CCNF_HUMAN
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 03-AUG-2022, entry version 192.
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}.
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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; 650.
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; P41002; -.
DR PeptideAtlas; P41002; -.
DR PRIDE; P41002; -.
DR ProteomicsDB; 55398; -.
DR Antibodypedia; 10421; 229 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 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; CHHQAKK; -.
DR OrthoDB; 607108at2759; -.
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; 68 hits in 1141 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 trabecular bone tissue and 162 other tissues.
DR ExpressionAtlas; P41002; baseline and differential.
DR Genevisible; P41002; HS.
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:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR CDD; cd00043; CYCLIN; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR039361; Cyclin.
DR InterPro; IPR013763; Cyclin-like.
DR InterPro; IPR036915; Cyclin-like_sf.
DR InterPro; IPR004367; Cyclin_C-dom.
DR InterPro; IPR006671; Cyclin_N.
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; PTHR10177; 1.
DR Pfam; PF02984; Cyclin_C; 1.
DR Pfam; PF00134; Cyclin_N; 1.
DR Pfam; PF00646; F-box; 1.
DR SMART; SM00385; CYCLIN; 2.
DR SMART; SM01332; Cyclin_C; 1.
DR SMART; SM00256; FBOX; 1.
DR SUPFAM; SSF47954; SSF47954; 2.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS00292; CYCLINS; 1.
DR PROSITE; PS50181; FBOX; 1.
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; unknown pathological
FT significance; impaired degradation by the ubiquitin
FT proteasome system (UPS); dbSNP:rs944306963)"
FT /evidence="ECO:0000269|PubMed:27080313"
FT /id="VAR_085177"
FT VARIANT 97
FT /note="K -> R (in FTDALS5; unknown pathological
FT significance; impaired degradation by the ubiquitin
FT proteasome system (UPS); dbSNP:rs1465313712)"
FT /evidence="ECO:0000269|PubMed:27080313"
FT /id="VAR_085178"
FT VARIANT 181
FT /note="T -> I (in FTDALS5; unknown pathological
FT significance; 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; unknown pathological
FT significance; impaired degradation by the ubiquitin
FT proteasome system (UPS); dbSNP:rs954539468)"
FT /evidence="ECO:0000269|PubMed:27080313"
FT /id="VAR_085181"
FT VARIANT 509
FT /note="S -> P (in FTDALS5; unknown pathological
FT significance; impaired degradation by the ubiquitin
FT proteasome system (UPS); dbSNP:rs760953006)"
FT /evidence="ECO:0000269|PubMed:27080313"
FT /id="VAR_085182"
FT VARIANT 543
FT /note="T -> I (in FTDALS5; unknown pathological
FT significance; 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; unknown pathological
FT significance; impaired degradation by the ubiquitin
FT proteasome system (UPS); 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
