Human Gene FBXO4 (ENST00000281623.8) from GENCODE V44
Description: Homo sapiens F-box protein 4 (FBXO4), transcript variant 1, mRNA. (from RefSeq NM_012176) RefSeq Summary (NM_012176): This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]. Gencode Transcript: ENST00000281623.8 Gencode Gene: ENSG00000151876.13 Transcript (Including UTRs) Position: hg38 chr5:41,925,281-41,941,743 Size: 16,463 Total Exon Count: 7 Strand: + Coding Region Position: hg38 chr5:41,925,310-41,941,281 Size: 15,972 Coding Exon Count: 7
ID:FBX4_HUMAN DESCRIPTION: RecName: Full=F-box only protein 4; 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. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: 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. INTERACTION: P54274:TERF1; NbExp=2; IntAct=EBI-960421, EBI-710997; P54274-2:TERF1; NbExp=3; IntAct=EBI-960421, EBI-711018; P62258:YWHAE; NbExp=5; IntAct=EBI-960409, EBI-356498; P62260:Ywhae (xeno); NbExp=2; IntAct=EBI-960409, EBI-356462; SUBCELLULAR LOCATION: Cytoplasm (By similarity). PTM: 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. SIMILARITY: Contains 1 F-box domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UKT5
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004842 ubiquitin-protein transferase activity GO:0005515 protein binding GO:0042803 protein homodimerization activity GO:0061630 ubiquitin protein ligase activity
Biological Process: GO:0000209 protein polyubiquitination GO:0000723 telomere maintenance GO:0006511 ubiquitin-dependent protein catabolic process GO:0007568 aging GO:0010608 posttranscriptional regulation of gene expression GO:0016567 protein ubiquitination GO:0019725 cellular homeostasis GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process GO:0031398 positive regulation of protein ubiquitination GO:0031647 regulation of protein stability GO:0031648 protein destabilization GO:0032212 positive regulation of telomere maintenance via telomerase GO:0035726 common myeloid progenitor cell proliferation GO:0043687 post-translational protein modification GO:0048147 negative regulation of fibroblast proliferation GO:0071479 cellular response to ionizing radiation GO:1900181 negative regulation of protein localization to nucleus GO:1902916 positive regulation of protein polyubiquitination GO:2000001 regulation of DNA damage checkpoint
AK024075 - Homo sapiens cDNA FLJ14013 fis, clone Y79AA1002487, highly similar to F-box only protein 4. BC048098 - Homo sapiens F-box protein 4, mRNA (cDNA clone MGC:57207 IMAGE:4830192), complete cds. AK001003 - Homo sapiens cDNA FLJ10141 fis, clone HEMBA1003199. BC040011 - Homo sapiens F-box protein 4, mRNA (cDNA clone IMAGE:5747586). HQ447994 - Synthetic construct Homo sapiens clone IMAGE:100071363; CCSB010711_03 F-box protein 4 (FBXO4) gene, encodes complete protein. KJ893553 - Synthetic construct Homo sapiens clone ccsbBroadEn_02947 FBXO4 gene, encodes complete protein. AF129534 - Homo sapiens chromosome 5 F-box protein Fbx4 (FBX4) mRNA, complete cds. AF176703 - Homo sapiens F-box protein FBX4 mRNA, partial cds. CR749719 - Homo sapiens mRNA; cDNA DKFZp547N213 (from clone DKFZp547N213). JD361140 - Sequence 342164 from Patent EP1572962. JD515713 - Sequence 496737 from Patent EP1572962. JD323632 - Sequence 304656 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04120 - Ubiquitin mediated proteolysis
Reactome (by CSHL, EBI, and GO)
Protein Q9UKT5 (Reactome details) participates in the following event(s):
R-HSA-390470 Association of CCT/TriC with other substrates during biosynthesis (unknown chaperone) R-HSA-8952620 NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex R-HSA-8956200 MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex R-HSA-983147 Release of E3 from polyubiquitinated substrate R-HSA-8955241 CAND1 binds cytosolic CRL E3 ubiquitin ligases R-HSA-8952618 AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex R-HSA-8955289 COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes R-HSA-8956040 COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2 R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis R-HSA-390466 Chaperonin-mediated protein folding R-HSA-8951664 Neddylation R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation R-HSA-391251 Protein folding R-HSA-597592 Post-translational protein modification R-HSA-983169 Class I MHC mediated antigen processing & presentation R-HSA-392499 Metabolism of proteins R-HSA-1280218 Adaptive Immune System R-HSA-168256 Immune System