Protein: Runt-related transcription factor 1 (Acute myeloid leukemia 1 protein) (Core-binding factor subunit alpha-2) (CBF-alpha-2) (Oncogene AML-1) (Polyomavirus enhancer-binding protein 2 alpha B subunit) (PEA2-alpha B) (PEBP2-alpha B) (SL3-3 enhancer factor 1 alpha B subunit) (SL3/AKV core-binding factor alpha B subunit) (Q03347)
Organism: Mus musculus (Mouse)
Function: Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters (Probable). Essential for the development of normal hematopoiesis. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter. Inhibits KAT6B-dependent transcriptional activation (By similarity). Involved in lineage commitment of immature T cell precursors. CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation. CBF complexes binding to the transcriptional silencer is essential for recruitment of nuclear protein complexes that catalyze epigenetic modifications to establish epigenetic ZBTB7B silencing. Controls the anergy and suppressive function of regulatory T-cells (Treg) by associating with FOXP3. Activates the expression of IL2 and IFNG and down-regulates the expression of TNFRSF18, IL2RA and CTLA4, in conventional T-cells. Positively regulates the expression of RORC in T-helper 17 cells.
Subcellular location: Nucleus {ECO:0000269|PubMed:17377532}.
Sequence: MRIPVDASTSRRFTPPSTALSPGKMSEALPLGAPDGGPALASKLRSGDRSMVEVLADHPGELVRTDSPNFLCSVLPTHWRCNKTLPIAFKVVALGDVPDGTLVTVMAGNDENYSAELRNATAAMKNQVARFNDLRFVGRSGRGKSFTLTITVFTNPPQVATYHRAIKITVDGPREPRRHRQKLDDQTKPGSLSFSERLSELEQLRRTAMRVSPHHPAPTPNPRASLNHSTAFNPQPQSQMQDARQIQPSPPWSYDQSYQYLGSITSSSVHPATPISPGRASGMTSLSAELSSRLSTAPDLTAFGDPRQFPTLPSISDPRMHYPGAFTYSPPVTSGIGIGMSAMSSASRYHTYLPPPYPGSSQAQAGPFQTGSPSYHLYYGASAGSYQFSMVGGERSPPRILPPCTNASTGAALLNPSLPSQSDVVETEGSHSNSPTNMPPARLEEAVWRPY
InterPro domains: - IPR013711: Runx, C-terminal domain (domain) [361-451]
- IPR008967: p53-like transcription factor, DNA-binding domain superfamily (homologous_superfamily) [52-178]
- IPR013524: Runt domain (domain) [50-179]
- IPR000040: Acute myeloid leukemia 1 protein (AML1)/Runt (family) [4-451]
- IPR016554: Runt-related transcription factor RUNX (family) [1-451]
- IPR012346: p53/RUNT-type transcription factor, DNA-binding domain superfamily (homologous_superfamily) [48-189]
- IPR027384: Runx, central domain superfamily (homologous_superfamily) [306-345]
Interaction partners: - Forkhead box protein P3
- Core-binding factor subunit beta
- Endothelial transcription factor GATA-2
- Protein C-ets-1
- Protein CBFA2T1
- T-cell acute lymphocytic leukemia protein 1 homolog
- Histone deacetylase 1
- Trans-acting T-cell-specific transcription factor GATA-3
- CCAAT/enhancer-binding protein alpha
- Transcription factor PU.1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0140110 (transcription regulator activity), GO:1901363 (heterocyclic compound binding), GO:0003700 (DNA-binding transcription factor activity), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific), GO:0001067 (transcription regulatory region nucleic acid binding), GO:0003677 (DNA binding), GO:0003690 (double-stranded DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0000976 (transcription cis-regulatory region binding), GO:1990837 (sequence-specific double-stranded DNA binding), GO:0000987 (cis-regulatory region sequence-specific DNA binding), GO:0000977 (RNA polymerase II transcription regulatory region sequence-specific DNA binding), GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0040011 (locomotion), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0048856 (anatomical structure development), GO:0009653 (anatomical structure morphogenesis), GO:0042221 (response to chemical), GO:0042330 (taxis), GO:0051240 (positive regulation of multicellular organismal process), GO:0002684 (positive regulation of immune system process), GO:0042303 (molting cycle), GO:0051241 (negative regulation of multicellular organismal process), GO:0071840 (cellular component organization or biogenesis), GO:0051239 (regulation of multicellular organismal process), GO:0009892 (negative regulation of metabolic process), GO:0050793 (regulation of developmental process), GO:0002683 (negative regulation of immune system process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0023051 (regulation of signaling), GO:0021700 (developmental maturation), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0048869 (cellular developmental process), GO:0023056 (positive regulation of signaling), GO:0007275 (multicellular organism development), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0002682 (regulation of immune system process), GO:0022404 (molting cycle process), GO:0051094 (positive regulation of developmental process), GO:0048522 (positive regulation of cellular process), GO:0032989 (cellular component morphogenesis), GO:0010942 (positive regulation of cell death), GO:0002695 (negative regulation of leukocyte activation), GO:0048729 (tissue morphogenesis), GO:0042633 (hair cycle), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0009966 (regulation of signal transduction), GO:0030155 (regulation of cell adhesion), GO:0060255 (regulation of macromolecule metabolic process), GO:0002694 (regulation of leukocyte activation), GO:1903706 (regulation of hemopoiesis), GO:1903707 (negative regulation of hemopoiesis), GO:0071695 (anatomical structure maturation), GO:0051726 (regulation of cell cycle), GO:0000902 (cell morphogenesis), GO:0050866 (negative regulation of cell activation), GO:0007162 (negative regulation of cell adhesion), GO:0048469 (cell maturation), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0001942 (hair follicle development), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0045595 (regulation of cell differentiation), GO:0045786 (negative regulation of cell cycle), GO:0016043 (cellular component organization), GO:1903708 (positive regulation of hemopoiesis), GO:0006935 (chemotaxis), GO:0050865 (regulation of cell activation), GO:0009967 (positive regulation of signal transduction), GO:0045597 (positive regulation of cell