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

    Gene ID: 26190, updated on 5-May-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
    mouse all
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    Genomic context

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    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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