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 568982302  10 LQHIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQLC 46
Cdd:cd22137    8 MLRIFSFLDAFSLLQAAQVNKQWNKVADSDYLWRNLC 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 568982302  10 LQHIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQLC 46
Cdd:cd22137    8 MLRIFSFLDAFSLLQAAQVNKQWNKVADSDYLWRNLC 44

WD40 repeat [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982302  92 ISGHTGMIDQLAYvSPheyrfdeGARSVVcTVSSDCTVRAWDLQEGSEIWSSAVQPAPlVNVVAY-PQLQLVVTVDIQGL 170
Cdd:COG2319  242 LTGHSGSVRSVAF-SP-------DGRLLA-SGSADGTVRLWDLATGELLRTLTGHSGG-VNSVAFsPDGKLLASGSDDGT 311

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982302 171 IMGWKAKTGSEwaFFSLPASCSSMEACD-HPEGPFLLVACDEGTLYTMTVPQLQVVSRVPTFPHSSVSLTCSPDTQWVfV 249
Cdd:COG2319  312 VRLWDLATGKL--LRTLTGHTGAVRSVAfSPDGKTLASGSDDGTVRLWDLATGELLRTLTGHTGAVTSVAFSPDGRTL-A 388

                 ..
gi 568982302 250 SA 251
Cdd:COG2319  389 SG 390

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 568982302  10 LQHIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQLC 46
Cdd:cd22137    8 MLRIFSFLDAFSLLQAAQVNKQWNKVADSDYLWRNLC 44

F-box domain found in F-box/WD repeat-containing protein 5 (FBXW5) and similar proteins; FBXW5, also called F-box and WD-40 domain-containing protein 5, is the substrate-recognition component of both SCF (SKP1-CUL1-F-box protein) and DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes. 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 568982302  10 LQHIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQL 45
Cdd:cd22132    9 LLHIFSYLSPKDLLAAGQVCKQWYRVSRDEFLWKEL 44

F-box domain found in F-box/LRR-repeat protein 5 (FBXL5) and similar proteins; FBXL5, also called F-box and leucine-rich repeat protein 5, F-box protein FBL4/FBL5, or p45SKP2-like protein, is the substrate-recognition component of an SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2. 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 568982302   4 QLGPHELQHIFSFLEARDLLRAAQVNKVWNEVSMTKELW 42
Cdd:cd22118    3 SLPPEIMLKIFSYLNPQDLCRCAQVCTKWSQLARDGSLW 41

F-box domain found in F-box only protein 3 (FBXO3) and similar proteins; FBXO3, also called FBX3, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It mediates the ubiquitination of HIPK2 and probably that of EP300, leading to rapid degradation by the proteasome. It also promotes ubiquitylation and transcriptional activity of AIRE (autoimmune regulator). 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 568982302  10 LQHIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQLCLRRW 50
Cdd:cd22084    9 LLNILSFLDYRDLISCSQVCRRLNQLCSHDPLWKRLCKKYW 49

F-box domain found in F-box only protein 16 (FBXO16) and similar proteins; 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. 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 568982302  12 HIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQLCLRR 49
Cdd:cd22172   16 YIFSFLDPRSLCRCAQVCWYWKYLTELDQLWMPKCLRF 53

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
                 ....*....|....*....|....*....|....*.
gi 568982302  13 IFSFLEARDLLRAAQVNKVWNEVSMTKELWRQLCLR 48
Cdd:cd22094   14 IFSYLDPRSLCRAAQVSWYWKFLCESDELWLPKCLR 49

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        40
                 ....*....|....*....|....*....|....*....|
gi 568982302   7 PHE-LQHIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQL 45
Cdd:cd22091    5 PDEvLLKIFSYLLEQDLCRAAQVCKRFNTLANDPELWKRL 44

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        40
                 ....*....|....*....|....*....|....*....|.
gi 568982302   7 PHE-LQHIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQLC 46
Cdd:cd22093    5 PSEiLLKILSYLDASSLLCISCVNKLFYQLANDNALWRKLY 45

F-box domain found in F-box/LRR-repeat protein 12 (FBXL12) and similar proteins; FBXL12, also called F-box and leucine-rich repeat protein 12, or F-box protein FBL12, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It mediates the polyubiquitination and proteasomal degradation of calcium/calmodulin dependent protein kinase I (CAMK1) leading to disruption of cyclin D1/CDK4 complex assembly, which results in G1 cell cycle arrest in lung epithelia. It regulates T-cell differentiation in a cell-autonomous manner. 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 568982302  10 LQHIFSFLEARDLLRAAQVNKVWNEVSMTKELWR 43
Cdd:cd22123    9 LLEILSYLPVRDLLRISRVCKRWRRLVYDKTLWR 42

