ID FBXW7_HUMAN Reviewed; 707 AA. AC Q969H0; B7ZLP9; Q68DR0; Q96A16; Q96LE0; Q96RI2; Q9NUX6; DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 204. DE RecName: Full=F-box/WD repeat-containing protein 7 {ECO:0000305}; DE AltName: Full=Archipelago homolog {ECO:0000303|PubMed:11565033}; DE Short=hAgo {ECO:0000303|PubMed:11565033}; DE AltName: Full=F-box and WD-40 domain-containing protein 7 {ECO:0000305}; DE AltName: Full=F-box protein FBX30 {ECO:0000305|PubMed:10531037}; DE AltName: Full=SEL-10 {ECO:0000303|PubMed:12354302}; DE AltName: Full=hCdc4 {ECO:0000303|PubMed:11565034}; GN Name=FBXW7 {ECO:0000312|HGNC:HGNC:16712}; GN Synonyms=FBW7 {ECO:0000312|EMBL:AAK57547.1}, FBX30 GN {ECO:0000312|EMBL:AAK60269.1}, SEL10 {ECO:0000312|EMBL:AAL07271.1}; 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). 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 [MRNA] (ISOFORMS 1 AND 2), AND VARIANTS CYS-465 AND RP LEU-505. RX PubMed=11565033; DOI=10.1038/35095068; RA Moberg K.H., Bell D.W., Wahrer D.C.R., Haber D.A., Hariharan I.K.; RT "Archipelago regulates cyclin E levels in Drosophila and is mutated in RT human cancer cell lines."; RL Nature 413:311-316(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, IDENTIFICATION IN SCF RP COMPLEX, AND INTERACTION WITH CYCLIN E. RX PubMed=11565034; DOI=10.1038/35095076; RA Strohmaier H., Spruck C.H., Kaiser P., Won K.-A., Sangfelt O., Reed S.I.; RT "Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated RT in a breast cancer cell line."; RL Nature 413:316-322(2001). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, TISSUE SPECIFICITY, AND RP INTERACTION WITH PSEN1. RX PubMed=12354302; DOI=10.1046/j.1471-4159.2002.01105.x; RA Li J., Pauley A.M., Myers R.L., Shuang R., Brashler J.R., Yan R., RA Buhl A.E., Ruble C., Gurney M.E.; RT "SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and RT alters A-beta peptide production."; RL J. Neurochem. 82:1540-1548(2002). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Salivary gland; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND PARTIAL NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [7] RP PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP FUNCTION, AND INTERACTION WITH NOTCH1; NOTCH4 AND SKP1. RX PubMed=11585921; DOI=10.1128/mcb.21.21.7403-7415.2001; RA Wu G., Lyapina S., Das I., Li J., Gurney M., Pauley A., Chui I., RA Deshaies R.J., Kitajewski J.; RT "SEL-10 is an inhibitor of notch signaling that targets notch for RT ubiquitin-mediated protein degradation."; RL Mol. Cell. Biol. 21:7403-7415(2001). RN [9] RP FUNCTION, PATHWAY, COMPONENT OF THE SCF(FBXW7) COMPLEX, AND INTERACTION RP WITH MYC. RX PubMed=15103331; DOI=10.1038/sj.emboj.7600217; RA Yada M., Hatakeyama S., Kamura T., Nishiyama M., Tsunematsu R., Imaki H., RA Ishida N., Okumura F., Nakayama K., Nakayama K.I.; RT "Phosphorylation-dependent degradation of c-Myc is mediated by the F-box RT protein Fbw7."; RL EMBO J. 23:2116-2125(2004). RN [10] RP FUNCTION, AND INTERACTION WITH JUN. RX PubMed=14739463; DOI=10.1126/science.1092880; RA Nateri A.S., Riera-Sans L., Da Costa C., Behrens A.; RT "The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling."; RL Science 303:1374-1378(2004). RN [11] RP INTERACTION WITH SV40 LARGE T ANTIGEN (MICROBIAL INFECTION). RX PubMed=15611062; DOI=10.1074/jbc.m413377200; RA Welcker M., Clurman B.E.; RT "The SV40 large T antigen contains a decoy phosphodegron that mediates its RT interactions with Fbw7/hCdc4."; RL J. Biol. Chem. 280:7654-7658(2005). RN [12] RP FUNCTION, AND INTERACTION WITH MYC AND USP28. RX PubMed=17873522; DOI=10.4161/cc.6.19.4804; RA Popov N., Herold S., Llamazares M., Schulein C., Eilers M.; RT "Fbw7 and Usp28 regulate myc protein stability in response to DNA damage."; RL Cell Cycle 6:2327-2331(2007). RN [13] RP FUNCTION, INTERACTION WITH MYC AND USP28, AND SUBCELLULAR LOCATION. RX PubMed=17558397; DOI=10.1038/ncb1601; RA Popov N., Wanzel M., Madiredjo M., Zhang D., Beijersbergen R., Bernards R., RA Moll R., Elledge S.J., Eilers M.; RT "The ubiquitin-specific protease USP28 is required for MYC stability."; RL Nat. Cell Biol. 9:765-774(2007). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [15] RP PHOSPHORYLATION AT SER-227 BY SGK1, AND INTERACTION WITH SGK1 AND NOTCH1. RX PubMed=21147854; DOI=10.1242/jcs.073924; RA Mo J.S., Ann E.J., Yoon J.H., Jung J., Choi Y.H., Kim H.Y., Ahn J.S., RA Kim S.M., Kim M.Y., Hong J.A., Seo M.S., Lang F., Choi E.J., Park H.S.; RT "Serum- and glucocorticoid-inducible kinase 1 (SGK1) controls Notch1 RT signaling by downregulation of protein stability through Fbw7 ubiquitin RT ligase."; RL J. Cell Sci. 124:100-112(2011). RN [16] RP FUNCTION, HOMODIMERIZATION, INTERACTION WITH JUN AND PIN1, PHOSPHORYLATION RP AT THR-205, UBIQUITINATION, AND MUTAGENESIS OF SER-159; THR-205; SER-349 RP AND SER-372. RX PubMed=22608923; DOI=10.1016/j.molcel.2012.04.012; RA Min S.H., Lau A.W., Lee T.H., Inuzuka H., Wei S., Huang P., Shaik S., RA Lee D.Y., Finn G., Balastik M., Chen C.H., Luo M., Tron A.E., RA Decaprio J.A., Zhou X.Z., Wei W., Lu K.P.; RT "Negative regulation of the stability and tumor suppressor function of Fbw7 RT by the Pin1 prolyl isomerase."; RL Mol. Cell 46:771-783(2012). RN [17] RP FUNCTION, AND SUBUNIT. RX PubMed=22748924; DOI=10.1016/j.molcel.2012.05.044; RA Duda D.M., Olszewski J.L., Tron A.E., Hammel M., Lambert L.J., RA Waddell M.B., Mittag T., DeCaprio J.A., Schulman B.A.; RT "Structure of a glomulin-RBX1-CUL1 complex: inhibition of a RING E3 ligase RT through masking of its E2-binding surface."; RL Mol. Cell 47:371-382(2012). RN [18] RP INTERACTION WITH STOML1. RX PubMed=23082202; DOI=10.1371/journal.pone.0047736; RA Zhang W., MacDonald E.M., Koepp D.M.; RT "The stomatin-like protein SLP-1 and Cdk2 interact with the F-Box protein RT Fbw7-gamma."; RL PLoS ONE 7:E47736-E47736(2012). RN [19] RP INTERACTION WITH UBE2QL1. RX PubMed=24000165; DOI=10.1002/humu.22433; RA Wake N.C., Ricketts C.J., Morris M.R., Prigmore E., Gribble S.M., RA Skytte A.B., Brown M., Clarke N., Banks R.E., Hodgson S., Turnell A.S., RA Maher E.R., Woodward E.R.; RT "UBE2QL1 is disrupted by a constitutional translocation associated with RT renal tumor predisposition and is a novel candidate renal tumor suppressor RT gene."; RL Hum. Mutat. 34:1650-1661(2013). RN [20] RP INTERACTION WITH FAM83D. RX PubMed=24344117; DOI=10.18632/oncotarget.1581; RA Wang Z., Liu Y., Zhang P., Zhang W., Wang W., Curr K., Wei G., Mao J.H.; RT "FAM83D promotes cell proliferation and motility by downregulating tumor RT suppressor gene FBXW7."; RL Oncotarget 4:2476-2486(2013). RN [21] RP FUNCTION, PATHWAY, AND INTERACTION WITH RICTOR. RX PubMed=25897075; DOI=10.1074/jbc.m114.633057; RA Koo J., Wu X., Mao Z., Khuri F.R., Sun S.Y.; RT "Rictor Undergoes Glycogen Synthase Kinase 3 (GSK3)-dependent, FBXW7- RT mediated Ubiquitination and Proteasomal Degradation."; RL J. Biol. Chem. 290:14120-14129(2015). RN [22] RP FUNCTION (ISOFORM 3), INTERACTION WITH MYC AND USP28 (ISOFORM 3), AND RP SUBCELLULAR LOCATION (ISOFORM 3). RX PubMed=25775507; DOI=10.1073/pnas.1411713112; RA Sun X.X., He X., Yin L., Komada M., Sears R.C., Dai M.S.; RT "The nucleolar ubiquitin-specific protease USP36 deubiquitinates and RT stabilizes c-Myc."; RL Proc. Natl. Acad. Sci. U.S.A. 112:3734-3739(2015). RN [23] RP FUNCTION, PATHWAY, AND IDENTIFICATION IN SCF COMPLEX. RX PubMed=34741373; DOI=10.1111/cas.15188; RA Zhang E., Chen S., Tang H., Fei C., Yuan Z., Mu X., Qin Y., Liu H., Fan Y., RA Tan M., Wang X.; RT "CDK1/FBXW7 facilitates degradation and ubiquitination of MLST8 to inhibit RT progression of renal cell carcinoma."; RL Cancer Sci. 113:91-108(2022). RN [24] RP FUNCTION, AND INTERACTION WITH NR1D1. RX PubMed=27238018; DOI=10.1016/j.cell.2016.05.012; RA Zhao X., Hirota T., Han X., Cho H., Chong L.W., Lamia K., Liu S., RA Atkins A.R., Banayo E., Liddle C., Yu R.T., Yates J.R. III, Kay S.A., RA Downes M., Evans R.M.; RT "Circadian amplitude regulation via FBXW7-targeted REV-ERBalpha RT degradation."; RL Cell 165:1644-1657(2016). RN [25] RP IDENTIFICATION IN COMPLEX WITH JUN AND PRR7, AND INTERACTION WITH JUN AND RP PRR7. RX PubMed=27458189; DOI=10.15252/embj.201593070; RA Kravchick D.O., Karpova A., Hrdinka M., Lopez-Rojas J., Iacobas S., RA Carbonell A.U., Iacobas D.A., Kreutz M.R., Jordan B.A.; RT "Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates RT NMDA-mediated excitotoxicity."; RL EMBO J. 35:1923-1934(2016). RN [26] RP FUNCTION, IDENTIFICATION IN SCF COMPLEX, SUBCELLULAR LOCATION, RP PHOSPHORYLATION AT SER-26, AND MUTAGENESIS OF SER-26 AND SER-72. RX PubMed=26774286; DOI=10.1016/j.molcel.2015.12.010; RA Zhang Q., Karnak D., Tan M., Lawrence T.S., Morgan M.A., Sun Y.; RT "FBXW7 facilitates nonhomologous end-joining via K63-linked RT polyubiquitylation of XRCC4."; RL Mol. Cell 61:419-433(2016). RN [27] RP INTERACTION WITH MYCN. RX PubMed=27837025; DOI=10.1073/pnas.1610626113; RA Richards M.W., Burgess S.G., Poon E., Carstensen A., Eilers M., Chesler L., RA Bayliss R.; RT "Structural basis of N-Myc binding by Aurora-A and its destabilization by RT kinase inhibitors."; RL Proc. Natl. Acad. Sci. U.S.A. 113:13726-13731(2016). RN [28] RP FUNCTION, INTERACTION WITH STYX, IDENTIFICATION IN THE SCF(FBXW7) COMPLEX, RP SUBUNIT, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND RP CHARACTERIZATION OF VARIANT CYS-465. RX PubMed=28007894; DOI=10.15252/embj.201694795; RA Reiterer V., Figueras-Puig C., Le Guerroue F., Confalonieri S., Vecchi M., RA Jalapothu D., Kanse S.M., Deshaies R.J., Di Fiore P.P., Behrends C., RA Farhan H.; RT "The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits RT SCFFBXW7 function."; RL EMBO J. 36:260-273(2017). RN [29] RP FUNCTION, AND INTERACTION WITH NOTCH2. RX PubMed=29149593; DOI=10.1016/j.molcel.2017.10.018; RA Fukushima H., Shimizu K., Watahiki A., Hoshikawa S., Kosho T., Oba D., RA Sakano S., Arakaki M., Yamada A., Nagashima K., Okabe K., Fukumoto S., RA Jimi E., Bigas A., Nakayama K.I., Nakayama K., Aoki Y., Wei W., Inuzuka H.; RT "NOTCH2 Hajdu-Cheney mutations escape SCFFBW7-dependent proteolysis to RT promote osteoporosis."; RL Mol. Cell 68:645-658(2017). RN [30] RP FUNCTION, AND INTERACTION WITH MYC AND USP38. RX PubMed=34102342; DOI=10.1016/j.biocel.2021.106023; RA Xu Z., Hu H., Fang D., Wang J., Zhao K.; RT "The deubiquitinase USP38 promotes cell proliferation through stabilizing RT c-Myc."; RL Int. J. Biochem. 137:106023-106023(2021). RN [31] RP INVOLVEMENT IN DEDHIL, VARIANTS DEDHIL ALA-416; ILE-416; LEU-420; ARG-423; RP GLY-441; PRO-462; HIS-465; GLN-479; GLY-480; HIS-505; GLY-544; TYR-580; RP ALA-582; VAL-599; VAL-608; VAL-626; ARG-640; 647-LYS--LYS-707 DEL; PRO-674; RP TRP-674; GLN-689 AND TRP-689, CHARACTERIZATION OF VARIANTS DEDHIL ARG-423; RP GLY-480; GLY-544; ARG-640; PRO-674; TRP-674 AND GLN-689, AND FUNCTION. RX PubMed=35395208; DOI=10.1016/j.ajhg.2022.03.002; RG TUDP Study Group; RG Broad Center for Mendelian Genomics; RA Stephenson S.E.M., Costain G., Blok L.E.R., Silk M.A., Nguyen T.B., RA Dong X., Alhuzaimi D.E., Dowling J.J., Walker S., Amburgey K., RA Hayeems R.Z., Rodan L.H., Schwartz M.A., Picker J., Lynch S.A., Gupta A., RA Rasmussen K.J., Schimmenti L.A., Klee E.W., Niu Z., Agre K.E., Chilton I., RA Chung W.K., Revah-Politi A., Au P.Y.B., Griffith C., Racobaldo M., RA Raas-Rothschild A., Ben Zeev B., Barel O., Moutton S., Morice-Picard F., RA Carmignac V., Cornaton J., Marle N., Devinsky O., Stimach C., RA Wechsler S.B., Hainline B.E., Sapp K., Willems M., Bruel A.L., Dias K.R., RA Evans C.A., Roscioli T., Sachdev R., Temple S.E.L., Zhu Y., Baker J.J., RA Scheffer I.E., Gardiner F.J., Schneider A.L., Muir A.M., Mefford H.C., RA Crunk A., Heise E.M., Millan F., Monaghan K.G., Person R., Rhodes L., RA Richards S., Wentzensen I.M., Cogne B., Isidor B., Nizon M., Vincent M., RA Besnard T., Piton A., Marcelis C., Kato K., Koyama N., Ogi T., Goh E.S., RA Richmond C., Amor D.J., Boyce J.O., Morgan A.T., Hildebrand M.S., Kaspi A., RA Bahlo M., Fridriksdottir R., Katrinardottir H., Sulem P., Stefansson K., RA Bjoernsson H.T., Mandelstam S., Morleo M., Mariani M., Scala M., RA Accogli A., Torella A., Capra V., Wallis M., Jansen S., Weisfisz Q., RA de Haan H., Sadedin S., Lim S.C., White S.M., Ascher D.B., Schenck A., RA Lockhart P.J., Christodoulou J., Tan T.Y.; RT "Germline variants in tumor suppressor FBXW7 lead to impaired RT ubiquitination and a neurodevelopmental syndrome."; RL Am. J. Hum. Genet. 109:601-617(2022). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 263-707 IN COMPLEX WITH SKP1 AND RP CCNE1 PHOSPHORYLATED PEPTIDE, FUNCTION, DOMAIN, SUBUNIT, AND MUTAGENESIS OF RP 252-ALA--ILE-257. RX PubMed=17434132; DOI=10.1016/j.molcel.2007.02.022; RA Hao B., Oehlmann S., Sowa M.E., Harper J.W., Pavletich N.P.; RT "Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated RT substrate recognition by SCF ubiquitin ligases."; RL Mol. Cell 26:131-143(2007). RN [33] {ECO:0007744|PDB:5IBK} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 263-323 IN COMPLEX WITH SKIP1 AND RP UBIQUITIN, FUNCTION, AND SUBUNIT. RX PubMed=26976582; DOI=10.1073/pnas.1519389113; RA Gorelik M., Orlicky S., Sartori M.A., Tang X., Marcon E., Kurinov I., RA Greenblatt J.F., Tyers M., Moffat J., Sicheri F., Sidhu S.S.; RT "Inhibition of SCF ubiquitin ligases by engineered ubiquitin variants that RT target the Cul1 binding site on the Skp1-F-box interface."; RL Proc. Natl. Acad. Sci. U.S.A. 113:3527-3532(2016). RN [34] {ECO:0007744|PDB:5V4B} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 263-706 IN COMPLEX WITH SKIP1 AND RP DISC1 PEPTIDE, AND FUNCTION. RX PubMed=28727686; DOI=10.1038/mp.2017.138; RA Yalla K., Elliott C., Day J.P., Findlay J., Barratt S., Hughes Z.A., RA Wilson L., Whiteley E., Popiolek M., Li Y., Dunlop J., Killick R., RA Adams D.R., Brandon N.J., Houslay M.D., Hao B., Baillie G.S.; RT "FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system."; RL Mol. Psychiatry 23:1278-1286(2018). RN [35] RP VARIANTS [LARGE SCALE ANALYSIS] HIS-465; LEU-505 AND LEU-582. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [36] RP VARIANT LYS-117. RX PubMed=17224074; DOI=10.1186/bcr1637; RA Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A., Presswalla S., RA Kaaresen R., Strausberg R.L., Gerhard D.S., Kristensen V., Perou C.M., RA Boerresen-Dale A.-L.; RT "Somatic sequence alterations in twenty-one genes selected by expression RT profile analysis of breast carcinomas."; RL Breast Cancer Res. 9:R5-R5(2007). CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box CC protein) E3 ubiquitin-protein ligase complex which mediates the CC ubiquitination and subsequent proteasomal degradation of target CC proteins (PubMed:22748924, PubMed:34741373, PubMed:17434132, CC PubMed:26976582, PubMed:28727686, PubMed:35395208). Recognizes and CC binds phosphorylated sites/phosphodegrons within target proteins and CC thereafter brings them to the SCF complex for ubiquitination CC (PubMed:22748924, PubMed:34741373, PubMed:26774286, PubMed:17434132, CC PubMed:26976582, PubMed:28727686). Identified substrates include CC cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch CC intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, MLST8, RICTOR, and CC probably PSEN1 (PubMed:11565034, PubMed:12354302, PubMed:11585921, CC PubMed:15103331, PubMed:14739463, PubMed:17558397, PubMed:17873522, CC PubMed:22608923, PubMed:22748924, PubMed:29149593, PubMed:25775507, CC PubMed:28007894, PubMed:26976582, PubMed:28727686, PubMed:25897075, CC PubMed:34102342). Acts as a negative regulator of JNK signaling by CC binding to phosphorylated JUN and promoting its ubiquitination and CC subsequent degradation (PubMed:14739463). Involved in bone homeostasis CC and negative regulation of osteoclast differentiation CC (PubMed:29149593). Regulates the amplitude of the cyclic expression of CC hepatic core clock genes and genes involved in lipid and glucose CC metabolism via ubiquitination and proteasomal degradation of their CC transcriptional repressor NR1D1; CDK1-dependent phosphorylation of CC NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination CC (PubMed:27238018). Also able to promote 'Lys-63'-linked ubiquitination CC in response to DNA damage (PubMed:26774286). The SCF(FBXW7) complex CC facilitates double-strand break repair following phosphorylation by CC ATM: phosphorylation promotes localization to sites of double-strand CC breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, CC enhancing DNA non-homologous end joining (PubMed:26774286). CC {ECO:0000269|PubMed:11565034, ECO:0000269|PubMed:11585921, CC ECO:0000269|PubMed:14739463, ECO:0000269|PubMed:15103331, CC ECO:0000269|PubMed:17434132, ECO:0000269|PubMed:17558397, CC ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:22608923, CC ECO:0000269|PubMed:22748924, ECO:0000269|PubMed:25775507, CC ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:26774286, CC ECO:0000269|PubMed:26976582, ECO:0000269|PubMed:27238018, CC ECO:0000269|PubMed:28007894, ECO:0000269|PubMed:28727686, CC ECO:0000269|PubMed:29149593, ECO:0000269|PubMed:34102342, CC ECO:0000269|PubMed:34741373, ECO:0000269|PubMed:35395208, CC ECO:0000305|PubMed:12354302}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:25897075, CC ECO:0000269|PubMed:34741373}. CC -!- SUBUNIT: Homodimer; homodimerization plays a role in substrate binding CC and/or ubiquitination and degradation (PubMed:22608923, CC PubMed:17434132, PubMed:28007894). Component of the SCF(FBXW7) complex CC consisting of CUL1, RBX1, SKP1 and FBXW7 (PubMed:11565034, CC PubMed:15103331, PubMed:22748924, PubMed:34741373, PubMed:26774286, CC PubMed:28007894, PubMed:26976582, PubMed:28727686). Interacts (via F- CC box domain) with SKP1 (PubMed:11585921, PubMed:17434132, CC PubMed:28007894, PubMed:26976582, PubMed:28727686). Interacts (via F- CC box domain) with pseudophosphatase STYX; the interaction is direct and CC prevents FBXW7 interaction with SKP1 (PubMed:28007894). Interacts with CC cyclin-E (CCNE1 or CCNE2) (PubMed:11565034, PubMed:17434132). Interacts CC with PSEN1 (PubMed:12354302). Forms a trimeric complex with NOTCH1 and CC SGK1 (PubMed:21147854). Interacts with NOTCH1 intracellular domain/NICD CC and NOTCH4 intracellular domain/NICD (PubMed:11585921). Interacts with CC NOTCH2 intracellular domain (N2ICD) (PubMed:29149593). Interacts with CC MYC (when phosphorylated) (PubMed:17873522, PubMed:25775507, CC PubMed:28007894). Interacts with USP28, counteracting ubiquitination of CC MYC (PubMed:17873522). Interacts with JUN (PubMed:14739463, CC PubMed:22608923). Found in a complex with JUN and PRR7 CC (PubMed:27458189). Interacts with JUN and PRR7; the interaction CC inhibits ubiquitination-mediated JUN degradation, promoting its CC phosphorylation and transcriptional activity (PubMed:27458189). CC Interacts (when phosphorylated at Thr-205) with PIN1, disrupting FBXW7 CC dimerization and promoting FBXW7 autoubiquitination and degradation CC (PubMed:22608923). Interacts with UBE2QL1 (PubMed:24000165). Interacts CC with FAM83D; promotes FBXW7 degradation (PubMed:24344117). Interacts CC with MYCN; FBXW7 competes with AURKA for binding to unphosphorylated CC MYCN but not for binding to phosphorylated MYCN (PubMed:27837025). CC Interacts with STOML1 (PubMed:23082202). Interacts with NFE2L1 (By CC similarity). Interacts with USP36, counteracting ubiquitination of MYC CC (PubMed:25775507). Interacts with NR1D1 (PubMed:27238018). Interacts CC with RICTOR; mediates RICTOR ubiquitination and degradation CC (PubMed:25897075). Interacts with USP38, counteracting ubiquitination CC of MYC (PubMed:34102342). {ECO:0000250|UniProtKB:Q8VBV4, CC ECO:0000269|PubMed:11565034, ECO:0000269|PubMed:11585921, CC ECO:0000269|PubMed:12354302, ECO:0000269|PubMed:14739463, CC ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:15611062, CC ECO:0000269|PubMed:17434132, ECO:0000269|PubMed:17558397, CC ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:21147854, CC ECO:0000269|PubMed:22608923, ECO:0000269|PubMed:23082202, CC ECO:0000269|PubMed:24000165, ECO:0000269|PubMed:24344117, CC ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:26774286, CC ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:27458189, CC ECO:0000269|PubMed:27837025, ECO:0000269|PubMed:28007894, CC ECO:0000269|PubMed:29149593, ECO:0000269|PubMed:34102342, CC ECO:0000269|PubMed:34741373}. CC -!- SUBUNIT: (Microbial infection) Interacts (via WD repeats) with SV40 CC large T antigen (via CPD region). {ECO:0000269|PubMed:15611062}. CC -!- INTERACTION: CC Q969H0; Q16204: CCDC6; NbExp=9; IntAct=EBI-359574, EBI-1045350; CC Q969H0; Q13616: CUL1; NbExp=8; IntAct=EBI-359574, EBI-359390; CC Q969H0; Q969H0: FBXW7; NbExp=3; IntAct=EBI-359574, EBI-359574; CC Q969H0; P01106: MYC; NbExp=7; IntAct=EBI-359574, EBI-447544; CC Q969H0; P46531: NOTCH1; NbExp=11; IntAct=EBI-359574, EBI-636374; CC Q969H0; P63208: SKP1; NbExp=11; IntAct=EBI-359574, EBI-307486; CC Q969H0; P63208-1: SKP1; NbExp=2; IntAct=EBI-359574, EBI-307497; CC Q969H0; Q8WUJ0: STYX; NbExp=10; IntAct=EBI-359574, EBI-20979851; CC Q969H0; Q9Z0Z7: Klf5; Xeno; NbExp=2; IntAct=EBI-359574, EBI-647919; CC Q969H0; Q91LX9; Xeno; NbExp=5; IntAct=EBI-359574, EBI-15662601; CC Q969H0-1; Q8WUJ0: STYX; NbExp=4; IntAct=EBI-6162410, EBI-20979851; CC Q969H0-2; P13051-2: UNG; NbExp=3; IntAct=EBI-359594, EBI-25834258; CC Q969H0-4; P24941: CDK2; NbExp=2; IntAct=EBI-6502391, EBI-375096; CC Q969H0-4; Q9UBI4: STOML1; NbExp=3; IntAct=EBI-6502391, EBI-2681162; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleoplasm CC {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:25775507, CC ECO:0000269|PubMed:28007894}. Chromosome {ECO:0000269|PubMed:26774286}. CC Note=Localizes to site of double-strand breaks following CC phosphorylation by ATM. {ECO:0000269|PubMed:26774286}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm CC {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:28007894}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Nucleus, nucleolus CC {ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:25775507, CC ECO:0000269|PubMed:28007894}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Archipelago alpha {ECO:0000303|PubMed:11565033}, CC FBW7alpha {ECO:0000303|PubMed:17873522, ECO:0000303|PubMed:25775507}, CC 110K, common; CC IsoId=Q969H0-1; Sequence=Displayed; CC Name=2; Synonyms=Archipelago beta {ECO:0000303|PubMed:11565033}, CC FBW7beta {ECO:0000303|PubMed:17873522}, 69K; CC IsoId=Q969H0-2; Sequence=VSP_009483, VSP_009484; CC Name=3; Synonyms=Archipelago gamma, FBW7gamma CC {ECO:0000303|PubMed:17873522, ECO:0000303|PubMed:25775507}, CC Hippocampal; CC IsoId=Q969H0-4; Sequence=VSP_009482, VSP_009485; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Widely expressed. CC {ECO:0000269|PubMed:12354302}. CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in brain. CC {ECO:0000269|PubMed:12354302}. CC -!- DOMAIN: The WD repeats mediate interaction with substrates of the SCF CC (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. CC {ECO:0000269|PubMed:17434132}. CC -!- DOMAIN: The F-box domain mediates interaction with SKP1. CC {ECO:0000269|PubMed:17434132, ECO:0000269|PubMed:28007894}. CC -!- PTM: Phosphorylation at Thr-205 promotes interaction with PIN1, leading CC to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination CC and degradation (PubMed:22608923). Phosphorylated by ATM at Ser-26 in CC response to DNA damage, promoting recruitment to DNA damage sites and CC 'Lys-63'-linked ubiquitination of phosphorylated XRCC4 CC (PubMed:26774286). {ECO:0000269|PubMed:22608923, CC ECO:0000269|PubMed:26774286}. CC -!- PTM: Ubiquitinated: autoubiquitinates following phosphorylation at Thr- CC 205 and subsequent interaction with PIN1. Ubiquitination leads to its CC proteasomal degradation (PubMed:22608923). CC {ECO:0000269|PubMed:22608923}. CC -!- DISEASE: Developmental delay, hypotonia, and impaired language (DEDHIL) CC [MIM:620012]: An autosomal dominant neurodevelopmental disorder CC characterized by global developmental delay, borderline to severe CC intellectual disability, language difficulties, hypotonia, and CC gastrointestinal problems. Brain imaging shows variable structural CC abnormalities affecting the cerebellum, corpus collosum, and white CC matter. {ECO:0000269|PubMed:35395208}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=BAA91986.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AY033553; AAK57547.1; -; mRNA. DR EMBL; AF383178; AAK60269.1; -; mRNA. DR EMBL; AF411971; AAL06290.1; -; mRNA. DR EMBL; AF411972; AAL06291.1; -; mRNA. DR EMBL; AY049984; AAL07271.1; -; mRNA. DR EMBL; AY008274; AAG16640.1; -; mRNA. DR EMBL; CR749305; CAH18160.1; -; mRNA. DR EMBL; BC037320; AAH37320.1; -; mRNA. DR EMBL; BC117244; AAI17245.1; -; mRNA. DR EMBL; BC117246; AAI17247.1; -; mRNA. DR EMBL; BC143944; AAI43945.1; -; mRNA. DR EMBL; AK001933; BAA91986.1; ALT_INIT; mRNA. DR CCDS; CCDS34078.1; -. [Q969H0-4] DR CCDS; CCDS3777.1; -. [Q969H0-1] DR CCDS; CCDS3778.1; -. [Q969H0-2] DR RefSeq; NP_001013433.1; NM_001013415.1. [Q969H0-4] DR RefSeq; NP_060785.2; NM_018315.4. [Q969H0-2] DR RefSeq; NP_361014.1; NM_033632.3. [Q969H0-1] DR RefSeq; XP_011530385.1; XM_011532083.1. DR RefSeq; XP_011530386.1; XM_011532084.1. [Q969H0-1] DR RefSeq; XP_011530387.1; XM_011532085.1. [Q969H0-1] DR RefSeq; XP_016863851.1; XM_017008362.1. DR PDB; 2OVP; X-ray; 2.90 A; B=263-707. DR PDB; 2OVQ; X-ray; 2.60 A; B=263-707. DR PDB; 2OVR; X-ray; 2.50 A; B=263-707. DR PDB; 5IBK; X-ray; 2.50 A; B/E=263-323. DR PDB; 5V4B; X-ray; 2.60 A; B=263-706. DR PDB; 7T1Y; X-ray; 2.55 A; B=263-707. DR PDB; 7T1Z; X-ray; 2.77 A; B=263-707. DR PDBsum; 2OVP; -. DR PDBsum; 2OVQ; -. DR PDBsum; 2OVR; -. DR PDBsum; 5IBK; -. DR PDBsum; 5V4B; -. DR PDBsum; 7T1Y; -. DR PDBsum; 7T1Z; -. DR AlphaFoldDB; Q969H0; -. DR SMR; Q969H0; -. DR BioGRID; 120581; 1197. DR ComplexPortal; CPX-7763; SCF E3 ubiquitin ligase complex, FBXW7 variant. DR CORUM; Q969H0; -. DR DIP; DIP-27613N; -. DR ELM; Q969H0; -. DR IntAct; Q969H0; 65. DR MINT; Q969H0; -. DR STRING; 9606.ENSP00000474725; -. DR GlyGen; Q969H0; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q969H0; -. DR PhosphoSitePlus; Q969H0; -. DR BioMuta; FBXW7; -. DR DMDM; 44887885; -. DR EPD; Q969H0; -. DR jPOST; Q969H0; -. DR MassIVE; Q969H0; -. DR MaxQB; Q969H0; -. DR PaxDb; 9606-ENSP00000281708; -. DR PeptideAtlas; Q969H0; -. DR ProteomicsDB; 75759; -. [Q969H0-1] DR ProteomicsDB; 75760; -. [Q969H0-2] DR ProteomicsDB; 75762; -. [Q969H0-4] DR Antibodypedia; 27779; 777 antibodies from 36 providers. DR DNASU; 55294; -. DR Ensembl; ENST00000281708.10; ENSP00000281708.3; ENSG00000109670.17. [Q969H0-1] DR Ensembl; ENST00000296555.11; ENSP00000296555.4; ENSG00000109670.17. [Q969H0-4] DR Ensembl; ENST00000393956.9; ENSP00000377528.4; ENSG00000109670.17. [Q969H0-2] DR Ensembl; ENST00000603548.6; ENSP00000474725.1; ENSG00000109670.17. [Q969H0-1] DR Ensembl; ENST00000603841.1; ENSP00000474971.1; ENSG00000109670.17. [Q969H0-1] DR GeneID; 55294; -. DR KEGG; hsa:55294; -. DR MANE-Select; ENST00000281708.10; ENSP00000281708.3; NM_001349798.2; NP_001336727.1. DR UCSC; uc003imq.4; human. [Q969H0-1] DR AGR; HGNC:16712; -. DR CTD; 55294; -. DR DisGeNET; 55294; -. DR GeneCards; FBXW7; -. DR HGNC; HGNC:16712; FBXW7. DR HPA; ENSG00000109670; Tissue enhanced (brain). DR MalaCards; FBXW7; -. DR MIM; 606278; gene. DR MIM; 620012; phenotype. DR neXtProt; NX_Q969H0; -. DR OpenTargets; ENSG00000109670; -. DR PharmGKB; PA28054; -. DR VEuPathDB; HostDB:ENSG00000109670; -. DR eggNOG; KOG0274; Eukaryota. DR GeneTree; ENSGT00940000154986; -. DR InParanoid; Q969H0; -. DR OMA; AMVPWED; -. DR OrthoDB; 587035at2759; -. DR PhylomeDB; Q969H0; -. DR TreeFam; TF101074; -. DR PathwayCommons; Q969H0; -. DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription. DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants. DR Reactome; R-HSA-2644607; Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling. DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants. DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis. DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity. [Q969H0-1] DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-9604323; Negative regulation of NOTCH4 signaling. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q969H0; -. DR SIGNOR; Q969H0; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 55294; 77 hits in 1215 CRISPR screens. DR ChiTaRS; FBXW7; human. DR EvolutionaryTrace; Q969H0; -. DR GeneWiki; FBXW7; -. DR GenomeRNAi; 55294; -. DR Pharos; Q969H0; Tbio. DR PRO; PR:Q969H0; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q969H0; Protein. DR Bgee; ENSG00000109670; Expressed in Brodmann (1909) area 23 and 212 other cell types or tissues. DR ExpressionAtlas; Q969H0; baseline and differential. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IDA:ParkinsonsUK-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:1990452; C:Parkin-FBXW7-Cul1 ubiquitin ligase complex; IPI:ParkinsonsUK-UCL. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0030332; F:cyclin binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0050816; F:phosphothreonine residue binding; IDA:UniProtKB. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central. DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0097027; F:ubiquitin-protein transferase activator activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0055088; P:lipid homeostasis; ISS:BHF-UCL. DR GO; GO:0030324; P:lung development; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL. DR GO; GO:2000346; P:negative regulation of hepatocyte proliferation; ISS:BHF-UCL. DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISS:BHF-UCL. DR GO; GO:2001205; P:negative regulation of osteoclast development; IMP:UniProtKB. DR GO; GO:2000639; P:negative regulation of SREBP signaling pathway; ISS:BHF-UCL. DR GO; GO:0010868; P:negative regulation of triglyceride biosynthetic process; ISS:BHF-UCL. DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl. DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IDA:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:BHF-UCL. DR GO; GO:1903378; P:positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL. DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; IDA:ParkinsonsUK-UCL. DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; IMP:ParkinsonsUK-UCL. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:ParkinsonsUK-UCL. DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IDA:BHF-UCL. DR GO; GO:0051443; P:positive regulation of ubiquitin-protein transferase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProt. DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl. DR GO; GO:0050821; P:protein stabilization; IDA:BHF-UCL. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; TAS:ParkinsonsUK-UCL. DR GO; GO:0090049; P:regulation of cell migration involved in sprouting angiogenesis; IEA:Ensembl. DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB. DR GO; GO:0010883; P:regulation of lipid storage; ISS:BHF-UCL. DR GO; GO:1901524; P:regulation of mitophagy; IMP:ParkinsonsUK-UCL. DR GO; GO:0032880; P:regulation of protein localization; ISS:BHF-UCL. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR GO; GO:0007062; P:sister chromatid cohesion; IMP:BHF-UCL. DR GO; GO:0010992; P:ubiquitin recycling; IBA:GO_Central. DR GO; GO:0001944; P:vasculature development; TAS:BHF-UCL. DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl. DR CDD; cd22133; F-box_FBXW7; 1. DR CDD; cd00200; WD40; 1. DR Gene3D; 1.20.1280.50; -; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR InterPro; IPR036047; F-box-like_dom_sf. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR020472; G-protein_beta_WD-40_rep. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR19849:SF1; F-BOX_WD REPEAT-CONTAINING PROTEIN 7; 1. DR PANTHER; PTHR19849; PHOSPHOLIPASE A-2-ACTIVATING PROTEIN; 1. DR Pfam; PF12937; F-box-like; 1. DR Pfam; PF00400; WD40; 7. DR PRINTS; PR00320; GPROTEINBRPT. DR SMART; SM00256; FBOX; 1. DR SMART; SM00320; WD40; 8. DR SUPFAM; SSF81383; F-box domain; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS50181; FBOX; 1. DR PROSITE; PS00678; WD_REPEATS_1; 5. DR PROSITE; PS50082; WD_REPEATS_2; 7. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR Genevisible; Q969H0; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Biological rhythms; Chromosome; KW Cytoplasm; Disease variant; DNA damage; DNA repair; Host-virus interaction; KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome; KW Repeat; Ubl conjugation; Ubl conjugation pathway; WD repeat. FT CHAIN 1..707 FT /note="F-box/WD repeat-containing protein 7" FT /id="PRO_0000050994" FT DOMAIN 278..324 FT /note="F-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080" FT REPEAT 378..418 FT /note="WD 1" FT REPEAT 420..456 FT /note="WD 2" FT REPEAT 459..498 FT /note="WD 3" FT REPEAT 500..536 FT /note="WD 4" FT REPEAT 539..578 FT /note="WD 5" FT REPEAT 580..618 FT /note="WD 6" FT REPEAT 622..659 FT /note="WD 7" FT REGION 1..151 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 17..31 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 32..58 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 67..91 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 92..130 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 26 FT /note="Phosphoserine; by ATM" FT /evidence="ECO:0000269|PubMed:26774286" FT MOD_RES 205 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:22608923" FT MOD_RES 227 FT /note="Phosphoserine; by SGK1" FT /evidence="ECO:0000269|PubMed:21147854" FT VAR_SEQ 1..118 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12354302" FT /id="VSP_009482" FT VAR_SEQ 1..80 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10531037, FT ECO:0000303|PubMed:11565033" FT /id="VSP_009483" FT VAR_SEQ 81..166 FT /note="NNRFISVDEDSSGNQEEQEEDEEHAGEQDEEDEEEEEMDQESDDFDQSDDSS FT REDEHTHTNSVTNSSSIVDLPVHQLSSPFYTKTT -> MCVPRSGLILSCICLYCGVLL FT PVLLPNLPFLTCLSMSTLESVTYLPEKGLYCQRLPSSRTHGGTESLKGKNTENMGFYGT FT LKMIFY (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10531037, FT ECO:0000303|PubMed:11565033" FT /id="VSP_009484" FT VAR_SEQ 119..167 FT /note="DQESDDFDQSDDSSREDEHTHTNSVTNSSSIVDLPVHQLSSPFYTKTTK -> FT MSKPGKPTLNHGLVPVDLKSAKEPLPHQTVMKIFSISIIAQGLPFCRRR (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:12354302" FT /id="VSP_009485" FT VARIANT 115 FT /note="E -> K (in dbSNP:rs6816935)" FT /id="VAR_017812" FT VARIANT 117 FT /note="E -> K (in a breast cancer sample; somatic mutation; FT dbSNP:rs991177157)" FT /evidence="ECO:0000269|PubMed:17224074" FT /id="VAR_033030" FT VARIANT 133 FT /note="R -> G (in dbSNP:rs6842544)" FT /id="VAR_017813" FT VARIANT 144 FT /note="T -> R (in dbSNP:rs7660281)" FT /id="VAR_017814" FT VARIANT 416 FT /note="T -> A (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087662" FT VARIANT 416 FT /note="T -> I (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087663" FT VARIANT 420 FT /note="H -> L (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087664" FT VARIANT 423 FT /note="G -> R (in DEDHIL; no effect on protein abundance; FT changed proteasome-mediated ubiquitin-dependent protein FT catabolic process)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087665" FT VARIANT 441 FT /note="R -> G (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087666" FT VARIANT 462 FT /note="S -> P (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087667" FT VARIANT 465 FT /note="R -> C (in an acute lymphoblastic leukemia cell FT line; loss of interaction with substrate; does not affect FT interaction with SKP1 or STYX; dbSNP:rs867384286)" FT /evidence="ECO:0000269|PubMed:11565033, FT ECO:0000269|PubMed:28007894" FT /id="VAR_017815" FT VARIANT 465 FT /note="R -> H (in DEDHIL; also found in a colorectal cancer FT sample; dbSNP:rs1057519895)" FT /evidence="ECO:0000269|PubMed:16959974, FT ECO:0000269|PubMed:35395208" FT /id="VAR_035880" FT VARIANT 479 FT /note="R -> Q (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087668" FT VARIANT 480 FT /note="D -> G (in DEDHIL; no effect on protein abundance; FT changed proteasome-mediated ubiquitin-dependent protein FT catabolic process)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087669" FT VARIANT 505 FT /note="R -> H (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087670" FT VARIANT 505 FT /note="R -> L (in an ovarian cancer cell line; FT dbSNP:rs1057519896)" FT /evidence="ECO:0000269|PubMed:11565033, FT ECO:0000269|PubMed:16959974" FT /id="VAR_017816" FT VARIANT 544 FT /note="V -> G (in DEDHIL; no effect on protein abundance; FT changed on proteasome-mediated ubiquitin-dependent protein FT catabolic process)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087671" FT VARIANT 580 FT /note="H -> Y (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087672" FT VARIANT 582 FT /note="S -> A (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087673" FT VARIANT 582 FT /note="S -> L (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035881" FT VARIANT 599 FT /note="A -> V (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087674" FT VARIANT 608 FT /note="I -> V (in DEDHIL; uncertain significance)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087675" FT VARIANT 626 FT /note="A -> V (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087676" FT VARIANT 640 FT /note="S -> R (in DEDHIL; no effect on protein abundance; FT changed proteasome-mediated ubiquitin-dependent protein FT catabolic process)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087677" FT VARIANT 647..707 FT /note="Missing (in DEDHIL; uncertain significance)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087678" FT VARIANT 668 FT /note="S -> G (in dbSNP:rs7679116)" FT /id="VAR_017817" FT VARIANT 674 FT /note="R -> P (in DEDHIL; no effect on protein abundance; FT changed on proteasome-mediated ubiquitin-dependent protein FT catabolic process)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087679" FT VARIANT 674 FT /note="R -> W (in DEDHIL; no effect on protein abundance; FT changed proteasome-mediated ubiquitin-dependent protein FT catabolic process)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087680" FT VARIANT 689 FT /note="R -> Q (in DEDHIL; decreased protein abundance; no FT effect on proteasome-mediated ubiquitin-dependent protein FT catabolic process)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087681" FT VARIANT 689 FT /note="R -> W (in DEDHIL)" FT /evidence="ECO:0000269|PubMed:35395208" FT /id="VAR_087682" FT MUTAGEN 26 FT /note="S->A: Abolished phosphorylation by ATM." FT /evidence="ECO:0000269|PubMed:26774286" FT MUTAGEN 72 FT /note="S->A: Does not affect phosphorylation by ATM." FT /evidence="ECO:0000269|PubMed:26774286" FT MUTAGEN 159 FT /note="S->A: Does not affect interaction with PIN1." FT /evidence="ECO:0000269|PubMed:22608923" FT MUTAGEN 205 FT /note="T->A: Impaired interaction with PIN1." FT /evidence="ECO:0000269|PubMed:22608923" FT MUTAGEN 252..257 FT /note="ALDELI->DDDEDD: Prevents homodimerization." FT /evidence="ECO:0000269|PubMed:17434132" FT MUTAGEN 349 FT /note="S->A: Does not affect interaction with PIN1." FT /evidence="ECO:0000269|PubMed:22608923" FT MUTAGEN 372 FT /note="S->A: Does not affect interaction with PIN1." FT /evidence="ECO:0000269|PubMed:22608923" FT CONFLICT 344 FT /note="P -> L (in Ref. 6; AAH37320)" FT /evidence="ECO:0000305" FT CONFLICT 377 FT /note="K -> N (in Ref. 6; AAH37320)" FT /evidence="ECO:0000305" FT CONFLICT 508 FT /note="Q -> R (in Ref. 6; AAH37320)" FT /evidence="ECO:0000305" FT HELIX 265..272 FT /evidence="ECO:0007829|PDB:2OVR" FT TURN 280..282 FT /evidence="ECO:0007829|PDB:2OVR" FT HELIX 286..293 FT /evidence="ECO:0007829|PDB:2OVR" FT HELIX 298..304 FT /evidence="ECO:0007829|PDB:2OVR" FT HELIX 309..315 FT /evidence="ECO:0007829|PDB:2OVR" FT HELIX 319..325 FT /evidence="ECO:0007829|PDB:2OVR" FT TURN 326..329 FT /evidence="ECO:0007829|PDB:2OVR" FT HELIX 350..367 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 374..377 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 384..390 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 393..398 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 403..407 FT /evidence="ECO:0007829|PDB:2OVR" FT TURN 408..410 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 413..416 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 424..430 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 433..438 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 443..447 FT /evidence="ECO:0007829|PDB:2OVR" FT TURN 448..451 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 452..457 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 464..470 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 473..478 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 481..490 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 493..498 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 504..509 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 514..518 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 523..527 FT /evidence="ECO:0007829|PDB:2OVR" FT HELIX 528..530 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 532..537 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 544..549 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 551..558 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 563..567 FT /evidence="ECO:0007829|PDB:2OVR" FT TURN 568..570 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 573..577 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 584..590 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 593..598 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 603..607 FT /evidence="ECO:0007829|PDB:2OVR" FT TURN 608..610 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 613..617 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 627..632 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 634..641 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 644..650 FT /evidence="ECO:0007829|PDB:2OVR" FT TURN 651..653 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 656..662 FT /evidence="ECO:0007829|PDB:2OVR" FT HELIX 666..668 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 671..677 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 679..687 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 689..693 FT /evidence="ECO:0007829|PDB:2OVR" FT STRAND 696..701 FT /evidence="ECO:0007829|PDB:2OVR" FT CONFLICT Q969H0-2:7 FT /note="G -> V (in Ref. 6; AAH37320)" FT /evidence="ECO:0000305" FT CONFLICT Q969H0-2:50 FT /note="L -> I (in Ref. 7; BAA91986)" FT /evidence="ECO:0000305" SQ SEQUENCE 707 AA; 79663 MW; E4A357F76DFD8203 CRC64; MNQELLSVGS KRRRTGGSLR GNPSSSQVDE EQMNRVVEEE QQQQLRQQEE EHTARNGEVV GVEPRPGGQN DSQQGQLEEN NNRFISVDED SSGNQEEQEE DEEHAGEQDE EDEEEEEMDQ ESDDFDQSDD SSREDEHTHT NSVTNSSSIV DLPVHQLSSP FYTKTTKMKR KLDHGSEVRS FSLGKKPCKV SEYTSTTGLV PCSATPTTFG DLRAANGQGQ QRRRITSVQP PTGLQEWLKM FQSWSGPEKL LALDELIDSC EPTQVKHMMQ VIEPQFQRDF ISLLPKELAL YVLSFLEPKD LLQAAQTCRY WRILAEDNLL WREKCKEEGI DEPLHIKRRK VIKPGFIHSP WKSAYIRQHR IDTNWRRGEL KSPKVLKGHD DHVITCLQFC GNRIVSGSDD NTLKVWSAVT GKCLRTLVGH TGGVWSSQMR DNIIISGSTD RTLKVWNAET GECIHTLYGH TSTVRCMHLH EKRVVSGSRD ATLRVWDIET GQCLHVLMGH VAAVRCVQYD GRRVVSGAYD FMVKVWDPET ETCLHTLQGH TNRVYSLQFD GIHVVSGSLD TSIRVWDVET GNCIHTLTGH QSLTSGMELK DNILVSGNAD STVKIWDIKT GQCLQTLQGP NKHQSAVTCL QFNKNFVITS SDDGTVKLWD LKTGEFIRNL VTLESGGSGG VVWRIRASNT KLVCAVGSRN GTEETKLLVL DFDVDMK //