FBXW7_HUMAN
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 03-AUG-2022, entry version 195.
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},
GN FBX30 {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, COMPONENT OF THE SCF(FBXW7) COMPLEX, AND INTERACTION 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, 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, 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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30] {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 [31] {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 [32]
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 [33]
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:17434132, PubMed:26976582,
CC PubMed:28727686). Recognizes and binds phosphorylated
CC sites/phosphodegrons within target proteins and thereafter brings them
CC to the SCF complex for ubiquitination (PubMed:22748924,
CC PubMed:26774286, PubMed:17434132, PubMed:26976582, PubMed:28727686).
CC Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN,
CC MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2,
CC MCL1, RICTOR, and probably PSEN1 (PubMed:11565034, PubMed:12354302,
CC PubMed:11585921, PubMed:15103331, PubMed:14739463, PubMed:17558397,
CC PubMed:17873522, PubMed:22608923, PubMed:22748924, PubMed:29149593,
CC PubMed:25775507, PubMed:28007894, PubMed:26976582, PubMed:28727686,
CC PubMed:25897075). 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:26774286, ECO:0000269|PubMed:26976582,
CC ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:28007894,
CC ECO:0000269|PubMed:28727686, ECO:0000269|PubMed:29149593,
CC ECO:0000305|PubMed:12354302}.
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:26774286, PubMed:28007894,
CC PubMed:26976582, PubMed:28727686). Interacts (via F-box domain) with
CC SKP1 (PubMed:11585921, PubMed:17434132, PubMed:28007894,
CC PubMed:26976582, PubMed:28727686). Interacts (via F-box domain) with
CC pseudophosphatase STYX; the interaction is direct and prevents FBXW7
CC interaction with SKP1 (PubMed:28007894). Interacts with cyclin-E (CCNE1
CC or CCNE2) (PubMed:11565034, PubMed:17434132). Interacts with PSEN1
CC (PubMed:12354302). Forms a trimeric complex with NOTCH1 and SGK1
CC (PubMed:21147854). Interacts with NOTCH1 intracellular domain/NICD and
CC 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). {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}.
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=5; 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 -!- SEQUENCE CAUTION:
CC Sequence=BAA91986.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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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; 1019.
DR CORUM; Q969H0; -.
DR DIP; DIP-27613N; -.
DR ELM; Q969H0; -.
DR IntAct; Q969H0; 63.
DR MINT; Q969H0; -.
DR STRING; 9606.ENSP00000281708; -.
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; Q969H0; -.
DR PeptideAtlas; Q969H0; -.
DR PRIDE; Q969H0; -.
DR ProteomicsDB; 75759; -. [Q969H0-1]
DR ProteomicsDB; 75760; -. [Q969H0-2]
DR ProteomicsDB; 75762; -. [Q969H0-4]
DR Antibodypedia; 27779; 681 antibodies from 36 providers.
DR DNASU; 55294; -.
DR Ensembl; ENST00000281708.10; ENSP00000281708.3; ENSG00000109670.16. [Q969H0-1]
DR Ensembl; ENST00000296555.11; ENSP00000296555.4; ENSG00000109670.16. [Q969H0-4]
DR Ensembl; ENST00000393956.9; ENSP00000377528.4; ENSG00000109670.16. [Q969H0-2]
DR Ensembl; ENST00000603548.6; ENSP00000474725.1; ENSG00000109670.16. [Q969H0-1]
DR Ensembl; ENST00000603841.1; ENSP00000474971.1; ENSG00000109670.16. [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 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 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; QLQMRDD; -.
DR OrthoDB; 927943at2759; -.
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 BioGRID-ORCS; 55294; 75 hits in 1132 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 210 other tissues.
DR ExpressionAtlas; Q969H0; baseline and differential.
DR Genevisible; Q969H0; HS.
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: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:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; 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:1903026; P:negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding; IEA:Ensembl.
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; IMP:ARUK-UCL.
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:1903146; P:regulation of autophagy of mitochondrion; IMP:ParkinsonsUK-UCL.
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: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 Gene3D; 2.130.10.10; -; 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; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
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; SSF50978; SSF50978; 1.
DR SUPFAM; SSF81383; SSF81383; 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.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Biological rhythms; Chromosome;
KW Cytoplasm; DNA damage; DNA repair; Host-virus interaction; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Ubl conjugation;
KW 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 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 a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1057519895)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035880"
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 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 668
FT /note="S -> G (in dbSNP:rs7679116)"
FT /id="VAR_017817"
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
