FBXW8 F-box and WD repeat domain containing 8 [Homo sapiens (human)] - Gene

Summary

Official Symbol: FBXW8provided by HGNC
Official Full Name: F-box and WD repeat domain containing 8provided by HGNC
Primary source: HGNC:HGNC:13597
See related: Ensembl:ENSG00000174989 MIM:609073; AllianceGenome:HGNC:13597
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FBW6; FBW8; FBX29; FBXW6; FBXO29
Summary: This gene encodes a member of the F-box protein family, members of which are characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into three 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 contains a WD-40 domain, in addition to an F-box motif, so it belongs to the Fbw class. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in thyroid (RPKM 4.3), ovary (RPKM 2.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q24.22

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (116910950..117031148)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (116892024..117012205)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (117348755..117468953)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Genome-wide admixture and association analysis identifies African ancestry-specific risk loci of eosinophilic esophagitis in African Americans.
Title: Genome-wide admixture and association analysis identifies African ancestry-specific risk loci of eosinophilic esophagitis in African Americans.
FBXW8 regulates G1 and S phases of cell cycle progression by restricting beta-TrCP1 function.
Title: FBXW8 regulates G1 and S phases of cell cycle progression by restricting β-TrCP1 function.
Frameshift mutation FBXW8 c.1312_1313delGT was considered functionally relevant and was investigated for its potential association with breast cancer risk through subsequent genotyping in two hospital-based breast cancer case-control series from Belarus and Germany, respectively, comprising a total of 2740 breast cancer cases and 2174 controls.
Title: Assessment of a FBXW8 frameshift mutation, c.1312_1313delGT, in breast cancer patients and controls from Central Europe.
FBXW8 and PARK2 are sequestrated into insolubility by ATXN2 PolyQ expansions, but only FBXW8 expression is dysregulated
Title: Both ubiquitin ligases FBXW8 and PARK2 are sequestrated into insolubility by ATXN2 PolyQ expansions, but only FBXW8 expression is dysregulated.
findings will shed light the role to mechanism of miR-218 in regulating JEG-3 cells proliferation via miR-218/Fbxw8 axis, and miR-218 may serve as a novel potential therapeutic target in human choriocarcinoma in the future
Title: MicroRNA-218 inhibits the proliferation of human choriocarcinoma JEG-3 cell line by targeting Fbxw8.
CUL7/Fbxw8 ubiquitin ligase-mediated HPK1 degradation revealed a direct link and novel role of CUL7/Fbxw8 ubiquitin ligase in the MAPK pathway, which plays a critical role in cell proliferation and differentiation.
Title: The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin ligase promotes degradation of hematopoietic progenitor kinase 1.
Dysregulation of Cul7 and Fbxw8 expression might affect trophoblast turnover in intrauterine growth restriction.
Title: Cullin 7 and Fbxw 8 expression in trophoblastic cells is regulated via oxygen tension: implications for intrauterine growth restriction?
Growth factor-stimulated TBC1D3 ubiquitination and degradation are regulated by its interaction with CUL7-Fbw8.
Title: Ubiquitination and degradation of the hominoid-specific oncoprotein TBC1D3 is mediated by CUL7 E3 ligase.
Fbxw8 plays an essential role in the proliferation of human trophoblast cells, especially JEG-3 cells.
Title: Fbxw8 is involved in the proliferation of human choriocarcinoma JEG-3 cells.
FBXW8 plays an essential role in cancer cell proliferation through proteolysis of cyclin D1. It may present new opportunities to develop therapies targeting destruction of cyclin D1 or its regulator E3 ligase selectively.
Title: A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Identification of common variants associated with human hippocampal and intracranial volumes. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-17693 (e-PCR)
- UniSTS:24085

RH102742 (e-PCR)
- UniSTS:97076

RH119390 (e-PCR)
- UniSTS:132931

SHGC-58215 (e-PCR)
- UniSTS:30276

SHGC-148976 (e-PCR)
- UniSTS:176715

RH98353 (e-PCR)
- UniSTS:90452

G64760 (e-PCR)
- UniSTS:164710

RH69770 (e-PCR)
- UniSTS:15478

RH103340 (e-PCR)
- UniSTS:97671

D11S2783 (e-PCR)
- UniSTS:151981

G44375 (e-PCR)
- UniSTS:95159

RH118527 (e-PCR)
- UniSTS:137925

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Golgi organization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in Golgi organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in cilium assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in labyrinthine layer blood vessel development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of dendrite morphogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of dendrite morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in protein ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of 3M complex	IDA Inferred from Direct Assay more info	PubMed
part_of Cul7-RING ubiquitin ligase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of Cul7-RING ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
part_of SCF ubiquitin ligase complex	IEA Inferred from Electronic Annotation more info
is_active_in centriole	IBA Inferred from Biological aspect of Ancestor more info
is_active_in ciliary basal body	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: F-box/WD repeat-containing protein 8

Names: F-box and WD-40 domain protein 8; F-box and WD-40 domain-containing protein 8; F-box only protein 29

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_012174.2 → NP_036306.1 F-box/WD repeat-containing protein 8 isoform 2

See identical proteins and their annotated locations for NP_036306.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame segment in the 5' coding region, as compared to variant 1. It encodes isoform 2, which is missing an internal segment, as compared to isoform 1.

Source sequence(s)

AC026368, AC083806, AC127164

Consensus CDS

CCDS44988.1

UniProtKB/TrEMBL

A8K0Q6

Related

ENSP00000389144.2, ENST00000455858.2

Conserved Domains (4) summary

COG2319
Location:125 → 504

WD40; WD40 repeat [General function prediction only]

pfam12937
Location:52 → 96

F-box-like; F-box-like

sd00039
Location:147 → 187

7WD40; WD40 repeat [structural motif]

cl02567
Location:129 → 435

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
NM_153348.3 → NP_699179.2 F-box/WD repeat-containing protein 8 isoform 1

See identical proteins and their annotated locations for NP_699179.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) is the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC026368, AC083806, AC127164

Consensus CDS

CCDS9182.1

UniProtKB/Swiss-Prot

Q8N3Y1, Q9UK95

UniProtKB/TrEMBL

A8K0Q6

Related

ENSP00000498999.1, ENST00000652555.1

Conserved Domains (4) summary

COG2319
Location:191 → 570

WD40; WD40 repeat [General function prediction only]

pfam12937
Location:118 → 162

F-box-like; F-box-like

sd00039
Location:213 → 253

7WD40; WD40 repeat [structural motif]

cl02567
Location:195 → 501

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

116910950..117031148

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024448937.2 → XP_024304705.2 F-box/WD repeat-containing protein 8 isoform X2
XM_017019176.2 → XP_016874665.1 F-box/WD repeat-containing protein 8 isoform X1

UniProtKB/TrEMBL

A8K0Q6
XM_017019175.3 → XP_016874664.1 F-box/WD repeat-containing protein 8 isoform X3

UniProtKB/TrEMBL

A0A499FIY5

Related

ENSP00000310686.6, ENST00000309909.10

Conserved Domains (4) summary

COG2319
Location:110 → 489

WD40; WD40 repeat [General function prediction only]

pfam12937
Location:37 → 81

F-box-like; F-box-like

sd00039
Location:132 → 172

7WD40; WD40 repeat [structural motif]

cl02567
Location:114 → 420

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
XM_047428699.1 → XP_047284655.1 F-box/WD repeat-containing protein 8 isoform X4