background:
DMP-1 is a member of the small integrin ligand N-linked glycoprotein family. It is important for the mineralization of bone and dentin. DMP-1 is expressed in bone, tooth and hypertrophic cartilage. It is synthesized by preosteoblasts and contains a large number of acidic domains. DMP-1 localizes to the nucleus of undifferentiated osteoblasts where it functions as a transcriptional regulator for osteoblast-specific gene activation and induces osteoblast differentiation. During osteoblast maturation, DMP-1 undergoes a conformational change and becomes phosphorylated by casein kinase II in response to an influx of calcium ions to the nucleus. DMP-1 is then exported to the extracellular matrix (ECM) where it regulates the nucleation of hydroxyapatite and the formation of calcified tissue. DMP-1 is proteolytically processed into N- and SLCterminal fragments in the ECM of bone and dentin. The protein has also been identified in bone as a high molecular weight proteoglycan comprised of the N-terminal DMP-1 fragment and chondroitin sulfate.The loss of DMP-1 can result in hypomineralized bone.
Function:
DMP1 is an extracellular matrix protein and a member of the small integrin binding ligand N-linked glycoprotein family. It is critical for proper mineralization of bone and dentin, and is present in diverse cells of bone and tooth tissues. DMP1 contains a large number of acidic domains, multiple phosphorylation sites, a functional arg-gly-asp cell attachment sequence, and a DNA binding domain. DMP1 may also have a dual function during osteoblast differentiation. In the nucleus of undifferentiated osteoblasts the unphosphorylated form acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the osteoblast to osteocyte transition phase it is phosphorylated and exported into the extracellular matrix, where it regulates nucleation of hydroxyapatite.
Subunit:
Interacts with importin alpha.
Subcellular Location:
Nucleus. Cytoplasm. Secreted; extracellular space; extracellular matrix. Note=In proliferating preosteoblasts it is nuclear, during early maturation stage is cytoplasmic and in mature osteoblast localizes in the mineralizated matrix. Export from the nucleus of differentiating osteoblast is triggered by the release of calcium from intracellular stores followed by a massive influx of this pool of calcium into the nucleus.
Tissue Specificity:
Expressed in tooth particularly in odontoblast, ameloblast and cementoblast.
Post-translational modifications:
Phosphorylated in the cytosol and extracellular matrix and unphosphorylated in the nucleus. Phosphorylation is necessary for nucleocytoplasmic transport and may be catalyzed by a nuclear isoform of CK2 and can be augmented by calcium. Phosphorylated (in vitro) by FAM20C in the extracellular medium at sites within the S-x-E/pS motif.
DISEASE:
Defects in DMP1 are the cause of rickets hypophosphatemic autosomal recessive type 1 (ARHR1) [MIM:241520]. A hereditary form of hypophosphatemic rickets, a disorder of proximal renal tubule function that causes phosphate loss, hypophosphatemia and skeletal deformities, including rickets and osteomalacia unresponsive to vitamin D. Symptoms are bone pain, fractures and growth abnormalities.
Database links:
UniProtKB/Swiss-Prot: Q13316.2
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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