C-terminal GTPase-like domain of F-Box Only Protein 4; F-box proteins are involved in substrate recognition as part of SCF (Skp1-Cul1-Rbx1-F-box protein) ubiquitin ligase complexes. Fbx4 (or Fbxo4) binds to the telomere repeat binding factor 1 (TRF1), whose activity at telomeres is regulated in part by selective ubiquitination and degradation. This ubiquitination of TRF1 is mediated by Fbx4, which binds to the TRFH domain of TRF1, via the C-terminal domain characterized by this model, a module resembling a small GTPase domain that lacks the GTP-binding site. When bound to telomeres, TIN2 acts to protect TRF1 from SCF-Fbx4 mediated ubiquitination. Tankyrase-mediated ADP-ribosylation releases TRF1 from telomeres, rendering them susceptible to ubiquitination and degradation, which in turn promotes telomere elongation. Fbx4 has also been reported to target cyclin D1 for degradation by the proteasome, a mechanism ensuring the fidelity of DNA replication. More recently, these findings have been disputed.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15834621 162 GAVTSFLHSLIIQNEPRFAMFGPGLEELNTSLVLSLMSSEELCPTAGLPQRQIDGIGSGVNFQLNNQHKFNILILYSTTR 241
Cdd:cd11656   1 GAVTSFLQSLIIQNEPRFAMFGPGLEELDTSLVTSLMSSEELLPVAGLPQRQIDGIGSGVSFQLNNQHKFNILTLYSTTR 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15834621 242 KERDRAREEHTSAVNKMFSRHNEGDDQQGSRYSVIPQIQKVCEVVDGFIYVANAEAHK 299
Cdd:cd11656  81 AERDRAREEDTSAVNKMFSRENEGDDQQGSRYSVIPQVQKVCEVVDGFIYVANAEAHK 138

C-terminal GTPase-like domain of F-Box Only Protein 4; F-box proteins are involved in substrate recognition as part of SCF (Skp1-Cul1-Rbx1-F-box protein) ubiquitin ligase complexes. Fbx4 (or Fbxo4) binds to the telomere repeat binding factor 1 (TRF1), whose activity at telomeres is regulated in part by selective ubiquitination and degradation. This ubiquitination of TRF1 is mediated by Fbx4, which binds to the TRFH domain of TRF1, via the C-terminal domain characterized by this model, a module resembling a small GTPase domain that lacks the GTP-binding site. When bound to telomeres, TIN2 acts to protect TRF1 from SCF-Fbx4 mediated ubiquitination. Tankyrase-mediated ADP-ribosylation releases TRF1 from telomeres, rendering them susceptible to ubiquitination and degradation, which in turn promotes telomere elongation. Fbx4 has also been reported to target cyclin D1 for degradation by the proteasome, a mechanism ensuring the fidelity of DNA replication. More recently, these findings have been disputed.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15834621 162 GAVTSFLHSLIIQNEPRFAMFGPGLEELNTSLVLSLMSSEELCPTAGLPQRQIDGIGSGVNFQLNNQHKFNILILYSTTR 241
Cdd:cd11656   1 GAVTSFLQSLIIQNEPRFAMFGPGLEELDTSLVTSLMSSEELLPVAGLPQRQIDGIGSGVSFQLNNQHKFNILTLYSTTR 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15834621 242 KERDRAREEHTSAVNKMFSRHNEGDDQQGSRYSVIPQIQKVCEVVDGFIYVANAEAHK 299
Cdd:cd11656  81 AERDRAREEDTSAVNKMFSRENEGDDQQGSRYSVIPQVQKVCEVVDGFIYVANAEAHK 138

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 15834621    59 LTRLPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWR 100
Cdd:pfam12937   1 LSSLPDEILLQIFSYLDPKDLLRLALVCRRWRELASDDSLWR 42

C-terminal GTPase-like domain of F-Box Only Protein 4; F-box proteins are involved in substrate recognition as part of SCF (Skp1-Cul1-Rbx1-F-box protein) ubiquitin ligase complexes. Fbx4 (or Fbxo4) binds to the telomere repeat binding factor 1 (TRF1), whose activity at telomeres is regulated in part by selective ubiquitination and degradation. This ubiquitination of TRF1 is mediated by Fbx4, which binds to the TRFH domain of TRF1, via the C-terminal domain characterized by this model, a module resembling a small GTPase domain that lacks the GTP-binding site. When bound to telomeres, TIN2 acts to protect TRF1 from SCF-Fbx4 mediated ubiquitination. Tankyrase-mediated ADP-ribosylation releases TRF1 from telomeres, rendering them susceptible to ubiquitination and degradation, which in turn promotes telomere elongation. Fbx4 has also been reported to target cyclin D1 for degradation by the proteasome, a mechanism ensuring the fidelity of DNA replication. More recently, these findings have been disputed.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15834621 162 GAVTSFLHSLIIQNEPRFAMFGPGLEELNTSLVLSLMSSEELCPTAGLPQRQIDGIGSGVNFQLNNQHKFNILILYSTTR 241
Cdd:cd11656   1 GAVTSFLQSLIIQNEPRFAMFGPGLEELDTSLVTSLMSSEELLPVAGLPQRQIDGIGSGVSFQLNNQHKFNILTLYSTTR 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15834621 242 KERDRAREEHTSAVNKMFSRHNEGDDQQGSRYSVIPQIQKVCEVVDGFIYVANAEAHK 299
Cdd:cd11656  81 AERDRAREEDTSAVNKMFSRENEGDDQQGSRYSVIPQVQKVCEVVDGFIYVANAEAHK 138

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 15834621    59 LTRLPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWR 100
Cdd:pfam12937   1 LSSLPDEILLQIFSYLDPKDLLRLALVCRRWRELASDDSLWR 42

F-box domain found in uncharacterized F-box protein group similar to F-box only protein 3 (FBXO3); This subfamily corresponds to a group of uncharacterized F-box proteins which show sequence similarity to F-box only protein 3 (FBXO3). FBXO3, also called FBX3, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex, that 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 15834621  62 LPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWRYFL 103
Cdd:cd22139   4 LPDELWLHIFSFLSPKDLCQVALVCRRFNRLASDESLWKQIC 45

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 15834621    59 LTRLPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWRY 101
Cdd:pfam00646   1 LLDLPDDLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWKK 43

F-box domain found in F-box/WD repeat-containing protein 7 (FBXW7) and similar proteins; FBXW7, also called Archipelago homolog (Ago), F-box and WD-40 domain-containing protein 7, F-box protein FBX30, SEL-10, or Cdc4, 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 cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NOTCH2, MCL1, and probably PSEN1. 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 15834621  62 LPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWR 100
Cdd:cd22133  21 LPKELALYVLSFLEPKDLLQAAQTCRYWRILAEDNLLWR 59

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 15834621  59 LTRLPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWR 100
Cdd:cd22106   1 LVRLPDKLLLYIISYLDLEDIARLSQTSKRFKKLCNSDELWE 42

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 15834621  59 LTRLPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWRYFLLR 105
Cdd:cd22117   1 FDLLPYELIQLILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKELNLQ 47

F-box domain found in Saccharomyces cerevisiae cell division control protein 4 (ScCDC4) and similar proteins; ScCDC4 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 is essential for initiation of DNA replication and separation of the spindle pole bodies to form the poles of the mitotic spindle. It also plays a role in bud development, fusion of zygotic nuclei after conjugation and various aspects of sporulation. 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 15834621  59 LTRLPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWRYFLL 104
Cdd:cd22141   1 IGNLPFEISLKIFNYLQFEDLLNSLGVSKKWNKIIRNTALWKKLLI 46

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 15834621  61 RLPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWRYFLLR 105
Cdd:cd22104   3 NLPSVVLVHIFSYLPPRDRLRASSTCRRWREALFHPSLWRSLRLH 47

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 15834621  60 TRLPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWR 100
Cdd:cd22173   4 TVLPRFLSLYIFSFLDPRSLCRAAQVSWHWKFLAEQDCLWM 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 15834621  59 LTRLPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWR 100
Cdd:cd22123   1 LDQLPENVLLEILSYLPVRDLLRISRVCKRWRRLVYDKTLWR 42

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 15834621  59 LTRLPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWRYFL 103
Cdd:cd22162   1 LEDLPEDCIALILSFTSPRDVCRLSAVSKTFRSAAESDVVWERFL 45

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 15834621  62 LPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWRYFL 103
Cdd:cd22087   4 LPPEIKLRILSLLDVRSLLSLSQVCRDLNSATNDQLLWRFLL 45

F-box domain found in Arabidopsis thaliana SKP1-interacting partner 22 (AtSKIP22) and similar proteins; AtSKIP22, also called F-box protein SKIP22, is a component of SCF (SKP1/ASK-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 and SPK1B/ASK2. 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 15834621  59 LTRLPIDVQLYILSFLSPHDLCQLGSTNHYWNETVRDPILWR 100
Cdd:cd22165   2 LMRLPTELKLKILELLPGVDLARMACVCSELRFLASNDDLWK 43