MGP Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MGP000427

UniProt Annotations

Entry Information
Gene Namerunt-related transcription factor 2
Protein Entry
UniProt IDQ32MY8
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; Synonyms=Cbfa1a; IsoId=Q13950-1; Sequence=Displayed; Name=2; IsoId=Q13950-2; Sequence=VSP_005937; Name=3; Synonyms=Cbfa1b; IsoId=Q13950-3; Sequence=VSP_005938; Note=Contains a phosphoserine at position 340.;
DiseaseCleidocranial 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:0000269|PubMed:10521292, ECO:0000269|PubMed:10545612, ECO:0000269|PubMed:10689183, ECO:0000269|PubMed:10980549, ECO:0000269|PubMed:11857736, ECO:0000269|PubMed:12081718, ECO:0000269|PubMed:12196916, ECO:0000269|PubMed:12424590, ECO:0000269|PubMed:16270353, ECO:0000269|PubMed:19744171, ECO:0000269|PubMed:20082269, ECO:0000269|PubMed:20648631, ECO:0000269|PubMed:9182765, ECO:0000269|PubMed:9207800}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseMetaphyseal 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:0000269|PubMed: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:0000269|PubMed:23290074}.
DomainA proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes and contains the phosphorylation sites.
FunctionTranscription 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:0000269|PubMed:11965546}.
InteractionQ13526:PIN1; NbExp=7; IntAct=EBI-976402, EBI-714158; O43541:SMAD6; NbExp=3; IntAct=EBI-976402, EBI-976374;
PtmPhosphorylated; 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. {ECO:0000250, ECO:0000269|PubMed:16407259}.
SimilarityContains 1 Runt domain. {ECO:0000255|PROSITE- ProRule:PRU00399}.
Subcellular LocationNucleus.
SubunitHeterodimer 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. {ECO:0000250, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:16407259}.
Tissue SpecificitySpecifically expressed in osteoblasts.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RUNX2ID42183ch6p21.html";
  logo