RUNX2

Runt-related transcription factor 2
PDB rendering based on 1cmo.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1cmo, 1co1, 1e50, 1h9d, 1hjb, 1hjc, 1io4, 1ljm
Identifiers
Symbols	RUNX2 ; AML3; CBF-alpha-1; CBFA1; CCD; CCD1; CLCD; OSF-2; OSF2; PEA2aA; PEBP2aA
External IDs	OMIM: 600211 MGI: 99829 HomoloGene: 68389 GeneCards: RUNX2 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • RNA polymerase II core promoter sequence-specific DNA binding • RNA polymerase II transcription factor activity, sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • protein binding • ATP binding • protein domain specific binding • histone deacetylase binding • bHLH transcription factor binding • repressing transcription factor binding Cellular component • nuclear chromatin • nucleoplasm • transcription factor complex • cytoplasm Biological process • ossification • osteoblast differentiation • endochondral ossification • osteoblast fate commitment • chondrocyte differentiation • chondrocyte development • osteoblast development • regulation of transcription from RNA polymerase II promoter • transcription initiation from RNA polymerase II promoter • positive regulation of cell proliferation • gene expression • hemopoiesis • neuron differentiation • T cell differentiation • BMP signaling pathway • positive regulation of chondrocyte differentiation • embryonic forelimb morphogenesis • regulation of fibroblast growth factor receptor signaling pathway • odontogenesis of dentin-containing tooth • regulation of odontogenesis of dentin-containing tooth • cellular response to fibroblast growth factor stimulus • regulation of cell differentiation • positive regulation of osteoblast differentiation • negative regulation of smoothened signaling pathway • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • cell maturation • embryonic cranial skeleton morphogenesis • stem cell differentiation • cellular response to BMP stimulus • positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	860	12393
Ensembl	ENSG00000124813	ENSMUSG00000039153
UniProt	Q13950	Q08775
RefSeq (mRNA)	NM_001015051	NM_001145920
RefSeq (protein)	NP_001015051	NP_001139392
Location (UCSC)	Chr 6: 45.33 – 45.66 Mb	Chr 17: 44.5 – 44.81 Mb
PubMed search	[1]	[2]

Runt-related transcription factor 2 (RUNX2) also known as core-binding factor subunit alpha-1 (CBF-alpha-1) is a protein that in humans is encoded by the RUNX2 gene. RUNX2 is a key transcription factor associated with osteoblast differentiation.

Function

This protein is a member of the RUNX family of transcription factors and has a Runt DNA-binding domain. It is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Transcript variants of the gene that encode different protein isoforms result from the use of alternate promoters as well as alternate splicing.

Differences in RUNX2 are hypothesized to be the cause of the skeletal differences between modern humans and early humans such as Neanderthals. These differences include a different shape of the skull, a bell-shaped chest in Neanderthals, etc.

The binding interactions of RUNX2 change as cells go through mitosis, with binding affinity increasing as chromosomes condense and then decreasing through subsequent mitotic phases. The increased residence of RUNX2 at mitotic chromosomes may reflect its epigenetic function in "bookmarking" of target genes in cancer cells.

Pathology

Mutations in Cbfa1/Runx2 are associated with the disease Cleidocranial dysostosis.

Co-factors

Runx proteins represent the alpha DNA binding subunit of a heteromeric protein complex that also includes the non-DNA binding beta-subunit which increases the DNA binding affinity of the alpha subunit. In addition, there is a large cohort of regulatory proteins that bind to the C-terminus of Runx2 to modify its transcriptional function.

Interactions

RUNX2 has been shown to interact with:

• AR
• ER-α
• C-Fos,
• C-jun,
• HDAC3,
• MYST4,
• SMAD1
• SMAD3, and
• STUB1.

miR-133 directly inhibits Runx2.

See also

• RUNX1
• RUNX3

External links

• GeneReviews/NCBI/NIH/UW entry on Cleidocranial Dysplasia
• Runx2 protein at the US National Library of Medicine Medical Subject Headings (MeSH)