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    FBXO21 F-box protein 21 [ Homo sapiens (human) ]

    Gene ID: 23014, updated on 9-Dec-2024

    Summary

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    Official Symbol
    FBXO21provided by HGNC
    Official Full Name
    F-box protein 21provided by HGNC
    Primary source
    HGNC:HGNC:13592
    See related
    Ensembl:ENSG00000135108 MIM:609095; AllianceGenome:HGNC:13592
    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
    FBX21
    Summary
    This gene encodes a member of the F-box protein family which is 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 3 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 belongs to the Fbxs class. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis (RPKM 31.4), ovary (RPKM 26.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FBXO21 in Genome Data Viewer
    Location:
    12q24.22
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (117141991..117190470, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (117123006..117171512, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (117579796..117628275, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117477181-117478126 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117478127-117479070 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:117479989-117480493 Neighboring gene Sharpr-MPRA regulatory region 12461 Neighboring gene Sharpr-MPRA regulatory region 12935 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117490883-117491488 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117492095-117492700 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117500995-117501771 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117500218-117500994 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4910 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4911 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:117537215-117537353 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:117538220-117538437 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117540353-117540852 Neighboring gene uncharacterized LOC105370010 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7102 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117556298-117556892 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:117580597-117581796 Neighboring gene tescalcin Neighboring gene TESC antisense RNA 1 (head to head) Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4913 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4914 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7104 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4915 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4916 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4917 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117645205-117645705 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117657550-117658106 Neighboring gene MPRA-validated peak1985 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr12:117670646-117670812 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117674186-117674690 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117674691-117675195 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:117718941-117719440 Neighboring gene nitric oxide synthase 1 Neighboring gene elongin C pseudogene 32 Neighboring gene NOS1 1f and 1g alternate promoter region Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117826376-117826876 Neighboring gene NOS1 1c alternate promoter Neighboring gene uncharacterized LOC105370012 Neighboring gene kinase suppressor of ras 2

    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. FBXO21 mediated degradation of p85α regulates proliferation and survival of acute myeloid leukemia. Dobish KK, et al. Leukemia, 2023 Nov. PMID 37689825, Free PMC Article
    2. circRNA-MSR regulates the expression of FBXO21 to inhibit chondrocyte autophagy by targeting miR-761 in osteoarthritis. Jia Z, et al. Kaohsiung J Med Sci, 2022 Dec. PMID 36278814
    3. Targeting the KRT16-vimentin axis for metastasis in lung cancer. Wang W, et al. Pharmacol Res, 2023 Jul. PMID 37315823
    4. CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination. Ravindranath AK, et al. Oncotarget, 2015 Sep 22. PMID 26299618, Free PMC Article
    5. FBXO21 mediates the ubiquitylation and proteasomal degradation of EID1. Watanabe K, et al. Genes Cells, 2015 Aug. PMID 26085330

    See all (52) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. FBXO21 mediated degradation of p85alpha regulates proliferation and survival of acute myeloid leukemia.
      Title: FBXO21 mediated degradation of p85α regulates proliferation and survival of acute myeloid leukemia.
    2. circRNA-MSR regulates the expression of FBXO21 to inhibit chondrocyte autophagy by targeting miR-761 in osteoarthritis.
      Title: circRNA-MSR regulates the expression of FBXO21 to inhibit chondrocyte autophagy by targeting miR-761 in osteoarthritis.
    3. JUNB-FBXO21-ERK axis promotes cartilage degeneration in osteoarthritis by inhibiting autophagy.
      Title: JUNB-FBXO21-ERK axis promotes cartilage degeneration in osteoarthritis by inhibiting autophagy.
    4. Ser291-phosphorylated form of the multifunctional protein and stem cell marker, CD44, inhibits FBXO21-directed degradation of P-gp.
      Title: CD44 promotes multi-drug resistance by protecting P-glycoprotein from FBXO21-mediated ubiquitination.
    5. SCF(FBXO21) polyubiquitylates EID1 both in vitro and in vivo and is required for the efficient degradation of EID1 in both cycling and quiescent cells.
      Title: Peptidic degron in EID1 is recognized by an SCF E3 ligase complex containing the orphan F-box protein FBXO21.
    6. The results suggest that EID1 is a bona fide substrate of FBXO21 and that the control of EID1 abundance by SCF(FBXO)(21) might affect the transcriptional repression activity of EID1.
      Title: FBXO21 mediates the ubiquitylation and proteasomal degradation of EID1.
    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)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of F-box protein 21 (FBXO21) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ90233, KIAA0875, MGC26682, DKFZp434G058

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin-protein transferase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in ubiquitin-dependent protein catabolic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    part_of ubiquitin ligase complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    F-box only protein 21

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_015002.3 → NP_055817.1  F-box only protein 21 isoform 2

      See identical proteins and their annotated locations for NP_055817.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks a 21 nt fragment within the coding region, and thus encodes a 7 aa shorter isoform than variant 1.
      Source sequence(s)
      AB020682, AC026368, BC034045, BC042333, BI550121
      Consensus CDS
      CCDS44989.1
      UniProtKB/TrEMBL
      Q4G104
      Related
      ENSP00000483508.1, ENST00000622495.5
      Conserved Domains (3) summary
      TIGR02097
      Location:493 → 590
      yccV; hemimethylated DNA binding domain
      smart00256
      Location:33 → 74
      FBOX; A Receptor for Ubiquitination Targets
      pfam13369
      Location:215 → 388
      Transglut_core2; Transglutaminase-like superfamily

    2. NM_033624.3 → NP_296373.1  F-box only protein 21 isoform 1

      See identical proteins and their annotated locations for NP_296373.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) contains an additional 21 nt fragment within the coding region, and thus encodes a 7 aa longer isoform than variant 2.
      Source sequence(s)
      AB020682, AC026368, AL136899, BC034045, BC042333, BI550121
      Consensus CDS
      CCDS9184.1
      UniProtKB/Swiss-Prot
      B3KMF0, O94952, Q5BJG0, Q9H087
      UniProtKB/TrEMBL
      Q4G104
      Related
      ENSP00000328187.5, ENST00000330622.9
      Conserved Domains (3) summary
      TIGR02097
      Location:500 → 597
      yccV; hemimethylated DNA binding domain
      smart00256
      Location:33 → 74
      FBOX; A Receptor for Ubiquitination Targets
      pfam13369
      Location:215 → 388
      Transglut_core2; Transglutaminase-like superfamily

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      117141991..117190470 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017019038.3 → XP_016874527.1  F-box only protein 21 isoform X2

      UniProtKB/TrEMBL
      H0YIE9
      Related
      ENSP00000449264.1, ENST00000550180.5
      Conserved Domains (3) summary
      TIGR02097
      Location:433 → 530
      yccV; hemimethylated DNA binding domain
      smart00256
      Location:33 → 74
      FBOX; A Receptor for Ubiquitination Targets
      COG2912
      Location:252 → 331
      SirB1; Regulator of sirC expression, contains transglutaminase-like and TPR domains [Signal transduction mechanisms]

    2. XM_017019037.3 → XP_016874526.1  F-box only protein 21 isoform X1

      UniProtKB/TrEMBL
      H0YIE9

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      117123006..117171512 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371465.1 → XP_054227440.1  F-box only protein 21 isoform X2

      UniProtKB/TrEMBL
      H0YIE9

    2. XM_054371464.1 → XP_054227439.1  F-box only protein 21 isoform X1

      UniProtKB/TrEMBL
      H0YIE9
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O94952.2 GenPept UniProtKB/Swiss-Prot:O94952

    Gene LinkOut

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

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