CBFA2T3 (core-binding factor, runt domain, alpha subunit 2; translocated to, 3)

2005-10-01   Anthony J Bais  

Department of Haematology, Genetic Pathology, Flinders University, Bedford Park, Adelaide, SA 5042, Australia

Identity

HGNC
CBFA2T3
LOCATION
16q24.3
LOCUSID
863
ALIAS
ETO2,MTG16,MTGR2,RUNX1T3,ZMYND4
FUSION GENES
Show Gene Fusions

DNA/RNA

Description

CBFA2T3 encodes two alternative transcripts, CBFA2T3A and CBFA2T3B, via the use of alternative start sites at exons 1A and 1B, respectively.
  • CBFA2T3A is 4,265-bp in length, composed of 13 exons (1A and 2 to 12) spanning approximately 130-kb of genomic DNA, and has an ORF of 1,959-bp encoding a protein of 653 amino acids.
  • CBFA2T3B is 4,034-bp in length, composed of 12 exons (1B to 12 splicing out exon 3) spanning approximately 50-kb of genomic DNA, and has an ORF of 1,701-bp encoding a protein of 567 amino acids.
  • Additional CBFA2T3C and CBFA2T3D isoforms have been identified in leukemic and HEL cell lines. CBFA2T3C encodes a protein that lacks exons 2 and 3, and CBFA2T3D is a truncated protein with out-of-frame splicing of exon 1A to exon 5.
  • The CBFA2T3A open-reading-frame (ORF) may include an additional 177 amino acids beyond the originally proposed methionine start codon.
  • The CBFA2T3B isoform contains a high-density 1-kb CpG island within and five prime to the exon 1B start site.
  • A hypothetical protein FLJ26728 located within and proximal to the CpG island transcribes antisense to CBFA2T3. Another hypothetical protein FLJ23429 transcribes antisense starting from within the first alternative intron.

    • Pseudogene

    None identified.

    Proteins

    Description

    ETO proteins are composed of four evolutionarily conserved domains termed nervy homology regions (NHR1 to 4) and three proline-serine-threonine (PST) rich regions. The fourth NHR region is also referred to as the zinc-finger MYND (zf myeloid-nervy-DEAF-1) domain.
  • NHR1 shares significant homology to human TATA-binding protein (TBP)-associated factor 130 (hTAF 130), hTAF 105, Drosophila accessory or activation factor TAF 110, and is often referred to as the TAF 110 domain.
  • NHR2 is a small region containing homo and heterodimerization domains and a hydrophobic heptad repeat (HHR) unit.
  • The sequence of NHR3 is unremarkable in homology and often referred to as the nervy domain.
  • The C-terminal NHR4 domain exists in numerous human, murine, Caenorhabditis elegans and Drosophila proteins, and contains a MYND zinc-finger motif. The motif is composed of CXXC and two (C-H)XXXC regions which correspond to cysteine-histidine knuckle structures that are the basic building blocks of many zinc-finger proteins. The zinc-finger is common to the developmental proteins rat programmed cell death (RP-8), the human homolog programmed cell death 2 (PDCD2), deformed epidermal autoregulatory factor-1 (DEAF-1), suppressin (SPN), BLU or zinc-finger MYND domain containing 10 (ZMYND10), adenovirus 5 E1A binding protein (BS69), and CD8 beta opposite (BOP).

    • Expression

    CBFA2T3 is widely expressed in B-cells, blood, brain, breast, cervix, colon, eye, kidney tumor, lymph, marrow, muscle, pancreas, placenta and tonsil. CBFA2T3 exists predominantly as 4.5 and 4.2-kb transcripts along with several other minor RNAs in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocyte.

    Localisation

    All ETO members contain nuclear localization signals (NLS), some of which may be abrogated through five prime variations to enable extracellular targeting. For instance, CBFA2T1 has been detected in the cytoplasm of Purkinje cells in adult human brain, and both CBFA2T1 and CBFA2T3B have been detected in the Golgi apparatus, where they may function as cAMP-dependent protein kinase anchoring proteins. The majority of ETO proteins presumably remain in the nucleus for transcriptional regulation.

    Function

    CBFA2T3 has been considered to function as a transcriptional repressor via interaction with corepressor complexes.
  • The CBFA2T3A isoform oligomerizes and drags MTG8 and MTGR1 to the nucleus, oligomerizes with RUNX1-MTG16 fusion proteins in the nucleoplasm, interacts with nuclear HDACs 1 and 3, and when overexpressed accumulates at the periphery of nucleoli in characteristic rings. Because clustered arrays of inactive methylated ribosomal DNA (rDNA) repeats are also found at the nucleoli periphery, it has been speculated that CBFAT23A could be involved in methylation silencing of rDNA in the nucleolus.
  • The CBFA2T3B isoform has been shown to function in T lymphocytes as a kinase anchorage protein, and interact with cyclic nucleotide phosphodiesterases, suggesting it may function in T cell activation and inflammatory response. CBFA2T3B has been shown to function as a transcriptional repressor when tethered to a GAL4 DNA-binding domain in gene reporter assays, and inhibit the growth of breast tumor cell lines with reduced expression when ectopically expressed using retrovirus.

    CBFA2T3 has been found to interact with a novel zinc finger protein KIA00924 to mediate potent transcriptional repression as determined by CAT reporter gene assays. The presence of a zinc-finger motif common to developmental proteins suggests that CBFA2T3 might function in regulating differentiation and morphogenesis. The RP-8 and human homolog PDCD2 proteins assume a role in programmed cell death, a process essential for epithelial turnover. DEAF-1 is essential for early embryonic dorsal epidermal, eye and wing development in Drosophila. BOP encodes a muscle-restricted protein essential for cardiomyocyte differentiation and morphogenesis. BLU is a candidate tumor suppressor gene from the 3p21.3 LOH region in many human cancers, and SPN from rat functions as a potent tumor suppressor of leukemia, lymphoma and thymoma cells and tumor cells from the brain, breast, pituitary and adrenal glands.
    CBFA2T3 transcripts of CD34(+) progenitor cells have been shown to be rapidly reduced by cytokine-induced differentiation into myeloid or erythroid lineages, supporting suggestion that CBFA2T3 may function in hematopoietic differentiation. The CBFA2T3B CpG island contains several Specificity protein 1 (Sp1), homeotic, epidermal and insulin growth factor recognition sites. High conserved binding sites include GATA-1, CREB, F-1 and PKNOX1.

    • Homology

    The human gene CBFA2T3 is a member of the eight-twenty-one (ETO) family of proteins. The human ETO family consists of the ETO gene, also known as the myeloid translocation gene 8 (MTG8, CBFA2T1), the myeloid translocation gene related protein-1 (EHT, MTGR1, CBFA2T2), and the myeloid translocation gene 16 (MTG16, MTGR2, ZMYND4, HGNC:1537, CBFA2T3).
    Murine homologs of the ETO family include mETO (cbfa2t1h), ET0-2 (cbfa2t3h), and cbfa2t2h, the latter of which is uncharacterised. Chicken cETO and Drosophila nervy homologs have also been identified.
    The ETO protein family members and NHRs are highly homologous and conserved to each other. The CBFA2T3A and B isoforms share significant homology to MTG8 (67 and 75%, respectively) and MTGR1 (54 and 61%, respectively), and approximately 30% homology to nervy. CBFA2T3 shares 86% homology to the murine ETO-2 (cbfa2t3h), which in turn shares 75 and 60% homology to MTG8 and MTGR1, respectively, suggesting that ETO-2 is the murine homolog of CBFA2T3. MTG8 is approximately 99, 65 and 30% homologous to murine ETO, MTGR1 and nervy, respectively.

    Mutations

    Note

    None recorded.

