Elucidation of the Sequence and the Genomic Organization of the Human Dentin Matrix Acidic Phosphoprotein 1 (DMP1) Gene: Exclusion of the Locus from a Causative Role in the Pathogenesis of Dentinogenesis Imperfecta Type II

Hirst, K.; Simmons, Darrin; Feng, Jian Q.; Aplin, Helen; Dixon, Michael J.; MacDougall, Mary

doi:10.1006/geno.1997.4700

Cited by 62 publications

(63 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The human DMP1 gene (originally known as AG1; George et al, 1993) consists of six exons spanning about 14 kb of genomic DNA on the long arm of chromosome 4 (Hirst et al, 1997). DMP1 is an acidic calcium-binding secreted phosphoprotein of about 513 amino acids, most of which are encoded by exon 6 (Hirst et al, 1997).…”

Section: Dentin Matrix Proteinmentioning

confidence: 99%

“…DMP1 is an acidic calcium-binding secreted phosphoprotein of about 513 amino acids, most of which are encoded by exon 6 (Hirst et al, 1997). The protein is assumed to have some role in tissue mineralization based on its chemical properties and presence in the extracellular matrix of dentine and bone (Butler and Ritchie, 1995;Feng et al, 2003).…”

Section: Dentin Matrix Proteinmentioning

confidence: 99%

See 1 more Smart Citation

Phylogenetic Relationships and Classification of Didelphid Marsupials, an Extant Radiation of New World Metatherian Mammals

Voss

Jansa

2009

Bulletin of the American Museum of Natural History

311

443

View full text Add to dashboard Cite

Section: Dentin Matrix Proteinmentioning

confidence: 99%

Section: Dentin Matrix Proteinmentioning

confidence: 99%

Phylogenetic Relationships and Classification of Didelphid Marsupials, an Extant Radiation of New World Metatherian Mammals

Voss

Jansa

2009

Bulletin of the American Museum of Natural History

311

443

View full text Add to dashboard Cite

“…Although originally postulated to be dentin-specific, DMP1 expression was later detected in bone (3), brain (4), salivary gland (5), and kidney (6). The cDNA from a number of species has been cloned and sequenced, including that from rat (1), mouse (3), bovine (4), human (7), and chicken (8). The characteristic feature of DMP1 is that it contains an unusually large number of acidic domains, a property that would be consistent with a role in regulating matrix mineralization (1).…”

mentioning

confidence: 99%

A Chondroitin Sulfate Chain Attached to the Bone Dentin Matrix Protein 1 NH2-Terminal Fragment

Qin

Huang

Wygant

et al. 2006

Journal of Biological Chemistry

101

View full text Add to dashboard Cite

Dentin matrix protein 1 (DMP1) is an acidic noncollagenous protein shown by gene ablations to be critical for the proper mineralization of bone and dentin. In the extracellular matrix of these tissues DMP1 is present as fragments representing the NH 2 -terminal (37 kDa) and COOH-terminal (57 kDa) portions of the cDNA-deduced amino acid sequence. During our separation of bone noncollagenous proteins, we observed a high molecular weight, DMP1-related component (designated DMP1-PG). We purified DMP1-PG with a monoclonal anti-DMP1 antibody affinity column. Amino acid analysis and Edman degradation of tryptic peptides proved that the core protein for DMP1-PG is the 37-kDa fragment of DMP1. Chondroitinase treatments demonstrated that the slower migration rate of DMP1-PG is due to the presence of glycosaminoglycan. Quantitative disaccharide analysis indicated that the glycosaminoglycan is made predominantly of chondroitin 4-sulfate. Further analysis on tryptic peptides led us to conclude that a single glycosaminoglycan chain is linked to the core protein via Ser 74 , located in the Ser 74 -Gly 75 dipeptide, an amino acid sequence specific for the attachment of glycosaminoglycans. Our findings show that in addition to its existence as a phosphoprotein, the NH 2 -terminal fragment from DMP1 occurs as a proteoglycan. Amino acid sequence alignment analysis showed that the Ser 74 -Gly 75 dipeptide and its flanking regions are highly conserved among a wide range of species from caiman to the Homo sapiens, indicating that this glycosaminoglycan attachment domain has survived an extremely long period of evolution pressure, suggesting that the glycosaminoglycan may be critical for the basic biological functions of DMP1.Dentin matrix protein 1 (DMP1), 2 first identified by cDNA cloning using a rat odontoblast mRNA library (1), is a member of the SIBLING protein family (2). Although originally postulated to be dentin-specific, DMP1 expression was later detected in bone (3), brain (4), salivary gland (5), and kidney (6). The cDNA from a number of species has been cloned and sequenced, including that from rat (1), mouse (3), bovine (4), human (7), and chicken (8). The characteristic feature of DMP1 is that it contains an unusually large number of acidic domains, a property that would be consistent with a role in regulating matrix mineralization (1). This purported biological function is supported by observations that transgenic MC3T3-E1 cells overexpressing DMP1 demonstrated higher levels of in vitro mineralization (9). Findings from gene knock-out mice further indicate a role for DMP1 in mineralization; mice lacking the Dmp1 gene demonstrate profound defects in bone and dentin mineralization (10, 11). The observation that the expression of DMP1 in osteocytes is elevated by mechanical stress suggests that this molecule may be involved in the mechanical transduction pathways (12).Other in vitro studies indicate that DMP1 may have non-mineralization-related functions. DMP1 secreted into the blood binds Factor H and blocks the alterna...

show abstract

“…Although it was first proposed to be dentin specific, the message for DMP1 has been identified in a number of other mineralized tissues as well as brain (6,13). In 1997, Hirst et al (14) published the genomic organization of the human DMP1 gene and excluded the locus from a causative role in at least two families with dentinogenesis imperfecta type II (14).…”

mentioning

confidence: 99%

Three SIBLINGs (SmallIntegrin-Binding LIgand, -linked Glycoproteins) Enhance Factor H's Cofactor Activity Enabling MCP-like Cellular Evasion of Complement-mediated Attack

Jain¹,

Karadağ²,

Fohr³

et al. 2002

Journal of Biological Chemistry

109

View full text Add to dashboard Cite

Previously we have shown that two members of the newly named SIBLING (small integrin-binding ligand, N-linked glycoproteins) family of proteins, bone sialoprotein, and osteopontin, bound first to a cell surface receptor and then to complement Factor H thereby blocking the lytic activity of the alternative pathway of complement. Another member of this family, dentin matrix protein 1, is shown in this paper to be very similar to osteopontin in that it can bind strongly to Factor H (K a ϳ 1 nM) and block the lytic activity through either the vitronectin receptor (␣ V ␤ 3 integrin) or CD44. Binding of Factor H to SIBLING localized to the cells surface was demonstrated by fluorescence-activated cell sorting. Extensive overlapping fragment analyses suggests that both dentin matrix protein 1 and osteopontin interact with cell surface CD44 through their amino termini. Similar fragments of bone sialoprotein, like the intact protein, did not functionally interact with CD44. All three proteins are shown to act in conjunction with Factor I, a serum protease that, when complexed to appropriate cofactors, stops the lytic pathway by digesting the bound C3b in a series of proteolytic steps. These results show that at least three members of this family confer membrane cofactor protein-like activity (MCP or CD46) upon cells expressing RGD-binding integrins or CD44. The required order of the assembly of the complex suggests that this cofactor activity is limited to short diffusional distances.

show abstract

Elucidation of the Sequence and the Genomic Organization of the Human Dentin Matrix Acidic Phosphoprotein 1 (DMP1) Gene: Exclusion of the Locus from a Causative Role in the Pathogenesis of Dentinogenesis Imperfecta Type II

Cited by 62 publications

References 28 publications

Phylogenetic Relationships and Classification of Didelphid Marsupials, an Extant Radiation of New World Metatherian Mammals

Phylogenetic Relationships and Classification of Didelphid Marsupials, an Extant Radiation of New World Metatherian Mammals

A Chondroitin Sulfate Chain Attached to the Bone Dentin Matrix Protein 1 NH2-Terminal Fragment

Three SIBLINGs (SmallIntegrin-Binding LIgand, -linked Glycoproteins) Enhance Factor H's Cofactor Activity Enabling MCP-like Cellular Evasion of Complement-mediated Attack

Contact Info

Product

Resources

About