ID CCNF_HUMAN Reviewed; 786 AA. AC P41002; B2R8H3; Q96EG9; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2002, sequence version 2. DT 27-MAR-2024, entry version 201. DE RecName: Full=Cyclin-F; DE AltName: Full=F-box only protein 1; GN Name=CCNF; Synonyms=FBX1, FBXO1; 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], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION. RX PubMed=7813445; DOI=10.1002/j.1460-2075.1994.tb06955.x; RA Bai C., Richman R., Elledge S.J.; RT "Human cyclin F."; RL EMBO J. 13:6087-6098(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=7896286; DOI=10.1006/geno.1994.1578; RA Kraus B., Pohlschmidt M., Leung A.L.S., Germino G.G., Snarey A., RA Schneider M.C., Reeders S.T., Frischauf A.-M.; RT "A novel cyclin gene (CCNF) in the region of the polycystic kidney disease RT gene (PKD1)."; RL Genomics 24:27-33(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thymus; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Eye; 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 [6] RP FUNCTION, AND INTERACTION WITH SKP1. RX PubMed=8706131; DOI=10.1016/s0092-8674(00)80098-7; RA Bai C., Sen P., Hofmann K., Ma L., Goebl M., Harper J.W., Elledge S.J.; RT "SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery RT through a novel motif, the F-box."; RL Cell 86:263-274(1996). RN [7] RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, DOMAIN, AND INTERACTION RP WITH CCNB1. RX PubMed=10716937; DOI=10.1093/emboj/19.6.1378; RA Kong M., Barnes E.A., Ollendorff V., Donoghue D.J.; RT "Cyclin F regulates the nuclear localization of cyclin B1 through a cyclin- RT cyclin interaction."; RL EMBO J. 19:1378-1388(2000). RN [8] RP INTERACTION WITH SKP1, AND DEGRADATION. RX PubMed=12122006; DOI=10.1074/jbc.m205503200; RA Fung T.K., Siu W.Y., Yam C.H., Lau A., Poon R.Y.; RT "Cyclin F is degraded during G2-M by mechanisms fundamentally different RT from other cyclins."; RL J. Biol. Chem. 277:35140-35149(2002). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE SCF(CCNF) COMPLEX RP WITH SKP1 AND CUL1, INTERACTION WITH CP110, AND MUTAGENESIS OF RP 35-LEU-PRO-36; MET-309 AND LEU-352. RX PubMed=20596027; DOI=10.1038/nature09140; RA D'Angiolella V., Donato V., Vijayakumar S., Saraf A., Florens L., RA Washburn M.P., Dynlacht B., Pagano M.; RT "SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through RT CP110 degradation."; RL Nature 466:138-142(2010). RN [10] RP FUNCTION, INTERACTION WITH RRM2, SUBCELLULAR LOCATION, INDUCTION BY DNA RP DAMAGE, AND MUTAGENESIS OF 35-LEU-PRO-36; MET-309 AND LEU-352. RX PubMed=22632967; DOI=10.1016/j.cell.2012.03.043; RA D'Angiolella V., Donato V., Forrester F.M., Jeong Y.T., Pellacani C., RA Kudo Y., Saraf A., Florens L., Washburn M.P., Pagano M.; RT "Cyclin F-mediated degradation of ribonucleotide reductase M2 controls RT genome integrity and DNA repair."; RL Cell 149:1023-1034(2012). RN [11] RP INTERACTION WITH CCP110. RX PubMed=22441691; DOI=10.1038/embor.2012.40; RA Li J., Kim S., Kobayashi T., Liang F.X., Korzeniewski N., Duensing S., RA Dynlacht B.D.; RT "Neurl4, a novel daughter centriole protein, prevents formation of ectopic RT microtubule organizing centres."; RL EMBO Rep. 13:547-553(2012). RN [12] RP FUNCTION, INTERACTION WITH MYBL2, AND MUTAGENESIS OF 309-MET-ARG-310. RX PubMed=25557911; DOI=10.1038/ncomms6800; RA Klein D.K., Hoffmann S., Ahlskog J.K., O'Hanlon K., Quaas M., Larsen B.D., RA Rolland B., Roesner H.I., Walter D., Kousholt A.N., Menzel T., Lees M., RA Johansen J.V., Rappsilber J., Engeland K., Soerensen C.S.; RT "Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint RT control."; RL Nat. Commun. 6:5800-5800(2015). RN [13] RP FUNCTION, INTERACTION WITH FZR1/CDH1 AND CDC20, DEVELOPMENTAL STAGE, RP DOMAIN, UBIQUITINATION, D BOX MOTIFS, AND MUTAGENESIS OF 310-ARG--LEU-313 RP AND 351-ARG--LEU-354. RX PubMed=27653696; DOI=10.1016/j.celrep.2016.08.058; RA Choudhury R., Bonacci T., Arceci A., Lahiri D., Mills C.A., Kernan J.L., RA Branigan T.B., DeCaprio J.A., Burke D.J., Emanuele M.J.; RT "APC/C and SCF(cyclin F) Constitute a Reciprocal Feedback Circuit RT Controlling S-Phase Entry."; RL Cell Rep. 16:3359-3372(2016). RN [14] RP FUNCTION, INTERACTION WITH CDC6 AND CUL1, AND SUBCELLULAR LOCATION. RX PubMed=26818844; DOI=10.1038/ncomms10530; RA Walter D., Hoffmann S., Komseli E.S., Rappsilber J., Gorgoulis V., RA Soerensen C.S.; RT "SCF(Cyclin F)-dependent degradation of CDC6 suppresses DNA re- RT replication."; RL Nat. Commun. 7:10530-10530(2016). RN [15] RP INVOLVEMENT IN FTDALS5, VARIANTS FTDALS5 GLY-3; ARG-97; ILE-181; ARG-195; RP THR-392; PRO-509; ILE-543; GLY-621; LYS-624 AND THR-772, CHARACTERIZATION RP OF VARIANTS FTDALS5 GLY-3; ARG-97; ARG-195; THR-392; PRO-509; GLY-621; RP LYS-624 AND THR-772, AND FUNCTION. RX PubMed=27080313; DOI=10.1038/ncomms11253; RA Williams K.L., Topp S., Yang S., Smith B., Fifita J.A., Warraich S.T., RA Zhang K.Y., Farrawell N., Vance C., Hu X., Chesi A., Leblond C.S., Lee A., RA Rayner S.L., Sundaramoorthy V., Dobson-Stone C., Molloy M.P., RA van Blitterswijk M., Dickson D.W., Petersen R.C., Graff-Radford N.R., RA Boeve B.F., Murray M.E., Pottier C., Don E., Winnick C., McCann E.P., RA Hogan A., Daoud H., Levert A., Dion P.A., Mitsui J., Ishiura H., RA Takahashi Y., Goto J., Kost J., Gellera C., Gkazi A.S., Miller J., RA Stockton J., Brooks W.S., Boundy K., Polak M., Munoz-Blanco J.L., RA Esteban-Perez J., Rabano A., Hardiman O., Morrison K.E., Ticozzi N., RA Silani V., de Belleroche J., Glass J.D., Kwok J.B., Guillemin G.J., RA Chung R.S., Tsuji S., Brown R.H. Jr., Garcia-Redondo A., Rademakers R., RA Landers J.E., Gitler A.D., Rouleau G.A., Cole N.J., Yerbury J.J., RA Atkin J.D., Shaw C.E., Nicholson G.A., Blair I.P.; RT "CCNF mutations in amyotrophic lateral sclerosis and frontotemporal RT dementia."; RL Nat. Commun. 7:11253-11253(2016). RN [16] RP CHARACTERIZATION OF VARIANT FTDALS5 GLY-621, AND FUNCTION. RX PubMed=28852778; DOI=10.1007/s00018-017-2632-8; RA Lee A., Rayner S.L., Gwee S.S.L., De Luca A., Shahheydari H., RA Sundaramoorthy V., Ragagnin A., Morsch M., Radford R., Galper J., RA Freckleton S., Shi B., Walker A.K., Don E.K., Cole N.J., Yang S., RA Williams K.L., Yerbury J.J., Blair I.P., Atkin J.D., Molloy M.P., RA Chung R.S.; RT "Pathogenic mutation in the ALS/FTD gene, CCNF, causes elevated Lys48- RT linked ubiquitylation and defective autophagy."; RL Cell. Mol. Life Sci. 75:335-354(2018). 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:20596027, PubMed:22632967, PubMed:27653696, CC PubMed:26818844, PubMed:27080313, PubMed:28852778). The SCF(CCNF) E3 CC ubiquitin-protein ligase complex is an integral component of the CC ubiquitin proteasome system (UPS) and links proteasome degradation to CC the cell cycle (PubMed:8706131, PubMed:20596027, PubMed:27653696, CC PubMed:26818844). Mediates the substrate recognition and the CC proteasomal degradation of various target proteins involved in the CC regulation of cell cycle progression and in the maintenance of genome CC stability (PubMed:20596027, PubMed:22632967, PubMed:27653696, CC PubMed:26818844). Mediates the ubiquitination and proteasomal CC degradation of CP110 during G2 phase, thereby acting as an inhibitor of CC centrosome reduplication (PubMed:20596027). In G2, mediates the CC ubiquitination and subsequent degradation of ribonucleotide reductase CC RRM2, thereby maintaining a balanced pool of dNTPs and genome integrity CC (PubMed:22632967). In G2, mediates the ubiquitination and proteasomal CC degradation of CDC6, thereby suppressing DNA re-replication and CC preventing genome instability (PubMed:26818844). Involved in the CC ubiquitination and degradation of the substrate adapter CDH1 of the CC anaphase-promoting complex (APC/C), thereby acting as an antagonist of CC APC/C in regulating G1 progression and S phase entry (PubMed:27653696). CC May play a role in the G2 cell cycle checkpoint control after DNA CC damage, possibly by promoting the ubiquitination of MYBL2/BMYB CC (PubMed:25557911). {ECO:0000269|PubMed:20596027, CC ECO:0000269|PubMed:22632967, ECO:0000269|PubMed:25557911, CC ECO:0000269|PubMed:26818844, ECO:0000269|PubMed:27080313, CC ECO:0000269|PubMed:27653696, ECO:0000269|PubMed:28852778, CC ECO:0000269|PubMed:8706131}. CC -!- SUBUNIT: Component of the SCF(CCNF) complex consisting of CUL1, RBX1, CC SKP1 and CCNF (PubMed:20596027). Interacts with SKP1 (PubMed:8706131, CC PubMed:12122006). Interacts with CUL1 (PubMed:26818844). Interacts with CC CCNB1; interaction is required for nuclear localization of CCNB1 CC (PubMed:10716937, PubMed:20596027). Interacts with CCP110; this CC interaction leads to CCP110 ubiquitination and degradation via the CC proteasome pathway (PubMed:22441691). Interacts (via the Cyclin N- CC terminal domain) with MYBL2/BMYB (PubMed:25557911). Interacts with CC FZR1/CDH1 (via N-terminus) (PubMed:27653696). Interacts with RRM2 (via CC Cy motif and when phosphorylated at 'Thr-33'); the interaction occurs CC exclusively in G2 and early M (PubMed:22632967). Interacts with CDC6 CC (via Cy motif); the interaction takes place during G2 and M phase CC (PubMed:26818844). {ECO:0000269|PubMed:10716937, CC ECO:0000269|PubMed:12122006, ECO:0000269|PubMed:20596027, CC ECO:0000269|PubMed:22441691, ECO:0000269|PubMed:22632967, CC ECO:0000269|PubMed:25557911, ECO:0000269|PubMed:26818844, CC ECO:0000269|PubMed:27653696, ECO:0000269|PubMed:8706131}. CC -!- INTERACTION: CC P41002; O43303: CCP110; NbExp=9; IntAct=EBI-1207574, EBI-1566217; CC P41002; Q13616: CUL1; NbExp=5; IntAct=EBI-1207574, EBI-359390; CC P41002; P31350: RRM2; NbExp=12; IntAct=EBI-1207574, EBI-2339245; CC P41002; P63208: SKP1; NbExp=6; IntAct=EBI-1207574, EBI-307486; CC P41002; P63208-1: SKP1; NbExp=6; IntAct=EBI-1207574, EBI-307497; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10716937, CC ECO:0000269|PubMed:22632967, ECO:0000269|PubMed:26818844, CC ECO:0000269|PubMed:7813445}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:7813445}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome, centriole {ECO:0000269|PubMed:20596027}. CC Note=Localization to the centrosome is rare in S phase cells and CC increases in G2 cells. Localizes to both the mother and daughter CC centrioles. Localization to centrosomes is not dependent on CP110. CC Localizes to the nucleus in G2 phase. {ECO:0000269|PubMed:20596027, CC ECO:0000269|PubMed:26818844}. CC -!- TISSUE SPECIFICITY: Widely expressed, with expression detected in the CC heart, brain, placenta, lung, liver, skeletal muscle, kidney and CC pancreas. {ECO:0000269|PubMed:7813445}. CC -!- DEVELOPMENTAL STAGE: Appears in S phase, peaks in G2 phase, decreases CC in mitosis, lowest in early G1 phase and then accumulates again in late CC G1 and S phase (at protein level). {ECO:0000269|PubMed:27653696, CC ECO:0000269|PubMed:7813445}. CC -!- INDUCTION: Down-regulated in an ATR-dependent manner in response to DNA CC damage induced by doxorubicin, camptothecin, UV-C, methyl CC methanesulfonate, nocodazole, or gamma-irradiation. Down-regulation in CC response to DNA damage is required to allow RRM2 accumulation within CC the nucleus and for efficient DNA repair. CC {ECO:0000269|PubMed:22632967}. CC -!- DOMAIN: The nuclear localization signals mediate the localization to CC the nucleus and are required for CCNB1 localization to the nucleus. CC {ECO:0000269|PubMed:10716937}. CC -!- DOMAIN: The D box motifs 1-5 (amino acid sequence RxxL) are involved in CC substrate binding, such as FZR1/CDH1, and may be ubiquitinated. CC {ECO:0000269|PubMed:27653696}. CC -!- PTM: Degraded when the spindle assembly checkpoint is activated during CC the G2-M transition. Degradation depends on the C-terminal PEST CC sequence. {ECO:0000269|PubMed:12122006}. CC -!- PTM: Phosphorylated just before cells enter into mitosis. CC {ECO:0000269|PubMed:7813445}. CC -!- PTM: Ubiquitinated by the anaphase-promoting complex (APC/C); leading CC to its degradation by the proteasome. {ECO:0000269|PubMed:27653696}. CC -!