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RUNX2

GeneName

RUNX2

Summary

RUNX2, also known as runt related transcription factor 2 or Cbfa1, is a 57 kDa transcription factor that plays a pivotal role in bone and cartilage development. It is predominantly expressed in osteoblasts and chondrocytes, where it regulates key processes such as osteoblast differentiation, bone mineralization, and chondrocyte maturation. RUNX2 functions as a sequence-specific DNA-binding transcription factor, interacting with various regulatory elements to modulate gene expression involved in skeletal development. Its activity is essential for endochondral ossification and the morphogenesis of the embryonic cranial skeleton and forelimbs. RUNX2 is localised in the nucleus and cytoplasm, and it is part of transcription regulator complexes that influence the transcription of target genes.

Importance

RUNX2 is relevant to: - Bone disorders, including osteoporosis and osteogenesis imperfecta, due to its central role in osteoblast function and bone formation. - Cartilage-related diseases such as osteoarthritis, as it regulates chondrocyte differentiation and function. - Developmental biology, particularly in the context of limb and craniofacial morphogenesis, highlighting its importance in congenital skeletal abnormalities. - Cancer research, as aberrant RUNX2 expression has been linked to tumour progression and metastasis in certain cancers.

Top Products

For researchers investigating RUNX2, we recommend two excellent primary antibodies. The first is the well-cited monoclonal antibody, Anti-RUNX2 antibody [2B9] (ab76956), which has garnered 391 citations, reflecting its reliability in Western blotting (WB), immunocytochemistry (ICC), and flow cytometry (FC). Additionally, we offer the recombinant antibody, Anti-RUNX2 antibody [EPR14334] (ab192256), which is validated for use in a broader range of applications, including immunohistochemistry (IHC), WB, ICC, and FC. With 174 citations, this recombinant product ensures batch-to-batch consistency, making it an excellent choice for researchers seeking dependable RUNX2 detection.

Abcam Product Citation Summary

The data indicates a strong focus on the role of RUNX2 in osteoblast activity and differentiation across various species, particularly in mouse and rat models. The use of multiple applications, primarily Western blotting and immunohistochemistry, highlights the importance of RUNX2 in studies related to bone metabolism, osteogenic differentiation, and related conditions. The presence of studies involving human cells also suggests its relevance in clinical contexts, such as periodontal and mesenchymal stem cell research.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab192256
Mouse
IHC
Osteoblast activity
29907830
ab192256
Mouse
WB
Osteoblastic differentiation
32436939
ab192256
Mouse
WB
Osteogenic differentiation of MC3T3-E1 cells
32436939
ab236639
Rat
WB
Bone metabolism
35769158
ab76956
Mouse
WB
Osteoblast differentiation
24618832
ab76956
Human
WB
Osteoblastic differentiation
26763307
ab76956
Human
WB
Osteoblastic differentiation
26276681
ab76956
Rat
WB
Intervertebral disc degeneration
29372627
ab76956
Rat
WB
Effect of leptin
29372627
ab76956
Mouse
IHC
Osteogenic differentiation of MSCs
32206106
ab76956
Rat
IHC
Bone defect healing
30746871
ab76956
Rat
WB
Congenital scoliosis
32448279
ab76956
Rat
WB
Calcium deposition in vascular smooth muscle cells
32377301
ab76956
Human
ICC
Osteogenic differentiation
32083238
ab76956
Rat
WB
Osteogenic differentiation of BMMSCs
32198976
ab76956
Mouse
WB
Osteoblastic differentiation
32914833
ab92336
Pig
WB
Follicles
32365901
ab92336
Human
ChIP, WB
ER+ breast cancer cells
25415051

Domain

A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes and contains the phosphorylation sites.

Function

Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis (PubMed:28505335, PubMed:28703881, PubMed:28738062). 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.

Involvement in disease

Cleidocranial dysplasia 1

CLCD1

A form of cleidocranial dysplasia, a rare skeletal disorder with significant clinical variability, even within families. Patients typically present with delayed closure of cranial sutures and fontanels with multiple Wormian bones, retarded ossification of the skull, shortening of the distal phalanges, dental anomalies including supernumerary teeth and eruption failure, clavicular hypoplasia or aplasia, wide pubic symphysis, vertebral anomalies, and short stature. CLCD1 inheritance is autosomal dominant.

None

The disease is caused by variants affecting the gene represented in this entry.

Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly

MDMHB

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.

None

The disease is caused by variants 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).

Post-translational modifications

Phosphorylated; probably by MAP kinases (MAPK). Phosphorylation by HIPK3 is required for the SPEN/MINT and FGF2 transactivation during osteoblastic differentiation (By similarity). Phosphorylation at Ser-451 by CDK1 promotes endothelial cell proliferation required for tumor angiogenesis probably by facilitating cell cycle progression. Isoform 3 is phosphorylated on Ser-340.

Tissue Specificity

Specifically expressed in osteoblasts.

Cellular localization

Alternative names

AML3, CBFA1, OSF2, PEBP2A, RUNX2, Runt-related transcription factor 2, Acute myeloid leukemia 3 protein, Core-binding factor subunit alpha-1, Oncogene AML-3, Osteoblast-specific transcription factor 2, Polyomavirus enhancer-binding protein 2 alpha A subunit, SL3-3 enhancer factor 1 alpha A subunit, SL3/AKV core-binding factor alpha A subunit, CBF-alpha-1, OSF-2, PEA2-alpha A, PEBP2-alpha A

swissprot:Q13950 entrezGene:860 omim:600211

Other research areas