InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RUNX2

Summary

InnateDB Protein

IDBP-89687.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RUNX2

Protein Name

runt-related transcription factor 2

Synonyms

AML3; CBF-alpha-1; CBFA1; CCD; CCD1; CLCD; OSF-2; OSF2; PEA2aA; PEBP2aA;

Species

Homo sapiens

Ensembl Protein

ENSP00000352514

InnateDB Gene

IDBG-89685 (RUNX2)

Protein Structure

UniProt Annotation

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. {ECO:0000250, ECO:0000269PubMed:11965546}.

Subcellular Localization

Nucleus.

Disease Associations

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. {ECO:0000269PubMed:10521292, ECO:0000269PubMed:10545612, ECO:0000269PubMed:10689183, ECO:0000269PubMed:10980549, ECO:0000269PubMed:11857736, ECO:0000269PubMed:12081718, ECO:0000269PubMed:12196916, ECO:0000269PubMed:12424590, ECO:0000269PubMed:16270353, ECO:0000269PubMed:19744171, ECO:0000269PubMed:20082269, ECO:0000269PubMed:20648631, ECO:0000269PubMed:9182765, ECO:0000269PubMed:9207800}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. {ECO:0000269PubMed:23290074}. 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). {ECO:0000269PubMed:23290074}.

Tissue Specificity

Specifically expressed in osteoblasts.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 74 experimentally validated interaction(s) in this database.
They are also associated with 17 interaction(s) predicted by orthology.

Experimentally validated
Total	74 [view]
Protein-Protein	66 [view]
Protein-DNA	5 [view]
Protein-RNA	0
DNA-DNA	3 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	17 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0005524	ATP binding

Biological Process

GO:0001503	ossification
GO:0001649	osteoblast differentiation
GO:0006355	regulation of transcription, DNA-templated
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0010467	gene expression
GO:0030509	BMP signaling pathway
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0071773	cellular response to BMP stimulus
GO:1901522	positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus

Cellular Component

GO:0000790	nuclear chromatin
GO:0005634	nucleus

Protein Structure and Domains

PDB ID

InterPro

IPR000040 Acute myeloid leukemia 1 protein (AML1)/Runt
IPR008967 p53-like transcription factor, DNA-binding
IPR013524 Runt domain
IPR013711 Runx, C-terminal domain
IPR016554 Runt-related transcription factor RUNX

PFAM

PF00853
PF08504

PRINTS

PR00967

PIRSF

PIRSF009374

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt