Q9UKT4 (FBX5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
F-box only protein 5

Alternative name(s):
Early mitotic inhibitor 1

Gene names

Name:	FBXO5
Synonyms:	EMI1, FBX5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	447 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulates progression through early mitosis by inhibiting the anaphase promoting complex/cyclosome (APC). Binds to the APC activators CDC20 and FZR1/CDH1 to prevent APC activation. Can also bind directly to the APC to inhibit substrate-binding. Ref.2 Ref.11
Subunit structure	Part of a SCF (SKP1-cullin-F-box) protein ligase complex By similarity. Interacts with BTRC, FZR1/CDH1 and the N-terminal substrate-binding domain of CDC20. Also interacts with EVI5 which blocks its phosphorylation by PLK1 and prevents its subsequent binding to BTRC and degradation. Ref.2 Ref.7 Ref.10
Subcellular location	Nucleus. Cytoplasm. Cytoplasm › cytoskeleton › spindle. Note: In interphase, localizes in a punctate manner in the nucleus and cytoplasm with some perinuclear concentration. In mitotic cells, localizes throughout the cell, particularly at the spindle. Ref.2 Ref.8
Developmental stage	Accumulates in late G1 phase, levels rise during S phase and drop in early mitosis. Ref.2
Domain	The C-terminal region is required for inhibition of APC activity.
Post-translational modification	Phosphorylation by CDK2 and subsequently by PLK1 triggers degradation during early mitosis through ubiquitin-mediated proteolysis by the SCF ubiquitin ligase complex containing the F-box protein BTRC. This degradation is necessary for the activation of APC in late mitosis and subsequent mitotic progression. Ubiquitinated by the by the SCF(BTRC) complex following phosphorylation by PLK1. Ref.7 Ref.8 Ref.9
Sequence similarities	Contains 1 F-box domain. Contains 1 IBR-type zinc finger.

Ontologies

Keywords
Biological process	Cell cycle Cell division Mitosis Ubl conjugation pathway
Cellular component	Cytoplasm Cytoskeleton Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Traceable author statement. Source: Reactome cell division Inferred from electronic annotation. Source: UniProtKB-KW inhibition of mitotic anaphase-promoting complex activity Inferred from direct assay Ref.9. Source: UniProtKB microtubule polymerization Inferred from electronic annotation. Source: Compara mitotic metaphase Inferred from electronic annotation. Source: Compara mitotic metaphase/anaphase transition Traceable author statement. Source: Reactome oocyte maturation Inferred from electronic annotation. Source: Compara positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome regulation of meiosis Inferred from electronic annotation. Source: Compara regulation of transcription involved in G1/S phase of mitotic cell cycle Traceable author statement. Source: Reactome spindle assembly involved in female meiosis I Inferred from electronic annotation. Source: Compara vesicle organization Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome spindle Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC27	P30260	2	EBI-852298,EBI-994813
EVI5	O60447	6	EBI-852298,EBI-852291

