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Q9UKT4 (FBX5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
F-box only protein 5
Alternative name(s):
Early mitotic inhibitor 1
Gene names
Name:FBXO5
Synonyms:EMI1, FBX5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length447 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Cytoplasmcytoskeletonspindle. 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 processCell cycle
Cell division
Mitosis
Ubl conjugation pathway
   Cellular componentCytoplasm
Cytoskeleton
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainZinc-finger
   LigandMetal-binding
Zinc
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Traceable author statement. Source: Reactome

anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process

Traceable author statement. Source: Reactome

inhibition of mitotic anaphase-promoting complex activity

Inferred from direct assay Ref.9. Source: UniProtKB

metaphase/anaphase transition of mitotic cell cycle

Traceable author statement. Source: Reactome

microtubule polymerization

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle

Traceable author statement. Source: Reactome

negative regulation of meiosis

Inferred from electronic annotation. Source: Ensembl

negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle

Inferred from direct assay Ref.2Ref.11. Source: UniProtKB

oocyte maturation

Inferred from electronic annotation. Source: Ensembl

positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle

Traceable author statement. Source: Reactome

regulation of mitotic cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription involved in G1/S transition of mitotic cell cycle

Traceable author statement. Source: Reactome

regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle

Traceable author statement. Source: Reactome

spindle assembly involved in female meiosis I

Inferred from electronic annotation. Source: Ensembl

vesicle organization

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay Ref.2. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.2. Source: UniProtKB

spindle

Inferred from direct assay Ref.8. Source: UniProtKB

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase binding

Inferred from physical interaction Ref.9. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CDC27P302602EBI-852298,EBI-994813
EVI5O604476EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 447447F-box only protein 5
PRO_0000119881

Regions

Domain250 – 29647F-box
Zinc finger357 – 41963IBR-type
Region135 – 244110Interaction with EVI5

Natural variations

Alternative sequence1 – 4646Missing in isoform 2.
VSP_041362
Natural variant1071Q → E. Ref.3 Ref.6
Corresponds to variant rs2073260 [ dbSNP | Ensembl ].
VAR_024440
Natural variant1641L → F.
Corresponds to variant rs7763565 [ dbSNP | Ensembl ].
VAR_049038

Experimental info

Mutagenesis1431E → A: Delays degradation. Ref.8
Mutagenesis1451S → E: Degraded in similar manner to wild-type. Ref.7 Ref.8 Ref.9
Mutagenesis1451S → N: Not mitotically degraded. Shows impaired interaction with BTRC and reduced phosphate incorporation; when associated with N-149. Ref.7 Ref.8 Ref.9
Mutagenesis1481S → A: Degraded in similar manner to wild-type. Ref.8
Mutagenesis1491S → E: Degraded in similar manner to wild-type. Ref.7 Ref.8 Ref.9
Mutagenesis1491S → N: Not mitotically degraded. Shows impaired interaction with BTRC and reduced phosphate incorporation; when associated with N-145. Ref.7 Ref.8 Ref.9
Mutagenesis1821S → A: Shows impaired interaction with BTRC. Ref.7
Mutagenesis210 – 2167KRNPKVD → AAAAAAA: Loss of interaction with EVI5. Ref.10
Mutagenesis4011C → S: Reduced inhibition of APC. Ref.11
Sequence conflict2121N → D in BAG51487. Ref.3

Secondary structure

........... 447
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 196FBC2578F92120

FASTA44750,146
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 8E9E775625E62A4F
Show »

FASTA40145,353

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
RefSeqNP_001135994.1. NM_001142522.1.
NP_036309.1. NM_012177.3.
UniGeneHs.520506.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2M6NNMR-A363-447[»]
ProteinModelPortalQ9UKT4.
SMRQ9UKT4. Positions 374-419.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117655. 32 interactions.
IntActQ9UKT4. 10 interactions.
MINTMINT-4789777.
STRING9606.ENSP00000229758.

PTM databases

PhosphoSiteQ9UKT4.

Polymorphism databases

DMDM24636847.

Proteomic databases

PaxDbQ9UKT4.
PRIDEQ9UKT4.

Protocols and materials databases

DNASU26271.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000229758; ENSP00000229758; ENSG00000112029. [Q9UKT4-1]
ENST00000367241; ENSP00000356210; ENSG00000112029. [Q9UKT4-2]
GeneID26271.
KEGGhsa:26271.
UCSCuc003qpg.3. human. [Q9UKT4-1]

Organism-specific databases

CTD26271.
GeneCardsGC06M153291.
HGNCHGNC:13584. FBXO5.
HPACAB008106.
HPA029048.
MIM606013. gene.
neXtProtNX_Q9UKT4.
PharmGKBPA28045.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG45978.
HOGENOMHOG000035122.
HOVERGENHBG010089.
InParanoidQ9UKT4.
KOK10292.
OMASTTWKKI.
OrthoDBEOG783MXX.
PhylomeDBQ9UKT4.
TreeFamTF101170.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.

Gene expression databases

BgeeQ9UKT4.
CleanExHS_FBXO5.
GenevestigatorQ9UKT4.

Family and domain databases

InterProIPR001810. F-box_dom.
[Graphical view]
PfamPF00646. F-box. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFBXO5.
GenomeRNAi26271.
NextBio48561.
PROQ9UKT4.
SOURCESearch...

Entry information

Entry nameFBX5_HUMAN
AccessionPrimary (citable) accession number: Q9UKT4
Secondary accession number(s): B3KNX5 expand/collapse secondary AC list , Q5TF47, Q8WV29, Q9UGC8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM