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 1046888286 280 FDKLPYELIQLILNHLSLPDLCRLAQTCRLLHQHCCDPLQYIHLNLQ 326
Cdd:cd22117     1 FDLLPYELIQLILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKELNLQ 47

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 1046888286 280 FDKLPYELIQLILNHLSLPDLCRLAQTCRLLHQHCCDPLQYIHLNLQ 326
Cdd:cd22117     1 FDLLPYELIQLILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKELNLQ 47

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

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1046888286 280 FDKLPYELIQLILNHLSLPDLCRLAQTCRLLHQHCCDPL 318
Cdd:pfam12937   1 LSSLPDEILLQIFSYLDPKDLLRLALVCRRWRELASDDS 39

Leucine-rich repeat - CC (cysteine-containing) subfamily;

                           10        20
                   ....*....|....*....|....*.
gi 1046888286  478 CKSLRTLDLWRCKNITENGIAELASG 503
Cdd:smart00367   1 CPNLRELDLSGCTNITDEGLQALAKG 26

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 1046888286 280 FDKLPYELIQLILNHLSLPDLCRLAQTCRLLHQHCCDPLQYIHLNLQ 326
Cdd:cd22117     1 FDLLPYELIQLILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKELNLQ 47

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046888286 373 CGSELVRLELSCSHFLNDACLEVISEMCPNLQDLNLSSCDklppqafghiaklrslkrlilyrtKVEQTALLSILNFCAE 452
Cdd:cd09293    50 NCNKLKKLILPGSKLIDDEGLIALAQSCPNLQVLDLRACE------------------------NITDSGIVALATNCPK 105

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046888286 453 LQHLSLG---SCVMIEDYDVIAsmIGAKCKSLRTLDLWRCkNITENGIAELASGCAL-LEELDLGWCPTL 518
Cdd:cd09293   106 LQTINLGrhrNGHLITDVSLSA--LGKNCTFLQTVGFAGC-DVTDKGVWELASGCSKsLERLSLNNCRNL 172

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 1046888286 281 DKLPYELIQLILNHLSLPDLCRLAQTCRLLHQHCC 315
Cdd:cd09917     1 SDLPDEILLKILSYLDPRDLLRLSLVCKRWRELAS 35

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046888286 490 KNITENGIAELASG-CALLEELDLGWCPTLQSSTGCFARLArqlpNLQKLFLTANRSVCDTDIEELASNCTRLQQLDILG 568
Cdd:cd09293    12 GQITQSNISQLLRIlHSGLEWLELYMCPISDPPLDQLSNCN----KLKKLILPGSKLIDDEGLIALAQSCPNLQVLDLRA 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1046888286 569 TRMVSPASLRKLLESCKDLSLLDVSF---CSQIDNRAVLELNASFPKV 613
Cdd:cd09293    88 CENITDSGIVALATNCPKLQTINLGRhrnGHLITDVSLSALGKNCTFL 135

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 1046888286 280 FDKLPYELIQLILNHLSLPDLCRLAQTCRLLHQHCCDPLQYIH 322
Cdd:pfam00646   1 LLDLPDDLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWKK 43

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
                  ....*....|....*....|....*....|
gi 1046888286 283 LPYELIQLILNHLSLPDLCRLAQTCRLLHQ 312
Cdd:cd22090     5 LPLELWRLILAYLPVRDLCRCCQVCRAWYE 34

F-box domain found in F-box/WD repeat-containing protein 4 (FBXW4) and similar proteins; FBXW4, also called dactylin, or F-box and WD-40 domain-containing protein 4, probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. It is likely to be involved in key signaling pathways crucial for normal limb development. It may participate in Wnt signaling and act as a novel tumor suppressor that regulates important cellular processes. 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 1046888286 283 LPYELIQLILNHLSLPDLCRLAQTCRLLHQ 312
Cdd:cd20090     5 LPDDLLFLIFSYLDPASLGRLSQVCRRLYR 34

F-box domain found in F-box only protein 24 (FBXO24) and similar proteins; FBXO24, also called FBX24, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It recognizes deacetylated nucleoside diphosphate kinase A (NDPK-A) to enhance its 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 1046888286 283 LPYELIQLILNHLSLPDLCRLAQTCRLLHQhCCD 316
Cdd:cd22098     5 LPPEILDRIISFLPVKDIVSLGQTCRYFHE-VCN 37

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
                  ....*....|....*....|....*....|.
gi 1046888286 279 YFD-KLPYELIQLILNHLSLPDLCRLAQTCR 308
Cdd:cd22134     2 FFDiQLPRELALKIFQYLSVTDLCRCAQVSK 32

Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond to structural units consisting of a beta strand (LxxLxLxxN/CxL conserved pattern) and an alpha helix. This alignment contains 12 strands corresponding to 11 full repeats, consistent with the extent observed in the subfamily acting as Ran GTPase Activating Proteins (RanGAP1).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046888286 441 TALLSILNFCAELQHLSLGSCVMIEDYDVIASMIGAKCKSLRTLDLWRCkNITENGIAELASGCAL----LEELDLGWCP 516
Cdd:cd00116   183 RALAEGLKANCNLEVLDLNNNGLTDEGASALAETLASLKSLEVLNLGDN-NLTDAGAAALASALLSpnisLLTLSLSCND 261

                          90       100
                  ....*....|....*....|....*...
gi 1046888286 517 TLQSSTGCFARLARQLPNLQKLFLTANR 544
Cdd:cd00116   262 ITDDGAKDLAEVLAEKESLLELDLRGNK 289