Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A.
Fetuins are serum proteins with diverse functions including the regulation of osteogenesis and inhibition of unwanted mineralization. Besides the alpha2-Heremans and Schmid glycoprotein/fetuin-A, the recently identified fetuin-B is a second member of the fetuin family [Olivier, Soury, Risler, Smih, Schneider, Lochner, Jouzeau, Fey and Salier (1999) Genomics 57, 352-364; Olivier, Soury, Ruminy, Husson, Parmentier, Daveau and Salier (2000) Biochem. J. 350, 589-597], which belongs to the cystatin superfamily. We compared the expressions of fetuin-B and fetuin-A at the RNA level and established that both genes are most highly expressed in liver tissue. Like fetuin-A, fetuin-B mRNA is also highly expressed in tongue and placenta tissues. We demonstrated for the first time that fetuin-B is also expressed at the protein level in sera and several organs of mouse, rat and human. We isolated contiguous genomic clones containing both fetuin-B and fetuin-A genes, indicating that these genes are closely linked at the genome level. The close proximity of both these genes may explain our observation that fetuin-B expression was decreased in fetuin-A-deficient mice. Unlike fetuin-A, the amount of fetuin-B protein in human serum varied with gender and was higher in females than in males. Functional analysis revealed that fetuin-B, similarly to fetuin-A, is an inhibitor of basic calcium phosphate precipitation, albeit less active when compared with fetuin-A. Therefore fetuin-B may have a function that is partly overlapping, if not identical, with the function of fetuin-A.
Denecke
Bernd
B
Interdisciplinary Center for Clinical Research on Biomaterials (IZKF BIOMAT), University Hospital, Pauwelsstrasse 30, D-52074 Aachen, Germany. bernd.denecke@rwth-aachen.de
Gräber
Steffen
S
Schäfer
Cora
C
Heiss
Alexander
A
Wöltje
Michael
M
Jahnen-Dechent
Willi
W
D000818:Animals; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D002130:Calcium Phosphates / Q000737:chemistry; D011232:Chemical Precipitation; D018076:DNA, Complementary; D005260:Female; D060752:Fetuin-B; D040461:Gene Components; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012737:Sex Factors; D014018:Tissue Distribution; D060749:alpha-2-HS-Glycoprotein; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
C556354:AHSG protein, human; C556357:Ahsg protein, mouse; D001798:Blood Proteins; D002130:Calcium Phosphates; D018076:DNA, Complementary; C504687:FETUB protein, human; C504688:Fetub protein, mouse; C504689:Fetub protein, rat; D060752:Fetuin-B; D012333:RNA, Messenger; D060749:alpha-2-HS-Glycoprotein; D000509:alpha-Fetoproteins; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous