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

Summary

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; AllianceGenome:HGNC:1539
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: CLCD2; 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: mouse all
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Genomic context

Location:: 16q22.1

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (67029149..67101058)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (72823442..72895354)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (67063052..67134961)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Heterozygous pathogenic variants involving CBFB cause a new skeletal disorder resembling cleidocranial dysplasia.
Title: Heterozygous pathogenic variants involving CBFB cause a new skeletal disorder resembling cleidocranial dysplasia.
Dysregulation of Mitochondrial Translation Caused by CBFB Deficiency Cooperates with Mutant PIK3CA and Is a Vulnerability in Breast Cancer.
Title: Dysregulation of Mitochondrial Translation Caused by CBFB Deficiency Cooperates with Mutant PIK3CA and Is a Vulnerability in Breast Cancer.
The RUNX/CFBbeta Complex in Breast Cancer: A Conundrum of Context.
Title: The RUNX/CBFβ Complex in Breast Cancer: A Conundrum of Context.
Mutual exclusivity between the fusion gene CBFB::MYH11 and somatic mitochondrial mutations in acute myeloid leukaemia.
Title: Mutual exclusivity between the fusion gene CBFB::MYH11 and somatic mitochondrial mutations in acute myeloid leukaemia.
[Molecular Genetic Characteristics of Acute Myeloid Leukemia Patients with CBFbeta-MYH11 Positive].
Title: [Molecular Genetic Characteristics of Acute Myeloid Leukemia Patients with CBFβ-MYH11 Positive].
Cancer-Associated Exosomal CBFB Facilitates the Aggressive Phenotype, Evasion of Oxidative Stress, and Preferential Predisposition to Bone Prometastatic Factor of Breast Cancer Progression.
Title: Cancer-Associated Exosomal CBFB Facilitates the Aggressive Phenotype, Evasion of Oxidative Stress, and Preferential Predisposition to Bone Prometastatic Factor of Breast Cancer Progression.
TET2 deficiency cooperates with CBFB-MYH11 to induce acute myeloid leukaemia and represents an early leukaemogenic event.
Title: TET2 deficiency cooperates with CBFB-MYH11 to induce acute myeloid leukaemia and represents an early leukaemogenic event.
3'CBFB deletion in CBFB-rearranged acute myeloid leukemia retains morphological features associated with inv(16), but patients have higher risk of relapse and may require stem cell transplant.
Title: 3'CBFB deletion in CBFB-rearranged acute myeloid leukemia retains morphological features associated with inv(16), but patients have higher risk of relapse and may require stem cell transplant.
Non-age-related neoplastic loss of sex chromosome correlated with prolonged survival in real-world CBF-AML patients.
Title: Non-age-related neoplastic loss of sex chromosome correlated with prolonged survival in real-world CBF-AML patients.
Incidental identification of inv(16)(p13.1q22)/CBFB-MYH11 variant transcript in a patient with therapy-related acute myeloid leukemia by routine leukemia translocation panel screen: implications for diagnosis and therapy.
Title: Incidental identification of inv(16)(p13.1q22)/CBFB-MYH11 variant transcript in a patient with therapy-related acute myeloid leukemia by routine leukemia translocation panel screen: implications for diagnosis and therapy.

Submit: New GeneRIF Correction See all GeneRIFs (81)

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

Associated conditions

Description	Tests
Cleidocranial dysplasia 2 MedGen: C5774243 OMIM: 620099 GeneReviews: Not available	not available

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

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
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

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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

RH67901 (e-PCR)
- UniSTS:771

CBFB (e-PCR)
- UniSTS:503416

RH78908 (e-PCR)
- UniSTS:45529

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
contributes_to sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables transcription coactivator activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in cell maturation	IEA Inferred from Electronic Annotation more info
involved_in definitive hemopoiesis	IEA Inferred from Electronic Annotation more info
involved_in lymphocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in myeloid cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of CD4-positive, alpha-beta T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in osteoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of CD8-positive, alpha-beta T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in protein polyubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of core-binding factor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of core-binding factor complex	TAS Traceable Author Statement more info	PubMed
located_in membrane	HDA more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info

General protein information

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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

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.

Genomic

NG_009281.1 RefSeqGene

Range

5003..76912

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1364

mRNA and Protein(s)

NM_001368707.1 → NP_001355636.1 core-binding factor subunit beta isoform 3

Status: REVIEWED

Description

Transcript Variant: Variants 3 and 4 encode isoforms that are the same length, but have distinct protein sequences.

Source sequence(s)

AC009084, AC074143

Conserved Domains (1) summary

pfam02312
Location:1 → 128

CBF_beta; Core binding factor beta subunit
NM_001368708.1 → NP_001355637.1 core-binding factor subunit beta isoform 4

Status: REVIEWED

Description

Transcript Variant: Variants 3 and 4 encode isoforms that are the same length, but have distinct protein sequences.

Source sequence(s)

AC009084, AC074143

Conserved Domains (1) summary

pfam02312
Location:1 → 128

CBF_beta; Core binding factor beta subunit
NM_001368709.1 → NP_001355638.1 core-binding factor subunit beta isoform 5

Status: REVIEWED

Description

Transcript Variant: Variants 5 and 6 encode isoforms that are the same length, but have distinct protein sequences.

Source sequence(s)

AC009084, AC074143

Conserved Domains (1) summary

pfam02312
Location:1 → 128

CBF_beta; Core binding factor beta subunit
NM_001368710.1 → NP_001355639.1 core-binding factor subunit beta isoform 6

Status: REVIEWED

Description

Transcript Variant: Variants 5 and 6 encode isoforms that are the same length, but have distinct protein sequences.

Source sequence(s)

AC009084, AC074143

Conserved Domains (1) summary

pfam02312
Location:1 → 128

CBF_beta; Core binding factor beta subunit
NM_001755.3 → NP_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

A8K347, Q13124, Q13951, Q9HCT2

UniProtKB/TrEMBL

A8K719

Related

ENSP00000290858.6, ENST00000290858.11

Conserved Domains (1) summary

pfam02312
Location:1 → 167

CBF_beta; Core binding factor beta subunit
NM_022845.3 → NP_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 longest isoform (1).

Source sequence(s)

BC018509, BM679848, L20298

Consensus CDS

CCDS45508.1

UniProtKB/TrEMBL

A8K719

Related

ENSP00000415151.2, ENST00000412916.7

Conserved Domains (1) summary

pfam02312
Location:1 → 167

CBF_beta; Core binding factor beta subunit