    Implicated in

    Entity name
    t(16;21)(q24;q22) in therapy related acute myeloid leukemia (t-AML) --> CBFA2T3/ RUNX1
    Note
    CBFA2T3 or MTG16 was identified by molecular characterization of a second less common therapy-related AML translocation involving t(16;21). Characterization of the t(16;21) demonstrated that RUNX1-MTG16 fusion transcripts similar to RUNX1-ETO were generated
    Fusion protein
  • The RUNX1-MTG8, and to a lesser extent the RUNX1-MTG16, fusion transcripts of the t(8;21)(q22;q22) and t(16;21) events are most recognized for their ability to function as transcriptional repressors of genes normally activated by RUNX1 through their interaction with corepressor complexes involving N-CoR, mSin3A, SMRT, and HDACs.
  • The MTG8 or CBFA2T1 gene is the most studied member of the ETO family and is additionally recognized for its ability to function independently as a nuclear transcriptional repressor through nuclear corepressor complex interaction. Gene targeting experiments demonstrating that homozygous mutant mice with an inactivating insertion of LacZ in exon 2 of the MTG8 locus resulted in massive gastrointestinal defects, have also shown that MTG8 and perhaps ETO family members are essential for gastrointestinal development .
  • Multiple NHRs of the ETO family of proteins are required and cooperate to mediate transcriptional repression. Most of the proteins that interact with NHRs have been assigned from studies of RUNX1-MTG8 and its interacting proteins. Studies originally demonstrated that MTG8s NHR2 and NHR4 were required for AML-MTG8 to inhibit RUNX1 mediated transcriptional activation and initiated the search for corepressor complexes that bind to these regions. Several yeast two-hybrid systems using portions of MTG8 as bait demonstrated that specific portions of NHR2, NHR3 and NHR4 interact with the human nuclear receptor co-repressor (HuN-CoR)-mSin3A-HDAC1 corepressor complex.
  • The N-CoR protein was originally described to interact with DNA-bound nuclear receptors to repress transcription of target genes through recruitment of HDAC containing complexes and was latter shown to form complexes with mammalian Sin3 to alter chromatin structure and mediate transcriptional repression via nuclear receptors and oncoregulatory proteins.
  • A similar yeast two-hybrid approach also established that the corepressor silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) interacts with MTG8. The zinc-finger NHR4 is necessary but not sufficient for repression and interaction with SMRT and N-CoR in vitro. The direct physical association of MTG8 with corepressors is more complex. A core-repressor domain containing NHR2 and the neighboring amino and carboxy terminal sequences was defined and found to be the strongest region of interaction with mSin3a and transcriptional repression.
  • In the RUNX1-MTG8 translocation product associated with myeloid malignancies, the transactivation domain of the RUNX1 gene, which normally binds the transcriptional coactivators p300-CBP, is replaced by almost the entire MTG8 protein. The resultant fusion protein recruits a corepressor complex containing HDAC activity instead of the coactivators p300-CBP to RUNX1 responsive genes giving rise to leukemia. The repression activity of the MTG8 protein was demonstrated from a GAL4 DNA binding domain (DBD) MTG8 fusion construct which mediated strong repression through multimerized GAL4 binding sites upstream of a minimal promoter driving a reporter gene. Consistent with a mechanism involving MTG8 and HDAC corepressor interactions, the repressive effect of MTG8 was partially overcome with the addition of the HDAC inhibitor trichostatin A (TSA). Mutational studies of RUNX1-MTG8 have shown that NHR4 is responsible for repression of the multidrug resistance 1 promoter.
  • MTG8 has also been shown to interact with the Dentato-rubral and Pallido-luysian atrophy gene product, atrophin-1, in a yeast two-hybrid assay. Both Dentato-rubral and Pallido-luysian atrophies are neurodegenerative disorders caused by expansion of polyglutamine tracts.
  • Several other transcriptional repressors have been shown to interact with MTG8. The promyelocytic leukemia zinc-finger ( PLZF), a transcriptional repressor found in hematopoietic cells and down-regulated during differentiation of myeloid cell lines was shown to exhibit enhanced repressor activity when interacting with MTG8 in 293T cells and assayed using a reporter plasmid containing four copies of a high affinity PLZF binding site linked to firefly luciferase. The ability of MTG8 to enhance repression was abolished upon addition of HDAC inhibitors TSA and sodium butyrate, suggesting that the MTG8 enhanced repression by PLZF is also mediated through the recruitment of HDACs.
  • The Growth factor independence-1 (Gfi-1), a HDAC interacting transcriptional repressor found in hematopoietic cells, was shown in vitro and in vivo to interact with NHR1 and NHR2 of MTG8. These interactions together with gene targeting experiments demonstrating MTG8s involvement in gastrointestinal development, the well established interactions with corepressor complexes, and the presence of a zinc-finger motif common to numerous developmental proteins, suggests that ETO family members including CBFA2T3 may play function in regulating cell cycle transcription during differentiation and proliferation of specific cell type-lineages, for example hematopoietic cells as indicated for MTG8.
    • Entity name
    Loss of heterozygosity (LOH) of 16q22-qter in breast cancer, prostate cancer, and several other cancers
    Note
    This region is frequently deleted in several human cancers causing loss of heterozygosity. The 16q24.3 region including CBFA2T3 spans approximately 3-Mb from the marker D16S498 to the telomere and contains at least two smallest regions of overlap (SROs). These SROs are most frequently deleted in early and late stage breast cancer and in prostate cancer. Loss of normal function of CBFA2T3 may be a key event in the early stage of breast cancer. LOH on the whole 16q22-qter region is frequently detected in breast and prostate cancer.
    CBFA2T3B is a potential tumor suppressor gene affected by LOH, aberrant gene expression and promoter methylation in breast cancer. Quantitative gene expression analysis of 78 genes in the 16q24.3 region demonstrated that CBFA2T3 was the only gene with an aberrant expression profile distinctly similar to the known tumor suppressors SYK and CDKN2A. 68 genes displayed normal expression, six displayed mildly aberrant expression (DPEP1, CDH15, Hs.17074, Hs.189419, SLC7A5 and AA994450), one displayed excessively reduced expression (CA5A), and two displayed moderately aberrant expression (CYBA and FBX031). The CBFA2T3B promoter region displays aberrant hypo and hypermethylation in breast tumor cell lines and primary breast tumor samples in correlation with aberrant gene expression.
    Disease
    16q22-qter LOH is detected in bilateral breast cancer and ductal lavage, in rare inflammatory breast cancer, and in several other cancers, including central nervous system neuroectodermal and primary ependymomas, colorectal liver metastases, gastric tumor, head and neck squamous cell carcinoma, hepatocellular carcinoma, lung tumor, nasopharyngeal tumor, ovarian tumor, rhabdomyosarcoma, and Wilms tumor. 16q22-qter LOH in ovarian, hepatocellular and particularly breast and prostate cancers, exhibit similar SROs, suggesting common molecular pathways are affected.

