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        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1039737424  35 VELLPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRNNDSLWKPHC 80
Cdd:cd22113     1 IELLPPEMSLRIFSQLDVQSLCRASQTCKTWNDLIENSDYLWRPHC 46

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        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1039737424  35 VELLPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRNNDSLWKPHC 80
Cdd:cd22113     1 IELLPPEMSLRIFSQLDVQSLCRASQTCKTWNDLIENSDYLWRPHC 46

A Receptor for Ubiquitination Targets;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1039737424   38 LPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRNNDSLWK 77
Cdd:smart00256   1 LPDEILEEILSKLDPKDLLRLRKVSRKWRSLIDSHDFWFK 40

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        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1039737424  35 VELLPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRNNDSLWKPHC 80
Cdd:cd22113     1 IELLPPEMSLRIFSQLDVQSLCRASQTCKTWNDLIENSDYLWRPHC 46

F-box domain found in Schizosaccharomyces pombe Skp1-binding protein 1 (SpPof1) and similar proteins; SpPof1, also called F-box/WD repeat-containing protein pof1, probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. It is required for the inactivation of zip1 via ubiquitination. This subfamily also includes Saccharomyces cerevisiae methionine-requiring protein 30 (ScMET30, also called E3 ubiquitin ligase complex SCF(Met30) subunit MET30), Aspergillus niger sulfur controller B (AnSCONB, also called sulfur metabolite repression control protein B) and Neurospora crassa sulfur controller 2 (NcSCON2, also called sulfur metabolite repression control protein 2). ScMET30 acts as a transcriptional inhibitor that negatively regulates the expression of sulfur amino acid biosynthesis genes. It controls cell cycle function (being required for the G1/S transition and M-phase but not the S-phase), sulfur metabolism, and methionine biosynthesis as part of the E3 ubiquitin ligase complex SCF(Met30). AnSCONB and NcSCON2 are components of the SCF (sconB/scon-2) E3 ubiquitin ligase complexes involved in the regulation of sulfur metabolite repression, probably by mediating the inactivation or degradation of the metR transcription factor. 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 1039737424  34 FVELLPLEVTYKIFSQLDIQSLCRASRTCTGWNcAIRNNDSLWKPHC 80
Cdd:cd22147     1 FLSALPVELSLKILSYLDAKSLCRAAQVSKKWR-NLADDDELWKRMC 46

A Receptor for Ubiquitination Targets;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1039737424   38 LPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRNNDSLWK 77
Cdd:smart00256   1 LPDEILEEILSKLDPKDLLRLRKVSRKWRSLIDSHDFWFK 40

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 1039737424  38 LPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIR 70
Cdd:cd09917     3 LPDEILLKILSYLDPRDLLRLSLVCKRWRELAS 35

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        40
                  ....*....|....*....|....*....|....*....|
gi 1039737424  38 LPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRNNDSLWK 77
Cdd:pfam00646   4 LPDDLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWKK 43

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        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1039737424  34 FVELLPLEVTYKIFSQLDIQSLCRASRTCTGWNcAIRNNDSLWKPHCL 81
Cdd:cd22172     5 FTRVLPRVLSLYIFSFLDPRSLCRCAQVCWYWK-YLTELDQLWMPKCL 51

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
                  ....*....|....*....|....*....|....*....
gi 1039737424  33 NFVELLPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRN 71
Cdd:cd22131     1 DFLKLLPLELSFYLLSFLDPESLLTCCLVSKQWNKVISS 39

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        40
                  ....*....|....*....|....*....|....*....|..
gi 1039737424  35 VELLPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRNNdSLW 76
Cdd:cd22118     1 ISSLPPEIMLKIFSYLNPQDLCRCAQVCTKWSQLARDG-SLW 41

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        40
                  ....*....|....*....|....*....|....*....|..
gi 1039737424  36 ELLPLEVTYKIFSQLDIQSLCRASRTCTGWnCAIRNNDSLWK 77
Cdd:cd22132     2 PLLPDSLLLHIFSYLSPKDLLAAGQVCKQW-YRVSRDEFLWK 42

F-box domain found in epithelial cell-transforming sequence 2 oncogene-like (ECT2L) and similar proteins; 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 1039737424  33 NFVELLPLEVTYKIFSQLDIQSLCRASRTCTGWNcAIRNNDSLWKPHCL 81
Cdd:cd22173     1 DFTTVLPRFLSLYIFSFLDPRSLCRAAQVSWHWK-FLAEQDCLWMPKCV 48

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        40
                  ....*....|....*....|....*....|....*....|....
gi 1039737424  37 LLPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRnNDSLWKPHC 80
Cdd:cd22151     2 KLPDDLLQEIFKRLDPKSLARAACVCRRWRAAAR-SESLWENAC 44

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        40
                  ....*....|....*....|....*....|....*....|..
gi 1039737424  35 VELLPLEVTYKIFSQLDIQSLCRASRTCTGWNcAIRNNDSLW 76
Cdd:cd22124     1 ISLLPRKAALKIFSYLDLRDLARCAQVCRSWK-VITQSSSLW 41

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        40
                  ....*....|....*....|....*....|....*....|.
gi 1039737424  37 LLPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIrNNDSLWK 77
Cdd:cd22087     3 ALPPEIKLRILSLLDVRSLLSLSQVCRDLNSAT-NDQLLWR 42

F-box domain found in Saccharomyces cerevisiae protein Digs into agar protein 2 (ScDIA2) and similar proteins; ScDIA2 is a replication origin-binding protein that plays a role in regulating DNA replication. It is a component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. 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 1039737424  34 FVELLPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRNNDSLWK 77
Cdd:cd22142     1 RWENLPLDILPLIFQKFSTKELITLSHVCSSWRAKILDFPHLWK 44

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        40
                  ....*....|....*....|....*....|....*....|...
gi 1039737424  35 VELLPLEVTYKIFSQLDIQSLCRASRTCTGWNcAIRNNDSLWK 77
Cdd:cd22123     1 LDQLPENVLLEILSYLPVRDLLRISRVCKRWR-RLVYDKTLWR 42

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 1039737424  35 VELLPLEVTYKIFSQLDIQSLCRASRTCTGWNcAIRNNDSLWKPHC 80
Cdd:cd22084     1 LDDLPSDPLLNILSFLDYRDLISCSQVCRRLN-QLCSHDPLWKRLC 45

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 1039737424  36 ELLPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRNND 73
Cdd:cd22157     1 SSLPDDLVEEILSRLPAKSLLRFRCVCKQWNSLISSPS 38

F-box domain found in F-box only protein 33 (FBXO33) and similar proteins; FBXO33, also called FBX33, 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 exerts similar functions as F-box involved in polyQ pathogenesis (FipoQ) in modulating the ubiquitination and solubility of expanded SCA3-polyQ proteins. 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 1039737424  36 ELLPLEVTYKIFSQLDIQSLCRASRTCTGWNCAIRnNDSLWK 77
Cdd:cd22104     2 ANLPSVVLVHIFSYLPPRDRLRASSTCRRWREALF-HPSLWR 42

F-box domain found in F-box/LRR-repeat protein 1 (FBXL1) and similar proteins; FBXL1, also called S-phase kinase-associated protein 2, cyclin-A/CDK2-associated protein p45, F-box protein Skp2, or p45skp2, 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 involved in cell cycle progression, signal transduction and transcription. It specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. 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 1039737424  38 LPLEVTYKIFSQLDIQSLCRASRTCTGWnCAIRNNDSLW 76
Cdd:cd22114     4 LPDELLLGIFSCLCLPDLLKVSQVCKRW-YRLASDESLW 41