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    CBFB core-binding factor subunit beta [ Homo sapiens (human) ]

    Gene ID: 865, updated on 3-Jun-2018
    Official Symbol
    CBFBprovided by HGNC
    Official Full Name
    core-binding factor subunit betaprovided by HGNC
    Primary source
    HGNC:HGNC:1539
    See related
    Ensembl:ENSG00000067955 MIM:121360; Vega:OTTHUMG00000137520
    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
    PEBP2B
    Summary
    The protein encoded by this gene is the beta subunit of a heterodimeric core-binding transcription factor belonging to the PEBP2/CBF transcription factor family which master-regulates a host of genes specific to hematopoiesis (e.g., RUNX1) and osteogenesis (e.g., RUNX2). The beta subunit is a non-DNA binding regulatory subunit; it allosterically enhances DNA binding by alpha subunit as the complex binds to the core site of various enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers and GM-CSF promoters. Alternative splicing generates two mRNA variants, each encoding a distinct carboxyl terminus. In some cases, a pericentric inversion of chromosome 16 [inv(16)(p13q22)] produces a chimeric transcript consisting of the N terminus of core-binding factor beta in a fusion with the C-terminal portion of the smooth muscle myosin heavy chain 11. This chromosomal rearrangement is associated with acute myeloid leukemia of the M4Eo subtype. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in lymph node (RPKM 12.7), appendix (RPKM 9.3) and 25 other tissues See more
    Orthologs
    See CBFB in Genome Data Viewer
    Location:
    16q22.1
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 16 NC_000016.10 (67029147..67101058)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (67063050..67134961)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene carboxylesterase 4A Neighboring gene RNA, 7SL, cytoplasmic 543, pseudogene Neighboring gene chromosome 16 open reading frame 70 Neighboring gene UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 9 Neighboring gene TNFRSF1A associated via death domain

    • 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 Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated (2012-02-22)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated (2012-02-22)

    ClinGen Genome Curation Page

    Replication interactions

    Interaction Pubs
    HIV-1 infectivity with Vif-deficient strains is enhanced by knockdown of CBFB because restrictive APOBEC3 expression is dependent upon CBFB expression PubMed
    Knockdown of core-binding factor, beta subunit (CBFB) by siRNA/shRNA inhibits HIV-1 replication in 293T cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif HIV-1 Vif-mediated degradation of APOBEC3G requires CBFB PubMed
    vif HIV-1 Vif (N-terminal domain) interacts with CBFB in H9 cells PubMed
    vif HIV-1 Vif binds CBFB to inhibit RUNX1 transcriptional activator, which can be disrupted by mutating residue F68 in CBFB PubMed
    vif HIV-1 Vif is stabilized by CBFB PubMed
    vif HIV-1 Vif interacts with CBFB as demonstrated by co-immunoprecipitation assay PubMed
    vif HIV-1 Vif-mediated rescue of HIV-1 infectivity requires CBFB PubMed
    vif HIV-1 Vif interacts with CBFB in HEK293T and Jurkat T cells PubMed
    vif HIV-1 Vif, CBF-beta, CUL5, and ELOB/C form a complex that is required for Vif-mediated downregulation of A3G and A3F. CBF-beta regulates HIV-1 infectivity only in the presence of A3G PubMed
    vif Multiple lysine mutants in HIV-1 Vif, but not single lysine to arginine mutants, lack responsiveness to CBF-beta, indicating that more than one lysine in Vif mediates the ability of CBF-beta to stabilize Vif PubMed
    vif Amino-acid residues 125-141 at the C-terminal region of HIV-1 Vif are required for the Vif-CBF-beta interaction and the H108A, C114A, C133A, and H139A mutants show a decreased interaction with CBF-beta PubMed
    vif HIV-1 Vif residues 102 to 109 are critical for CBF-beta binding, and the remainder of the zinc finger (residues 100-140) strengthens the interaction PubMed
    vif An overall crystal structure indicates that the Vif-CBF-beta-CUL5-ELOB-ELOC complex has a U-shape architecture, including the two straight arms Vif-CBF-beta and CUL5 and the bent arm formation between ELOC and CUL5 and Vif interactions PubMed
    vif The loop 3 (amino acids 69-90) and helix 4 (amino acids 129-140) regions of CBF-beta and the N-terminal regions (amino acids 1-98) of HIV-1 Vif are important for the interaction between CBF-beta and Vif PubMed
    vif CBF-beta-mediated increase of HIV-1 Vif steady-state levels results in decreased cellular levels of all Vif-sensitive APOBEC proteins (A3C, A3D, A3F, A3G, and A3H haplotype II) PubMed
    vif Sucrose gradient centrifugation analysis demonstrates that CBF-beta disrupts the oligomerization status of HIV-1 Vif but not FIV Vif PubMed
    vif The solubility of HIV-1 Vif is significantly enhanced by co-expression of EloB, EloC, and CBF-beta in vitro PubMed
    vif The interaction of HIV-1 Vif with EloB/EloC complex is important for the binding of Vif to CBF-beta in cells. The Vif SOCS box mutant (SLQ to AAA) significantly disrupt its interaction with the EloB/EloC complex PubMed
    vif HIV-1 Vif can assemble into the Cul5-containing E3 ligase, the CUL5-RBX2-CBF-beta-ELOB-ELOC complex, in the presence of CBF-beta PubMed
    vif The HIV-1 Vif mutant G84A and 86SIEW/AAAA89 has a complete loss of the binding to CBF-beta, indicating that G84 and 86SIEW89 are critical for the Vif-CBF-beta interaction PubMed
    vif Simultaneous substitution of the three Vif-interacting residues L52, W53, and D55 and the two ELOC-interacting residues P41 and H48 in CUL5 impairs the ability of CUL5 to interact with the Vif-CBF-beta-ELOB-ELOC protein complex PubMed
    vif The N-terminal peptide (residues 6-12) of Vif forms an antiparallel beta-sheet with beta-strand S3 from CBF-beta. Vif residues W5, V7, and I9 point to the beta-barrel region and make hydrophobic contacts with their neighboring residues of CBF-beta PubMed
    vif The absence of Vif-CBF-beta reduces the interaction between the CUL5 and the EloC-EloB complex, indicating that the former two proteins have a critical role in promoting assembly of the pentameric complex PubMed
    vif HIV-1 Vif mutants W5S, W21S, W38S, W89S, F112S, and F115S have a reduced ability to interact with CBF-beta and these Vif hydrophobic residues are important for Vif-mediated degradation of A3F and A3G PubMed
    vif HIV-1 Vif residues 5 to 126 are required to form a stable complex with CBF-beta and Vif residues W5, W21, W38, W89, F112, and F115 contribute to hydrophobic interactions with CBF-beta PubMed
    vif HIV-1 Vif mutant E88A/W89A fails to bind to CBF-beta, which impairs Vif-mediated degradation of both A3F and A3G proteins and HIV-1 replication in non-permissive CEM cells PubMed
    vif CBF-beta enhances the rate of HIV-1 Vif biosynthesis at a posttranscriptional level PubMed
    vif CBFbeta1-126 is fully functional in the HIV-1 Vif-mediated degradation of A3G, but a further deletion of the C-terminal six amino acid residues (CBFbeta1-120) almost completely abolish its ability to contribute to Vif-induced A3G degradation PubMed
    vif The substitution of Leu64 or Ile66 with serine abolishes the ability of CBF-beta to interact with the Vif-EloB/EloC complex, while the substitution of Thr68 or Tyr69 with alanine has an intermediate effect on the interaction of CBF-beta with the complex PubMed
    vif CUL5/RBX2/ELOB/ELOC/Vif/CBF-beta complex catalyzes polyubiquitin chain formation on A3G in the presence of ubiquitin E2 UBE2R1 (CDC34) or UBCH5b (UBE2D2) PubMed
    vif HIV-1 Vif W21A and Vif W38A mutants have a reduced ability to interact with CBF-beta when compared to full-length Vif PubMed
    vif HIV-1 Vif induces ubiquitination of CBF-beta in cells PubMed
    vif The binding of HIV-1 Vif to CBF-beta is mutually exclusive of endogenous RUNX transcriptional factors in cells. Vif inhibits transcription of a RUNX1 reporter gene by competition with CBF-beta PubMed
    vif The interaction between the HIV-1 Vif PPLP motif (residues 161-164) and the 34-amino-acid C-terminal tail (residues 85-118) of EloB plays a role in promoting recruitment of CBF-beta to the Vif-Cul5 E3 complex PubMed
    vif UBE2F and RBX2 are required for activation of the polyubiquitin synthesis activity of Vif/CBF-beta/CUL5, leading to HIV-1 Vif-mediated degradation of A3G in cells PubMed
    vif The first six amino acids (residues 68-73) in loop 3 of CBFbeta are important for HIV-1 Vif binding and function PubMed
    vif The C-terminal tail (residues 131-182) of CBFbeta is dispensable for both Vif-induced A3G degradation and RUNX1-mediated gene transcription PubMed
    vif CBFbeta1-130, but not CBFbeta1-126, can fully support RUNX1-mediated gene transcription, indicating CBFbeta acts through different domains in its interaction with Vif and RUNX1 PubMed
    vif HIV-1 Vif coprecipitates with CBF-beta in HIV-1-infected H9 cells and transfected 293T cells PubMed
    vif CBF-beta and the N-terminal half of HIV-1 Vif enhance the affinity of Cul5 for Vif PubMed
    vif CBF-beta isoform 1 and isoform 2 stabilize HIV-1 Vif to degrade A3G and increase viral infectivity. CBF-beta stabilizes Vif proteins from multiple HIV-1 subtypes (A, B, C, D, AE, F, and G) PubMed
    vif CBF-beta isoform 1 and isoform 2 have a direct physical interaction with HIV-1 Vif and improves the solubility of Vif PubMed
    vif HIV-1 Vif is identified to have a physical interaction with core-binding factor, beta subunit (CBFB) in human HEK293 and Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    vif A mutagenesis screen of CBF-beta surface residues reveals that a single amino acid change, F68D, disrupts HIV-1 Vif binding and its ability to degrade APOBEC3G PubMed
    vif Seven amino acid substitutions in CBF-beta result in either a significant reduction (Q8R, G61A, N63K, I102E, N104A, or E135R) or complete ablation (N104K) of the CBF-beta/RUNX1 interaction, which does not disrupt the interaction with HIV-1 Vif PubMed