- DISEASE: Frontotemporal dementia and/or amyotrophic lateral sclerosis 5 CC (FTDALS5) [MIM:619141]: A neurodegenerative disorder characterized by CC frontotemporal dementia and/or amyotrophic lateral sclerosis in CC affected individuals. There is high intrafamilial variation. CC Frontotemporal dementia is characterized by frontal and temporal lobe CC atrophy associated with neuronal loss, gliosis, and dementia. Patients CC exhibit progressive changes in social, behavioral, and/or language CC function. Amyotrophic lateral sclerosis is characterized by the death CC of motor neurons in the brain, brainstem, and spinal cord, resulting in CC fatal paralysis. FTDALS5 is an autosomal dominant form with age- CC dependent penetrance. Penetrance is estimated to be 50% by age 56 and CC 100% by age 61. {ECO:0000269|PubMed:27080313, CC ECO:0000269|PubMed:28852778}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Founding member of the F-box domain protein family, CC which obtained its name from cyclin-F. {ECO:0000305|PubMed:8706131}. CC -!- MISCELLANEOUS: Member of the cyclin family, however, unlike most CC members of the cyclin family, it does not bind or activate a cyclin- CC dependent kinase. {ECO:0000305|PubMed:7813445}. CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin AB subfamily. CC {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; U17105; AAB60342.1; -; mRNA. DR EMBL; Z36714; CAA85308.1; -; mRNA. DR EMBL; AK313371; BAG36170.1; -; mRNA. DR EMBL; AC106820; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC012349; AAH12349.1; -; mRNA. DR CCDS; CCDS10467.1; -. DR PIR; A55501; A55501. DR RefSeq; NP_001752.2; NM_001761.2. DR AlphaFoldDB; P41002; -. DR SMR; P41002; -. DR BioGRID; 107339; 2799. DR ComplexPortal; CPX-7846; SCF E3 ubiquitin ligase complex, CCNF variant. DR CORUM; P41002; -. DR DIP; DIP-44939N; -. DR IntAct; P41002; 6. DR MINT; P41002; -. DR STRING; 9606.ENSP00000380256; -. DR iPTMnet; P41002; -. DR PhosphoSitePlus; P41002; -. DR BioMuta; CCNF; -. DR DMDM; 20178283; -. DR jPOST; P41002; -. DR MassIVE; P41002; -. DR MaxQB; P41002; -. DR PaxDb; 9606-ENSP00000380256; -. DR PeptideAtlas; P41002; -. DR ProteomicsDB; 55398; -. DR Pumba; P41002; -. DR Antibodypedia; 10421; 255 antibodies from 33 providers. DR DNASU; 899; -. DR Ensembl; ENST00000397066.9; ENSP00000380256.4; ENSG00000162063.13. DR GeneID; 899; -. DR KEGG; hsa:899; -. DR MANE-Select; ENST00000397066.9; ENSP00000380256.4; NM_001761.3; NP_001752.2. DR UCSC; uc002cqd.2; human. DR AGR; HGNC:1591; -. DR CTD; 899; -. DR DisGeNET; 899; -. DR GeneCards; CCNF; -. DR HGNC; HGNC:1591; CCNF. DR HPA; ENSG00000162063; Tissue enhanced (lymphoid). DR MalaCards; CCNF; -. DR MIM; 600227; gene. DR MIM; 619141; phenotype. DR neXtProt; NX_P41002; -. DR OpenTargets; ENSG00000162063; -. DR Orphanet; 803; Amyotrophic lateral sclerosis. DR PharmGKB; PA26156; -. DR VEuPathDB; HostDB:ENSG00000162063; -. DR eggNOG; KOG0654; Eukaryota. DR GeneTree; ENSGT00810000125541; -. DR HOGENOM; CLU_020348_0_0_1; -. DR InParanoid; P41002; -. DR OMA; HQAKKSC; -. DR OrthoDB; 3020936at2759; -. DR PhylomeDB; P41002; -. DR TreeFam; TF101006; -. DR PathwayCommons; P41002; -. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; P41002; -. DR SIGNOR; P41002; -. DR BioGRID-ORCS; 899; 72 hits in 1220 CRISPR screens. DR ChiTaRS; CCNF; human. DR GeneWiki; CCNF; -. DR GenomeRNAi; 899; -. DR Pharos; P41002; Tbio. DR PRO; PR:P41002; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; P41002; Protein. DR Bgee; ENSG00000162063; Expressed in primordial germ cell in gonad and 162 other cell types or tissues. DR ExpressionAtlas; P41002; baseline and differential. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0005814; C:centriole; IDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:HPA. DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0010997; F:anaphase-promoting complex binding; IDA:UniProtKB. DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; IBA:GO_Central. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0044772; P:mitotic cell cycle phase transition; IBA:GO_Central. DR GO; GO:0010826; P:negative regulation of centrosome duplication; IDA:UniProtKB. DR GO; GO:0001890; P:placenta development; IEA:Ensembl. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0000320; P:re-entry into mitotic cell cycle; IEA:Ensembl. DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR CDD; cd20521; CYCLIN_CCNF_rpt1; 1. DR CDD; cd22082; F-box_FBXO1; 1. DR Gene3D; 1.10.472.10; Cyclin-like; 2. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1. DR InterPro; IPR039361; Cyclin. DR InterPro; IPR013763; Cyclin-like_dom. DR InterPro; IPR036915; Cyclin-like_sf. DR InterPro; IPR004367; Cyclin_C-dom. DR InterPro; IPR006671; Cyclin_N. DR InterPro; IPR048258; Cyclins_cyclin-box. DR InterPro; IPR036047; F-box-like_dom_sf. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR PANTHER; PTHR10177:SF496; CYCLIN-F; 1. DR PANTHER; PTHR10177; CYCLINS; 1. DR Pfam; PF02984; Cyclin_C; 1. DR Pfam; PF00134; Cyclin_N; 1. DR Pfam; PF12937; F-box-like; 1. DR SMART; SM00385; CYCLIN; 2. DR SMART; SM01332; Cyclin_C; 1. DR SMART; SM00256; FBOX; 1. DR SUPFAM; SSF47954; Cyclin-like; 2. DR SUPFAM; SSF81383; F-box domain; 1. DR PROSITE; PS00292; CYCLINS; 1. DR PROSITE; PS50181; FBOX; 1. DR Genevisible; P41002; HS. PE 1: Evidence at protein level; KW Amyotrophic lateral sclerosis; Cell cycle; Cell division; Cyclin; KW Cytoplasm; Cytoskeleton; Disease variant; Mitosis; Neurodegeneration; KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation; KW Ubl conjugation pathway. FT CHAIN 1..786 FT /note="Cyclin-F" FT /id="PRO_0000080463" FT DOMAIN 29..76 FT /note="F-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080" FT DOMAIN 288..405 FT /note="Cyclin N-terminal" FT /evidence="ECO:0000255" FT REGION 564..593 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 582..766 FT /note="PEST" FT REGION 675..738 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 20..28 FT /note="Nuclear localization signal 1" FT /evidence="ECO:0000269|PubMed:10716937" FT MOTIF 310..313 FT /note="D box 1" FT /evidence="ECO:0000269|PubMed:27653696" FT MOTIF 343..346 FT /note="D box 2" FT /evidence="ECO:0000269|PubMed:27653696" FT MOTIF 349..352 FT /note="D box 3" FT /evidence="ECO:0000269|PubMed:27653696" FT MOTIF 351..354 FT /note="D box 4" FT /evidence="ECO:0000269|PubMed:27653696" FT