Ucma, a Novel Secreted Cartilage-specific Protein with Implications in Osteogenesis

Abstract

Here we report on the structure, expression, and function of a novel cartilage-specific gene coding for a 17-kDa small, highly charged, and secreted protein that we termed Ucma (unique cartilage matrix-associated protein). The protein is processed by a furin-like protease into an N-terminal peptide of 37 amino acids and a C-terminal fragment (Ucma-C) of 74 amino acids. Ucma is highly conserved between mouse, rat, human, dog, clawed frog, and zebrafish, but has no homology to other known proteins. Remarkable and of and the C-terminal the Ucma is the and of and Ucma is secreted into the an and the cartilage Ucma the processed C-terminal fragment the cartilage that is of an Ucma the of and of of but of and that Ucma the of of of cartilage and the Here we report on the structure, expression, and function of a novel cartilage-specific gene coding for a 17-kDa small, highly charged, and secreted protein that we termed Ucma (unique cartilage matrix-associated protein). The protein is processed by a furin-like protease into an N-terminal peptide of 37 amino acids and a C-terminal fragment (Ucma-C) of 74 amino acids. Ucma is highly conserved between mouse, rat, human, dog, clawed frog, and zebrafish, but has no homology to other known proteins. Remarkable and of and the C-terminal the Ucma is the and of and Ucma is secreted into the an and the cartilage Ucma the processed C-terminal fragment the cartilage that is of an Ucma the of and of of but of and that Ucma the of of of cartilage and the of is for of but of for on the of cartilage cartilage and of cartilage of the of a cartilage and of by the of cartilage-specific and and by the of and the and of and by the of and by the of and for and for and and for for and and for to the of a by and and of is on the the of a for we a highly protein that is the of and The termed a for Ucma a for of Here we report on the of Ucma the between of and of Ucma is of and but by of the Ucma and is by a furin-like protease into and C-terminal of 37 and 74 amino we that the of the of Ucma is to of Ucma expression, the C-terminal fragment is the cartilage of Ucma the of and of we that protein of we that protein a function the and of the cartilage of and cartilage by of and of and of of and and and and of of by of of of by of by of of and of 37 for by 37 of to the of of and into by a of by the for of the of the Ucma of Ucma by of the to the the a gene and for and The of the into by and to the the of of for and the to the the for to the the and to the of The for of by and and of and and for Ucma by the of a to of the and a on of for Ucma and and for Ucma of the Ucma by and into the of and of a peptide for and the to of peptide by The by a Ucma and the termed and of Ucma by for by and termed of protein by protein Ucma protein a Ucma protein by and a on the Ucma an and for 37 and for the and to the and for to to and and and for the and a the by of of of Ucma the coding of Ucma the peptide and and into the into by on a and by on and of protein by and an The peptide by N-terminal on an amino protein for protein for of and the 37 protein and the and and The for on for into The and a and an of The between and and and for The a an a and and an the and for a of and The to the a The by processed and The the for the of the the of the the protein to The peptide Ucma protein the amino acids of the secreted of Ucma acids The to a by of the by the of the of Ucma a of the by of and to gene the of the The that by is to the gene and of Ucma gene is on is of a of the of and and the of an the The an of The a of amino acids a of The amino a peptide by the peptide Ucma a by a furin-like protease the gene has an a a cartilage the C-terminal fragment is and amino the C-terminal amino acids and conserved by of and and amino a homology of and conserved of Ucma other rat, dog, clawed frog, and The is conserved the and on the function of and for of and Ucma protein the a to the Ucma protein and and a Ucma the of Ucma the Ucma protein a The N-terminal of Ucma by amino that Ucma processed by a furin-like protease into a C-terminal fragment of 74 amino the the and an N-terminal fragment of 37 amino acids The of the secreted C-terminal Ucma fragment (Ucma-C) to the of amino and and of of 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novel protein cartilage matrix-associated is highly conserved and by is is to of the the of Ucma an Ucma gene for a small, secreted protein a conserved for Ucma protein of of the C-terminal fragment of Ucma N-terminal of of the Ucma protein by a the a of of secreted of the and and peptide cartilage a of protein known to processed by and of the peptide for and the the of has for the of the The that the Ucma protein the cartilage that Ucma the the and to of the of of cartilage and a of for of Ucma for Ucma and cartilage is the of of is to cartilage and to the that is for Ucma of the amino of and that fragment that the C-terminal the of the N-terminal peptide acids a homology of between and human, the homology of the C-terminal of conserved to the amino of the C-terminal peptide is conserved of 74 amino Ucma secreted to to of the and of Ucma protein cartilage to to a for Ucma a of the cartilage is of the and of a of and is Ucma a of the a but of by and and that Ucma is to the of and The that we Ucma of the is Ucma is to to Ucma we that is a for a of Ucma of of Ucma of and cartilage the of the Ucma the for and