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
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    115332362001ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain.Amann JM et al
    117335282002The conserved Mynd domain of BS69 binds cellular and oncoviral proteins through a common PXLXP motif.Ansieau S et al
    154700202004A-kinase anchoring proteins interact with phosphodiesterases in T lymphocyte cell lines.Asirvatham AL et al
    153016882004Aberrant CBFA2T3B gene promoter methylation in breast tumors.Bais AJ et al
    97907521998CBFA2T1, a gene rearranged in human leukemia, is a member of a multigene family.Calabi F et al
    114638462001Gene targeting reveals a crucial role for MTG8 in the gut.Calabi F et al
    19789381990Allelic loss of chromosomes 16q and 10q in human prostate cancer.Carter BS et al
    75661271995A transcriptional co-repressor that interacts with nuclear hormone receptors.Chen JD et al
    94610101998Frequent allelic loss on chromosomes 4q and 16q associated with human hepatocellular carcinoma in Taiwan.Chou YH et al
    115611582001The role of promyelocytic leukemia zinc finger and promyelocytic leukemia in leukemogenesis and development.Costoya JA et al
    125595622003The ETO (MTG8) gene family.Davis JN et al
    100228201999ETO-2, a new member of the ETO-family of nuclear proteins.Davis JN et al
    125082472003Genetic profiling of colorectal cancer liver metastases by combined comparative genomic hybridization and G-banding analysis.Diep CB et al
    13919461992Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt.Erickson P et al
    81372931994The ETO portion of acute myeloid leukemia t(8;21) fusion transcript encodes a highly evolutionarily conserved, putative transcription factor.Erickson PF et al
    74987381995Identification of homeotic target genes in Drosophila melanogaster including nervy, a proto-oncogene homologue.Feinstein PG et al
    97871951998EHT, a new member of the MTG8/ETO gene family, maps on 20q11 region and is deleted in acute myeloid leukemias.Fracchiolla NS et al
    115934312001MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes.Fukuyama T et al
    95966461998The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8(ETO) family.Gamou T et al
    98194051998Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO.Gelmetti V et al
    93091161997Allelic imbalance mapping of chromosome 16 shows two regions of common deletion in prostate adenocarcinoma.Godfrey TE et al
    119238732002Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis.Gottlieb PD et al
    107114432000Allelic imbalance on 16q in small, unifocal hepatocellular carcinoma: correlation with HBV and HCV infections and cellular proliferation rate.Gramantieri L et al
    88876561996The Gfi-1 proto-oncoprotein contains a novel transcriptional repressor domain, SNAG, and inhibits G1 arrest induced by interleukin-2 withdrawal.Grimes HL et al
    86172431996DEAF-1, a novel protein that binds an essential region in a Deformed response element.Gross CT et al
    153897802005Loss of heterozygosity in chromosomal region 16q24.3 associated with progression of prostate cancer.Härkönen P et al
    75661141995Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor.Hörlein AJ et al
    125471492002Allelic imbalance in selected chromosomal regions in ovarian cancer.Hansen LL et al
    115873632001Mechanisms of transcriptional repression by the t(8;21)-, t(12;21)-, and inv(16)-encoded fusion proteins.Heibert SW et al
    91398201997A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression.Heinzel T et al
    111503062001Multiple regions of ETO cooperate in transcriptional repression.Hildebrand D et al
    76787801993Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators.Hoey T et al
    122426702002The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies.Hoogeveen AT et al
    75909681995Bop: a new T-cell-restricted gene located upstream of and opposite to mouse CD8b.Hwang I et al
    152316652004AML1-ETO decreases ETO-2 (MTG16) interactions with nuclear receptor corepressor, an effect that impairs granulocyte differentiation.Ibañez V et al
    110205462000Lithium treatment in ovo: effects on embryonic heart rate, natural death of ciliary ganglion neurons, and brain expression of a highly conserved chicken homolog of human MTG8/ETO.Ikonomov OC et al
    94479811998The AML1-MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8(ETO/CDR) family, MTGR1.Kitabayashi I et al
    121834142002CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast cancer loss of heterozygosity region at 16q24.3.Kochetkova M et al
    90672711997Loss of heterozygosity at chromosome 16q in prostate adenocarcinoma: identification of three independent regions.Latil A et al
    111040332000Loss of heterozygosity at chromosomes 3, 6, 8, 11, 16, and 17 in ovarian cancer: correlation to clinicopathological variables.Launonen V et al
