Biomarker: FBXW7

Histology type: endometrial serous carcinomas

Stage: risk

Country: USA

Region: Rochester, Minnesota

Study type: retrospective study

Followed up time :

Subgroup 1 name : USC

Subgroup 1 number: 36

Subgroup 2 name: TCGA data set USC

Subgroup 2 number: 109

Conclusion: Higher FBXW7 (F-box and WD repeat domain containing 7) expression were associated with a decreased risk of progression, after adjusting for stage

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : high expression

Expression elevation: Expression was evaluated by considering the percentage of cells exhibiting immunoreaction, as well as the localization of signalling (nuclear and/or cytoplasmic). 

Statictics: Mean (SD);Range

Cohort age: 72.2± 9.0;54.8–89.8

Subgroup 1 age: 58.5 ;38–81

Subgroup 2 age: 46;38–73

Funtion Uniprot: Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:22748924, PubMed:17434132, PubMed:26976582, PubMed:28727686). Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination (PubMed:22748924, PubMed:26774286, PubMed:17434132, PubMed:26976582, PubMed:28727686). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, RICTOR, and probably PSEN1 (PubMed:11565034, PubMed:12354302, PubMed:11585921, PubMed:15103331, PubMed:14739463, PubMed:17558397, PubMed:17873522, PubMed:22608923, PubMed:22748924, PubMed:29149593, PubMed:25775507, PubMed:28007894, PubMed:26976582, PubMed:28727686, PubMed:25897075). Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (PubMed:14739463). Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593). Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination (PubMed:27238018). Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage (PubMed:26774286). The SCF(FBXW7) complex facilitates double-strand break repair following phosphorylation by ATM: phosphorylation promotes localization to sites of double-strand breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, enhancing DNA non-homologous end joining (PubMed:26774286).

UniProt ID: Q969H0

UniProt Link: https://www.uniprot.org/uniprotkb/Q969H0/entry

Biological function from UniProt: #Biological rhythms #DNA damage #DNA repair #Host-virus interaction #Ubl conjugation pathway

Molecular function from UniProt:

Tissue specificity from UniProt: Isoform 1 Widely expressed;Isoform 3 Expressed in brain;

Subcellular UniProt: #Chromosome #Cytoplasm #Nucleus

Alternative name from UniProt:

Recommended name: F-box/WD repeat-containing protein 7

Gene name from HGNC: FBXW7 (AGO, CDC4, FBW7, FBX30, FBXW6, FLJ11071, SEL-10, SEL10)

HPA class: Cancer-related genes

AlphaFold DB: Q969H0

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q969H0

HPA link: https://www.proteinatlas.org/ENSG00000109670-FBXW7

Tissue specificity RNA from HPA: Tissue enhanced (brain)

Tissue expression from HPA: Ubiquitous nuclear expression

Single cell type specificity Cell type enhanced (Excitatory neurons, Basal keratinocytes)

Immune cell specificity: Immune cell enhanced (basophil)

Subcellular summary HPA Located in Nucleoplasm, Vesicles

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000109670-FBXW7/pathology/endometrial+cancer

Pathology endo: https://www.proteinatlas.org/ENSG00000109670-FBXW7/pathology/endometrial+cancer

Expression figure legend: Immunohistochemistry-based protein profiling of uterine serous carcinomas (UCS) patients

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076151/figure/Fig2/

Survival figure legend: Kaplan–Meier curves for progression-free survival (a) and overall survival (b), according to stage

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076151/figure/Fig1/

OMIM: 606278

OMIM link2: https://www.omim.org/entry/606278

HGNC ID: HGNC:16712

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16712