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FBXW2 F-box and WD repeat domain containing 2 [ Homo sapiens (human) ]

Gene ID: 26190, updated on 3-Apr-2024

Summary

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Official Symbol
FBXW2provided by HGNC
Official Full Name
F-box and WD repeat domain containing 2provided by HGNC
Primary source
HGNC:HGNC:13608
See related
Ensembl:ENSG00000119402 MIM:609071; AllianceGenome:HGNC:13608
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
Md6; FBW2; Fwd2
Summary
F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 amino acid motif, the F box. Some F-box proteins have been shown to be critical for the ubiquitin-mediated degradation of cellular regulatory proteins. In fact, F-box proteins are one of the four subunits of ubiquitin protein ligases, called SCFs. SCF ligases bring ubiquitin conjugating enzymes to substrates that are specifically recruited by the different F-box proteins. Mammalian F-box proteins are classified into three groups based on the presence of either WD-40 repeats, leucine-rich repeats, or the presence or absence of other protein-protein interacting domains. This gene encodes the second identified member of the F-box gene family and contains multiple WD-40 repeats. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in lung (RPKM 8.4), thyroid (RPKM 8.1) and 25 other tissues See more
Orthologs
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Genomic context

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See FBXW2 in Genome Data Viewer
Location:
9q33.2
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (120756974..120793416, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (132953124..132989576, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (123519252..123555694, complement)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene multiple EGF like domains 9 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20222 Neighboring gene NFE2L2 motif-containing MPRA enhancer 171 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr9:123455017-123455827 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20223 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28893 Neighboring gene adenosylhomocysteinase pseudogene 2 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr9:123530344-123531012 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:123555395-123556025 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28894 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28895 Neighboring gene beta-1,3-galactosyltransferase 9 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:123587005-123587204 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:123595637-123596180 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:123603211-123603712 Neighboring gene Sharpr-MPRA regulatory regions 2033 and 13781 Neighboring gene proteasome 26S subunit, non-ATPase 5

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. FBXW2 inhibits prostate cancer proliferation and metastasis via promoting EGFR ubiquitylation and degradation. Zhou T, et al. Cell Mol Life Sci, 2022 May 2. PMID 35499593, Free PMC Article
  2. E3 Ligase FBXW2 Is a New Therapeutic Target in Obesity and Atherosclerosis. Wang C, et al. Adv Sci (Weinh), 2020 Oct. PMID 33101872, Free PMC Article
  3. The FBXW2-MSX2-SOX2 axis regulates stem cell property and drug resistance of cancer cells. Yin Y, et al. Proc Natl Acad Sci U S A, 2019 Oct 8. PMID 31548378, Free PMC Article
  4. RACK1 (receptor for activated C-kinase 1) interacts with FBW2 (F-box and WD-repeat domain-containing 2) to up-regulate GCM1 (glial cell missing 1) stability and placental cell migration and invasion. Wang CC, et al. Biochem J, 2013 Jul 15. PMID 23651062
  5. Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours. Schoenmakers EF, et al. Nat Genet, 1995 Aug. PMID 7670494

See all (50) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. FBXW2 suppresses breast tumorigenesis by targeting AKT-Moesin-SKP2 axis.
    Title: FBXW2 suppresses breast tumorigenesis by targeting AKT-Moesin-SKP2 axis.
  2. FBXW2 inhibits prostate cancer proliferation and metastasis via promoting EGFR ubiquitylation and degradation.
    Title: FBXW2 inhibits prostate cancer proliferation and metastasis via promoting EGFR ubiquitylation and degradation.
  3. TAK1 Is a Novel Target in Hepatocellular Carcinoma and Contributes to Sorafenib Resistance.
    Title: TAK1 Is a Novel Target in Hepatocellular Carcinoma and Contributes to Sorafenib Resistance.
  4. High FBXW2 expression is associated with drug resistance in lung cancer.
    Title: The FBXW2-MSX2-SOX2 axis regulates stem cell property and drug resistance of cancer cells.
  5. Study demonstrates that FBXW2 inhibits tumor migration, invasion and metastasis in lung cancer cells by targeting beta-catenin for degradation.
    Title: FBXW2 suppresses migration and invasion of lung cancer cells via promoting β-catenin ubiquitylation and degradation.
  6. BTrCP-FBXW2-SKP2 axis forms an oncogene-tumour suppressor-oncogene cascade to control cancer cell growth with FBXW2 acting as a tumour suppressor by promoting SKP2 degradation.
    Title: The β-TrCP-FBXW2-SKP2 axis regulates lung cancer cell growth with FBXW2 acting as a tumour suppressor.
  7. RACK1 competes with GCM1 for FBW2 and thereby prevents GCM1 ubiquitination, which is also supported by the observation that GCM1 is destabilized in RACK1-knockdown BeWo placental cells
    Title: RACK1 (receptor for activated C-kinase 1) interacts with FBW2 (F-box and WD-repeat domain-containing 2) to up-regulate GCM1 (glial cell missing 1) stability and placental cell migration and invasion.
  8. UBE2D2 is required for GCMa ubiquitination and for association with the SCF(FBXW2) complex.
    Title: Ubiquitin-conjugating enzyme UBE2D2 is responsible for FBXW2 (F-box and WD repeat domain containing 2)-mediated human GCM1 (glial cell missing homolog 1) ubiquitination and degradation.
  9. the SCF(hFBW2) E3 complex has a key role in targeting hGCMa to the ubiquitin-proteasome degradation system
    Title: FBW2 targets GCMa to the ubiquitin-proteasome degradation system.
Submit: New GeneRIF Correction

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC117371

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in protein modification process TAS
Traceable Author Statement
more info
 PubMed 
involved_in proteolysis TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
F-box/WD repeat-containing protein 2
Names
F-box and WD-40 domain protein 2
F-box and WD-40 domain-containing protein 2

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)

  1. NM_001375888.1 → NP_001362817.1  F-box/WD repeat-containing protein 2 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AL138836, AL161911
    Consensus CDS
    CCDS43872.1
    UniProtKB/Swiss-Prot
    B3KRL8, Q4VXH2, Q7Z4V6, Q8WV51, Q9HA09, Q9UKA3, Q9UKT8
    UniProtKB/TrEMBL
    B2RAW3
    Conserved Domains (3) summary
    smart00256
    Location:60 → 94
    FBOX; A Receptor for Ubiquitination Targets
    cd00200
    Location:140 → 447
    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 ...
    sd00039
    Location:151 → 185
    7WD40; WD40 repeat [structural motif]

  2. NM_001375889.1 → NP_001362818.1  F-box/WD repeat-containing protein 2 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AL138836, AL161911
    Consensus CDS
    CCDS94471.1
    UniProtKB/TrEMBL
    B4DT60
    Conserved Domains (2) summary
    cd00200
    Location:11 → 318
    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 ...
    sd00039
    Location:22 → 56
    7WD40; WD40 repeat [structural motif]

  3. NM_001375890.1 → NP_001362819.1  F-box/WD repeat-containing protein 2 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AL138836, AL161911
    UniProtKB/TrEMBL
    B2RAW3
    Conserved Domains (3) summary
    smart00256
    Location:92 → 126
    FBOX; A Receptor for Ubiquitination Targets
    cd00200
    Location:172 → 479
    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 ...
    sd00039
    Location:183 → 217
    7WD40; WD40 repeat [structural motif]

  4. NM_012164.4 → NP_036296.2  F-box/WD repeat-containing protein 2 isoform 1

    See identical proteins and their annotated locations for NP_036296.2

    Status: REVIEWED

    Source sequence(s)
    AL138836, AL161911, BC110334, DA703966
    Consensus CDS
    CCDS43872.1
    UniProtKB/Swiss-Prot
    B3KRL8, Q4VXH2, Q7Z4V6, Q8WV51, Q9HA09, Q9UKA3, Q9UKT8
    UniProtKB/TrEMBL
    B2RAW3
    Related
    ENSP00000476369.1, ENST00000608872.6
    Conserved Domains (3) summary
    smart00256
    Location:60 → 94
    FBOX; A Receptor for Ubiquitination Targets
    cd00200
    Location:140 → 447
    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 ...
    sd00039
    Location:151 → 185
    7WD40; WD40 repeat [structural motif]

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

  1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

    Range
    120756974..120793416 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047423218.1 → XP_047279174.1  F-box/WD repeat-containing protein 2 isoform X6

  2. XM_017014615.3 → XP_016870104.1  F-box/WD repeat-containing protein 2 isoform X3

    UniProtKB/TrEMBL
    B2RAW3
    Conserved Domains (3) summary
    smart00256
    Location:60 → 94
    FBOX; A Receptor for Ubiquitination Targets
    sd00039
    Location:165 → 200
    7WD40; WD40 repeat [structural motif]
    cl29593
    Location:162 → 382
    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 ...

  3. XM_006717049.4 → XP_006717112.1  F-box/WD repeat-containing protein 2 isoform X1

    See identical proteins and their annotated locations for XP_006717112.1

    UniProtKB/TrEMBL
    B2RAW3
    Conserved Domains (3) summary
    smart00256
    Location:92 → 126
    FBOX; A Receptor for Ubiquitination Targets
    cd00200
    Location:172 → 479
    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 ...
    sd00039
    Location:183 → 217
    7WD40; WD40 repeat [structural motif]

  4. XM_047423217.1 → XP_047279173.1  F-box/WD repeat-containing protein 2 isoform X6

  5. XM_047423214.1 → XP_047279170.1  F-box/WD repeat-containing protein 2 isoform X4

    UniProtKB/TrEMBL
    B4DT60
    Related
    ENSP00000508243.1, ENST00000684405.1

  6. XM_024447509.2 → XP_024303277.1  F-box/WD repeat-containing protein 2 isoform X3

    UniProtKB/TrEMBL
    B2RAW3
    Conserved Domains (3) summary
    smart00256
    Location:60 → 94
    FBOX; A Receptor for Ubiquitination Targets
    sd00039
    Location:165 → 200
    7WD40; WD40 repeat [structural motif]
    cl29593
    Location:162 → 382
    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 ...

  7. XM_006717051.3 → XP_006717114.1  F-box/WD repeat-containing protein 2 isoform X2

    See identical proteins and their annotated locations for XP_006717114.1

    UniProtKB/TrEMBL
    B2RAW3
    Conserved Domains (3) summary
    smart00256
    Location:92 → 126
    FBOX; A Receptor for Ubiquitination Targets
    sd00039
    Location:197 → 232
    7WD40; WD40 repeat [structural motif]
    cl29593
    Location:194 → 418
    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 ...

  8. XM_047423215.1 → XP_047279171.1  F-box/WD repeat-containing protein 2 isoform X4

    UniProtKB/TrEMBL
    B4DT60

  9. XM_047423213.1 → XP_047279169.1  F-box/WD repeat-containing protein 2 isoform X1

  10. XM_047423216.1 → XP_047279172.1  F-box/WD repeat-containing protein 2 isoform X5

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060933.1 Alternate T2T-CHM13v2.0

    Range
    132953124..132989576 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054362715.1 → XP_054218690.1  F-box/WD repeat-containing protein 2 isoform X6

  2. XM_054362710.1 → XP_054218685.1  F-box/WD repeat-containing protein 2 isoform X3

  3. XM_054362707.1 → XP_054218682.1  F-box/WD repeat-containing protein 2 isoform X1

  4. XM_054362714.1 → XP_054218689.1  F-box/WD repeat-containing protein 2 isoform X6

  5. XM_054362712.1 → XP_054218687.1  F-box/WD repeat-containing protein 2 isoform X4

    UniProtKB/TrEMBL
    B4DT60

  6. XM_054362711.1 → XP_054218686.1  F-box/WD repeat-containing protein 2 isoform X3

  7. XM_054362709.1 → XP_054218684.1  F-box/WD repeat-containing protein 2 isoform X2

  8. XM_054362708.1 → XP_054218683.1  F-box/WD repeat-containing protein 2 isoform X1

  9. XM_054362713.1 → XP_054218688.1  F-box/WD repeat-containing protein 2 isoform X5

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UKT8.2 GenPept UniProtKB/Swiss-Prot:Q9UKT8

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