the a of is that the the cartilage but the of and by a protein of the of is by the the of for the Ucma has no on of the of that to to by a of Ucma on and is for between and the of Ucma a the between the cartilage the on between and cartilage on the and the of by by other the to Ucma a between and the of a and of cartilage and of of highly and the for protein by and an of the cartilage the of and The of and is to of is for of but of for on the of cartilage cartilage and of cartilage of the of a cartilage and of by the of cartilage-specific and and by the of and the and of and by the of and by the of and for and for and and for for and and for to the of a by and and of is on the the of a for we a highly protein that is the of and The termed a for Ucma a for of Here we report on the of Ucma the between of and of Ucma is of and but by of the Ucma and is by a furin-like protease into and C-terminal of 37 and 74 amino we that the of the of Ucma is to of Ucma expression, the C-terminal fragment is the cartilage of Ucma the of and of we that protein of we that protein a function the and of the cartilage of and cartilage by of and of and of of and and and and of of by of of of by of by of of and of 37 for by 37 of to the of of and into by a of by the for of the of the Ucma of Ucma by of the to the the a gene and for and The of the into by and to the the of of for and the to the the for to the the and to the of The for of by and and of and and for Ucma by the of a to of the and a on of for Ucma and and for Ucma of the Ucma by and into the of and of a peptide for and the to of peptide by The by a Ucma and the termed and of Ucma by for by and termed of protein by protein Ucma protein a Ucma protein by and a on the Ucma an and for 37 and for the and to the and for to to and and and for the and a the by of of of Ucma the coding of Ucma the peptide and and into the into by on a and by on and of protein by and an The peptide by N-terminal on an amino protein for protein for of and the 37 protein and the and and The for on for into The and a and an of The between and and and for The a an a and and an the and for a of and The to the a The by processed and The the for the of the the of the the protein to The peptide Ucma protein the amino acids of the secreted of Ucma acids The to a by of the by the of the and of of and and and and of of by of of of of of by of by of of and of 37 for by 37 of to the of of and into by a of by the for of the of the Ucma of Ucma by of the to the the a gene and for and The of the into by and to the the of of for and the to the the for to the the and to the of The for of by and and of and and for Ucma by the of a to of the and a on of for Ucma and and for Ucma of the Ucma by and into the of and of a peptide for and the to of peptide by The by a Ucma and the termed and of Ucma by for by and termed of protein by protein Ucma protein a Ucma protein by and a on the Ucma an and for 37 and for the and to the and for to to and and and for the and a the by of of of Ucma the coding of Ucma the peptide and and into the into by on a and by on and of protein by and an The peptide by N-terminal on an amino protein for protein for of and the 37 protein and the and and The for on for into The and The a and an of The between and and and for The a an a and and an the and for a of and The The to the a The by processed and The the for the of the the of the the protein to The peptide Ucma protein the amino acids of the secreted of Ucma acids The to a by of the by the of the of Ucma a of the by of and to gene the of the The that by is to the gene and of Ucma gene is on is of a of the of and and the of an the The an of The a of amino acids a of The amino a peptide by the peptide Ucma a by a furin-like protease the gene has an a a cartilage the C-terminal fragment is and amino the C-terminal amino acids and conserved by of and and amino a homology of and conserved of Ucma other rat, dog, clawed frog, and The is conserved the and on the function of and for of and Ucma protein the a to the Ucma protein and and a Ucma the of Ucma the Ucma protein a The N-terminal of Ucma by amino that Ucma processed by a furin-like protease into a C-terminal fragment of 74 amino the the and an N-terminal fragment of 37 amino acids The of the secreted C-terminal Ucma fragment (Ucma-C) to the of amino and a Ucma peptide the and that the the of and the Ucma of Ucma of an amino acids the Ucma is by is secreted and of the secreted by protein a of the the protein acids acids and acids for for peptide the of a the on peptide but the that peptide of and to of Ucma of to of protein and by of and peptide the of Ucma and we on and for the coding for the Ucma the of a and Ucma the and of cartilage of the and and The the and for Ucma is cartilage of and of on of and and of and Ucma the a and is the of the the of Ucma the of the and Ucma into the and of the and Ucma and to the of cartilage and the of the the and the and of the and Ucma of the and of the and to the the of the and the and the the of the and and cartilage by Ucma the of the the of the to for the Ucma to the of the and and a the the and and protein cartilage of and The Ucma and Ucma and the and Ucma the cartilage of the and and and the that is cartilage and of and and of that Ucma is to but a The that Ucma a of the the of the the and of Ucma Ucma into the the of the Ucma we a peptide of the the the Ucma but on of and the the Ucma to cartilage the of and and and cartilage a to Ucma and of Ucma the but of