MOTIF 568..574 FT /note="Nuclear localization signal 2" FT /evidence="ECO:0000269|PubMed:10716937" FT MOTIF 767..770 FT /note="D box 5" FT /evidence="ECO:0000269|PubMed:27653696" FT COMPBIAS 693..736 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VARIANT 3 FT /note="S -> G (in FTDALS5; uncertain significance; impaired FT degradation by the ubiquitin proteasome system (UPS); FT dbSNP:rs944306963)" FT /evidence="ECO:0000269|PubMed:27080313" FT /id="VAR_085177" FT VARIANT 97 FT /note="K -> R (in FTDALS5; uncertain significance; impaired FT degradation by the ubiquitin proteasome system (UPS); FT dbSNP:rs1465313712)" FT /evidence="ECO:0000269|PubMed:27080313" FT /id="VAR_085178" FT VARIANT 181 FT /note="T -> I (in FTDALS5; uncertain significance; FT dbSNP:rs745821656)" FT /evidence="ECO:0000269|PubMed:27080313" FT /id="VAR_085179" FT VARIANT 195 FT /note="S -> R (in FTDALS5; impaired degradation by the FT ubiquitin proteasome system (UPS); dbSNP:rs1371569927)" FT /evidence="ECO:0000269|PubMed:27080313" FT /id="VAR_085180" FT VARIANT 392 FT /note="R -> T (in FTDALS5; uncertain significance; impaired FT degradation by the ubiquitin proteasome system (UPS); FT dbSNP:rs954539468)" FT /evidence="ECO:0000269|PubMed:27080313" FT /id="VAR_085181" FT VARIANT 509 FT /note="S -> P (in FTDALS5; uncertain significance; impaired FT degradation by the ubiquitin proteasome system (UPS); FT dbSNP:rs760953006)" FT /evidence="ECO:0000269|PubMed:27080313" FT /id="VAR_085182" FT VARIANT 543 FT /note="T -> I (in FTDALS5; uncertain significance; FT dbSNP:rs756914411)" FT /evidence="ECO:0000269|PubMed:27080313" FT /id="VAR_085183" FT VARIANT 621 FT /note="S -> G (in FTDALS5; increased 'Lys-48'-linked FT polyubiquitination of proteins targeted for proteasomal FT degradation, but no increase in 'Lys-63'-linked FT polyubiquitinated proteins; accumulation of ubiquitinated FT proteins including RRM2 and TARDBP/TDP43; impaired FT autophagosome-lysosome fusion; impaired degradation by the FT ubiquitin proteasome system (UPS); increased levels of FT ubiquitinated autophagy receptor SQSTM1/p62; FT dbSNP:rs778264897)" FT /evidence="ECO:0000269|PubMed:27080313, FT ECO:0000269|PubMed:28852778" FT /id="VAR_085184" FT VARIANT 624 FT /note="E -> K (in FTDALS5; impaired degradation by the FT ubiquitin proteasome system (UPS); dbSNP:rs771621178)" FT /evidence="ECO:0000269|PubMed:27080313" FT /id="VAR_085185" FT VARIANT 772 FT /note="I -> T (in FTDALS5; uncertain significance; impaired FT degradation by the ubiquitin proteasome system (UPS); FT dbSNP:rs762663630)" FT /evidence="ECO:0000269|PubMed:27080313" FT /id="VAR_085186" FT MUTAGEN 35..36 FT /note="LP->AA: Impairs interaction with SKP1 and CUL1 and FT prevents degradation of CP110, leading to promote the FT formation of micronuclei. Increased interaction with RRM2 FT and lack of RRM2 ubiquitination." FT /evidence="ECO:0000269|PubMed:20596027, FT ECO:0000269|PubMed:22632967" FT MUTAGEN 309..310 FT /note="MR->AA: Reduces the interaction with MYBL2/BMYB. FT Disrupts the interaction with CDC6. Does not disrupt FT interaction with CUL1." FT /evidence="ECO:0000269|PubMed:25557911, FT ECO:0000269|PubMed:26818844" FT MUTAGEN 309 FT /note="M->A: Reduced degradation of RRM2 after UV-induced FT DNA-damage. Abolishes the interaction with CP110 and RRM2; FT when associated with A-352." FT /evidence="ECO:0000269|PubMed:20596027, FT ECO:0000269|PubMed:22632967" FT MUTAGEN 310..313 FT /note="RYIL->AYIA: Reduces the interaction with FZR1/CDH1. FT Reduced ubiquitination. Abolishes the interaction with FT FZR1/CDH1; when associated with 351-R--L-354. Loss of FT ubiquitination and impaired degradation; when associated FT with 351-R--L-354." FT /evidence="ECO:0000269|PubMed:27653696" FT MUTAGEN 343..346 FT /note="RRRL->ARRA: Reduces the interaction with FZR1/CDH1." FT /evidence="ECO:0000269|PubMed:27653696" FT MUTAGEN 349..352 FT /note="RYRL->AYRA: Reduces the interaction with FZR1/CDH1." FT /evidence="ECO:0000269|PubMed:27653696" FT MUTAGEN 351..354 FT /note="RLQL->ALQA: Reduces the interaction with FZR1/CDH1. FT Abolishes the interaction with FZR1/CDH1; when associated FT with 310-R--L-313. Loss of ubiquitination and impaired FT degradation; when associated with 310-R--L-313." FT /evidence="ECO:0000269|PubMed:27653696" FT MUTAGEN 352 FT /note="L->A: Abolishes the interaction with CP110 and RRM2; FT when associated with A-309." FT /evidence="ECO:0000269|PubMed:20596027, FT ECO:0000269|PubMed:22632967" FT MUTAGEN 767..770 FT /note="RINL->AINA: Reduces the interaction with FZR1/CDH1." FT /evidence="ECO:0000269|PubMed:27653696" FT CONFLICT 252 FT /note="A -> R (in Ref. 2; CAA85308)" FT /evidence="ECO:0000305" FT CONFLICT 324 FT /note="K -> N (in Ref. 2; CAA85308)" FT /evidence="ECO:0000305" FT CONFLICT 434 FT /note="L -> H (in Ref. 3; BAG36170)" FT /evidence="ECO:0000305" FT CONFLICT 600 FT /note="L -> V (in Ref. 2; CAA85308)" FT /evidence="ECO:0000305" FT CONFLICT 662 FT /note="D -> A (in Ref. 2; CAA85308)" FT /evidence="ECO:0000305" FT CONFLICT 710 FT /note="P -> S (in Ref. 1; AAB60342)" FT /evidence="ECO:0000305" FT CONFLICT 731 FT /note="D -> H (in Ref. 2; CAA85308)" FT /evidence="ECO:0000305" SQ SEQUENCE 786 AA; 87640 MW; ADB2FE41BC708898 CRC64; MGSGGVVHCR CAKCFCYPTK RRIRRRPRNL TILSLPEDVL FHILKWLSVE DILAVRAVHS QLKDLVDNHA SVWACASFQE LWPSPGNLKL FERAAEKGNF EAAVKLGIAY LYNEGLSVSD EARAEVNGLK ASRFFSLAER LNVGAAPFIW LFIRPPWSVS GSCCKAVVHE SLRAECQLQR THKASILHCL GRVLSLFEDE EKQQQAHDLF EEAAHQGCLT SSYLLWESDR RTDVSDPGRC LHSFRKLRDY AAKGCWEAQL SLAKACANAN QLGLEVRASS EIVCQLFQAS QAVSKQQVFS VQKGLNDTMR YILIDWLVEV ATMKDFTSLC LHLTVECVDR YLRRRLVPRY RLQLLGIACM VICTRFISKE ILTIREAVWL TDNTYKYEDL VRMMGEIVSA LEGKIRVPTV VDYKEVLLTL VPVELRTQHL CSFLCELSLL HTSLSAYAPA RLAAAALLLA RLTHGQTQPW TTQLWDLTGF SYEDLIPCVL SLHKKCFHDD APKDYRQVSL TAVKQRFEDK RYGEISQEEV LSYSQLCAAL GVTQDSPDPP TFLSTGEIHA FLSSPSGRRT KRKRENSLQE DRGSFVTTPT AELSSQEETL LGSFLDWSLD CCSGYEGDQE SEGEKEGDVT APSGILDVTV VYLNPEQHCC QESSDEEACP EDKGPQDPQA LALDTQIPAT PGPKPLVRTS REPGKDVTTS GYSSVSTASP TSSVDGGLGA LPQPTSVLSL DSDSHTQPCH HQARKSCLQC RPPSPPESSV PQQQVKRINL CIHSEEEDMN LGLVRL //