Six genes expressed in bones and teeth encode the current members of the SIBLING family of proteins.
Bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), enamelin (ENAM), matrix extracellular phosphoglycoprotein (MEPE), and osteopontin (OPN) are glycophosphoproteins expressed in bones and/or teeth. Direct comparison of their amino acid sequences do not suggest that they belong to a single genetic family, but a detailed analysis of their chromosomal location and gene structure does. Analysis of human brain mRNA by RT-PCR has led to the discovery of two additional exons thereby making it more convincing that MEPE is a member of the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family. We propose that the members of this SIBLING family are extended, flexible proteins in solution that can facilitate the formation of a number of different complexes. For example, OPN can bridge complement Factor H to either an RGD-dependent integrin or to CD44 forming a membrane-bound complex that actively suppresses the alternate complement pathway. Two possible mechanisms for inhibiting the lytic pathway of alternate complement are presented.
Fisher
Larry W
LW
Matrix Biochemistry Unit, Craniofacial & Skeletal Diseases Branch, NIDCR, NIH, HHS, Bethesda, Maryland 20892-4320, USA. LFISHER@dir.nidcr.nih.gov
Fedarko
Neal S
NS
D000818:Animals; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D003746:Dental Enamel Proteins / Q000235:genetics; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D051379:Mice; D053495:Osteopontin; D010750:Phosphoproteins / Q000235:genetics*; D011498:Protein Precursors; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012795:Sialoglycoproteins / Q000235:genetics*; D014070:Tooth / Q000737:chemistry / Q000378:metabolism*; D000099311:Dentin Sialophosphoprotein
D003746:Dental Enamel Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D058574:Integrin-Binding Sialoprotein; D053495:Osteopontin; D010750:Phosphoproteins; D011498:Protein Precursors; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C513309:DMP1 protein, human; C513308:Dmp1 protein, mouse; C546871:IBSP protein, human; C546872:Ibsp protein, mouse; C546873:Ibsp protein, rat; C486579:MEPE protein, human; C506895:SPP1 protein, human; C506896:Spp1 protein, mouse; C506897:Spp1 protein, rat; C038456:tuftelin