differentiation), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0008285 (negative regulation of cell population proliferation), GO:0031069 (hair follicle morphogenesis), GO:0045785 (positive regulation of cell adhesion), GO:0031324 (negative regulation of cellular metabolic process), GO:0050867 (positive regulation of cell activation), GO:0002696 (positive regulation of leukocyte activation), GO:2000026 (regulation of multicellular organismal development), GO:0042127 (regulation of cell population proliferation), GO:0010941 (regulation of cell death), GO:0009888 (tissue development), GO:0010646 (regulation of cell communication), GO:0045596 (negative regulation of cell differentiation), GO:0009889 (regulation of biosynthetic process), GO:0031323 (regulation of cellular metabolic process), GO:0010647 (positive regulation of cell communication), GO:0009890 (negative regulation of biosynthetic process), GO:0022405 (hair cycle process), GO:0080090 (regulation of primary metabolic process), GO:0051216 (cartilage development), GO:0030030 (cell projection organization), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0022409 (positive regulation of cell-cell adhesion), GO:0043067 (regulation of programmed cell death), GO:0097485 (neuron projection guidance), GO:0022407 (regulation of cell-cell adhesion), GO:0061448 (connective tissue development), GO:0032990 (cell part morphogenesis), GO:0002009 (morphogenesis of an epithelium), GO:0043588 (skin development), GO:0050678 (regulation of epithelial cell proliferation), GO:0051250 (negative regulation of lymphocyte activation), GO:0010468 (regulation of gene expression), GO:0048666 (neuron development), GO:0000904 (cell morphogenesis involved in differentiation), GO:0051251 (positive regulation of lymphocyte activation), GO:0007399 (nervous system development), GO:0001501 (skeletal system development), GO:0008544 (epidermis development), GO:1902105 (regulation of leukocyte differentiation), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0022408 (negative regulation of cell-cell adhesion), GO:0048858 (cell projection morphogenesis), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0051249 (regulation of lymphocyte activation), GO:1902106 (negative regulation of leukocyte differentiation), GO:0043068 (positive regulation of programmed cell death), GO:0060284 (regulation of cell development), GO:0010720 (positive regulation of cell development), GO:2001235 (positive regulation of apoptotic signaling pathway), GO:2001233 (regulation of apoptotic signaling pathway), GO:0022008 (neurogenesis), GO:0050680 (negative regulation of epithelial cell proliferation), GO:1902107 (positive regulation of leukocyte differentiation), GO:0002062 (chondrocyte differentiation), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0060429 (epithelium development), GO:0010721 (negative regulation of cell development), GO:0051253 (negative regulation of RNA metabolic process), GO:0030182 (neuron differentiation), GO:0042981 (regulation of apoptotic process), GO:0045619 (regulation of lymphocyte differentiation), GO:0050863 (regulation of T cell activation), GO:2001141 (regulation of RNA biosynthetic process), GO:0045621 (positive regulation of lymphocyte differentiation), GO:0120039 (plasma membrane bounded cell projection morphogenesis), GO:0098773 (skin epidermis development), GO:0048730 (epidermis morphogenesis), GO:0007411 (axon guidance), GO:0048699 (generation of neurons), GO:1903038 (negative regulation of leukocyte cell-cell adhesion), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0048667 (cell morphogenesis involved in neuron differentiation), GO:0043065 (positive regulation of apoptotic process), GO:0050870 (positive regulation of T cell activation), GO:2001238 (positive regulation of extrinsic apoptotic signaling pathway), GO:0120036 (plasma membrane bounded cell projection organization), GO:0006355 (regulation of DNA-templated transcription), GO:0045620 (negative regulation of lymphocyte differentiation), GO:0031175 (neuron projection development), GO:1903037 (regulation of leukocyte cell-cell adhesion), GO:2001236 (regulation of extrinsic apoptotic signaling pathway), GO:1903039 (positive regulation of leukocyte cell-cell adhesion), GO:0050868 (negative regulation of T cell activation), GO:0048812 (neuron projection morphogenesis), GO:0061564 (axon development), GO:0045582 (positive regulation of T cell differentiation), GO:0045892 (negative regulation of DNA-templated transcription), GO:0046634 (regulation of alpha-beta T cell activation), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0045581 (negative regulation of T cell differentiation), GO:0007409 (axonogenesis), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0046635 (positive regulation of alpha-beta T cell activation), GO:0046636 (negative regulation of alpha-beta T cell activation), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:0045580 (regulation of T cell differentiation), GO:0046639 (negative regulation of alpha-beta T cell differentiation), GO:0000122 (negative regulation of transcription by RNA polymerase II), GO:2000515 (negative regulation of CD4-positive, alpha-beta T cell activation), GO:2001185 (regulation of CD8-positive, alpha-beta T cell activation), GO:2000514 (regulation of CD4-positive, alpha-beta T cell activation), GO:0046637 (regulation of alpha-beta T cell differentiation), GO:0046638 (positive regulation of alpha-beta T cell differentiation), GO:0043370 (regulation of CD4-positive, alpha-beta T cell differentiation), GO:0043371 (negative regulation of CD4-positive, alpha-beta T cell differentiation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0000785 (chromatin), GO:0140513 (nuclear protein-containing complex), GO:0005667 (transcription regulator complex), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0090575 (RNA polymerase II transcription regulator complex), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043228 (non-membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0031981 (nuclear lumen), GO:0005694 (chromosome), GO:0005634 (nucleus)