Skip Header

Contribute Send feedback
Read comments (?) or add your own

Q9UKT5 (FBX4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | 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
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 4
Gene names
Name:FBXO4
Synonyms:FBX4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length387 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes ubiquitination of CCND1 and its subsequent proteasomal degradation. Recognizes TERF1 and promotes its ubiquitination together with UBE2D1. Ref.1 Ref.5 Ref.6 Ref.8 Ref.9

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Homodimer. Directly interacts with SKP1 and CUL1. Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO4) formed of CUL1, SKP1, RBX1 and FBXO4. Interacts with TERF1. This interaction is prevented in the presence of GNL3L. Identified in a complex with CRYAB and CCND1. Ref.1 Ref.5 Ref.6 Ref.8 Ref.9

Subcellular location

Cytoplasm By similarity.

Post-translational modification

Phosphorylation at Ser-12 varies during the cell cycle. It is low in resting cells and high in the S phase and the G2/M phase of the cell cycle. Phosphorylation is decreased during late G1 phase By similarity. Phosphorylation at Ser-12 promotes homodimerization and is necessary for optimal ubiquitin ligase activity towards CCND1.

Sequence similarities

Contains 1 F-box domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TERF1P542742EBI-960421,EBI-710997
TERF1P54274-23EBI-960421,EBI-711018
YWHAEP622585EBI-960409,EBI-356498
YwhaeP622602EBI-960409,EBI-356462From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UKT5-1)

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: Q9UKT5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     300-307: RHEWQDEF → SKYSYVHF
     308-387: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 387387F-box only protein 4
PRO_0000119879

Regions

Domain56 – 10247F-box

Amino acid modifications

Modified residue121Phosphoserine Ref.6 Ref.7

Natural variations

Alternative sequence300 – 3078RHEWQDEF → SKYSYVHF in isoform 2.
VSP_012977
Alternative sequence308 – 38780Missing in isoform 2.
VSP_012978
Natural variant81S → R in esophagus cancer samples. Ref.6
VAR_063500
Natural variant121S → L in esophagus cancer sample; impairs homodimerization and reduces ubiquitin ligase activity. Ref.6
VAR_063501
Natural variant131P → S in esophagus cancer sample. Ref.6
VAR_063502
Natural variant231L → Q in esophagus cancer samples. Ref.6
VAR_063503
Natural variant761P → T in esophagus cancer samples; impairs interaction with SKP1. Ref.6
VAR_063504

Experimental info

Mutagenesis121S → A: Reduces homodimerization. Reduces ubiquitination of CCND1.
Mutagenesis121S → E: No effect on homodimerization.
Mutagenesis131P → A: Reduces homodimerization.
Mutagenesis231L → A: Abolishes homodimerization.
Mutagenesis3411C → W: Abolishes interaction with TERF1. Ref.8
Mutagenesis3451A → R: Abolishes interaction with TERF1. Ref.8
Sequence conflict411E → D in AAF04468. Ref.1
Sequence conflict951D → N in AAF04468. Ref.1
Sequence conflict120 – 1223DLE → YLQ in AAF04468. Ref.1
Sequence conflict1321T → S in AAF04468. Ref.1
Sequence conflict1441R → L in AAF04468. Ref.1
Sequence conflict1741Q → P in AAF04468. Ref.1
Sequence conflict1811M → L in AAF04468. Ref.1
Sequence conflict1851G → R in AAF04468. Ref.1
Sequence conflict1881E → Q in AAF04468. Ref.1
Sequence conflict1981M → L in AAF04468. Ref.1
Sequence conflict268 – 2692QQ → RP in AAF04468. Ref.1
Sequence conflict2821V → L in AAF04468. Ref.1

Secondary structure

1 ........................................................... 387
Helix Strand Turn

Details...

Sequences

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

Last modified March 1, 2005. Version 2.
Checksum: BD5E8DD14B9733E9

FASTA38744,136
        10         20         30         40         50         60 
MAGSEPRSGT NSPPPPFSDW GRLEAAILSG WKTFWQSVSK ERVARTTSRE EVDEAASTLT 

        70         80         90        100        110        120 
RLPIDVQLYI LSFLSPHDLC QLGSTNHYWN ETVRDPILWR YFLLRDLPSW SSVDWKSLPD 

       130        140        150        160        170        180 
LEILKKPISE VTDGAFFDYM AVYRMCCPYT RRASKSSRPM YGAVTSFLHS LIIQNEPRFA 

       190        200        210        220        230        240 
MFGPGLEELN TSLVLSLMSS EELCPTAGLP QRQIDGIGSG VNFQLNNQHK FNILILYSTT 

       250        260        270        280        290        300 
RKERDRAREE HTSAVNKMFS RHNEGDDQQG SRYSVIPQIQ KVCEVVDGFI YVANAEAHKR 

       310        320        330        340        350        360 
HEWQDEFSHI MAMTDPAFGS SGRPLLVLSC ISQGDVKRMP CFYLAHELHL NLLNHPWLVQ 

       370        380 
DTEAETLTGF LNGIEWILEE VESKRAR

« Hide

Isoform 2 [UniParc].

Checksum: 62C85CD92410CC33
Show »

FASTA30735,003

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), FUNCTION, INTERACTION WITH SKP1 AND CUL1.
[2]"A family of mammalian F-box proteins."
Winston J.T., Koepp D.M., Zhu C., Elledge S.J., Harper J.W.
Curr. Biol. 9:1180-1182(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"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).
Tissue: Testis.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-387.
Tissue: Fetal brain.
[5]"The F-box protein FBX4 targets PIN2/TRF1 for ubiquitin-mediated degradation and regulates telomere maintenance."
Lee T.H., Perrem K., Harper J.W., Lu K.P., Zhou X.Z.
J. Biol. Chem. 281:759-768(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TERF1, FUNCTION IN UBIQUITINATION OF TERF1.
[6]"Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer."
Barbash O., Zamfirova P., Lin D.I., Chen X., Yang K., Nakagawa H., Lu F., Rustgi A.K., Diehl J.A.
Cancer Cell 14:68-78(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, INTERACTION WITH SKP1, PHOSPHORYLATION AT SER-12, VARIANTS ARG-8; LEU-12; SER-13; GLN-23 AND THR-76, CHARACTERIZATION OF VARIANTS LEU-12; SER-13 AND GLN-23.
[7]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, MASS SPECTROMETRY.
Tissue: Leukemic T-cell.
[8]"Structural basis of selective ubiquitination of TRF1 by SCFFbx4."
Zeng Z., Wang W., Yang Y., Chen Y., Yang X., Diehl J.A., Liu X., Lei M.
Dev. Cell 18:214-225(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 162-387 IN COMPLEX WITH TERF1, FUNCTION, MUTAGENESIS OF CYS-341 AND ALA-345, SUBUNIT.
[9]"Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase."
Li Y., Hao B.
J. Biol. Chem. 285:13896-13906(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 55-387 IN COMPLEX WITH SKP1, FUNCTION, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF176703 mRNA. Translation: AAF03703.1.
BC048098 mRNA. Translation: AAH48098.1.
CR749719 mRNA. Translation: CAH18486.1.
AF129534 mRNA. Translation: AAF04468.1.
IPIIPI00073357.
IPI00245689.
RefSeqNP_036308.1. NM_012176.2.
NP_277019.1. NM_033484.2.
UniGeneHs.165575.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3L2OX-ray2.80B55-387[»]
3L82X-ray2.40B162-387[»]
ProteinModelPortalQ9UKT5.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9UKT5. 7 interactions.
MINTMINT-108507.
STRING9606.ENSP00000281623.

PTM databases

PhosphoSiteQ9UKT5.

Polymorphism databases

DMDM60416426.

Proteomic databases

PaxDbQ9UKT5.
PRIDEQ9UKT5.

Protocols and materials databases

DNASU26272.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000281623; ENSP00000281623; ENSG00000151876.
ENST00000296812; ENSP00000296812; ENSG00000151876.
GeneID26272.
KEGGhsa:26272.
UCSCuc003jmp.3. human.
uc003jmq.3. human.

Organism-specific databases

CTD26272.
GeneCardsGC05P041925.
HGNCHGNC:13583. FBXO4.
MIM609090. gene.
neXtProtNX_Q9UKT5.
PharmGKBPA28044.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39270.
HOGENOMHOG000112550.
HOVERGENHBG051585.
InParanoidQ9UKT5.
KOK10291.
OMAHEWQDEF.
OrthoDBEOG4VQ9PC.
PhylomeDBQ9UKT5.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
REACT_6900. Immune System.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9UKT5.
BgeeQ9UKT5.
CleanExHS_FBXO4.
GenevestigatorQ9UKT5.
GermOnlineENSG00000151876. Homo sapiens.

Family and domain databases

InterProIPR001810. F-box_dom_cyclin-like.
[Graphical view]
PfamPF00646. F-box. 1 hit.
[Graphical view]
SMARTSM00256. FBOX. 1 hit.
[Graphical view]
SUPFAMSSF81383. F-box_dom_Skp2-like. 1 hit.
PROSITEPS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9UKT5.
GenomeRNAi26272.
NextBio48565.
SOURCESearch...

Entry information

Entry nameFBX4_HUMAN
AccessionPrimary (citable) accession number: Q9UKT5
Secondary accession number(s): Q68CU8, Q86VT8, Q9UK98
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: March 1, 2005
Last modified: May 1, 2013
This is version 103 of the entry and version 2 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

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents