ID FBXW8_HUMAN Reviewed; 598 AA. AC Q8N3Y1; Q9UK95; DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 10-JUN-2026, entry version 194. DE RecName: Full=F-box/WD repeat-containing protein 8; DE AltName: Full=F-box and WD-40 domain-containing protein 8; DE AltName: Full=F-box only protein 29; GN Name=FBXW8 {ECO:0000303|PubMed:17205132, ECO:0000312|HGNC:HGNC:13597}; GN Synonyms=FBW6, FBW8, FBX29, FBXO29, FBXW6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT GLN-192. RX PubMed=10531037; DOI=10.1016/s0960-9822(00)80021-4; RA Winston J.T., Koepp D.M., Zhu C., Elledge S.J., Harper J.W.; RT "A family of mammalian F-box proteins."; RL Curr. Biol. 9:1180-1182(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-192. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP IDENTIFICATION IN SCF-LIKE COMPLEX. RX PubMed=12481031; DOI=10.1073/pnas.252646399; RA Dias D.C., Dolios G., Wang R., Pan Z.Q.; RT "CUL7: a DOC domain-containing cullin selectively binds Skp1.Fbx29 to form RT an SCF-like complex."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16601-16606(2002). RN [5] RP IDENTIFICATION IN A COMPLEX WITH CUL7; SKP1; RBX1 AND GLMN. RX PubMed=12904573; DOI=10.1073/pnas.1733908100; RA Arai T., Kasper J.S., Skaar J.R., Ali S.H., Takahashi C., DeCaprio J.A.; RT "Targeted disruption of p185/Cul7 gene results in abnormal vascular RT morphogenesis."; RL Proc. Natl. Acad. Sci. U.S.A. 100:9855-9860(2003). RN [6] RP FUNCTION, PATHWAY, IDENTIFICATION IN SCF-LIKE COMPLEX, AND SUBCELLULAR RP LOCATION. RX PubMed=17205132; DOI=10.1371/journal.pone.0000128; RA Okabe H., Lee S.H., Phuchareon J., Albertson D.G., McCormick F., Tetsu O.; RT "A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer RT cell proliferation."; RL PLoS ONE 1:e128-e128(2006). RN [7] RP INTERACTION WITH CUL7. RX PubMed=17332328; DOI=10.1158/0008-5472.can-06-3241; RA Skaar J.R., Florens L., Tsutsumi T., Arai T., Tron A., Swanson S.K., RA Washburn M.P., DeCaprio J.A.; RT "PARC and CUL7 form atypical cullin RING ligase complexes."; RL Cancer Res. 67:2006-2014(2007). RN [8] RP FUNCTION, AND PATHWAY. RX PubMed=18498745; DOI=10.1016/j.molcel.2008.03.009; RA Xu X., Sarikas A., Dias-Santagata D.C., Dolios G., Lafontant P.J., RA Tsai S.C., Zhu W., Nakajima H., Nakajima H.O., Field L.J., Wang R., RA Pan Z.Q.; RT "The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for RT ubiquitin-dependent degradation."; RL Mol. Cell 30:403-414(2008). RN [9] RP FUNCTION, INTERACTION WITH OBSL1; CUL1; CUL2; CUL7; SKP1; CCT6B; PFDN5; RP CCT2; CCT3; CCT6A; CCT7; VBP1; CCDC8; ARF1; TRIP13; PDCD5 AND GORASP1, AND RP SUBCELLULAR LOCATION. RX PubMed=21572988; DOI=10.1371/journal.pbio.1001060; RA Litterman N., Ikeuchi Y., Gallardo G., O'Connell B.C., Sowa M.E., RA Gygi S.P., Harper J.W., Bonni A.; RT "An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates Golgi RT morphology and dendrite patterning."; RL PLoS Biol. 9:E1001060-E1001060(2011). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [11] RP FUNCTION, AND INTERACTION WITH CUL7 AND MAP4K1. RX PubMed=24362026; DOI=10.1074/jbc.m113.520106; RA Wang H., Chen Y., Lin P., Li L., Zhou G., Liu G., Logsdon C., Jin J., RA Abbruzzese J.L., Tan T.H., Wang H.; RT "The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin RT ligase promotes degradation of hematopoietic progenitor kinase 1."; RL J. Biol. Chem. 289:4009-4017(2014). RN [12] RP FUNCTION. RX PubMed=24793695; DOI=10.1016/j.molcel.2014.03.047; RA Yan J., Yan F., Li Z., Sinnott B., Cappell K.M., Yu Y., Mo J., Duncan J.A., RA Chen X., Cormier-Daire V., Whitehurst A.W., Xiong Y.; RT "The 3M complex maintains microtubule and genome integrity."; RL Mol. Cell 54:791-804(2014). RN [13] {ECO:0007744|PDB:7Z8B} RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN CUL7-RING(FBXW8) RP COMPLEX, FUNCTION, SUBUNIT, AND INTERACTION WITH CUL7 AND SKP1. RX PubMed=35982156; DOI=10.1038/s41594-022-00815-6; RA Hopf L.V.M., Baek K., Kluegel M., von Gronau S., Xiong Y., Schulman B.A.; RT "Structure of CRL7FBXW8 reveals coupling with CUL1-RBX1/ROC1 for multi- RT cullin-RING E3-catalyzed ubiquitin ligation."; RL Nat. Struct. Mol. Biol. 29:854-862(2022). CC -!