ID FBX7_HUMAN Reviewed; 522 AA. AC Q9Y3I1; B4DNB3; B4DWX5; Q5TGC4; Q5TI86; Q96HM6; Q9UF21; Q9UKT2; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 02-OCT-2024, entry version 209. DE RecName: Full=F-box only protein 7; GN Name=FBXO7; Synonyms=FBX7; 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 1). RX PubMed=10945468; DOI=10.1006/geno.2000.6211; RA Ilyin G.P., Rialland M., Pigeon C., Guguen-Guillouzo C.; RT "cDNA cloning and expression analysis of new members of the mammalian F-box RT protein family."; RL Genomics 67:40-47(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12529303; DOI=10.1101/gr.695703; RA Collins J.E., Goward M.E., Cole C.G., Smink L.J., Huckle E.J., Knowles S., RA Bye J.M., Beare D.M., Dunham I.; RT "Reevaluating human gene annotation: a second-generation analysis of RT chromosome 22."; RL Genome Res. 13:27-36(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT RP ILE-115. RC TISSUE=Heart, and Testis; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-115. RC TISSUE=Pancreas; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 42-522 (ISOFORM 1), AND VARIANT ILE-115. RX PubMed=10531035; DOI=10.1016/s0960-9822(00)80020-2; RA Cenciarelli C., Chiaur D.S., Guardavaccaro D., Parks W., Vidal M., RA Pagano M.; RT "Identification of a family of human F-box proteins."; RL Curr. Biol. 9:1177-1179(1999). RN [8] RP INTERACTION WITH DLGAP5, AND IDENTIFICATION IN SCF COMPLEX. RX PubMed=12527899; DOI=10.1038/sj.onc.1206129; RA Tsou A.-P., Yang C.-W., Huang C.-Y.F., Yu R.C.-T., Lee Y.-C.G., RA Chang C.-W., Chen B.-R., Chung Y.-F., Fann M.-J., Chi C.-W., Chiu J.-H., RA Chou C.-K.; RT "Identification of a novel cell cycle regulated gene, HURP, overexpressed RT in human hepatocellular carcinoma."; RL Oncogene 22:298-307(2003). RN [9] RP INTERACTION WITH DLGAP5; CUL1 AND SKP1, AND FUNCTION IN UBIQUITINATION OF RP DLGAP5. RX PubMed=15145941; DOI=10.1074/jbc.m404950200; RA Hsu J.-M., Lee Y.-C.G., Yu C.-T.R., Huang C.-Y.F.; RT "Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-phosphorylated RT hepatoma up-regulated protein (HURP) proteolysis by a proline-rich RT region."; RL J. Biol. Chem. 279:32592-32602(2004). RN [10] RP INTERACTION WITH CDK6, AND SUBCELLULAR LOCATION. RX PubMed=16096642; DOI=10.1038/sj.emboj.7600775; RA Laman H., Funes J.M., Ye H., Henderson S., Galinanes-Garcia L., Hara E., RA Knowles P., McDonald N., Boshoff C.; RT "Transforming activity of Fbxo7 is mediated specifically through regulation RT of cyclin D/cdk6."; RL EMBO J. 24:3104-3116(2005). RN [11] RP INTERACTION WITH BIRC2, AND FUNCTION IN UBIQUITINATION OF BIRC2. RX PubMed=16510124; DOI=10.1016/j.bbrc.2006.02.061; RA Chang Y.F., Cheng C.M., Chang L.K., Jong Y.J., Yuo C.Y.; RT "The F-box protein Fbxo7 interacts with human inhibitor of apoptosis RT protein cIAP1 and promotes cIAP1 ubiquitination."; RL Biochem. Biophys. Res. Commun. 342:1022-1026(2006). RN [12] RP INTERACTION WITH SKP1; PSMF1 AND CDK6, SUBCELLULAR LOCATION, SUBUNIT, RP IDENTIFICATION IN A COMPLEX WITH SKP1 AND CUL1, AND MUTAGENESIS OF VAL-253. RX PubMed=18495667; DOI=10.1074/jbc.m709900200; RA Kirk R., Laman H., Knowles P.P., Murray-Rust J., Lomonosov M., RA Meziane E.K., McDonald N.Q.; RT "Structure of a conserved dimerization domain within the F-box protein RT Fbxo7 and the PI31 proteasome inhibitor."; RL J. Biol. Chem. 283:22325-22335(2008). RN [13] RP FUNCTION IN UBIQUITINATION OF TRAF2 AND BIRC2. RX PubMed=22212761; DOI=10.1111/j.1582-4934.2012.01524.x; RA Kuiken H.J., Egan D.A., Laman H., Bernards R., Beijersbergen R.L., RA Dirac A.M.; RT "Identification of F-box only protein 7 as a negative regulator of NF- RT kappaB signalling."; RL J. Cell. Mol. Med. 16:2140-2149(2012). RN [14] RP FUNCTION, INTERACTION WITH PRKN AND PINK1, SUBCELLULAR LOCATION, RP MUTAGENESIS OF THR-22, AND CHARACTERIZATION OF VARIANT PARK15 GLY-378. RX PubMed=23933751; DOI=10.1038/nn.3489; RA Burchell V.S., Nelson D.E., Sanchez-Martinez A., Delgado-Camprubi M., RA Ivatt R.M., Pogson J.H., Randle S.J., Wray S., Lewis P.A., Houlden H., RA Abramov A.Y., Hardy J., Wood N.W., Whitworth A.J., Laman H., RA Plun-Favreau H.; RT "The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to RT mediate mitophagy."; RL Nat. Neurosci. 16:1257-1265(2013). RN [15] RP FUNCTION IN UBIQUITINATION OF UXT, AND SUBCELLULAR LOCATION. RX PubMed=33010352; DOI=10.1016/j.bbagen.2020.129754; RA Spagnol V., Oliveira C.A.B., Randle S.J., Passos P.M.S., RA Correia C.R.S.T.B., Simaroli N.B., Oliveira J.S., Mevissen T.E.T., RA Medeiros A.C., Gomes M.D., Komander D., Laman H., Teixeira F.R.; RT "The E3 ubiquitin ligase SCF(Fbxo7) mediates proteasomal degradation of UXT RT isoform 2 (UXT-V2) to inhibit the NF-kappaB signaling pathway."; RL Biochim. Biophys. Acta 1865:129754-129754(2021). RN [16] RP FUNCTION. RX PubMed=34791250; DOI=10.1093/hmg/ddab330; RA Palmer M.C.L., Neudorf N.M., Farrell A.C., Razi T., Lichtensztejn Z., RA McManus K.J.; RT "The F-box protein, FBXO7, is required to maintain chromosome stability in RT humans."; RL Hum. Mol. Genet. 31:1471-1486(2022). RN [17] RP FUNCTION IN UBIQUITINATION OF SIRT7, AND MUTAGENESIS OF ARG-378. RX PubMed=36646384; DOI=10.1016/j.jbc.2023.102909; RA Lee S.H., Lee Y.J., Jung S., Chung K.C.; RT "E3 ligase adaptor FBXO7 contributes to ubiquitination and proteasomal RT degradation of SIRT7 and promotes cell death in response to hydrogen RT peroxide."; RL J. Biol. Chem. 0:0-0(2023). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 180-335. RX PubMed=24419388; DOI=10.1107/s1399004713025820; RA Shang J., Wang G., Yang Y., Huang X., Du Z.; RT "Structure of the FP domain of Fbxo7 reveals a novel mode of protein- RT protein interaction."; RL Acta Crystallogr. D 70:155-164(2014). RN [19] RP VARIANT PARK15 GLY-378, AND VARIANT ILE-115. RX PubMed=18513678; DOI=10.1016/j.ajhg.2008.05.005; RA Shojaee S., Sina F., Banihosseini S.S., Kazemi M.H., Kalhor R., RA Shahidi G.-A., Fakhrai-Rad H., Ronaghi M., Elahi E.; RT "Genome-wide linkage analysis of a Parkinsonian-pyramidal syndrome pedigree RT by 500 K SNP arrays."; RL Am. J. Hum. Genet. 82:1375-1384(2008). RN [20] RP VARIANT CYS-481. RX PubMed=20853184; DOI=10.1007/s10048-010-0259-0; RA Santoro L., Breedveld G.J., Manganelli F., Iodice R., Pisciotta C., RA Nolano M., Punzo F., Quarantelli M., Pappata S., Di Fonzo A., Oostra B.A., RA Bonifati V.; RT "Novel ATP13A2 (PARK9) homozygous mutation in a family with marked RT phenotype variability."; RL Neurogenetics 12:33-39(2011). RN [21] RP VARIANT PARK15 ARG-34. RX PubMed=32892229; DOI=10.1007/s00401-020-02219-6; RA Tesson C., Lohmann E., Devos D., Bertrand H., Lesage S., Brice A.; RT "Segregation of ATP10B variants in families with autosomal recessive RT parkinsonism."; RL Acta Neuropathol. 140:783-785(2020). 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 and plays a role in several biological processes such as cell CC cycle, cell proliferation, or maintenance of chromosome stability CC (PubMed:15145941, PubMed:34791250). Recognizes and ubiquitinates BIRC2 CC and the cell cycle regulator DLGAP5 (PubMed:15145941, PubMed:16510124, CC PubMed:22212761). Plays a role downstream of PINK1 in the clearance of CC damaged mitochondria via selective autophagy (mitophagy) by targeting CC PRKN to dysfunctional depolarized mitochondria. Promotes MFN1 CC ubiquitination. Mediates the ubiquitination and proteasomal degradation CC of UXT isoform 2, thereby impairing the NF-kappa-B signaling pathway CC (PubMed:33010352). Inhibits NF-kappa-B pathway also by promoting the CC ubiquitination of TRAF2 (PubMed:22212761). Affects the assembly state CC and activity of the proteasome in the cells including neurons by CC ubiquitinating the proteasomal subunit PSMA2 via 'Lys-63'-linked CC polyubiquitin chains (By similarity). Promotes 'Lys-48'-linked CC polyubiquitination SIRT7, leading to the hydrogen peroxide-induced cell CC death (PubMed:36646384). {ECO:0000250|UniProtKB:Q3U7U3, CC ECO:0000269|PubMed:15145941, ECO:0000269|PubMed:16510124, CC ECO:0000269|PubMed:22212761, ECO:0000269|PubMed:23933751, CC ECO:0000269|PubMed:33010352, ECO:0000269|PubMed:34791250, CC ECO:0000269|PubMed:36646384}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase CC complex SCF(FBXO7) formed of CUL1, SKP1, RBX1 and FBXO7. Interacts via CC its C-terminal proline-rich region with DLGAP5. Interacts with BIRC2. CC Interacts with CDK6 and promotes its interaction with D-type cyclin. CC Interacts with PSMF1. {ECO:0000269|PubMed:12527899, CC ECO:0000269|PubMed:15145941, ECO:0000269|PubMed:16096642, CC ECO:0000269|PubMed:16510124, ECO:0000269|PubMed:18495667, CC ECO:0000269|PubMed:23933751}. CC -!- SUBUNIT: [Isoform 1]: Interacts (via the N-terminal Ubl domain) with CC PRKN (PubMed:23933751). Interact (via N-terminal region) with PINK1 CC (PubMed:23933751). {ECO:0000269|PubMed:23933751}. CC -!- SUBUNIT: [Isoform 2]: Interact (via N-terminal region) with PINK1. CC {ECO:0000269|PubMed:23933751}. CC -!- INTERACTION: CC Q9Y3I1; P22607: FGFR3; NbExp=3; IntAct=EBI-1161222, EBI-348399; CC Q9Y3I1; Q9BXM7: PINK1; NbExp=8; IntAct=EBI-1161222, EBI-2846068; CC Q9Y3I1; O60260: PRKN; NbExp=10; IntAct=EBI-1161222, EBI-716346; CC Q9Y3I1; P25788: PSMA3; NbExp=6; IntAct=EBI-1161222, EBI-348380; CC Q9Y3I1; P61289: PSME3; NbExp=3; IntAct=EBI-1161222, EBI-355546; CC Q9Y3I1; Q92530: PSMF1; NbExp=11; IntAct=EBI-1161222, EBI-945916; CC Q9Y3I1; P63208: SKP1; NbExp=11; IntAct=EBI-1161222, EBI-307486; CC Q9Y3I1; Q9Y649; NbExp=3; IntAct=EBI-1161222, EBI-25900580; CC Q9Y3I1-1; Q9BXM7: PINK1; NbExp=2; IntAct=EBI-9102965, EBI-2846068; CC Q9Y3I1-1; O60260: PRKN; NbExp=2; IntAct=EBI-9102965, EBI-716346; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16096642, CC ECO:0000269|PubMed:18495667}. Nucleus {ECO:0000269|PubMed:16096642, CC ECO:0000269|PubMed:18495667, ECO:0000269|PubMed:33010352}. CC Mitochondrion {ECO:0000269|PubMed:23933751}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:23933751}. Note=Predominantly cytoplasmic CC (PubMed:16096642). A minor proportion is detected in the nucleus CC (PubMed:16096642). Relocates from the cytosol to depolarized CC mitochondria (PubMed:23933751). {ECO:0000269|PubMed:16096642, CC ECO:0000269|PubMed:23933751}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9Y3I1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y3I1-2; Sequence=VSP_041073, VSP_041074; CC Name=3; CC IsoId=Q9Y3I1-3; Sequence=VSP_044723; CC -!- DOMAIN: The ubiquitin-like region mediates interaction with PRKN. CC {ECO:0000269|PubMed:23933751}. CC -!- DOMAIN: The proline-rich region is important for protein-protein CC interactions. CC -!- DISEASE: Parkinson disease 15 (PARK15) [MIM:260300]: A CC neurodegenerative disorder characterized by parkinsonian and pyramidal CC signs. Clinical manifestations include tremor, bradykinesia, rigidity, CC postural instability, spasticity, mainly in the lower limbs, and CC hyperreflexia. {ECO:0000269|PubMed:18513678, CC ECO:0000269|PubMed:23933751, ECO:0000269|PubMed:32892229}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAF04471.1; Type=Erroneous initiation; Note=Extended 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; AF233225; AAF67155.1; -; mRNA. DR EMBL; AL050254; CAB43356.1; -; mRNA. DR EMBL; CR456491; CAG30377.1; -; mRNA. DR EMBL; AK297841; BAG60175.1; -; mRNA. DR EMBL; AK301716; BAG63187.1; -; mRNA. DR EMBL; AL021937; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL035068; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z71183; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC008361; AAH08361.1; -; mRNA. DR EMBL; AF129537; AAF04471.1; ALT_INIT; mRNA. DR CCDS; CCDS13907.1; -. [Q9Y3I1-1] DR CCDS; CCDS46695.1; -. [Q9Y3I1-2] DR CCDS; CCDS58806.1; -. [Q9Y3I1-3] DR RefSeq; NP_001028196.1; NM_001033024.1. [Q9Y3I1-2] DR RefSeq; NP_001244919.1; NM_001257990.1. [Q9Y3I1-3] DR RefSeq; NP_036311.3; NM_012179.3. [Q9Y3I1-1] DR PDB; 4L9C; X-ray; 2.10 A; A/B=180-335. DR PDB; 4L9H; X-ray; 2.00 A; A=180-335. DR PDBsum; 4L9C; -. DR PDBsum; 4L9H; -. DR AlphaFoldDB; Q9Y3I1; -. DR SMR; Q9Y3I1; -. DR BioGRID; 117326; 619. DR ComplexPortal; CPX-7906; SCF E3 ubiquitin ligase complex, FBXO7 variant. DR DIP; DIP-36125N; -. DR IntAct; Q9Y3I1; 111. DR MINT; Q9Y3I1; -. DR STRING; 9606.ENSP00000266087; -. DR GlyCosmos; Q9Y3I1; 2 sites, 1 glycan. DR GlyGen; Q9Y3I1; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q9Y3I1; -. DR PhosphoSitePlus; Q9Y3I1; -. DR SwissPalm; Q9Y3I1; -. DR BioMuta; FBXO7; -. DR DMDM; 13124249; -. DR jPOST; Q9Y3I1; -. DR MassIVE; Q9Y3I1; -. DR PaxDb; 9606-ENSP00000266087; -. DR PeptideAtlas; Q9Y3I1; -. DR ProteomicsDB; 65179; -. DR ProteomicsDB; 86039; -. [Q9Y3I1-1] DR ProteomicsDB; 86040; -. [Q9Y3I1-2] DR Pumba; Q9Y3I1; -. DR Antibodypedia; 25270; 202 antibodies from 32 providers. DR DNASU; 25793; -. DR Ensembl; ENST00000266087.12; ENSP00000266087.7; ENSG00000100225.18. [Q9Y3I1-1] DR Ensembl; ENST00000397426.5; ENSP00000380571.1; ENSG00000100225.18. [Q9Y3I1-3] DR Ensembl; ENST00000452138.3; ENSP00000388547.2; ENSG00000100225.18. [Q9Y3I1-2] DR GeneID; 25793; -. DR KEGG; hsa:25793; -. DR MANE-Select; ENST00000266087.12; ENSP00000266087.7; NM_012179.4; NP_036311.3. DR UCSC; uc003amq.4; human. [Q9Y3I1-1] DR AGR; HGNC:13586; -. DR CTD; 25793; -. DR DisGeNET; 25793; -. DR GeneCards; FBXO7; -. DR GeneReviews; FBXO7; -. DR HGNC; HGNC:13586; FBXO7. DR HPA; ENSG00000100225; Tissue enhanced (bone). DR MalaCards; FBXO7; -. DR MIM; 260300; phenotype. DR MIM; 605648; gene. DR neXtProt; NX_Q9Y3I1; -. DR OpenTargets; ENSG00000100225; -. DR Orphanet; 171695; Parkinsonian-pyramidal syndrome. DR PharmGKB; PA28047; -. DR VEuPathDB; HostDB:ENSG00000100225; -. DR eggNOG; ENOG502QTNJ; Eukaryota. DR GeneTree; ENSGT00390000006670; -. DR HOGENOM; CLU_039588_0_0_1; -. DR InParanoid; Q9Y3I1; -. DR OMA; QRPNLPH; -. DR OrthoDB; 3020676at2759; -. DR PhylomeDB; Q9Y3I1; -. DR TreeFam; TF329830; -. DR PathwayCommons; Q9Y3I1; -. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q9Y3I1; -. DR SIGNOR; Q9Y3I1; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 25793; 41 hits in 1197 CRISPR screens. DR ChiTaRS; FBXO7; human. DR EvolutionaryTrace; Q9Y3I1; -. DR GeneWiki; FBXO7; -. DR GenomeRNAi; 25793; -. DR Pharos; Q9Y3I1; Tbio. DR PRO; PR:Q9Y3I1; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q9Y3I1; protein. DR Bgee; ENSG00000100225; Expressed in trabecular bone tissue and 213 other cell types or tissues. DR ExpressionAtlas; Q9Y3I1; baseline and differential. DR GO; GO:0097414; C:classical Lewy body; IDA:ParkinsonsUK-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:ParkinsonsUK-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0097409; C:glial cytoplasmic inclusion; IDA:ParkinsonsUK-UCL. DR GO; GO:1990037; C:Lewy body core; IDA:ParkinsonsUK-UCL. DR GO; GO:1990038; C:Lewy body corona; IDA:ParkinsonsUK-UCL. DR GO; GO:0097462; C:Lewy neurite; IDA:ParkinsonsUK-UCL. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL. DR GO; GO:0032991; C:protein-containing complex; IDA:LIFEdb. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ParkinsonsUK-UCL. DR GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0043130; F:ubiquitin binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:1990756; F:ubiquitin-like ligase-substrate adaptor activity; IDA:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:ProtInc. DR GO; GO:0000422; P:autophagy of mitochondrion; IMP:UniProtKB. DR GO; GO:0030098; P:lymphocyte differentiation; IEA:Ensembl. DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0045620; P:negative regulation of lymphocyte differentiation; IEA:Ensembl. DR GO; GO:1903377; P:negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL. DR GO; GO:1903599; P:positive regulation of autophagy of mitochondrion; IBA:GO_Central. DR GO; GO:1901526; P:positive regulation of mitophagy; IDA:ParkinsonsUK-UCL. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProt. DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProt. DR GO; GO:0006626; P:protein targeting to mitochondrion; IMP:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IDA:ParkinsonsUK-UCL. DR GO; GO:0040012; P:regulation of locomotion; IDA:ParkinsonsUK-UCL. DR GO; GO:0010975; P:regulation of neuron projection development; IMP:ParkinsonsUK-UCL. DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:ParkinsonsUK-UCL. DR CDD; cd22087; F-box_FBXO7; 1. DR Gene3D; 1.20.1280.50; -; 1. DR Gene3D; 3.40.1000.30; -; 1. DR InterPro; IPR036047; F-box-like_dom_sf. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR047118; Fbxo7. DR InterPro; IPR021625; PI31_Prot_N. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR PANTHER; PTHR15537; F-BOX ONLY PROTEIN 7; 1. DR PANTHER; PTHR15537:SF2; F-BOX ONLY PROTEIN 7; 1. DR Pfam; PF12937; F-box-like; 1. DR Pfam; PF11566; PI31_Prot_N; 1. DR SMART; SM00256; FBOX; 1. DR SUPFAM; SSF81383; F-box domain; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS50181; FBOX; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; KW Methylation; Mitochondrion; Neurodegeneration; Nucleus; Parkinson disease; KW Parkinsonism; Proteomics identification; Reference proteome; KW Ubl conjugation pathway. FT CHAIN 1..522 FT /note="F-box only protein 7" FT /id="PRO_0000119885" FT DOMAIN 329..375 FT /note="F-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080" FT REGION 1..88 FT /note="Ubiquitin-like" FT REGION 85..144 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 92..129 FT /note="Important for interaction with PINK1" FT /evidence="ECO:0000269|PubMed:23933751" FT REGION 129..169 FT /note="Important for interaction with CDK6" FT REGION 180..324 FT /note="Important for dimerization and interaction with FT PSMF1" FT /evidence="ECO:0000269|PubMed:18495667" FT REGION 381..522 FT /note="Important for interaction with CDK6" FT REGION 483..522 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 481..484 FT /note="RFDP motif" FT MOD_RES 432 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q3U7U3" FT MOD_RES 451 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q3U7U3" FT MOD_RES 518 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000250|UniProtKB:Q3U7U3" FT VAR_SEQ 1..114 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044723" FT VAR_SEQ 1..79 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041073" FT VAR_SEQ 80..91 FT /note="DDIPAPNIPSST -> MARPPGGSGPLL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041074" FT VARIANT 34 FT /note="L -> R (in PARK15; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32892229" FT /id="VAR_084192" FT