| IED ID | IndEnz0002007204 |
| Enzyme Type ID | protease007204 |
| Protein Name |
F-box/WD repeat-containing protein 7 Archipelago homolog hAgo F-box and WD-40 domain-containing protein 7 F-box protein FBX30 SEL-10 hCdc4 |
| Gene Name | FBXW7 FBW7 FBX30 SEL10 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MNQELLSVGSKRRRTGGSLRGNPSSSQVDEEQMNRVVEEEQQQQLRQQEEEHTARNGEVVGVEPRPGGQNDSQQGQLEENNNRFISVDEDSSGNQEEQEEDEEHAGEQDEEDEEEEEMDQESDDFDQSDDSSREDEHTHTNSVTNSSSIVDLPVHQLSSPFYTKTTKMKRKLDHGSEVRSFSLGKKPCKVSEYTSTTGLVPCSATPTTFGDLRAANGQGQQRRRITSVQPPTGLQEWLKMFQSWSGPEKLLALDELIDSCEPTQVKHMMQVIEPQFQRDFISLLPKELALYVLSFLEPKDLLQAAQTCRYWRILAEDNLLWREKCKEEGIDEPLHIKRRKVIKPGFIHSPWKSAYIRQHRIDTNWRRGELKSPKVLKGHDDHVITCLQFCGNRIVSGSDDNTLKVWSAVTGKCLRTLVGHTGGVWSSQMRDNIIISGSTDRTLKVWNAETGECIHTLYGHTSTVRCMHLHEKRVVSGSRDATLRVWDIETGQCLHVLMGHVAAVRCVQYDGRRVVSGAYDFMVKVWDPETETCLHTLQGHTNRVYSLQFDGIHVVSGSLDTSIRVWDVETGNCIHTLTGHQSLTSGMELKDNILVSGNADSTVKIWDIKTGQCLQTLQGPNKHQSAVTCLQFNKNFVITSSDDGTVKLWDLKTGEFIRNLVTLESGGSGGVVWRIRASNTKLVCAVGSRNGTEETKLLVLDFDVDMK |
| Enzyme Length | 707 |
| Uniprot Accession Number | Q969H0 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Substrate recognition 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 (PubMed:22748924, PubMed:17434132, PubMed:26976582, PubMed:28727686). Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter bring them to the SCF complex for ubiquitination (PubMed:22748924, PubMed:26774286, PubMed:17434132, PubMed:26976582, PubMed:28727686). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, and probably PSEN1 (PubMed:11565034, PubMed:12354302, PubMed:11585921, PubMed:15103331, PubMed:14739463, PubMed:17558397, PubMed:17873522, PubMed:22608923, PubMed:22748924, PubMed:29149593, PubMed:25775507, PubMed:28007894, PubMed:26976582, PubMed:28727686). Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (PubMed:14739463). Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593). Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination (PubMed:27238018). Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage (PubMed:26774286). The SCF(FBXW7) complex facilitates double-strand break repair following phosphorylation by ATM: phosphorylation promotes localization to sites of double-strand breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, enhancing DNA non-homologous end joining (PubMed:26774286). {ECO:0000269|PubMed:11565034, ECO:0000269|PubMed:11585921, ECO:0000269|PubMed:14739463, ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:17434132, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:22608923, ECO:0000269|PubMed:22748924, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:26976582, ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:28007894, ECO:0000269|PubMed:28727686, ECO:0000269|PubMed:29149593, ECO:0000305|PubMed:12354302}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (4); Beta strand (33); Chain (1); Compositional bias (4); Domain (1); Erroneous initiation (1); Helix (8); Modified residue (3); Mutagenesis (7); Natural variant (9); Region (1); Repeat (7); Sequence conflict (5); Turn (7) |
| Keywords | 3D-structure;Alternative splicing;Biological rhythms;Chromosome;Cytoplasm;DNA damage;DNA repair;Host-virus interaction;Nucleus;Phosphoprotein;Reference proteome;Repeat;Ubl conjugation;Ubl conjugation pathway;WD repeat |
| Interact With | Q16204; Q13616; Itself; P01106; P46531; P63208; P63208-1; Q8WUJ0; Q9Z0Z7; Q91LX9; Q8WUJ0; P13051-2; P24941; Q9UBI4 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleoplasm {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:28007894}. Chromosome {ECO:0000269|PubMed:26774286}. Note=Localizes to site of double-strand breaks following phosphorylation by ATM. {ECO:0000269|PubMed:26774286}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:28007894}.; SUBCELLULAR LOCATION: [Isoform 3]: Nucleus, nucleolus {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:28007894}. |
| Modified Residue | MOD_RES 26; /note=Phosphoserine; by ATM; /evidence=ECO:0000269|PubMed:26774286; MOD_RES 205; /note=Phosphothreonine; /evidence=ECO:0000269|PubMed:22608923; MOD_RES 227; /note=Phosphoserine; by SGK1; /evidence=ECO:0000269|PubMed:21147854 |
