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

Gene ID: 865, updated on 8-May-2016
Official Symbol
CBFBprovided by HGNC
Official Full Name
core-binding factor, beta subunitprovided by HGNC
Primary source
HGNC:HGNC:1539
See related
Ensembl:ENSG00000067955 HPRD:00418; 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]
Orthologs
Location:
16q22.1
Exon count:
6
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 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 3 Neighboring gene carboxylesterase 4A Neighboring gene chromosome 16 open reading frame 70 Neighboring gene uncharacterized LOC105371319 Neighboring gene UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 9

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
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, 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 IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
transcription coactivator activity IEA
Inferred from Electronic Annotation
more info
 
transcription factor activity, sequence-specific DNA binding TAS
Traceable Author Statement
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
 
osteoblast differentiation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of transcription from RNA polymerase II promoter IEA
Inferred from Electronic Annotation
more info
 
protein polyubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
transcription from RNA polymerase II promoter TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
membrane IDA
Inferred from Direct Assay
more info
PubMed 
nucleus IEA
Inferred from Electronic Annotation
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
polyomavirus enhancer binding protein 2, 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, OTTHUMP00000174817, ENST00000290858, OTTHUMT00000268843
    Conserved Domains (1) summary
    pfam02312
    Location:1170
    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, OTTHUMP00000249581, ENST00000412916, OTTHUMT00000421059
    Conserved Domains (1) summary
    pfam02312
    Location:1171
    CBF_beta; Core binding factor beta subunit

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000016.10 Reference GRCh38.p2 Primary Assembly

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

mRNA and Protein(s)

  1. XM_005256212.3XP_005256269.1  

    See identical proteins and their annotated locations for XP_005256269.1

    Conserved Domains (1) summary
    pfam02312
    Location:1132
    CBF_beta; Core binding factor beta subunit
  2. XM_006721321.2XP_006721384.1  

    See identical proteins and their annotated locations for XP_006721384.1

    Conserved Domains (1) summary
    pfam02312
    Location:1132
    CBF_beta; Core binding factor beta subunit

Alternate CHM1_1.1

Genomic

  1. NC_018927.2 Alternate CHM1_1.1

    Range
    68470009..68542269
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)