VARIANT 115 FT /note="M -> I (in dbSNP:rs11107)" FT /evidence="ECO:0000269|PubMed:10531035, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:18513678" FT /id="VAR_021408" FT VARIANT 378 FT /note="R -> G (in PARK15; no effect on interaction with FT PRKN; dbSNP:rs71799110)" FT /evidence="ECO:0000269|PubMed:18513678, FT ECO:0000269|PubMed:23933751" FT /id="VAR_047938" FT VARIANT 481 FT /note="R -> C (found in two patients with Kufor-Rakeb FT syndrome also carrying R-877 in ATP13A2; FT dbSNP:rs148272407)" FT /evidence="ECO:0000269|PubMed:20853184" FT /id="VAR_066022" FT MUTAGEN 22 FT /note="T->M: Impairs interaction with PRKN." FT /evidence="ECO:0000269|PubMed:23933751" FT MUTAGEN 253 FT /note="V->E: Abolishes interaction with PSMF1." FT /evidence="ECO:0000269|PubMed:18495667" FT MUTAGEN 378 FT /note="R->G: Loss of SIRT7 ubiquitination." FT /evidence="ECO:0000269|PubMed:36646384" FT CONFLICT 79 FT /note="Q -> H (in Ref. 7; AAF04471)" FT /evidence="ECO:0000305" FT CONFLICT 84 FT /note="A -> P (in Ref. 7; AAF04471)" FT /evidence="ECO:0000305" FT CONFLICT 154 FT /note="N -> S (in Ref. 4; BAG63187)" FT /evidence="ECO:0000305" FT CONFLICT 169 FT /note="M -> L (in Ref. 7; AAF04471)" FT /evidence="ECO:0000305" FT CONFLICT 224 FT /note="M -> L (in Ref. 7; AAF04471)" FT /evidence="ECO:0000305" FT CONFLICT 241 FT /note="P -> H (in Ref. 7; AAF04471)" FT /evidence="ECO:0000305" FT CONFLICT 328 FT /note="D -> N (in Ref. 7; AAF04471)" FT /evidence="ECO:0000305" FT CONFLICT 413 FT /note="M -> L (in Ref. 7; AAF04471)" FT /evidence="ECO:0000305" FT CONFLICT 475 FT /note="F -> L (in Ref. 7; AAF04471)" FT /evidence="ECO:0000305" FT HELIX 181..190 FT /evidence="ECO:0007829|PDB:4L9H" FT HELIX 195..209 FT /evidence="ECO:0007829|PDB:4L9H" FT STRAND 213..216 FT /evidence="ECO:0007829|PDB:4L9H" FT TURN 220..222 FT /evidence="ECO:0007829|PDB:4L9H" FT STRAND 228..230 FT /evidence="ECO:0007829|PDB:4L9H" FT STRAND 233..239 FT /evidence="ECO:0007829|PDB:4L9H" FT HELIX 241..243 FT /evidence="ECO:0007829|PDB:4L9C" FT STRAND 247..255 FT /evidence="ECO:0007829|PDB:4L9H" FT STRAND 258..267 FT /evidence="ECO:0007829|PDB:4L9H" FT STRAND 270..279 FT /evidence="ECO:0007829|PDB:4L9H" FT HELIX 281..283 FT /evidence="ECO:0007829|PDB:4L9H" FT HELIX 287..289 FT /evidence="ECO:0007829|PDB:4L9H" FT HELIX 294..297 FT /evidence="ECO:0007829|PDB:4L9H" FT HELIX 301..311 FT /evidence="ECO:0007829|PDB:4L9H" FT HELIX 313..323 FT /evidence="ECO:0007829|PDB:4L9H" SQ SEQUENCE 522 AA; 58503 MW; C4E5E70A0747287A CRC64; MRLRVRLLKR TWPLEVPETE PTLGHLRSHL RQSLLCTWGY SSNTRFTITL NYKDPLTGDE ETLASYGIVS GDLICLILQD DIPAPNIPSS TDSEHSSLQN NEQPSLATSS NQTSMQDEQP SDSFQGQAAQ SGVWNDDSML GPSQNFEAES IQDNAHMAEG TGFYPSEPML CSESVEGQVP HSLETLYQSA DCSDANDALI VLIHLLMLES GYIPQGTEAK ALSMPEKWKL SGVYKLQYMH PLCEGSSATL TCVPLGNLIV VNATLKINNE IRSVKRLQLL PESFICKEKL GENVANIYKD LQKLSRLFKD QLVYPLLAFT RQALNLPDVF GLVVLPLELK LRIFRLLDVR SVLSLSAVCR DLFTASNDPL LWRFLYLRDF RDNTVRVQDT DWKELYRKRH IQRKESPKGR FVMLLPSSTH TIPFYPNPLH PRPFPSSRLP PGIIGGEYDQ RPTLPYVGDP ISSLIPGPGE TPSQFPPLRP RFDPVGPLPG PNPILPGRGG PNDRFPFRPS RGRPTDGRLS FM //