Protein:FBXO4 |
Protein Summary |
 Gene summary |
| Gene name: FBXO4 | ASpdb.0 ID: 26272 | Gene | Gene symbol | FBXO4 | Gene ID | 26272 |
| Gene name | F-box protein 4 |
| Synonyms | FBX4 |
| Cytomap | 5p13.1 |
| Type of gene | protein-coding |
| Description | F-box only protein 4F-box protein Fbx4 |
| Modification date | 20240411 |
| UniProtAcc | Q9UKT5 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | FBXO4 | GO:0000151 | ubiquitin ligase complex | 10531035 |
| Gene | FBXO4 | GO:0000209 | protein polyubiquitination | 20181953 |
| Gene | FBXO4 | GO:0004842 | ubiquitin-protein transferase activity | 10531035 |
| Gene | FBXO4 | GO:0005737 | cytoplasm | 21378169 |
| Gene | FBXO4 | GO:0016567 | protein ubiquitination | 10531035|16275645 |
| Gene | FBXO4 | GO:0019005 | SCF ubiquitin ligase complex | 20181953 |
| Gene | FBXO4 | GO:0031146 | SCF-dependent proteasomal ubiquitin-dependent protein catabolic process | 20159592|29142209 |
| Gene | FBXO4 | GO:0031398 | positive regulation of protein ubiquitination | 24389012 |
| Gene | FBXO4 | GO:0031647 | regulation of protein stability | 24389012 |
| Gene | FBXO4 | GO:1990756 | ubiquitin-like ligase-substrate adaptor activity | 29142209 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| Q9UKT5-1 | Q9UKT5-1_3l2o_B.pdb | 3L2O | X-ray | 2.8 | B | 55 | 383 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| Q9UKT5 | FBXO4 | Q9UKT5-1 | Q9UKT5-2 | 387 | 307 | 300 | 307 | Substitution | RHEWQDEF | SKYSYVHF | 300 | 307 |
| Q9UKT5 | FBXO4 | Q9UKT5-1 | Q9UKT5-2 | 387 | 307 | 308 | 387 | Deletion | none | none | 307 | 307 |
| Multiple sequence alignment of our canonical and alternatively spliced FBXO4 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of FBXO4 |
| UniProt-id | ENSG | ENST | ENSP |
| Q9UKT5-1 | ENSG00000151876.13 | ENST00000281623.8 | ENSP00000281623.3 |
| Q9UKT5-2 | ENSG00000151876.13 | ENST00000296812.6 | ENSP00000296812.2 |
| UniProt-id | NM ID | NP ID |
| Q9UKT5-1 | NM_012176.2 | NP_036308.1 |
| Q9UKT5-2 | NM_033484.2 | NP_277019.1 |
| Amino acid sequences of our canonical and alternatively spliced FBXO4 |
| accession_id | Protein sequence |
| Q9UKT5-1 | MAGSEPRSGTNSPPPPFSDWGRLEAAILSGWKTFWQSVSKERVARTTSREEVDEAASTLTRLPIDVQLYILSFLSPHDLCQLGSTNHYWN ETVRDPILWRYFLLRDLPSWSSVDWKSLPDLEILKKPISEVTDGAFFDYMAVYRMCCPYTRRASKSSRPMYGAVTSFLHSLIIQNEPRFA MFGPGLEELNTSLVLSLMSSEELCPTAGLPQRQIDGIGSGVNFQLNNQHKFNILILYSTTRKERDRAREEHTSAVNKMFSRHNEGDDQQG SRYSVIPQIQKVCEVVDGFIYVANAEAHKRHEWQDEFSHIMAMTDPAFGSSGRPLLVLSCISQGDVKRMPCFYLAHELHLNLLNHPWLVQ |
| Q9UKT5-2 | MAGSEPRSGTNSPPPPFSDWGRLEAAILSGWKTFWQSVSKERVARTTSREEVDEAASTLTRLPIDVQLYILSFLSPHDLCQLGSTNHYWN ETVRDPILWRYFLLRDLPSWSSVDWKSLPDLEILKKPISEVTDGAFFDYMAVYRMCCPYTRRASKSSRPMYGAVTSFLHSLIIQNEPRFA MFGPGLEELNTSLVLSLMSSEELCPTAGLPQRQIDGIGSGVNFQLNNQHKFNILILYSTTRKERDRAREEHTSAVNKMFSRHNEGDDQQG |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| FBXO4 (go to UniProt):Q9UKT5 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
Gene Isoform Structures and Expression Levels for FBXO4 |
| Gene structures of our canonical and alternative spliced genes of FBXO4 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of Q9UKT5-1 |
| 3D view using mol* of Q9UKT5-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of Q9UKT5-1 |
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| pLDDT distribution across the protein length of Q9UKT5-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of Q9UKT5-1 |
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| Ramachandran plot of Q9UKT5-2 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| Q9UKT5-1 | 1.037 | 200 | 0.986 | 494.263 | 0.457 | 0.753 | 0.982 | 0.436 | 1.244 | 0.351 | 0.675 | 182,183,184,186,187,188,190,236,237,238,244,247,24 8,251,252,253,254,255,256,258,259,260,261,273,291, 294,296,298,299,300,301,302,305,306,309 |
| Q9UKT5-2 | 1.019 | 211 | 1.05 | 599.564 | 0.559 | 0.702 | 0.946 | 0.72 | 0.955 | 0.753 | 1.152 | 180,182,183,184,186,187,188,190,236,237,238,244,24 7,248,251,252,253,254,255,256,258,259,273,275,279, 282,283,289,291,293,294,295,296,298,299,300,303,30 4,305,306,307 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of Q9UKT5-1_Q9UKT5-1_3l2o_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q9UKT5-1_3l2o_B_Q9UKT5-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q9UKT5-1_Q9UKT5-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q9UKT5-1_vs_Q9UKT5-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q9UKT5-1_vs_Q9UKT5-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to FBXO4 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to FBXO4 |
| Previous studies relating to the alternative splicing of FBXO4 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| FBXO4 | 24704453 | Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer. | Fbx4 is a specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. Two isoforms of human Fbx4 protein, the full length Fbx4α and the C-terminal truncated Fbx4β have been identified, but their functions remain elusive. In this study, we demonstrated that the mRNA level of Fbx4 was significantly lower in hepatocellular carcinoma tissues than that in the corresponding non-tumor tissues. More importantly, we identified three novel splicing variants of Fbx4: Fbx4γ (missing 168-245 nt of exon1), Fbx4δ (missing exon6) and a N-terminal reading frame shift variant (missing exon2). Using cloning sequencing and RT-PCR, we demonstrated these novel splice variants are much more abundant in human cancer tissues and cell lines than that in normal tissues. When expressed in Sk-Hep1 and NIH3T3 cell lines, Fbx4β, Fbx4γ and Fbx4δ could promote cell proliferation and migration in vitro. Concordantly, these isoforms could disrupt cyclin D1 degradation and therefore increase cyclin D1 expression. Moreover, unlike the full-length isoform Fbx4α that mainly exists in cytoplasm, Fbx4β, Fbx4γ, and Fbx4δ locate in both cytoplasm and nucleus. Since cyclin D1 degradation takes place in cytoplasm, the nuclear distribution of these Fbx4 isoforms may not be involved in the down-regulation of cytoplasmic cyclin D1. These results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant cyclin D1 expression in human cancers. | D006528 | Carcinoma, Hepatocellular |
| FBXO4 | 24704453 | Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer. | Fbx4 is a specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. Two isoforms of human Fbx4 protein, the full length Fbx4α and the C-terminal truncated Fbx4β have been identified, but their functions remain elusive. In this study, we demonstrated that the mRNA level of Fbx4 was significantly lower in hepatocellular carcinoma tissues than that in the corresponding non-tumor tissues. More importantly, we identified three novel splicing variants of Fbx4: Fbx4γ (missing 168-245 nt of exon1), Fbx4δ (missing exon6) and a N-terminal reading frame shift variant (missing exon2). Using cloning sequencing and RT-PCR, we demonstrated these novel splice variants are much more abundant in human cancer tissues and cell lines than that in normal tissues. When expressed in Sk-Hep1 and NIH3T3 cell lines, Fbx4β, Fbx4γ and Fbx4δ could promote cell proliferation and migration in vitro. Concordantly, these isoforms could disrupt cyclin D1 degradation and therefore increase cyclin D1 expression. Moreover, unlike the full-length isoform Fbx4α that mainly exists in cytoplasm, Fbx4β, Fbx4γ, and Fbx4δ locate in both cytoplasm and nucleus. Since cyclin D1 degradation takes place in cytoplasm, the nuclear distribution of these Fbx4 isoforms may not be involved in the down-regulation of cytoplasmic cyclin D1. These results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant cyclin D1 expression in human cancers. | D008113 | Liver Neoplasms |
Clinically important variants in FBXO4 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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