F-box domain found in F-box only protein 48 (FBXO48) and similar proteins; FBXO48, also called FBX48, is one of the paralogs of the F-box only protein 7 (FBXO7), which is the causative gene for PARK15 (also known as Parkinsonian-pyramidal disease, PPD). 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 568982302  13 IFSFLEARDLLRAAQVNKVWNEV-SMTKELWRQLC 46
Cdd:cd22113   12 IFSQLDVQSLCRASQTCKTWNDLiENSDYLWRPHC 46

F-box domain found in F-box only protein 39 (FBXO39) and similar proteins; FBXO39, also called FBX39, likely functions as the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It acts as a cancer/testis antigen from colon cancer patients by serological analysis of recombinant cDNA expression libraries (SEREX). 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 568982302  10 LQHIFSFLEARDLLRAAQVNKVWNEVSMTKELWR 43
Cdd:cd22108    9 LRHVFRWLGDRDRSRAALVCKRWNQAMYSPALWR 42

WD40 repeat [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982302  92 ISGHTGMIDQLAYvSPheyrfdeGARSVVcTVSSDCTVRAWDLQEGSEIWSSAVQPAPlVNVVAY-PQLQLVVTVDIQGL 170
Cdd:COG2319  242 LTGHSGSVRSVAF-SP-------DGRLLA-SGSADGTVRLWDLATGELLRTLTGHSGG-VNSVAFsPDGKLLASGSDDGT 311

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568982302 171 IMGWKAKTGSEwaFFSLPASCSSMEACD-HPEGPFLLVACDEGTLYTMTVPQLQVVSRVPTFPHSSVSLTCSPDTQWVfV 249
Cdd:COG2319  312 VRLWDLATGKL--LRTLTGHTGAVRSVAfSPDGKTLASGSDDGTVRLWDLATGELLRTLTGHTGAVTSVAFSPDGRTL-A 388

                 ..
gi 568982302 250 SA 251
Cdd:COG2319  389 SG 390

F-box domain found in F-box only protein 10 (FBXO10) and similar proteins; FBXO10, also called FBX10, or PRMT11, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. The SCF(FBXO10) complex mediates ubiquitination and degradation of BCL2, an anti-apoptotic protein, thereby playing a role in apoptosis by controlling the stability of BCL2. It also associates with the receptor for advanced glycation end products (RAGE) to mediate its ubiquitination and 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 568982302   7 PHELQH-IFSFLEARDLLRAAQVNKVWNEV--SMTKELWRQLCL 47
Cdd:cd22090    6 PLELWRlILAYLPVRDLCRCCQVCRAWYELilSLDSTRWKQLYL 49

F-box domain found in F-box/WD repeat-containing protein 8 (FBXW8) and similar proteins; FBXW8, also called F-box and WD-40 domain-containing protein 8, or F-box only protein 29 (FBXO29), is the substrate-recognition component of a Cul7-RING ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as GORASP1, IRS1, MAP4K1/HPK1. 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 568982302   7 PHELQ-HIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQLC 46
Cdd:cd22134    8 PRELAlKIFQYLSVTDLCRCAQVSKSWKSLAEDELLWYRIC 48

F-box domain found in F-box only proteins FBXO6, FBXO44 and similar proteins; This subfamily includes FBXO6 and FBXO44. FBXO6, also called FBX6, F-box protein that recognizes sugar chains 2 (FBS2), or F-box/G-domain protein 2 (FBG2), is a substrate-recognition component of SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. It is involved in the endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins, by recognizing and binding sugar chains on unfolded glycoproteins that are retro-translocated into the cytosol and promoting their ubiquitination and subsequent degradation. FBXO6 can recognize and bind denatured glycoproteins, which are modified with not only high-mannose but also complex-type oligosaccharides. It also recognizes sulfated glycans. FBXO6 is involved in DNA damage response by specifically recognizing activated CHEK1 (phosphorylated on 'Ser-345'), promoting its ubiquitination and degradation. FBXO44, also called FBXO6A, FBX44, or F-box/G-domain protein 3 (FBG3), is a substrate-recognition component of an SCF-type E3 ubiquitin ligase complex. It interacts with SKP1 and CUL1. FBXO44 mediates BRCA1 ubiquitination and 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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568982302   8 HELQHIFSFLEARDLLRAAQ-VNKVWNEVSMTKELWRQLCLRRWASCKAFPvvVGTQTWKKYYFCRSE 74
Cdd:cd22168   10 DVLLEILSLVPARDLILSCRlVCSRWRDLVDLPTLWKRKCQREGFILKDWD--GPPKDWKIFYFLRLE 75

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        40
                 ....*....|....*....|....*....|....*....|....*.
gi 568982302   4 QLGPHEL-QHIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQLCLR 48
Cdd:cd22117    2 DLLPYELiQLILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKELNLQ 47

F-box domain found in F-box/LRR-repeat protein 13 (FBXL13) and similar proteins; FBXL13, also called F-box and leucine-rich repeat protein 13, or dynein regulatory complex subunit 6, is a component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. It is also the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. 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 568982302  13 IFSFLEARDLLRAAQVNKVWNEVSMTKELW 42
Cdd:cd22124   12 IFSYLDLRDLARCAQVCRSWKVITQSSSLW 41

F-box domain found in uncharacterized F-box protein group similar to F-box only protein 13 (FBXO13); The family corresponds to a group of uncharacterized F-box proteins which show sequence similarity to F-box only protein 13 (FBXO13). FBXO13, also called FBX13, or F-box/LRR-repeat protein 17 (FBL17), or F-box and leucine-rich repeat protein 17 (FBXL17), is the substrate-recognition component of the SCF(FBXL17) E3 ubiquitin ligase complex, a key component of a quality control pathway required to ensure functional dimerization of BTB domain-containing proteins (dimerization quality control, DQC). 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 568982302   4 QLGPHELQ-HIFSFLEARDLLRAAQVNKVWNEVSMTKELWR 43
Cdd:cd22138    2 QSLPVECQlKIFSFLSEVDKCLAATVCRSWSELIRSPRLWR 42

F-box domain found in the JmjC domain-containing histone demethylation protein (JHDM) family; The JHDM family includes F-box/LRR-repeat proteins FBXL10, FBXL11 and FBXL19. FBXL10 is also called lysine-specific demethylase 2B (KDM2B), CXXC-type zinc finger protein 2 (CXXC2), F-box and leucine-rich repeat protein 10 (FBL10), JmjC domain-containing histone demethylation protein 1B (JHDM1B), Jumonji domain-containing EMSY-interactor methyltransferase motif protein, protein JEMMA, protein-containing CXXC domain 2, [Histone-H3]-lysine-36 demethylase 1B, or NDY1. It is a histone demethylase that catalyzes the demethylation of H3K4me3 and H3K36me2, thereby playing a central role in the histone code. It preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation. FBXL10 may also serve as the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. FBXL11, also called KDM2A, CXXC8, F-box and leucine-rich repeat protein 11, F-box protein FBL7, F-box protein Lilina, JmjC domain-containing histone demethylation protein 1A (JHDM1A), or [Histone-H3]-lysine-36 demethylase 1A, is a histone H3 lysine 36 (H3K36) demethylase that regulates epithelial mesenchymal transition (EMT) and the metastasis of ovarian cancer. It plays an essential role in embryonic development and homeostasis by regulating cell proliferation and survival. FBXL11 may also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. It associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. It is required to sustain centromeric integrity and genomic stability, particularly during mitosis. FBXL19, also called F-box and leucine-rich repeat protein 19, is the substrate-recognition component of an SCF-type E3 ubiquitin ligase complex. It acts as a CpG island-binding protein in mouse embryonic stem (ES) cells and has been shown to associate with the CDK-Mediator complex. It promotes H2Bub1 at the promoters of CpG island-containing genes by interacting with RNF20. 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 568982302  12 HIFSFLEARDLLRAAQVNKVWNEVSMTKELWR 43
Cdd:cd22122   11 PVFQYLSPKDLCVCMRVCKTWNRWCCDPSLWK 42

F-box domain found in F-box only protein 36 (FBXO36) and similar proteins; FBXO36, also called FBX36, likely functions as the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. 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 568982302   7 PHELQ-HIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQL 45
Cdd:cd22106    5 PDKLLlYIISYLDLEDIARLSQTSKRFKKLCNSDELWEKI 44

F-box domain found in F-box only protein 31 (FBXO31) and similar proteins; FBXO31, also called FBX31, or FBXO14, is a component of an SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in G1 arrest following DNA damage. It specifically recognizes phosphorylated cyclin-D1 (CCND1), promoting its ubiquitination and degradation by the proteasome, resulting in G1 arrest. FBXO31 may act as a tumor 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        40
                 ....*....|....*....|....*....|....*....|..
gi 568982302   5 LGPHELQHIFSFLEARDLLRAAQVNKVWNEVSMTKELWRQLC 46
Cdd:cd22102    4 LPPELLVEIFSSLPGTDLPSLAQVCKKFREILNTDTIWQRRC 45