    Go to the HIV-1, Human Interaction Database

    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    DNA-binding transcription factor activity TAS
    Traceable Author Statement
    more info
    PubMed 
    RNA polymerase II transcription factor activity, sequence-specific DNA binding ISM
    Inferred from Sequence Model
    more info
    PubMed 
    RNA polymerase II transcription factor activity, sequence-specific DNA binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    contributes_to sequence-specific DNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    transcription coactivator activity IEA
    Inferred from Electronic Annotation
    more info
     
    transcription coregulator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    Process Evidence Code Pubs
    cell maturation IEA
    Inferred from Electronic Annotation
    more info
     
    definitive hemopoiesis IEA
    Inferred from Electronic Annotation
    more info
     
    lymphocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    myeloid cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of CD4-positive, alpha-beta T cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of transcription by RNA polymerase II ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    osteoblast differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of CD8-positive, alpha-beta T cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
     
    protein polyubiquitination IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of B cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    regulation of Wnt signaling pathway TAS
    Traceable Author Statement
    more info
     
    regulation of bicellular tight junction assembly TAS
    Traceable Author Statement
    more info
     
    regulation of cytokine-mediated signaling pathway TAS
    Traceable Author Statement
    more info
     
    regulation of hematopoietic stem cell differentiation TAS
    Traceable Author Statement
    more info
     
    regulation of intracellular estrogen receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    regulation of keratinocyte differentiation TAS
    Traceable Author Statement
    more info
     
    regulation of megakaryocyte differentiation TAS
    Traceable Author Statement
    more info
     
    regulation of myeloid cell differentiation TAS
    Traceable Author Statement
    more info
     
    regulation of regulatory T cell differentiation TAS
    Traceable Author Statement
    more info
     
    regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    transcription by RNA polymerase II TAS
    Traceable Author Statement
    more info
    PubMed 
    transcription initiation from RNA polymerase II promoter TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    core-binding factor complex TAS
    Traceable Author Statement
    more info
    PubMed 
    membrane HDA PubMed 
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    core-binding factor subunit beta
    Names
    CBF-beta
    PEA2-beta
    PEBP2-beta
    SL3-3 enhancer factor 1 beta subunit
    SL3-3 enhancer factor 1 subunit beta
    SL3/AKV core-binding factor beta subunit
    core-binding factor beta subunit
    polyomavirus enhancer binding protein 2, beta subunit

    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.

    Genomic

    1. NG_009281.1 RefSeqGene

      Range
      5001..76912
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001755.2NP_001746.1  core-binding factor subunit beta isoform 2

      See identical proteins and their annotated locations for NP_001746.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region compared to variant 1, that causes a frameshift. The resulting isoform (2) is shorter and has a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      BC018509, L20298
      Consensus CDS
      CCDS10827.1
      UniProtKB/Swiss-Prot
      Q13951
      UniProtKB/TrEMBL
      A0A024R6X2
      Related
      ENSP00000290858.6, OTTHUMP00000174817, ENST00000290858.10, OTTHUMT00000268843
      Conserved Domains (1) summary
      pfam02312
      Location:1165
      CBF_beta; Core binding factor beta subunit
    2. NM_022845.2NP_074036.1  core-binding factor subunit beta isoform 1

      See identical proteins and their annotated locations for NP_074036.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      BC018509, BM679848, L20298
      Consensus CDS
      CCDS45508.1
      UniProtKB/Swiss-Prot
      Q13951
      Related
      ENSP00000415151.2, OTTHUMP00000249581, ENST00000412916.6, OTTHUMT00000421059
      Conserved Domains (1) summary
      pfam02312
      Location:1165
      CBF_beta; Core binding factor beta subunit

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p12 Primary Assembly

      Range
      67029147..67101058
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017023813.1XP_016879302.1  core-binding factor subunit beta isoform X4

      Conserved Domains (1) summary
      pfam02312
      Location:1126
      CBF_beta; Core binding factor beta subunit
    2. XM_005256212.3XP_005256269.1  core-binding factor subunit beta isoform X2

      See identical proteins and their annotated locations for XP_005256269.1

      Conserved Domains (1) summary
      pfam02312
      Location:1126
      CBF_beta; Core binding factor beta subunit
    3. XM_017023812.1XP_016879301.1  core-binding factor subunit beta isoform X3

    4. XM_006721321.2XP_006721384.1  core-binding factor subunit beta isoform X1

      See identical proteins and their annotated locations for XP_006721384.1

      Conserved Domains (1) summary
      pfam02312
      Location:1126
      CBF_beta; Core binding factor beta subunit
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