Cyclin D1 binding domain; Ubiquitin-dependent proteolysis of cyclin D1 is associated with normal and tumour cell proliferation and survival. The best characterized member of this family is the SCF FBXO31 (Skp1-Cul1-Rbx1-FBXO31) ubiquitin ligase complex mediates genotoxic stress-induced cyclin D1 degradation. FBXO31 possesses a unique substrate-binding beta barrel domain, whereas cyclin D1 binds to FBXO31 by tucking its free C-terminal carboxylate tail into an open cavity of the C-terminal FBXO31 beta-barrel. Biophysical and functional studies demonstrated that SCFFBXO31 is capable of recruiting and ubiquitinating cyclin D1 in a phosphorylation-independent manner.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 670396050  370 PMPGREYAGLWGGTFGwppgrpDDGCKpkkalfFLLLSYEEDSE--GKlQLIATKvLEGTHYVvhPNGSSMFITRMSEPS 447
Cdd:pfam12014   8 PTLIRPFRGLFVGDYG------GHGLE------ILLLSFPDGARehGK-YAEATK-LTGDPNV--PAGEVTFEAHDGEIF 71

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 670396050  448 TEpFPWQT----------DGEFDVERSFAGEGIANGYGFRYPSSKPGSLFVLQNGLLAFVWRETGAVLTLQRLDLDE 514
Cdd:pfam12014  72 RE-FNEGSrvvqvgvrsrDQNYPRTCRFYGVGHIAGHGFRNPRRIPGVLILFDEDHLGFIWLELKHFSLFSRVDQDT 147

F-box domain found in Arabidopsis thaliana SKP1-interacting partner 3 (AtSKIP3) and similar proteins; AtSKIP3, also called F-box protein SKIP3, F-box protein PP2-B9, or protein PHLOEM PROTEIN 2-LIKE B9, is a component of SCF (SKP1-cullin-F-box protein) E3 ubiquitin ligase complexes, which may mediate the ubiquitination and subsequent proteasomal degradation of target proteins. It interacts with SKP1A/ASK1. This subfamily also includes many other Arabidopsis thaliana protein PHLOEM PROTEIN 2-LIKE 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 670396050  15 LPEDVLALISAHLRPRDLLALSAASRRLRRALSADKAWlaqcRRLLP 61
Cdd:cd22162    4 LPEDCIALILSFTSPRDVCRLSAVSKTFRSAAESDVVW----ERFLP 46

A Receptor for Ubiquitination Targets;

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 670396050    15 LPEDVLALISAHLRPRDLLALSAASRRLRRALSADKAW 52
Cdd:smart00256   1 LPDEILEEILSKLDPKDLLRLRKVSRKWRSLIDSHDFW 38

F-box domain found in Arabidopsis thaliana SKP1-interacting partner 3 (AtSKIP3) and similar proteins; AtSKIP3, also called F-box protein SKIP3, F-box protein PP2-B9, or protein PHLOEM PROTEIN 2-LIKE B9, is a component of SCF (SKP1-cullin-F-box protein) E3 ubiquitin ligase complexes, which may mediate the ubiquitination and subsequent proteasomal degradation of target proteins. It interacts with SKP1A/ASK1. This subfamily also includes many other Arabidopsis thaliana protein PHLOEM PROTEIN 2-LIKE 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 670396050  15 LPEDVLALISAHLRPRDLLALSAASRRLRRALSADKAWlaqcRRLLP 61
Cdd:cd22162    4 LPEDCIALILSFTSPRDVCRLSAVSKTFRSAAESDVVW----ERFLP 46

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 670396050  13 LSLPEDVLALISAHLRPRDLLALSAASRRLRRALS 47
Cdd:cd09917    1 SDLPDEILLKILSYLDPRDLLRLSLVCKRWRELAS 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 670396050   12 ILSLPEDVLALISAHLRPRDLLALSAASRRLRRALSADKAW 52
Cdd:pfam00646   1 LLDLPDDLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLW 41

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        40
                 ....*....|....*....|....*....|....*....|...
gi 670396050  11 LILSLPEDVLALISAHLRPRDLLALSAASRRLRRALSADKAWL 53
Cdd:cd20090    1 PLLDLPDDLLFLIFSYLDPASLGRLSQVCRRLYRLISRDAVWR 43

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 670396050  12 ILSLPEDVLALISAHLRPRDLLALSAASRRLRRALSADKAWLAQCR 57
Cdd:cd22102    1 ILDLPPELLVEIFSSLPGTDLPSLAQVCKKFREILNTDTIWQRRCK 46