ID:RUNX1_HUMAN DESCRIPTION: RecName: Full=Runt-related transcription factor 1; AltName: Full=Acute myeloid leukemia 1 protein; AltName: Full=Core-binding factor subunit alpha-2; Short=CBF-alpha-2; AltName: Full=Oncogene AML-1; AltName: Full=Polyomavirus enhancer-binding protein 2 alpha B subunit; Short=PEA2-alpha B; Short=PEBP2-alpha B; AltName: Full=SL3-3 enhancer factor 1 alpha B subunit; AltName: Full=SL3/AKV core-binding factor alpha B subunit; FUNCTION: CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters. The alpha subunit binds DNA and appears to have a role in the development of normal hematopoiesis. Isoform AML-1L interferes with the transactivation activity of RUNX1. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the mouse BLK promoter. Inhibits KAT6B- dependent transcriptional activation. SUBUNIT: Heterodimer with CBFB. RUNX1 binds DNA as a monomer and through the Runt domain. DNA-binding is increased by heterodimerization. Isoform AML-1L can neither bind DNA nor heterodimerize. Interacts with TLE1 and ALYREF/THOC4. Interacts with ELF1, ELF2 and SPI1. Interacts via its Runt domain with the ELF4 N-terminal region. Interaction with ELF2 isoform 2 (NERF-1a) may act to repress RUNX1-mediated transactivation. Interacts with KAT6A and KAT6B. Interacts with SUV39H1, leading to abrogation of transactivating and DNA-binding properties of RUNX1. Interacts with YAP1. Interacts with HIPK2 (By similarity). Interaction with CDK6 prevents myeloid differentiation, reducing its transcription transactivation activity. INTERACTION: Q15723:ELF2; NbExp=2; IntAct=EBI-925904, EBI-956941; P16371:gro (xeno); NbExp=4; IntAct=EBI-925940, EBI-153866; Q04724:TLE1; NbExp=3; IntAct=EBI-925944, EBI-711424; SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Expressed in all tissues examined except brain and heart. Highest levels in thymus, bone marrow and peripheral blood. DOMAIN: A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes. PTM: Phosphorylated in its C-terminus upon IL-6 treatment. Phosphorylation enhances interaction with KAT6A. PTM: Methylated. PTM: Phosphorylated in Ser-249 Thr-273 and Ser-276 by HIPK2 when associated with CBFB and DNA. This phosphorylation promotes subsequent EP300 phosphorylation. DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is a cause of M2 type acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1T1. DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is a cause of therapy-related myelodysplastic syndrome (T-MDS). Translocation t(3;21)(q26;q22) with EAP or MECOM. DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelogenous leukemia (CML). Translocation t(3;21)(q26;q22) with EAP or MECOM. DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is found in childhood acute lymphoblastic leukemia (ALL). Translocation t(12;21)(p13;q22) with TEL. The translocation fuses the 3'-end of TEL to the alternate 5'-exon of AML-1H. DISEASE: Note=A chromosomal aberration involving RUNX1 is found in acute leukemia. Translocation t(11,21)(q13;q22) that forms a MACROD1-RUNX1 fusion protein. DISEASE: Defects in RUNX1 are the cause of familial platelet disorder with associated myeloid malignancy (FPDMM) [MIM:601399]. FPDMM is an autosomal dominant disease characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukemia. DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is found in therapy-related myeloid malignancies. Translocation t(16;21)(q24;q22) that forms a RUNX1-CBFA2T3 fusion protein. DISEASE: Note=A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelomonocytic leukemia. Inversion inv(21)(q21;q22) with USP16. SIMILARITY: Contains 1 Runt domain. CAUTION: The fusion of AML1 with EAP in T-MDS induces a change of reading frame in the latter resulting in 17 AA unrelated to those of EAP. SEQUENCE CAUTION: Sequence=AAC05246.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAC05247.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/AML1.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RUNX1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q01196
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001047 core promoter binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005509 calcium ion binding GO:0005515 protein binding GO:0005524 ATP binding GO:0008134 transcription factor binding GO:0042803 protein homodimerization activity GO:0044212 transcription regulatory region DNA binding GO:0046982 protein heterodimerization activity
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001503 ossification GO:0001959 regulation of cytokine-mediated signaling pathway GO:0002062 chondrocyte differentiation GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter GO:0030097 hemopoiesis GO:0030099 myeloid cell differentiation GO:0030111 regulation of Wnt signaling pathway GO:0030853 negative regulation of granulocyte differentiation GO:0030854 positive regulation of granulocyte differentiation GO:0032743 positive regulation of interleukin-2 production GO:0033146 regulation of intracellular estrogen receptor signaling pathway GO:0043371 negative regulation of CD4-positive, alpha-beta T cell differentiation GO:0043378 positive regulation of CD8-positive, alpha-beta T cell differentiation GO:0045589 regulation of regulatory T cell differentiation GO:0045616 regulation of keratinocyte differentiation GO:0045637 regulation of myeloid cell differentiation GO:0045652 regulation of megakaryocyte differentiation GO:0045766 positive regulation of angiogenesis GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048935 peripheral nervous system neuron development GO:0050855 regulation of B cell receptor signaling pathway GO:0071425 hematopoietic stem cell proliferation GO:1902036 regulation of hematopoietic stem cell differentiation GO:2000810 regulation of bicellular tight junction assembly
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
