P41002 (CCNF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-F

Alternative name(s):
F-box only protein 1

Gene names

Name:	CCNF
Synonyms:	FBX1, FBXO1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	786 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of CP110 during G2 phase, thereby acting as an inhibitor of centrosome reduplication. Ref.9
Subunit structure	Component of the SCF(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF. Interacts with CCNB1; interaction is required for nuclear localization of CCNB1. Ref.6 Ref.7 Ref.8 Ref.9
Subcellular location	Nucleus. Cytoplasm › cytoskeleton › centrosome › centriole. Note: Localization in the centrosome is rare in S phase cells and increases in G2 cells, Localizes on both the mother and daughter centrioles. Localization to centrosomes is not dependent on CP110. Also localizes to the nucleus. Ref.1 Ref.7 Ref.9
Tissue specificity	Widely expressed. Ref.1
Developmental stage	Appears in S phase, peaks in G2 phase and disappears as cells enter into mitosis (at protein level). Ref.1
Domain	The nuclear localization signals mediate the localization to the nucleus and are required for CCNB1 localization to the nucleus. Ref.7
Post-translational modification	Degraded when the spindle assembly checkpoint is activated during the G2-M transition. Degradation is not dependent on the proteasome or ubiquitin and depends on the C-terminal PEST sequence. Phosphorylated just before cels enter into mitosis. Ref.1
Miscellaneous	Founding member of the F-box domain protein family, which obtained its name from cyclin-F (Ref.6).
Sequence similarities	Belongs to the cyclin family. Cyclin AB subfamily. Contains 1 cyclin N-terminal domain. Contains 1 F-box domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis Ubl conjugation pathway
Cellular component	Cytoplasm Cytoskeleton Nucleus
Molecular function	Cyclin
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.9. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW mitosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of centrosome duplication Inferred from direct assay Ref.9. Source: UniProtKB protein ubiquitination Inferred from direct assay Ref.9. Source: UniProtKB
Cellular component	SCF ubiquitin ligase complex Inferred from direct assay Ref.9. Source: UniProtKB centriole Inferred from direct assay Ref.9. Source: UniProtKB nucleus Inferred from direct assay Ref.9. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 786	786	Cyclin-F		PRO_0000080463
Regions
	Domain	29 – 76	48	F-box
	Domain	292 – 405	114	Cyclin N-terminal
	Region	582 – 766	185	PEST
	Motif	20 – 28	9	Nuclear localization signal 1 Ref.7
	Motif	568 – 574	7	Nuclear localization signal 2 Ref.7
Experimental info
	Mutagenesis	35 – 36	2	LP → AA: Impairs interaction with SKP1 and CUL1 and prevents degradation of CP110, leading to promote the formation of micronuclei.
	Mutagenesis	309	1	M → A: Abolishes ability to interact with CP110; when associated with A-352. Ref.9
	Mutagenesis	352	1	L → A: Abolishes ability to interact with CP110; when associated with A-309. Ref.9
	Sequence conflict	252	1	A → R in CAA85308. Ref.2
	Sequence conflict	324	1	K → N in CAA85308. Ref.2
	Sequence conflict	434	1	L → H in BAG36170. Ref.3
	Sequence conflict	600	1	L → V in CAA85308. Ref.2
	Sequence conflict	662	1	D → A in CAA85308. Ref.2
	Sequence conflict	710	1	P → S in AAB60342. Ref.1
	Sequence conflict	731	1	D → H in CAA85308. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P41002 [UniParc]. Last modified April 16, 2002. Version 2. Checksum: ADB2FE41BC708898	FASTA	786	87,640
	10 20 30 40 50 60 MGSGGVVHCR CAKCFCYPTK RRIRRRPRNL TILSLPEDVL FHILKWLSVE DILAVRAVHS 70 80 90 100 110 120 QLKDLVDNHA SVWACASFQE LWPSPGNLKL FERAAEKGNF EAAVKLGIAY LYNEGLSVSD 130 140 150 160 170 180 EARAEVNGLK ASRFFSLAER LNVGAAPFIW LFIRPPWSVS GSCCKAVVHE SLRAECQLQR 190 200 210 220 230 240 THKASILHCL GRVLSLFEDE EKQQQAHDLF EEAAHQGCLT SSYLLWESDR RTDVSDPGRC 250 260 270 280 290 300 LHSFRKLRDY AAKGCWEAQL SLAKACANAN QLGLEVRASS EIVCQLFQAS QAVSKQQVFS 310 320 330 340 350 360 VQKGLNDTMR YILIDWLVEV ATMKDFTSLC LHLTVECVDR YLRRRLVPRY RLQLLGIACM 370 380 390 400 410 420 VICTRFISKE ILTIREAVWL TDNTYKYEDL VRMMGEIVSA LEGKIRVPTV VDYKEVLLTL 430 440 450 460 470 480 VPVELRTQHL CSFLCELSLL HTSLSAYAPA RLAAAALLLA RLTHGQTQPW TTQLWDLTGF 490 500 510 520 530 540 SYEDLIPCVL SLHKKCFHDD APKDYRQVSL TAVKQRFEDK RYGEISQEEV LSYSQLCAAL 550 560 570 580 590 600 GVTQDSPDPP TFLSTGEIHA FLSSPSGRRT KRKRENSLQE DRGSFVTTPT AELSSQEETL 610 620 630 640 650 660 LGSFLDWSLD CCSGYEGDQE SEGEKEGDVT APSGILDVTV VYLNPEQHCC QESSDEEACP 670 680 690 700 710 720 EDKGPQDPQA LALDTQIPAT PGPKPLVRTS REPGKDVTTS GYSSVSTASP TSSVDGGLGA 730 740 750 760 770 780 LPQPTSVLSL DSDSHTQPCH HQARKSCLQC RPPSPPESSV PQQQVKRINL CIHSEEEDMN LGLVRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human cyclin F." Bai C., Richman R., Elledge S.J. EMBO J. 13:6087-6098(1994) [PubMed: 7813445] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, PHOSPHORYLATION.
[2]	"A novel cyclin gene (CCNF) in the region of the polycystic kidney disease gene (PKD1)." Kraus B., Pohlschmidt M., Leung A.L.S., Germino G.G., Snarey A., Schneider M.C., Reeders S.T., Frischauf A.-M. Genomics 24:27-33(1994) [PubMed: 7896286] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thymus.
[4]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[6]	"SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box." Bai C., Sen P., Hofmann K., Ma L., Goebl M., Harper J.W., Elledge S.J. Cell 86:263-274(1996) [PubMed: 8706131] [Abstract] Cited for: INTERACTION WITH SKP1.
[7]	"Cyclin F regulates the nuclear localization of cyclin B1 through a cyclin-cyclin interaction." Kong M., Barnes E.A., Ollendorff V., Donoghue D.J. EMBO J. 19:1378-1388(2000) [PubMed: 10716937] [Abstract] Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, DOMAIN, INTERACTION WITH CCNB1.
[8]	"Cyclin F is degraded during G2-M by mechanisms fundamentally different from other cyclins." Fung T.K., Siu W.Y., Yam C.H., Lau A., Poon R.Y. J. Biol. Chem. 277:35140-35149(2002) [PubMed: 12122006] [Abstract] Cited for: INTERACTION WITH SKP1, DEGRADATION.
[9]	"SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation." D'Angiolella V., Donato V., Vijayakumar S., Saraf A., Florens L., Washburn M.P., Dynlacht B., Pagano M. Nature 466:138-142(2010) [PubMed: 20596027] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE SCF(CYCLIN F) COMPLEX WITH SKP1 AND CUL1, INTERACTION WITH CP110, MUTAGENESIS OF 35-LEU-PRO-36; MET-309 AND LEU-352.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U17105 mRNA. Translation: AAB60342.1. Z36714 mRNA. Translation: CAA85308.1. AK313371 mRNA. Translation: BAG36170.1. AC106820 Genomic DNA. No translation available. BC012349 mRNA. Translation: AAH12349.1.
IPI	IPI00297860.
PIR	A55501.
RefSeq	NP_001752.2. NM_001761.2.
UniGene	Hs.1973.
3D structure databases
ProteinModelPortal	P41002.
SMR	P41002. Positions 276-531.
ModBase	Search...
Protein-protein interaction databases
IntAct	P41002. 2 interactions.
STRING	P41002.
PTM databases
PhosphoSite	P41002.
Polymorphism databases
DMDM	20178283.
Proteomic databases
PRIDE	P41002.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000397066; ENSP00000380256; ENSG00000162063.
GeneID	899.
KEGG	hsa:899.
UCSC	uc002cqd.1. human.
Organism-specific databases
CTD	899.
GeneCards	GC16P002479.
H-InvDB	HIX0202302.
HGNC	HGNC:1591. CCNF.
MIM	600227. gene.
neXtProt	NX_P41002.
PharmGKB	PA26156.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05986.
GeneTree	ENSGT00560000076692.
HOGENOM	HBG402815.
HOVERGEN	HBG050838.
InParanoid	P41002.
OMA	QTQPWTT.
OrthoDB	EOG4QJRMR.
PhylomeDB	P41002.
Gene expression databases
ArrayExpress	P41002.
Bgee	P41002.
CleanEx	HS_CCNF.
Genevestigator	P41002.
GermOnline	ENSG00000162063. Homo sapiens.
Family and domain databases
InterPro	IPR013763. Cyclin-like. IPR004367. Cyclin_C. IPR006671. Cyclin_N. IPR001810. F-box_dom_cyclin-like. IPR022364. F-box_dom_Skp2-like. IPR011990. TPR-like_helical. [Graphical view]
Gene3D	G3DSA:1.10.472.10. Cyclin_related. 2 hits. G3DSA:1.25.40.10. TPR-like_helical. 2 hits.
KO	K10289.
Pfam	PF02984. Cyclin_C. 1 hit. PF00134. Cyclin_N. 1 hit. PF00646. F-box. 1 hit. [Graphical view]
SMART	SM00385. CYCLIN. 2 hits. SM00256. FBOX. 1 hit. [Graphical view]
SUPFAM	SSF47954. Cyclin_like. 2 hits. SSF81383. F-box_dom_Skp2-like. 1 hit.
PROSITE	PS00292. CYCLINS. 1 hit. PS50181. FBOX. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	3714.
SOURCE	Search...

Entry information

Entry name

CCNF_HUMAN

Accession

Primary (citable) accession number: P41002
Secondary accession number(s): B2R8H3, Q96EG9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	April 16, 2002
Last modified:	January 25, 2012
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.