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core-binding factor [CBF]-alpha 2; runt-related transcription factor 1; acute myeloid leukemia 1 protein; polyomavirus enhancer binding protein 2 alpha B subunit; PEBP2-alpha B; SL3-3 enhancer factor 1 alpha B subunit;SL3/AKV core-binding factor alpha B subunit (RUNX1, AML1, CBFA2)

Function: - DNA-binding protein which specifically interacts with a sequence belonging to the group of enhancer core motifs, TGT/cGGT - CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers & promoters, including a) murine leukemia virus b) polyomavirus enhancer c) T-cell receptor enhancers d) osteocalcin e) osteopontin f) bone sialoprotein g) collagen-1 alpha-1 h) LCK i) IL-3 j) GM-CSF promoters - CBF-alpha subunit binds DNA & appears to have a role in development of normal hematopoiesis - essential for normal fetal liver hematopoiesis in mice [2] - isoform AML-1L interferes with the transactivation activity of RUNX1 - acts synergistically with ELF4 to transactivate IL-3 promoter & with ELF2 to transactivate mouse BLK promoter - inhibits MYST4-dependent transcriptional activation - heterodimer with CBFB - RUNX1 binds DNA as a monomer through the Runt domain - DNA-binding is increased by heterodimerization - isoform AML-1L can neither bind DNA nor heterodimerize - interacts with TLE1 & THOC4 - interacts with ELF1, ELF2 & 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 MYST3 & MYST4 - interacts with SUV39H1, leading to abrogate transactivating & DNA-binding properties of RUNX1 - phosphorylated in its C-terminus upon IL-6 treatment - phosphorylation enhances interaction with MYST3 Structure: - proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes - contains 1 Runt domain Compartment: nucleus Alternative splicing: - named isoforms=11 - additional isoforms seem to exist Expression: - expressed in all tissues examined except brain & heart - highest levels in thymus, bone marrow & peripheral blood Pathology: - chromosomal translocation t(8;21)(q22;q22) involving RUNX1 with RUNX1T1 is a cause acute myeloid leukemia-M2 (AML-M2) - chromosomal translocation t(3;21)(q26;q22) involving RUNX1 with with EAP, MSD1 or EVI1 is a cause of therapy-related myelodysplastic syndrome - chromosomal translocation t(3;21)(q26;q22) involving RUNX1 with EAP, MSD1 or EVI1 is a cause of chronic myelogenous leukemia (CML) - chromosomal translocation t(12;21)(p13;q22) involving RUNX1 with TEL is found in childhood acute lymphoblastic leukemia (ALL); the translocation fuses the 3'-end of TEL to the alternate 5'-exon of AML-1H - chromosomal translocation t(16;21)(q24;q22) involving RUNX1 with CBFA2T3 is found in therapy-related myeloid malignancies - defects in RUNX1 are the cause of familial platelet disorder with associated myeloid malignancy (FPDMM) Laboratory: - RUNX1 genotyping - chromosomal translocation t(12;21)(p13;q22.3)(ETV6,RUNX1) - chromosomal translocation t(3;21)(q26;q22.3)(MECOM,RUNX1) - chromosomal translocation t(8;21)(q22;q22.3)(RUNX1T1,RUNX1)

Related

AML1 or CBFA2 gene

General

core-binding factor [CBF]-alpha (PEBP2-alpha) phosphoprotein

Properties

SIZE: entity length = 453 aa MW = 49 kD COMPARTMENT: cell nucleus MOTIF: Thr phosphorylation site {T14} Ser phosphorylation site {S21} Runt {50-178} MOTIF: DNA interaction {80-84} binding site SITE: 112-112 FOR-BINDING-OF: Cl- binding site SITE: 116-116 FOR-BINDING-OF: Cl- DNA interaction {135-143} ATP-binding site NAME: ATP-binding site SITE: 138-145 MOTIF-SEQUENCE: GRSGRGKS binding site SITE: 139-139 FOR-BINDING-OF: Cl- DNA interaction {168-177} binding site SITE: 170-170 FOR-BINDING-OF: Cl- Breakpoint {177-178} threonine-rich region {187-453} MOTIF: threonine residue (SEVERAL) Breakpoint {241-242} MYST3 interaction {291-371} MYST4 interaction {307-400}

Database Correlations

OMIM correlations MORBIDMAP 151385 UniProt Q01196 PFAM correlations Entrez Gene 861 Kegg hsa:861

References

  1. Meyers et al, Identification of AML-1 and the (8;21) translocation protein (AML-1/ETO) as sequence-specific DNA-binding proteins: the runt homology domain is required for DNA binding and protein- protein interactions. Mol Cell Biol 13(10):6336 1993 PMID: 8413232
  2. Okuda et al. AML1, the target of multiple chromosomal translocations in in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 84:321-30 1996 PMID: 8565077
  3. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/AML1.html
  4. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=RUNX1
  5. UniProt :accession Q01196