAAELVCKEWYRVIADGMLWKK 51

D domain of beta-TrCP; This domain is found in eukaryotes, and is approximately 40 amino acids in length. It is found associated with pfam00646, pfam00400. The protein that contains this domain functions as a ubiquitin ligase. Ubiquitination is required to direct proteins towards the proteasome for degradation. This protein is part of the WD40 class of F box proteins. The D domain of these F box proteins is involved in mediating the dimerization of the protein. dimerization is necessary to polyubiquitinate substrates so this D domain is vital in directing substrates towards the proteasome for degradation.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1335348612 117 KYFEQWSESDQVEFVEHLISQMCHYQHGHINSYLKPMLQ 155
Cdd:pfam12125   1 KYFDKWNESDQVDFVEHLLSRMCHYQHGHINSYLKPMLQ 39

protein SPA1-RELATED; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 417 IVSASGDRTIKVWNTSTCEFVRTLNGHKRGIACLQYRD---RLVVSGSSDNTIRLWDIECGACLRVLEGHEELVrCIRFD 493
Cdd:PLN00181  548 VASSNFEGVVQVWDVARSQLVTEMKEHEKRVWSIDYSSadpTLLASGSDDGSVKLWSINQGVSIGTIKTKANIC-CVQFP 626

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348612 494 N---KRIVSGAYDGKIKVWDLmaaldpRAPAGTLClrTLVEHSGRVFRLQF-DEFQIVSSSHDDTILIWDFLNDPAAHAE 569
Cdd:PLN00181  627 SesgRSLAFGSADHKVYYYDL------RNPKLPLC--TMIGHSKTVSYVRFvDSSTLVSSSTDNTLKLWDLSMSISGINE 698

                  ..
gi 1335348612 570 PP 571
Cdd:PLN00181  699 TP 700

F-box-like; This is an F-box-like family.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1335348612 159 ITALParglDHIAENILSYLDAKSLCAAELVCKEWYRVTSDGMLWKKL 206
Cdd:pfam12937   1 LSSLP----DEILLQIFSYLDPKDLLRLALVCRRWRELASDDSLWRRL 44

WD40 repeats; Note that these repeats are permuted with respect to the structural repeats (blades) of the beta propeller domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1335348612  310 TLECKRILTGHTGSVLCLQY--DERVIITGSSDSTVRVWD 347
Cdd:smart00320   1 SGELLKTLKGHTGPVTSVAFspDGKYLASGSDDGTIKLWD 40

WD domain, G-beta repeat;

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1335348612 474 GACLRVLEGHEELVRCIRF--DNKRIVSGAYDGKIKVWD 510
Cdd:pfam00400   1 GKLLKTLEGHTGSVTSLAFspDGKLLASGSDDGTVKVWD 39

A Receptor for Ubiquitination Targets;

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1335348612  168 DHIAENILSYLDAKSLCAAELVCKEWYRVTSDGMLWKKL 206
Cdd:smart00256   3 DEILEEILSKLDPKDLLRLRKVSRKWRSLIDSHDFWFKL 41

F-box domain superfamily; This short domain is commonly found at the N-terminus of various proteins, and typically co-occurs with one or more other conserved domains or motifs, such as leucine rich repeats, WD40 repeats, kelch, tub, spry, and others. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression. One of the best researched roles of F-box proteins is their participation in SCF (Skp1-Cul1-F-box protein), a multi-protein complex that functions as a ubiquitin E3 ligase, where the role of the F-box protein is to recruit target substrates. Gene families containing the F-box are found greatly expanded in narrow taxonomic lineages, such as flowering plants and nematodes. In this hierarchical classification, many of the subfamilies are named according to their domain architectures.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1335348612 168 DHIAENILSYLDAKSLCAAELVCKEWYRVTS 198
Cdd:cd09917     5 DEILLKILSYLDPRDLLRLSLVCKRWRELAS 35

F-box domain found in F-box/LRR-repeat protein 4 (FBXL4) and similar proteins; FBXL4, also called F-box and leucine-rich repeat protein 4, or F-box protein FBL4/FBL5, is part of an SCF (SKP1-cullin-F-box) protein ligase complex. It serves as a clock output molecule that regulates sleep through promotion of rhythmic degradation of the GABA(A) receptor. Biallelic pathogenic variants in FBXL4 are associated with an encephalopathic mtDNA maintenance defect syndrome that is a multi-system disease characterized by lactic acidemia, developmental delay, and hypotonia. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1335348612 174 ILSYLDAKSLCAAELVCKEWYRVTSDGMLWKKL 206
Cdd:cd22117    12 ILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKEL 44

F-box domain found in F-box only protein 41 (FBXO41) and similar proteins; FBXO41, also called FBX41, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It acts as a novel central nervous system (CNS)-specific F-box protein that localizes to the centrosome and the cytoplasm of neurons and promotes neuronal migration. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1335348612 161 ALPARGLDHIaenILSYLDAKSLCAAELVCKEWYRVTSDGMLWKKL 206
Cdd:cd22109     4 SLRRRDALFC---VFSYLDTKSLLRCAEVCREWRDVSRHPALWQRV 46

WD40 repeats; Note that these repeats are permuted with respect to the structural repeats (blades) of the beta propeller domain.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1335348612  395 TLRRVLVGHRAAVNVVDF--DDKYIVSASGDRTIKVWN 430
Cdd:smart00320   3 ELLKTLKGHTGPVTSVAFspDGKYLASGSDDGTIKLWD 40

F-box domain found in F-box only protein 11 (FBXO11) and similar proteins; FBXO11, also called FBX11, protein arginine N-methyltransferase 9 (PRMT9), or vitiligo-associated protein 1 (VIT-1), is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1335348612 168 DHIAENILSYLDAKSLCAAELVCKEWYRVTSDGMLWKKL 206
Cdd:cd22091     6 DEVLLKIFSYLLEQDLCRAAQVCKRFNTLANDPELWKRL 44

WD domain, G-beta repeat;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1335348612 395 TLRRVLVGHRAAVNVVDF--DDKYIVSASGDRTIKVWN 430
Cdd:pfam00400   2 KLLKTLEGHTGSVTSLAFspDGKLLASGSDDGTVKVWD 39

F-box domain found in F-box only protein 15 (FBXO15) and similar proteins; FBXO15, also called FBX15, has a novel dual molecular function by controlling transcriptional repression and being part of SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligases, which is essential for stress response, gliotoxin production and virulence in the opportunistic human pathogen Aspergillus fumigatus. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1335348612 174 ILSYLDAKSLCAAELVCKEWYRVTSDGMLWKKL 206
Cdd:cd22093    12 ILSYLDASSLLCISCVNKLFYQLANDNALWRKL 44

F-box domain found in F-box/WD repeat-containing protein 2 (FBXW2) and similar proteins; FBXW2, also called F-box and WD-40 domain-containing protein 2, or protein MD6, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It acts as a tumor suppressor by promoting SKP2 degradation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1335348612 157 DFITALPARgldhIAENILSYLDAKSLCAAELVCKEWYRVTS 198
Cdd:cd22131     1 DFLKLLPLE----LSFYLLSFLDPESLLTCCLVSKQWNKVIS 38

F-box domain found in Arabidopsis thaliana F-box/WD-40 repeat-containing protein 1 (AtFBW1) and similar proteins; AtFBW1, also called WD-40-associated F-box protein 1, is an F-box protein that contains four WD-40 repeats, which are separated from each other by a spacer region. Like other F-box proteins, AtFBW1 may be a component of SCF (Skp1 Cdc53 F-box protein) E3 ubiquitin ligase complexes, which may mediate the ubiquitination and subsequent proteasomal degradation of target proteins. This subfamily also contains many F-box only proteins that do not have any WD repeat. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1335348612 168 DHIAENILSYLDAKSLCAAELVCKEWYRVTSD 199
Cdd:cd22157     5 DDLVEEILSRLPAKSLLRFRCVCKQWNSLISS 36

F-box domain; This domain is approximately 50 amino acids long, and is usually found in the N-terminal half of a variety of proteins. Two motifs that are commonly found associated with the F-box domain are the leucine rich repeats (LRRs; pfam00560 and pfam07723) and the WD repeat (pfam00400). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1335348612 168 DHIAENILSYLDAKSLCAAELVCKEWYRVTSDGMLWKK 205
Cdd:pfam00646   6 DDLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWKK 43

F-box domain found in F-box only protein 16 (FBXO16), epithelial cell-transforming sequence 2 oncogene-like (ECT2L) and similar proteins; This family includes FBXO16 and ECT2L. FBXO16, also called FBX16, is part of an SCF (SKP1-cullin-F-box) protein ligase complex. It probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. It functions as a tumor suppressor by attenuating nuclear beta-catenin function. ECT2L, also called lung-specific F-box and DH domain-containing protein, or putative guanine nucleotide exchange factor LFDH, may act as a guanine nucleotide exchange factor (GEF). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1335348612 157 DFITALPARgldhIAENILSYLDAKSLCAAELVCKEWYRVTSDGMLWK 204
Cdd:cd22094     1 DFTRVLPRF----LSLYIFSYLDPRSLCRAAQVSWYWKFLCESDELWL 44

F-box domain found in F-box only protein 45 (FBXO45) and similar proteins; FBXO45, also called FBX45, or F-box/SPRY domain-containing protein 1, functions as the substrate-recognition component of E3 ubiquitin ligase complexes. It is critical for synaptogenesis, neuronal migration, and synaptic transmission. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1335348612 160 TALPARGLdhiaENILSYLDAKSLCAAELVCKEWYRVTS 198
Cdd:cd22111     2 ARLPSRVL----EVIFSYLDLPDLRNCSLVCKSWYRLLN 36

F-box domain found in F-box only protein 7 (FBXO7) and similar proteins; FBXO7, also called FBX7, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It recognizes BIRC2 and DLGAP5. FBXO7 plays a role downstream of PINK1 in the clearance of damaged mitochondria via selective autophagy (mitophagy) by targeting PRKN to dysfunctional depolarized mitochondria. It promotes MFN1 ubiquitination. FBXO7 acts as a cell cycle regulator by enhancing cyclin D/cyclin-dependent kinase 6 (Cdk6) complex formation and stabilizing levels of p27, a cyclin-dependent kinase inhibitor. Mutations in the FBXO7 (PARK15) gene have been implicated in a juvenile form of parkinsonism called parkinsonian pyramidal syndrome (PPS), characterized by Parkinsonian symptoms and pyramidal tract signs. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1335348612 173 NILSYLDAKSLCAAELVCKEWYRVTSDGMLWKKL 206
Cdd:cd22087    11 RILSLLDVRSLLSLSQVCRDLNSATNDQLLWRFL 44

F-box domain found in F-box/WD repeat-containing protein 12 (FBXW12) and similar proteins; FBXW12, also called F-box and WD-40 domain-containing protein 12, or F-box only protein 35 (FBXO35), is the substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It functions as an epithelial growth suppressor. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1335348612 174 ILSYLDAKSLCAAELVCKEWYRVTSDGMLWKKL 206
Cdd:cd22137    11 IFSFLDAFSLLQAAQVNKQWNKVADSDYLWRNL 43

F-box domain found in Arabidopsis thaliana F-box protein GID2 and similar proteins; AtGID2, also called protein SLEEPY 1, is an essential component of the SCF-type E3 ligase complex, SCF(GID2), a complex that positively regulates the gibberellin signaling pathway. Upon gibberellin treatment, the SCF(GID2) complex mediates the ubiquitination and subsequent degradation of DELLA proteins (GAI, RGA and RGL2), some repressors of the gibberellin pathway, leading to the activation of the pathway. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1335348612 168 DHIAENILSYLDAKSLCAAELVCKEWYRVTSDGMLW 203
Cdd:cd22151     5 DDLLQEIFKRLDPKSLARAACVCRRWRAAARSESLW 40

WD40 repeats; Note that these repeats are permuted with respect to the structural repeats (blades) of the beta propeller domain.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1335348612  351 GEMLNTLIHHCEAVLHLRF--NNGMMVTCSKDRSIAVWD 387
Cdd:smart00320   2 GELLKTLKGHTGPVTSVAFspDGKYLASGSDDGTIKLWD 40