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Q9UKT5

- FBX4_HUMAN

UniProt

Q9UKT5 - FBX4_HUMAN

Protein

F-box only protein 4

Gene

FBXO4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 2 (01 Mar 2005)
      Previous versions | rss
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    Functioni

    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 UBE2D1.5 Publications

    Pathwayi

    GO - Molecular functioni

    1. protein binding Source: UniProtKB
    2. protein homodimerization activity Source: UniProtKB
    3. ubiquitin-protein transferase activity Source: UniProtKB

    GO - Biological processi

    1. positive regulation of protein ubiquitination Source: UniProtKB
    2. protein polyubiquitination Source: UniProtKB
    3. protein ubiquitination Source: UniProtKB
    4. SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
    5. telomere maintenance Source: UniProtKB
    6. ubiquitin-dependent protein catabolic process Source: UniProtKB

    Keywords - Biological processi

    Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiREACT_16907. Association of TriC/CCT with target proteins during biosynthesis.
    REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    F-box only protein 4
    Gene namesi
    Name:FBXO4
    Synonyms:FBX4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:13583. FBXO4.

    Subcellular locationi

    Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. SCF ubiquitin ligase complex Source: UniProtKB
    3. ubiquitin ligase complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi12 – 121S → A: Reduces homodimerization. Reduces ubiquitination of CCND1.
    Mutagenesisi12 – 121S → E: No effect on homodimerization.
    Mutagenesisi13 – 131P → A: Reduces homodimerization.
    Mutagenesisi23 – 231L → A: Abolishes homodimerization.
    Mutagenesisi341 – 3411C → W: Abolishes interaction with TERF1. 1 Publication
    Mutagenesisi345 – 3451A → R: Abolishes interaction with TERF1. 1 Publication

    Organism-specific databases

    PharmGKBiPA28044.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 387387F-box only protein 4PRO_0000119879Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei12 – 121Phosphoserine2 Publications

    Post-translational modificationi

    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.By similarity2 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9UKT5.
    PaxDbiQ9UKT5.
    PRIDEiQ9UKT5.

    PTM databases

    PhosphoSiteiQ9UKT5.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9UKT5.
    BgeeiQ9UKT5.
    CleanExiHS_FBXO4.
    GenevestigatoriQ9UKT5.

    Organism-specific databases

    HPAiHPA003362.

    Interactioni

    Subunit structurei

    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 CCND1.5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CUL1Q136162EBI-960409,EBI-359390
    TERF1P542742EBI-960421,EBI-710997
    TERF1P54274-23EBI-960421,EBI-711018
    YWHAEP622585EBI-960409,EBI-356498
    YwhaeP622602EBI-960409,EBI-356462From a different organism.

    Protein-protein interaction databases

    BioGridi117656. 14 interactions.
    IntActiQ9UKT5. 7 interactions.
    MINTiMINT-108507.
    STRINGi9606.ENSP00000281623.

    Structurei

    Secondary structure

    1
    387
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi58 – 614
    Helixi64 – 729
    Helixi76 – 838
    Helixi87 – 937
    Helixi96 – 1049
    Helixi107 – 1093
    Helixi115 – 1173
    Helixi122 – 1254
    Helixi139 – 1468
    Beta strandi167 – 1693
    Beta strandi178 – 1825
    Helixi184 – 1863
    Beta strandi188 – 1914
    Helixi193 – 1986
    Helixi201 – 2033
    Helixi210 – 2123
    Beta strandi215 – 2173
    Beta strandi221 – 2288
    Beta strandi230 – 2356
    Helixi279 – 2857
    Beta strandi287 – 2948
    Helixi303 – 31311
    Helixi316 – 3194
    Beta strandi325 – 3339
    Helixi341 – 3477
    Helixi350 – 3534
    Beta strandi357 – 3637
    Turni364 – 3663
    Helixi370 – 3778
    Turni378 – 3836

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3L2OX-ray2.80B55-387[»]
    3L82X-ray2.40B162-387[»]
    ProteinModelPortaliQ9UKT5.
    SMRiQ9UKT5. Positions 55-383.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UKT5.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini56 – 10247F-boxPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 F-box domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG39270.
    HOGENOMiHOG000112550.
    HOVERGENiHBG051585.
    InParanoidiQ9UKT5.
    KOiK10291.
    OMAiHEWQDEF.
    PhylomeDBiQ9UKT5.
    TreeFamiTF331105.