    74786041995Functional domains of the t(8;21) fusion protein, AML-1/ETO.Lenny N et al
    124480042002Evidence of chromosome regions and gene involvement in inflammatory breast cancer.Lerebours F et al
    156762132005The Leukemia-associated ETO homologues are differently expressed during hematopoietic differentiation.Lindberg SR et al
    95842011998The MYND motif is required for repression of basal transcription from the multidrug resistance 1 promoter by the t(8;21) fusion protein.Lutterbach B et al
    107343132000The adenovirus E1A binding protein BS69 is a corepressor of transcription through recruitment of N-CoR.Masselink H et al
    124975832003Clinical significance of chromosome 8p, 10q, and 16q deletions in prostate cancer.Matsuyama H et al
    13172581992A third Wilms' tumor locus on chromosome 16q.Maw MA et al
    128748342003Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism.McGhee L et al
    110900812000AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein.Melnick A et al
    88342311995Indirect and direct disruption of transcriptional regulation in cancer: E2F and AML-1.Meyers S et al
    83349901993The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript.Miyoshi H et al
    17205411991t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1.Miyoshi H et al
    104088661999Chromosome band 16q24 is frequently deleted in human gastric cancer.Mori Y et al
    85757701995Cloning and gene mapping of the mouse homologue of the CBFA2T1 gene associated with human acute myeloid leukemia.Niwa-Kawakita M et al
    20729131991Identification of mRNAs associated with programmed cell death in immature thymocytes.Owens GP et al
    110148152000Regulation by homeoproteins: a comparison of deformed-responsive elements.Pederson JA et al
    122132002002Sequencing, transcript identification, and quantitative gene expression profiling in the breast cancer loss of heterozygosity region 16q24.3 reveal three potential tumor-suppressor genes.Powell JA et al
    75467291995When more is less: pathogenesis of glutamine repeat neurodegenerative diseases.Ross CA et al
    152031992004The MTG proteins: chromatin repression players with a passion for networking.Rossetti S et al
    96321371998Subcellular localization of the oncoprotein MTG8 (CDR/ETO) in neural cells.Sacchi N et al
    126209082003Fine mapping of Wilms' tumors with 16q loss of heterozygosity localizes the putative tumor suppressor gene to a region of 6.7 megabases.Safford SD et al
    13517531992Loss of heterozygosity on chromosome 16 in hepatocellular carcinoma.Sakai K et al
    95916281998Identification of a 910-kb region of common allelic loss in chromosome bands 16q24.1-q24.2 in human lung cancer.Sato M et al
    16820351991Accumulation of genetic alterations and progression of primary breast cancer.Sato T et al
    121496462002PDCD2 is a negative regulator of HCF-1 (C1).Scarr RB et al
    118234862002Identification and characterization of myeloid translocation gene 16b as a novel a kinase anchoring protein in T lymphocytes.Schillace RV et al
    76640421994Zinc mining for protein domains.Schwabe JW et al
    89462041996Three distinct commonly deleted regions of chromosome arm 16q in human primary and metastatic prostate cancers.Suzuki H et al
    16707631991Loss of heterozygosity on 6q, 16q, and 17p in human central nervous system primitive neuroectodermal tumors.Thomas GA et al
    21685601990Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma.Tsuda H et al
    121128742002DEAF-1 function is essential for the early embryonic development of Drosophila.Veraksa A et al
    93150991997Allelotype of pediatric rhabdomyosarcoma.Visser M et al
    97247951998ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex.Wang J et al
    103831271999Inhibitors of histone deacetylase relieve ETO-mediated repression and induce differentiation of AML1-ETO leukemia cells.Wang J et al
    100246911999Cervical metastases of head and neck squamous cell carcinoma correlate with loss of heterozygosity on chromosome 16q.Wang X et al
    109739862000Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription.Wood JD et al
    115265142001Identification of homozygous deletions at chromosome 16q23 in aflatoxin B1 exposed hepatocellular carcinoma.Yakicier MC et al
    117804682001Novel chromosomal alterations detected in primary nasopharyngeal carcinoma by comparative genomic hybridization.Yan J et al
    157564512005Loss of heterozygosity in ductal lavage for breast tumor and the contralateral breast.Yonekura Y et al
    111131902001Oligomerization of ETO is obligatory for corepressor interaction.Zhang J et al
    19705541990Frequent loss of heterozygosity on chromosomes 16 and 4 in human hepatocellular carcinoma.Zhang WD et al
    111040272000Comparative genomic hybridization detects losses of chromosomes 22 and 16 as the most common recurrent genetic alterations in primary ependymomas.Zheng PP et al

    Other Information

    Locus ID:

    NCBI: 863
    MIM: 603870
    HGNC: 1537
    Ensembl: ENSG00000129993

    Variants:

    dbSNP: 863
    ClinVar: 863
    TCGA: ENSG00000129993
    COSMIC: CBFA2T3

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000129993ENST00000268679O75081
    ENSG00000129993ENST00000327483O75081
    ENSG00000129993ENST00000562719H3BSI4
    ENSG00000129993ENST00000563640H3BNI7
    ENSG00000129993ENST00000564416H3BMZ0
    ENSG00000129993ENST00000566868J3QRB1
    ENSG00000129993ENST00000569443H3BU07
    ENSG00000129993ENST00000569464H3BNH2
    ENSG00000129993ENST00000570046H3BR72

    Expression (GTEx)

    0
    10
    20
    30
    40
    50
    60
    70
    Adipose - Subcutaneous
    Adipose - Visceral
    Adrenal Gland
    Artery - Aorta
    Artery - Tibial
    Bladder
    Brain - Amygdala
    Brain - Anterior cingulate cortex
    Brain - Caudate
    Brain - Cerebellar Hemisphere
    Brain - Cerebellum
    Brain - Cortex
    Brain - Frontal Cortex
    Brain - Hippocampus
    Brain - Hypothalamus
    Brain - Nucleus accumbens
    Brain - Putamen
    Brain - Spinal cord
    Brain - Substantia nigra
    Breast - Mammary Tissue
    Cells - Cultured fibroblasts
    Cells - EBV - transformed lymphocytes
    Cervix - Ectocervix
    Cervix - Endocervix
    Colon - Sigmoid
    Colon - Transverse
    Esophagus - Gastroesophageal Junction
    Esophagus - Mucosa
    Esophagus - Muscularis
    Fallopian Tube
    Heart - Atrial Appendage
    Heart - Left Ventricle
    Kidney - Cortex
    Kidney - Medulla
    Liver
    Lung
    Minor Salivary Gland
    Muscle - Skeletal
    Nerve - Tibial
    Ovary
    Pancreas
    Pituitary
    Prostate
    Skin - Not Sun Exposed
    Skin - Sun Exposed
    Small Intestine - Terminal Ileum
    Spleen
    Stomach
    Testis
    Thyroid
    Uterus
    Vagina
    Whole Blood

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High
    cerebral cortex
    cerebellum
    hippocampus
    caudate
    thyroid gland
    parathyroid gland
    adrenal gland
    nasopharynx
    bronchus
    lung
    oral mucosa
    salivary gland
    esophagus
    stomach 1
    stomach 2
    duodenum
    small intestine
    colon
    rectum
    liver
    gallbladder
    pancreas
    kidney
    urinary bladder
    testis
    epididymis
    seminal vesicle
    prostate
    vagina
    ovary
    fallopian tube
    endometrium 1
    endometrium 2
    cervix, uterine
    placenta
    breast
    heart muscle
    smooth muscle
    skeletal muscle
    soft tissue 1
    soft tissue 2
    adipose tissue
    skin 1
    skin 2
    appendix
    spleen
    lymph node
    tonsil
    bone marrow

    References

    Pubmed IDYearTitleCitations
    382433032024CNS erythroblastic sarcoma: a potential emerging pediatric tumor type characterized by NFIA::RUNX1T1/3 fusions.0
    382433032024CNS erythroblastic sarcoma: a potential emerging pediatric tumor type characterized by NFIA::RUNX1T1/3 fusions.0
    324349282020The transcriptional corepressor CBFA2T3 inhibits all-trans-retinoic acid-induced myeloid gene expression and differentiation in acute myeloid leukemia.7
    329602202020Embryonic erythropoiesis and hemoglobin switching require transcriptional repressor ETO2 to modulate chromatin organization.9
    324349282020The transcriptional corepressor CBFA2T3 inhibits all-trans-retinoic acid-induced myeloid gene expression and differentiation in acute myeloid leukemia.7
    329602202020Embryonic erythropoiesis and hemoglobin switching require transcriptional repressor ETO2 to modulate chromatin organization.9
    308585472019Kaiso is required for MTG16-dependent effects on colitis-associated carcinoma.7
    310401122019Myeloid translocation gene CBFA2T3 directs a relapse gene program and determines patient-specific outcomes in AML.12
    313700312019Genome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ(42) decline in non-demented elders.1
    308585472019Kaiso is required for MTG16-dependent effects on colitis-associated carcinoma.7
    310401122019Myeloid translocation gene CBFA2T3 directs a relapse gene program and determines patient-specific outcomes in AML.12
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    Citation

    Anthony J Bais

    CBFA2T3 (core-binding factor, runt domain, alpha subunit 2; translocated to, 3)

    Atlas Genet Cytogenet Oncol Haematol. 2005-10-01

    Online version: http://atlasgeneticsoncology.org/gene/428/mapkapk2-(mitogen-activated-protein-kinase-activated-protein-kinase-2)