- FUNCTION: Substrate-recognition component of the Cul7-RING(FBXW8) CC ubiquitin ligase complex, which mediates the ubiquitination and CC subsequent proteasomal degradation of target proteins (PubMed:17205132, CC PubMed:18498745, PubMed:21572988, PubMed:24362026, PubMed:35982156). CC The Cul7-RING(FBXW8) complex mediates ubiquitination and consequent CC degradation of GORASP1, acting as a component of the ubiquitin ligase CC pathway that regulates Golgi morphogenesis and dendrite patterning in CC brain (PubMed:21572988). Mediates ubiquitination and degradation of CC IRS1 in a mTOR-dependent manner: the Cul7-RING(FBXW8) complex CC recognizes and binds IRS1 previously phosphorylated by S6 kinase CC (RPS6KB1 or RPS6KB2) (PubMed:18498745). The Cul7-RING(FBXW8) complex CC also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds CC autophosphorylated MAP4K1/HPK1, leading to its degradation, thereby CC affecting cell proliferation and differentiation (PubMed:24362026). The CC Cul7-RING(FBXW8) complex also mediates ubiquitination of phosphorylated CC cyclin-D1 (CCND1) (PubMed:17205132). The Cul7-RING(FBXW8) complex is CC however not a major regulator of CCND1 stability during the G1/S CC transition (By similarity). Associated component of the 3M complex, CC suggesting that it mediates some of 3M complex functions CC (PubMed:24793695). {ECO:0000250|UniProtKB:Q8BIA4, CC ECO:0000269|PubMed:17205132, ECO:0000269|PubMed:18498745, CC ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24362026, CC ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:35982156}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:17205132, ECO:0000269|PubMed:18498745}. CC -!- SUBUNIT: Component of the Cul7-RING(FBXW8) complex consisting of CUL7, CC RBX1, SKP1 and FBXW8; within the complex interacts with CUL7 and SKP1 CC (PubMed:12904573, PubMed:17205132, PubMed:17332328, PubMed:21572988, CC PubMed:24362026, PubMed:35982156). Interacts with GLMN isoform 1 CC (PubMed:12904573). Interacts with OBSL1, CUL1, CUL2, CCT6B, PFDN5, CC CCT2, CCT3, CCT6A, CCT7, VBP1, CCDC8, ARF1, TRIP13, PDCD5 and GORASP1 CC (PubMed:21572988). Interacts with MAP4K1/HPK1 (when autophosphorylated) CC (PubMed:24362026). Associated component of the 3M complex CC (PubMed:24793695, PubMed:35982156). Interacts with POUF51 (when CC phosphorylated on 'Ser-355') (By similarity). CC {ECO:0000250|UniProtKB:Q8BIA4, ECO:0000269|PubMed:12904573, CC ECO:0000269|PubMed:17205132, ECO:0000269|PubMed:17332328, CC ECO:0000269|PubMed:21572988, ECO:0000269|PubMed:24362026, CC ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:35982156}. CC -!- INTERACTION: CC Q8N3Y1; P01106: MYC; NbExp=3; IntAct=EBI-914770, EBI-447544; CC Q8N3Y1; P63208: SKP1; NbExp=6; IntAct=EBI-914770, EBI-307486; CC Q8N3Y1-2; B1WBR1: Gorasp1; Xeno; NbExp=2; IntAct=EBI-15927105, EBI-15927064; CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:21572988}. Golgi apparatus CC {ECO:0000269|PubMed:21572988}. Cytoplasm {ECO:0000269|PubMed:17205132}. CC Note=Localizes to the cytosol when phosphorylated at Ser-85, promoting CC IRS1 ubiquitination. {ECO:0000250|UniProtKB:Q8BIA4}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8N3Y1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N3Y1-2; Sequence=VSP_008501; CC -!