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UKT4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9UKT4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 447	447	F-box only protein 5		PRO_0000119881
Regions
	Domain	250 – 296	47	F-box
	Zinc finger	357 – 419	63	IBR-type
	Region	135 – 244	110	Interaction with EVI5
Natural variations
	Alternative sequence	1 – 46	46	Missing in isoform 2.		VSP_041362
	Natural variant	107	1	Q → E. Ref.3 Ref.6 Corresponds to variant rs2073260 [ dbSNP | Ensembl ].		VAR_024440
	Natural variant	164	1	L → F. Corresponds to variant rs7763565 [ dbSNP | Ensembl ].		VAR_049038
Experimental info
	Mutagenesis	143	1	E → A: Delays degradation. Ref.8
	Mutagenesis	145	1	S → E: Degraded in similar manner to wild-type. Ref.7 Ref.8 Ref.9
	Mutagenesis	145	1	S → N: Not mitotically degraded. Shows impaired interaction with BTRC and reduced phosphate incorporation; when associated with N-149. Ref.7 Ref.8 Ref.9
	Mutagenesis	148	1	S → A: Degraded in similar manner to wild-type. Ref.8
	Mutagenesis	149	1	S → E: Degraded in similar manner to wild-type. Ref.7 Ref.8 Ref.9
	Mutagenesis	149	1	S → N: Not mitotically degraded. Shows impaired interaction with BTRC and reduced phosphate incorporation; when associated with N-145. Ref.7 Ref.8 Ref.9
	Mutagenesis	182	1	S → A: Shows impaired interaction with BTRC. Ref.7
	Mutagenesis	210 – 216	7	KRNPKVD → AAAAAAA: Loss of interaction with EVI5. Ref.10
	Mutagenesis	401	1	C → S: Reduced inhibition of APC. Ref.11
	Sequence conflict	212	1	N → D in BAG51487. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 196FBC2578F92120	FASTA	447	50,146
	10 20 30 40 50 60 MSRRPCSCAL RPPRCSCSAS PSAVTAAGRP RPSDSCKEES STLSVKMKCD FNCNHVHSGL 70 80 90 100 110 120 KLVKPDDIGR LVSYTPAYLE GSCKDCIKDY ERLSCIGSPI VSPRIVQLET ESKRLHNKEN 130 140 150 160 170 180 QHVQQTLNST NEIEALETSR LYEDSGYSSF SLQSGLSEHE EGSLLEENFG DSLQSCLLQI 190 200 210 220 230 240 QSPDQYPNKN LLPVLHFEKV VCSTLKKNAK RNPKVDREML KEIIARGNFR LQNIIGRKMG 250 260 270 280 290 300 LECVDILSEL FRRGLRHVLA TILAQLSDMD LINVSKVSTT WKKILEDDKG AFQLYSKAIQ 310 320 330 340 350 360 RVTENNNKFS PHASTREYVM FRTPLASVQK SAAQTSLKKD AQTKLSNQGD QKGSTYSRHN 370 380 390 400 410 420 EFSEVAKTLK KNESLKACIR CNSPAKYDCY LQRATCKREG CGFDYCTKCL CNYHTTKDCS 430 440 DGKLLKASCK IGPLPGTKKS KKNLRRL
	Isoform 2 [UniParc]. Checksum: 8E9E775625E62A4F	FASTA	401	45,353
	10 20 30 40 50 60 MKCDFNCNHV HSGLKLVKPD DIGRLVSYTP AYLEGSCKDC IKDYERLSCI GSPIVSPRIV 70 80 90 100 110 120 QLETESKRLH NKENQHVQQT LNSTNEIEAL ETSRLYEDSG YSSFSLQSGL SEHEEGSLLE 130 140 150 160 170 180 ENFGDSLQSC LLQIQSPDQY PNKNLLPVLH FEKVVCSTLK KNAKRNPKVD REMLKEIIAR 190 200 210 220 230 240 GNFRLQNIIG RKMGLECVDI LSELFRRGLR HVLATILAQL SDMDLINVSK VSTTWKKILE 250 260 270 280 290 300 DDKGAFQLYS KAIQRVTENN NKFSPHASTR EYVMFRTPLA SVQKSAAQTS LKKDAQTKLS 310 320 330 340 350 360 NQGDQKGSTY SRHNEFSEVA KTLKKNESLK ACIRCNSPAK YDCYLQRATC KREGCGFDYC 370 380 390 400 TKCLCNYHTT KDCSDGKLLK ASCKIGPLPG TKKSKKNLRR L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a family of human F-box proteins." Cenciarelli C., Chiaur D.S., Guardavaccaro D., Parks W., Vidal M., Pagano M. Curr. Biol. 9:1177-1179(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1)." Hsu J.Y., Reimann J.D.R., Sorensen C.S., Lukas J., Jackson P.K. Nat. Cell Biol. 4:358-366(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH FZR1, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLU-107.
[4]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLU-107. Tissue: Placenta.
[7]	"Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase." Margottin-Goguet F., Hsu J.Y., Loktev A., Hsieh H.-M., Reimann J.D.R., Jackson P.K. Dev. Cell 4:813-826(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BTRC; PHOSPHORYLATION, DEGRADATION, MUTAGENESIS OF SER-145; SER-149 AND SER-182.
[8]	"Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC inhibitor Emi1." Hansen D.V., Loktev A.V., Ban K.H., Jackson P.K. Mol. Biol. Cell 15:5623-5634(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION, UBIQUITINATION, MUTAGENESIS OF GLU-143; SER-145; SER-148 AND SER-149.
[9]	"Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome." Moshe Y., Boulaire J., Pagano M., Hershko A. Proc. Natl. Acad. Sci. U.S.A. 101:7937-7942(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, UBIQUITINATION, MUTAGENESIS OF SER-145 AND SER-149.
[10]	"The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1." Eldridge A.G., Loktev A.V., Hansen D.V., Verschuren E.W., Reimann J.D.R., Jackson P.K. Cell 124:367-380(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EVI5, MUTAGENESIS OF 210-LYS--ASP-216.
[11]	"Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor." Miller J.J., Summers M.K., Hansen D.V., Nachury M.V., Lehman N.L., Loktev A., Jackson P.K. Genes Dev. 20:2410-2420(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-401.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF129535 mRNA. Translation: AAF04469.1. AY079515 mRNA. Translation: AAL86610.1. AK055221 mRNA. Translation: BAG51487.1. AL080276 Genomic DNA. Translation: CAI18894.1. AL080276 Genomic DNA. Translation: CAI18895.1. CH471051 Genomic DNA. Translation: EAW47719.1. BC018905 mRNA. Translation: AAH18905.1.
IPI	IPI00016633. IPI00645436.
RefSeq	NP_001135994.1. NM_001142522.1. NP_036309.1. NM_012177.3.
UniGene	Hs.520506.
3D structure databases
ProteinModelPortal	Q9UKT4.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UKT4. 9 interactions.
MINT	MINT-4789777.
STRING	9606.ENSP00000229758.
PTM databases
PhosphoSite	Q9UKT4.
Polymorphism databases
DMDM	24636847.
Proteomic databases
PaxDb	Q9UKT4.
PRIDE	Q9UKT4.
Protocols and materials databases
DNASU	26271.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000229758; ENSP00000229758; ENSG00000112029. ENST00000367241; ENSP00000356210; ENSG00000112029.
GeneID	26271.
KEGG	hsa:26271.
UCSC	uc003qpg.3. human.
Organism-specific databases
CTD	26271.
GeneCards	GC06M153291.
HGNC	HGNC:13584. FBXO5.
HPA	CAB008106. HPA029048.
MIM	606013. gene.
neXtProt	NX_Q9UKT4.
PharmGKB	PA28045.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG45978.
HOGENOM	HOG000035122.
HOVERGEN	HBG010089.
InParanoid	Q9UKT4.
KO	K10292.
OMA	NESLKAC.
OrthoDB	EOG4H463S.
PhylomeDB	Q9UKT4.
Enzyme and pathway databases
Reactome	REACT_115566. Cell Cycle. REACT_21300. Mitotic M-M/G1 phases.
Gene expression databases
ArrayExpress	Q9UKT4.
Bgee	Q9UKT4.
CleanEx	HS_FBXO5.
Genevestigator	Q9UKT4.
GermOnline	ENSG00000112029. Homo sapiens.
Family and domain databases
InterPro	IPR001810. F-box_dom_cyclin-like. [Graphical view]
Pfam	PF00646. F-box. 1 hit. [Graphical view]
PROSITE	PS50181. FBOX. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	26271.
NextBio	48561.
SOURCE	Search...

Entry information

Entry name

FBX5_HUMAN

Accession

Primary (citable) accession number: Q9UKT4
Secondary accession number(s): B3KNX5 , Q5TF47, Q8WV29, Q9UGC8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 2002
Last sequence update:	May 1, 2000
Last modified:	April 3, 2013
This is version 104 of the entry and version 1 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.