    Family and domain databases

    InterProiIPR001810. F-box_dom.
    [Graphical view]
    PfamiPF00646. F-box. 1 hit.
    [Graphical view]
    SMARTiSM00256. FBOX. 1 hit.
    [Graphical view]
    SUPFAMiSSF81383. SSF81383. 1 hit.
    PROSITEiPS50181. FBOX. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9UKT5-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MAGSEPRSGT NSPPPPFSDW GRLEAAILSG WKTFWQSVSK ERVARTTSRE    50
    EVDEAASTLT RLPIDVQLYI LSFLSPHDLC QLGSTNHYWN ETVRDPILWR 100
    YFLLRDLPSW SSVDWKSLPD LEILKKPISE VTDGAFFDYM AVYRMCCPYT 150
    RRASKSSRPM YGAVTSFLHS LIIQNEPRFA MFGPGLEELN TSLVLSLMSS 200
    EELCPTAGLP QRQIDGIGSG VNFQLNNQHK FNILILYSTT RKERDRAREE 250
    HTSAVNKMFS RHNEGDDQQG SRYSVIPQIQ KVCEVVDGFI YVANAEAHKR 300
    HEWQDEFSHI MAMTDPAFGS SGRPLLVLSC ISQGDVKRMP CFYLAHELHL 350
    NLLNHPWLVQ DTEAETLTGF LNGIEWILEE VESKRAR 387
    Length:387
    Mass (Da):44,136
    Last modified:March 1, 2005 - v2
    Checksum:iBD5E8DD14B9733E9
    GO
    Isoform 2 (identifier: Q9UKT5-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         300-307: RHEWQDEF → SKYSYVHF
         308-387: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:307
    Mass (Da):35,003
    Checksum:i62C85CD92410CC33
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti41 – 411E → D in AAF04468. (PubMed:10531035)Curated
    Sequence conflicti95 – 951D → N in AAF04468. (PubMed:10531035)Curated
    Sequence conflicti120 – 1223DLE → YLQ in AAF04468. (PubMed:10531035)Curated
    Sequence conflicti132 – 1321T → S in AAF04468. (PubMed:10531035)Curated
    Sequence conflicti144 – 1441R → L in AAF04468. (PubMed:10531035)Curated
    Sequence conflicti174 – 1741Q → P in AAF04468. (PubMed:10531035)Curated
    Sequence conflicti181 – 1811M → L in AAF04468. (PubMed:10531035)Curated
    Sequence conflicti185 – 1851G → R in AAF04468. (PubMed:10531035)Curated
    Sequence conflicti188 – 1881E → Q in AAF04468. (PubMed:10531035)Curated
    Sequence conflicti198 – 1981M → L in AAF04468. (PubMed:10531035)Curated
    Sequence conflicti268 – 2692QQ → RP in AAF04468. (PubMed:10531035)Curated
    Sequence conflicti282 – 2821V → L in AAF04468. (PubMed:10531035)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti8 – 81S → R in esophagus cancer samples. 1 Publication
    Corresponds to variant rs2231917 [ dbSNP | Ensembl ].
    VAR_063500
    Natural varianti12 – 121S → L in esophagus cancer sample; impairs homodimerization and reduces ubiquitin ligase activity. 1 Publication
    VAR_063501
    Natural varianti13 – 131P → S in esophagus cancer sample. 1 Publication
    VAR_063502
    Natural varianti23 – 231L → Q in esophagus cancer samples. 1 Publication
    VAR_063503
    Natural varianti76 – 761P → T in esophagus cancer samples; impairs interaction with SKP1. 1 Publication
    VAR_063504

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei300 – 3078RHEWQDEF → SKYSYVHF in isoform 2. 1 PublicationVSP_012977
    Alternative sequencei308 – 38780Missing in isoform 2. 1 PublicationVSP_012978Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF176703 mRNA. Translation: AAF03703.1.
    BC048098 mRNA. Translation: AAH48098.1.
    CR749719 mRNA. Translation: CAH18486.1.
    AF129534 mRNA. Translation: AAF04468.1.
    CCDSiCCDS3938.1. [Q9UKT5-1]
    CCDS3939.1. [Q9UKT5-2]
    RefSeqiNP_036308.1. NM_012176.2. [Q9UKT5-1]
    NP_277019.1. NM_033484.2. [Q9UKT5-2]
    UniGeneiHs.165575.

    Genome annotation databases

    EnsembliENST00000281623; ENSP00000281623; ENSG00000151876. [Q9UKT5-1]
    ENST00000296812; ENSP00000296812; ENSG00000151876. [Q9UKT5-2]
    GeneIDi26272.
    KEGGihsa:26272.
    UCSCiuc003jmp.3. human. [Q9UKT5-2]
    uc003jmq.3. human. [Q9UKT5-1]

    Polymorphism databases

    DMDMi60416426.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF176703 mRNA. Translation: AAF03703.1 .
    BC048098 mRNA. Translation: AAH48098.1 .
    CR749719 mRNA. Translation: CAH18486.1 .
    AF129534 mRNA. Translation: AAF04468.1 .
    CCDSi CCDS3938.1. [Q9UKT5-1 ]
    CCDS3939.1. [Q9UKT5-2 ]
    RefSeqi NP_036308.1. NM_012176.2. [Q9UKT5-1 ]
    NP_277019.1. NM_033484.2. [Q9UKT5-2 ]
    UniGenei Hs.165575.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3L2O X-ray 2.80 B 55-387 [» ]
    3L82 X-ray 2.40 B 162-387 [» ]
    ProteinModelPortali Q9UKT5.
    SMRi Q9UKT5. Positions 55-383.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117656. 14 interactions.
    IntActi Q9UKT5. 7 interactions.
    MINTi MINT-108507.
    STRINGi 9606.ENSP00000281623.

    PTM databases

    PhosphoSitei Q9UKT5.

    Polymorphism databases

    DMDMi 60416426.

    Proteomic databases

    MaxQBi Q9UKT5.
    PaxDbi Q9UKT5.
    PRIDEi Q9UKT5.

    Protocols and materials databases

    DNASUi 26272.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000281623 ; ENSP00000281623 ; ENSG00000151876 . [Q9UKT5-1 ]
    ENST00000296812 ; ENSP00000296812 ; ENSG00000151876 . [Q9UKT5-2 ]
    GeneIDi 26272.
    KEGGi hsa:26272.
    UCSCi uc003jmp.3. human. [Q9UKT5-2 ]
    uc003jmq.3. human. [Q9UKT5-1 ]

    Organism-specific databases

    CTDi 26272.
    GeneCardsi GC05P041925.
    HGNCi HGNC:13583. FBXO4.
    HPAi HPA003362.
    MIMi 609090. gene.
    neXtProti NX_Q9UKT5.
    PharmGKBi PA28044.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG39270.
    HOGENOMi HOG000112550.
    HOVERGENi HBG051585.
    InParanoidi Q9UKT5.
    KOi K10291.
    OMAi HEWQDEF.
    PhylomeDBi Q9UKT5.
    TreeFami TF331105.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_16907. Association of TriC/CCT with target proteins during biosynthesis.
    REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.

    Miscellaneous databases

    EvolutionaryTracei Q9UKT5.
    GeneWikii FBXO4.
    GenomeRNAii 26272.
    NextBioi 48565.
    PROi Q9UKT5.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9UKT5.
    Bgeei Q9UKT5.
    CleanExi HS_FBXO4.
    Genevestigatori Q9UKT5.

    Family and domain databases

    InterProi IPR001810. F-box_dom.
    [Graphical view ]
    Pfami PF00646. F-box. 1 hit.
    [Graphical view ]
    SMARTi SM00256. FBOX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF81383. SSF81383. 1 hit.
    PROSITEi PS50181. FBOX. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH SKP1 AND CUL1.
    2. 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. 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      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.

    Entry informationi

    Entry nameiFBX4_HUMAN
    AccessioniPrimary (citable) accession number: Q9UKT5
    Secondary accession number(s): Q68CU8, Q86VT8, Q9UK98
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 26, 2001
    Last sequence update: March 1, 2005
    Last modified: October 1, 2014
    This is version 117 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3