| Post Translational Modification | PTM: Phosphorylation at Thr-205 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (PubMed:22608923). Phosphorylated by ATM at Ser-26 in response to DNA damage, promoting recruitment to DNA damage sites and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4 (PubMed:26774286). {ECO:0000269|PubMed:22608923, ECO:0000269|PubMed:26774286}.; PTM: Ubiquitinated: autoubiquitinates following phosphorylation at Thr-205 and subsequent interaction with PIN1. Ubiquitination leads to its proteasomal degradation (PubMed:22608923). {ECO:0000269|PubMed:22608923}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (5) |
| Cross Reference PDB | 2OVP; 2OVQ; 2OVR; 5IBK; 5V4B; |
| Mapped Pubmed ID | 10597293; 11461910; 11533444; 11961546; 12502735; 12504025; 12504026; 12553912; 12609982; 12646216; 14507635; 14603323; 14743216; 14871801; 14999283; 15070733; 15150404; 15467469; 15498494; 15537541; 15546612; 15688063; 15799966; 16054087; 16169070; 16210249; 16401342; 16647857; 16863506; 16938571; 16943200; 16954532; 17157259; 17183367; 17274947; 17314511; 17320938; 17497243; 17588203; 17646408; 17646409; 17909001; 17992009; 18093314; 18094723; 18206966; 18391985; 18414042; 18428053; 18485478; 18541364; 18559665; 18625840; 18660489; 18676680; 18765672; 18784078; 18787170; 18805092; 18826954; 18851830; 18926707; 18931460; 18938137; 19011634; 19028597; 19084516; 19109228; 19111882; 19124506; 19170196; 19245433; 19250909; 19340001; 19351817; 19366810; 19420964; 19489725; 19587092; 19617556; 19625176; 19635999; 19679664; 19692168; 19739118; 19748355; 19794083; 19847202; 19874575; 20332316; 20338046; 20388706; 20448329; 20484041; 20534483; 20558726; 20622901; 20638938; 20683149; 20815813; 20826802; 20852628; 20861909; 20861920; 20890303; 21098288; 21122106; 21134077; 21220517; 21368833; 21463634; 21597324; 21620836; 21778237; 21798897; 21820430; 21835957; 21863050; 21940857; 21953459; 21964756; 21995946; 22108521; 22144179; 22270966; 22388891; 22399798; 22405651; 22426484; 22576686; 22708077; 22710716; 22797700; 22814294; 22864569; 22923510; 22939624; 22959436; 23040356; 23095493; 23108047; 23166673; 23201271; 23219661; 23228967; 23232523; 23322298; 23324394; 23381582; 23453757; 23507969; 23514585; 23535662; 23535663; 23558291; 23563313; 23583660; 23670162; 23676439; 23747015; 23776410; 23791182; 23820376; 23857984; 23954152; 24053468; 24076655; 24091628; 24113472; 24165483; 24166518; 24298052; 24377525; 24398687; 24412244; 24424791; 24586741; 24686546; 24727676; 24731221; 24756126; 24820417; 24838835; 24853181; 24884509; 25036637; 25159729; 25204433; 25269767; 25314029; 25314076; 25342745; 25349211; 25355947; 25437563; 25445601; 25467444; 25493453; 25531226; 25555218; 25586348; 25622249; 25623537; 25640309; 25669969; 25670854; 25720964; 25749036; 25753158; 25860929; 25888377; 25893295; 25897075; 25918246; 25944166; 25955618; 26097998; 26163148; 26173098; 26206584; 26269414; 26306035; 26323375; 26341754; 26354767; 26458995; 26464659; 26482194; 26542806; 26602384; 26632597; 26774344; 26906416; 26954701; 26983463; 27152455; 27229929; 27232758; 27244218; 27247421; 27306418; 27350307; 27409838; 27423313; 27470268; 27485116; 27486687; 27565346; 27566146; 27625374; 27704356; 27751849; 27764699; 27773673; 27795300; 27852700; 28000896; 28000899; 28036276; 28069035; 28069547; 28184929; 28209614; 28242758; 28287082; 28407575; 28422719; 28423622; 28459460; 28464881; 28498285; 28581525; 28619760; 28656290; 28699179; 28716020; 28722108; 28760857; 28763841; 28765935; 28806398; 28829765; 28850619; 28903484; 29048664; 29072128; 29097832; 29135520; 29198712; 29200162; 29225075; 29324317; 29346117; 29355657; 29408378; 29427543; 29475832; 29534580; 29633504; 29638162; 29665239; 29701752; 29720189; 29735700; 29964355; 30086763; 30094882; 30098297; 30177679; 30284149; 30302867; 30365154; 30510140; 30535501; 30601691; 30606768; 30722038; 30742097; 30830867; 30854619; 30883339; 30898011; 30922330; 30981757; 31064356; 31161818; 31186535; 31202256; 31285543; 31289136; 31337255; 31346036; 31351478; 31371703; 31450901; 31519156; 31534970; 31612394; 31638140; 31740732; 31772025; 31843895; 31940492; 32032908; 32049388; 32086376; 32113998; 32124957; 32239181; 32248654; 32284542; 32308754; 32329846; 32345600; 32350066; 32353058; 32369227; 32371478; 32380038; 32396860; 32402537; 32433022; 32437091; 32444799; 32457290; 32572904; 32588541; 32588875; 32776544; 32791990; 32792479; 32907612; 32915667; 33086033; 33147048; 33494392; 33658012; 33676554; 33677796; 33824312; 33886022; 34217244; 34278448; 34288252; 34298040; 34372947; 34487730; 34741373; 9819444; |
| Motif | |
| Gene Encoded By | |
| Mass | 79,663 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |