TAG for RUNX2

Gene content

Symbol

RUNX2 ( by HUGO)

Name

Runt-Related Transcription Factor

Category

Oncogene

Alias

Runt-Related Transcription Factor 2
CBFA1
CCD
AML3
CCD1
Acute Myeloid Leukemia 3 Protein
Oncogene AML-3
Osteoblast-Specific Transcription Factor 2
Polyomavirus Enhancer-Binding Protein 2 Alpha A Subunit
CBF-alpha-1
OSF-2
OSF2
PEA2-Alpha A
PEBP2-Alpha A
SL3-3 Enhancer Factor 1 Alpha A Subunit
SL3/AKV Core-Binding Factor Alpha A Subunit
CLCD
PEA2aA
PEBP2aA
Core-Binding Factor
Runt Domain
Alpha Subunit 1
PEBP2A
Core-Binding Factor Subunit Alpha-1
PEBP2A1

Cytogenetic band

NCBI: 6p21 Ensembl: 6p21.1

Protein information

RUNX2_HUMAN

Size: 521 amino acids

Mass: 56648 Da

Subunit: Heterodimer of an alpha and a beta subunit. The alpha subunit binds DNA as a monomer and through the Runt domain. DNA-binding is increased by heterodimerization. Interacts with XRCC6 (Ku70) and XRCC5 (Ku80). Interacts with HIVEP3. Interacts with IFI204. Interaction with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors. Binds to HIPK3. Interacts (isoform 3) with DDX5. Interacts with FOXO1 (via a C-terminal region); the interaction inhibits RUNX2 transcriptional activity towards BGLAP. This interaction is prevented on insulin or IGF1 stimulation as FOXO1 is exported from the nucleus (By similarity). Interacts with CCNB1, KAT6A and KAT6B

Tissue specificity: Specifically expressed in osteoblasts [IMAGE] Pathway & Disease-focused RT2 Profiler PCR Arrays including RUNX2 (see all 8): Osteogenesis in human mouse rat Stem Cell Transcription Factors in human mouse rat Leukemia in human mouse rat Notch Signaling Tar

Function:

UniProtKB/Swiss-Prot Summary: RUNX2_HUMAN, Q13950 Function: Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis. Essential for the maturation of osteoblasts and both intramembranous and endochondral ossification. 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, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters. In osteoblasts, supports transcription activation: synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Inhibits KAT6B-dependent transcriptional activation

Similarity:

Contains 1 Runt domain [IMAGE]

Protein Domain/Family
Source	ID	Domain	Name	Type
InterPro	IPR000040	AML1_Runt	Acute myeloid leukemia 1 protein (AML 1)/Runt	Family
	IPR008967	p53-like_TF_DNA-bd	p53-like transcription factor, DNA-binding	Domain
	IPR012346	p53/RUNT-type_TF_DNA-bd	p53 and RUNT-type transcription factor, DNA-binding	Domain
Blocks	IPB000040	Acute myeloid leukemia 1 protein signature	Acute myeloid leukemia 1 protein signature

Gene Ontology
Type	Term	Evidence	Source	Pub
Biological Process	negative regulation of transcription, DNA-templated	IDA	GOA	11965546
	ossification	TAS	GOA	12217689
	osteoblast differentiation	TAS	GOA	12217689
	positive regulation of transcription, DNA-templated	IDA	GOA	11965546
Molecular Function	protein binding	IPI	GOA	11965546

Disorder & Mutation
Source	Disease
SWISS-PROT	Cleidocranial dysplasia (CLCD) [MIM:119600]: Autosomal dominant skeletal disorder with high penetrance and variable expressivity. It is due to defective endochondral and intramembranous bone formation. Typical features include hypoplasia/aplasia of clavicles, patent fontanelles, wormian bones (additional cranial plates caused by abnormal ossification of the calvaria), supernumerary teeth, short stature, and other skeletal changes. In some cases defects in RUNX2 are exclusively associated with dental anomalies. Note=The disease is caused by mutations affecting the gene represented in this entry
SWISS-PROT	Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly (MDMHB) [MIM:156510]: An autosomal dominant bone dysplasia characterized by metaphyseal flaring of long bones, enlargement of the medial halves of the clavicles, maxillary hypoplasia, variable brachydactyly, and dystrophic teeth. Note=The disease is caused by mutations affecting the gene represented in this entry. Analysis for copy-number variations revealed that a 105 kb duplication within RUNX2 segregated with the MDMHB phenotype in a region with maximum linkage. Real-time PCR for copy-number variation in genomic DNA in eight samples, as well as sequence analysis of fibroblast cDNA from one subject with MDMHB confirmed that affected family members were heterozygous for the presence of an intragenic duplication encompassing exons 3 to 5 of RUNX2. These three exons code for the Q/A domain and the functionally essential DNA-binding Runt domain of RUNX2. The RUNX2 duplication found in individuals with MDMHB leads to a gain of function (PubMed:23290074)

RUNX2 cross reference