- PTM: Phosphorylation at Ser-85 by mTORC2 promotes FBXW8 stabilization, CC allowing its translocation to the cytosol in response to insulin. CC {ECO:0000250|UniProtKB:Q8BIA4}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF03129.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAF03129.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF176707; AAF03129.1; ALT_SEQ; mRNA. DR EMBL; AC026368; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC083806; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC127164; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC037296; AAH37296.1; -; mRNA. DR CCDS; CCDS44988.1; -. [Q8N3Y1-2] DR CCDS; CCDS9182.1; -. [Q8N3Y1-1] DR RefSeq; NP_036306.1; NM_012174.2. [Q8N3Y1-2] DR RefSeq; NP_699179.2; NM_153348.2. [Q8N3Y1-1] DR PDB; 7Z8B; EM; 2.80 A; F=1-598. DR PDBsum; 7Z8B; -. DR AlphaFoldDB; Q8N3Y1; -. DR EMDB; EMD-14547; -. DR SMR; Q8N3Y1; -. DR BioGRID; 117645; 157. DR ComplexPortal; CPX-7784; SCF E3 ubiquitin ligase complex, FBXW8-CUL7 variant. DR CORUM; Q8N3Y1; -. DR DIP; DIP-37970N; -. DR FunCoup; Q8N3Y1; 1960. DR IntAct; Q8N3Y1; 51. DR MINT; Q8N3Y1; -. DR STRING; 9606.ENSP00000498999; -. DR GlyGen; Q8N3Y1; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8N3Y1; -. DR PhosphoSitePlus; Q8N3Y1; -. DR BioMuta; FBXW8; -. DR DMDM; 296434513; -. DR jPOST; Q8N3Y1; -. DR MassIVE; Q8N3Y1; -. DR PaxDb; 9606-ENSP00000498999; -. DR PeptideAtlas; Q8N3Y1; -. DR ProteomicsDB; 71847; -. [Q8N3Y1-1] DR ProteomicsDB; 71848; -. [Q8N3Y1-2] DR Pumba; Q8N3Y1; -. DR Antibodypedia; 31322; 146 antibodies from 21 providers. DR DNASU; 26259; -. DR Ensembl; ENST00000455858.2; ENSP00000389144.2; ENSG00000174989.15. [Q8N3Y1-2] DR Ensembl; ENST00000652555.1; ENSP00000498999.1; ENSG00000174989.15. [Q8N3Y1-1] DR GeneID; 26259; -. DR KEGG; hsa:26259; -. DR MANE-Select; ENST00000652555.1; ENSP00000498999.1; NM_153348.3; NP_699179.2. DR UCSC; uc001twf.2; human. [Q8N3Y1-1] DR AGR; HGNC:13597; -. DR ClinPGx; PA28039; -. DR CTD; 26259; -. DR DisGeNET; 26259; -. DR GeneCards; FBXW8; -. DR HGNC; HGNC:13597; FBXW8. DR HPA; ENSG00000174989; Low tissue specificity. DR MIM; 609073; gene. DR OpenTargets; ENSG00000174989; -. DR VEuPathDB; HostDB:ENSG00000174989; -. DR eggNOG; KOG0274; Eukaryota. DR GeneTree; ENSGT00390000017221; -. DR HOGENOM; CLU_024087_1_0_1; -. DR InParanoid; Q8N3Y1; -. DR OMA; LVFQECR; -. DR OrthoDB; 190105at2759; -. DR PAN-GO; Q8N3Y1; 5 GO annotations based on evolutionary models. DR PhylomeDB; Q8N3Y1; -. DR PathwayCommons; Q8N3Y1; -. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q8N3Y1; -. DR SIGNOR; Q8N3Y1; -. DR UniPathway; UPA00143; -. DR Agora; ENSG00000174989; -. DR BioGRID-ORCS; 26259; 9 hits in 1193 CRISPR screens. DR ChiTaRS; FBXW8; human. DR GeneWiki; FBXW8; -. DR GenomeRNAi; 26259; -. DR Pharos; Q8N3Y1; Tbio. DR PRO; PR:Q8N3Y1; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q8N3Y1; protein. DR Bgee; ENSG00000174989; Expressed in stromal cell of endometrium and 108 other cell types or tissues. DR ExpressionAtlas; Q8N3Y1; baseline and differential. DR GO; GO:0005814; C:centriole; IBA:GO_Central. DR GO; GO:0036064; C:ciliary basal body; IBA:GO_Central. DR GO; GO:0031467; C:Cul7-RING ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IEA:Ensembl. DR GO; GO:1990756; F:ubiquitin-like ligase-substrate adaptor activity; IDA:UniProtKB. DR GO; GO:0008283; P:cell population proliferation; IDA:UniProtKB. DR GO; GO:0060271; P:cilium assembly; IBA:GO_Central. DR GO; GO:0007030; P:Golgi organization; IGI:UniProtKB. DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:UniProt. DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IDA:UniProtKB. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; NAS:ComplexPortal. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR CDD; cd22134; F-box_FBXW8; 1. DR FunFam; 1.20.1280.50:FF:000025; F-box and WD repeat domain containing 8; 1. DR FunFam; 2.130.10.10:FF:000308; F-box and WD repeat domain containing 8; 1. DR FunFam; 2.130.10.10:FF:000428; F-box and WD repeat domain containing 8; 1. DR Gene3D; 1.20.1280.50; -; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 2. DR InterPro; IPR036047; F-box-like_dom_sf. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR011047; Quinoprotein_ADH-like_sf. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR InterPro; IPR050505; WDR55/POC1. DR PANTHER; PTHR44019:SF11; F-BOX_WD REPEAT-CONTAINING PROTEIN 8; 1. DR PANTHER; PTHR44019; WD REPEAT-CONTAINING PROTEIN 55; 1. DR Pfam; PF12937; F-box-like; 1. DR SMART; SM00256; FBOX; 1. DR SMART; SM00320; WD40; 5. DR SUPFAM; SSF81383; F-box domain; 1. DR SUPFAM; SSF50998; Quinoprotein alcohol dehydrogenase-like; 1. DR PROSITE; PS50181; FBOX; 1. DR PROSITE; PS00678; WD_REPEATS_1; 1. DR PROSITE; PS50082; WD_REPEATS_2; 1. DR PROSITE; PS50294; WD_REPEATS_REGION; 2. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Golgi apparatus; Phosphoprotein; Proteomics identification; KW Reference proteome; Repeat; Ubl conjugation pathway; WD repeat. FT CHAIN 1..598 FT /note="F-box/WD repeat-containing protein 8" FT /id="PRO_0000050997" FT DOMAIN 113..159 FT /note="F-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080" FT REPEAT 201..250 FT /note="WD 1" FT /evidence="ECO:0000269|PubMed:35982156, FT ECO:0007744|PDB:7Z8B" FT REPEAT 259..299 FT /note="WD 2" FT /evidence="ECO:0000269|PubMed:35982156, FT ECO:0007744|PDB:7Z8B" FT REPEAT 300..340 FT /note="WD 3" FT /evidence="ECO:0000269|PubMed:35982156, FT ECO:0007744|PDB:7Z8B" FT REPEAT 341..383 FT /note="WD 4" FT /evidence="ECO:0000269|PubMed:35982156, FT ECO:0007744|PDB:7Z8B" FT REPEAT 384..429 FT /note="WD 5" FT /evidence="ECO:0000269|PubMed:35982156, FT ECO:0007744|PDB:7Z8B" FT REPEAT 430..475 FT /note="WD 6" FT /evidence="ECO:0000269|PubMed:35982156, FT ECO:0007744|PDB:7Z8B" FT REPEAT 476..513 FT /note="WD 7" FT /evidence="ECO:0000269|PubMed:35982156, FT ECO:0007744|PDB:7Z8B" FT REPEAT 514..561 FT /note="WD 8" FT /evidence="ECO:0000269|PubMed:35982156, FT ECO:0007744|PDB:7Z8B" FT REGION 17..93 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 29..40 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 61..71 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 83 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BIA4" FT MOD_RES 85 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BIA4" FT VAR_SEQ 41..106 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10531037" FT /id="VSP_008501" FT VARIANT 192 FT /note="R -> Q (in dbSNP:rs4076700)" FT /evidence="ECO:0000269|PubMed:10531037, FT ECO:0000269|PubMed:15489334" FT /id="VAR_060326" FT VARIANT 211 FT /note="T -> A (in dbSNP:rs36021180)" FT /id="VAR_057597" FT VARIANT 536 FT /note="T -> M (in dbSNP:rs3741466)" FT /id="VAR_057598" FT VARIANT 563 FT /note="V -> M (in dbSNP:rs56350562)" FT /id="VAR_062096" FT CONFLICT 46 FT /note="G -> S (in Ref. 3; AAH37296)" FT /evidence="ECO:0000305" FT CONFLICT 58 FT /note="R -> G (in Ref. 3; AAH37296)" FT /evidence="ECO:0000305" FT CONFLICT 380 FT /note="L -> I (in Ref. 3; AAH37296)" FT /evidence="ECO:0000305" FT CONFLICT 510 FT /note="E -> K (in Ref. 1; AAF03129)" FT /evidence="ECO:0000305" FT HELIX 122..129 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 133..136 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 144..150 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 153..163 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 171..173 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 177..196 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 200..204 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 205..208 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 213..227 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 232..236 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 239..241 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 262..267 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 269..276 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 279..285 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 286..288 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 293..297 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 304..307 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 309..312 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 314..317 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 319..326 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 334..340 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 347..350 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 355..357 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 359..364 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 367..372 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 373..376 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 377..382 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 384..386 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 388..393 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 395..402 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 406..409 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 413..418 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 419..421 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 424..428 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 435..439 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 441..443 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 447..452 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 455..461 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 462..464 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 467..472 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 478..483 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 488..492 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 495..501 FT /evidence="ECO:0007829|PDB:7Z8B" FT TURN 502..505 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 506..512 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 517..523 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 526..531 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 555..561 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 563..565 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 567..569 FT /evidence="ECO:0007829|PDB:7Z8B" FT STRAND 571..575 FT /evidence="ECO:0007829|PDB:7Z8B" FT HELIX 580..592 FT /evidence="ECO:0007829|PDB:7Z8B" SQ SEQUENCE 598 AA; 67394 MW; 03B3C283BA46DB6B CRC64; MDDYSLDEFR RRWQEELAQA QAPKKRRRPE AAERRARRPE VGSGRGEQAS GDPALAQRLL EGAGRPPAAR ATRAEGQDVA SRSRSPLARE GAGGGEQLVD QLIRDLNEMN DVPFFDIQLP YELAINIFQY LDRKELGRCA QVSKTWKVIA EDEVLWYRLC QQEGHLPDSS ISDYSCWKLI FQECRAKEHM LRTNWKNRKG AVSELEHVPD TVLCDVHSHD GVVIAGYTSG DVRVWDTRTW DYVAPFLESE DEEDEPGMQP NVSFVRINSS LAVAAYEDGF LNIWDLRTGK YPVHRFEHDA RIQALALSQD DATVATASAF DVVMLSPNEE GYWQIAAEFE VPKLVQYLEI VPETRRYPVA VAAAGDLMYL LKAEDSARTL LYAHGPPVTC LDVSANQVAF GVQGLGWVYE GSKILVYSLE AGRRLLKLGN VLRDFTCVNL SDSPPNLMVS GNMDGRVRIH DLRSGNIALS LSAHQLRVSA VQMDDWKIVS GGEEGLVSVW DYRMNQKLWE VYSGHPVQHI SFSSHSLITA NVPYQTVMRN ADLDSFTTHR RHRGLIRAYE FAVDQLAFQS PLPVCRSSCD AMATHYYDLA LAFPYNHV //