the and and and a protein Ucma Ucma is the and of cartilage the is the and a and and of a and and and of and and is the of Ucma by of cartilage the Ucma the but and the and is secreted by an Ucma the the on of cartilage of of cartilage Ucma the cartilage The of the of Ucma and C-terminal of Ucma the to the of by the cartilage and and the the is for Ucma and Ucma a of of the C-terminal fragment the cartilage for the and the and and and and the for Ucma of Ucma and of the cartilage the of for and to and to Ucma of Ucma a of and for Ucma by and Ucma expression, Ucma the and of Ucma and of Ucma Ucma to the of Ucma the of Ucma by Ucma Ucma and and Ucma highly and to a of of Ucma but Ucma a and of a of the that of to to the Ucma the of of Ucma a on the of Ucma and that Ucma an of the of of Ucma of by Ucma and Ucma and of and on by the of by Ucma that Ucma the of cartilage but and the Ucma that Ucma the is a on Ucma by to the and we and of for a of Ucma to and Ucma expression, the of the and by of Ucma protein of a that a the of Ucma and is by and of for Ucma by Ucma by of Ucma expression, by of and of Ucma the protein for The to Ucma protein by on the but the of on and and a of and protein of to for to no on of of of a gene and by Ucma of a known to to and and and of by by of Ucma and by by a and of by and of and by and on that to of and an of Ucma of Ucma and of and to and and and protein and and and of and a and for that to on of Ucma by and to and and of of and of and by and and and for of to an of the secreted Ucma on and an for the between and of Ucma a of the by of and to gene the of the The that by is to the gene and of Ucma gene is on is of a of the of and and the of an the The an of The a of amino acids a of The amino a peptide by the peptide Ucma a by a furin-like protease the gene has an a a cartilage the C-terminal fragment is and amino the C-terminal amino acids and conserved by of and and amino a homology of and conserved of Ucma other rat, dog, clawed frog, and The is conserved the Ucma and on the function of and for of and Ucma protein the a to the Ucma protein and and a Ucma the of Ucma the Ucma protein a The N-terminal of Ucma by amino that Ucma processed by a furin-like protease into a C-terminal fragment of 74 amino the the and an N-terminal fragment of 37 amino acids The of the secreted C-terminal Ucma fragment (Ucma-C) to the of amino and a Ucma peptide the and that the the of and the Ucma of Ucma The of an amino acids the Ucma is by is secreted and of the secreted by protein a of the the protein acids acids and acids for for peptide the of a the on peptide but the that peptide of and to Ucma the of Ucma and we on and for the coding for the Ucma the of a and Ucma the and of cartilage of the and and The the and for Ucma the and of the and Ucma of the and of the and to the the of the and the and the the of the and and cartilage by Ucma the of the the of the to for the Ucma to the of the and and a the the and and and of that Ucma is to but a The that Ucma a of the the of the the and of Ucma Ucma into the the of the Ucma we a peptide of the the the Ucma but on of and the the Ucma to cartilage the of and and and cartilage a to Ucma and of Ucma the but of the and and and is the of Ucma by of cartilage the Ucma the but and the and The C-terminal of Ucma the to the of by the cartilage and and the the is for Ucma and Ucma a of of the C-terminal fragment the cartilage for the and the and and and and the for Ucma of Ucma and of the cartilage the of for and to and to Ucma of Ucma a of and for Ucma by and Ucma expression, Ucma the and of Ucma and of Ucma Ucma to the of Ucma the of Ucma by Ucma a and of a of the that of to to the Ucma the of of Ucma a on the of Ucma and that Ucma an of the of Ucma that Ucma the of cartilage but and the Ucma that Ucma the is a on Ucma by to the and we and of for a of Ucma to and Ucma expression, the of the and by of Ucma protein of a that a the of Ucma and but the of on and and a of and protein of to for to no on of of of a gene and by Ucma of a known to to and and and of by by of Ucma and by by a and of by and of and by and on that to of and an of Ucma of Ucma and to an of the secreted Ucma on and an for the between and we a novel of a small, secreted cartilage-specific is processed and that Ucma is is an of Ucma by to of we termed novel protein cartilage matrix-associated is highly conserved and by is is to of the the of Ucma an Ucma gene for a small, secreted protein a conserved for Ucma protein of of the C-terminal fragment of Ucma N-terminal of of the Ucma protein by a the a of of secreted of the and and peptide cartilage a of protein known to processed by and of the peptide for and the the of has for the of the The that the Ucma protein the cartilage that Ucma the the and to of the of of cartilage and a of for of Ucma for Ucma and cartilage is the of of is to cartilage and to the that is for Ucma of the amino of and that fragment that the C-terminal the of the N-terminal peptide acids a homology of between and human, the homology of the C-terminal of conserved to the amino of the C-terminal peptide is conserved of 74 amino Ucma secreted to to of the and of Ucma protein cartilage to to a for Ucma a of the cartilage is of the and of a of and is Ucma a of the a but of by and and that Ucma is to the of and The that we Ucma of the is Ucma is to to Ucma we that is a for a of Ucma of of Ucma of and cartilage the of the Ucma the for and the a of is that the the cartilage but the of and by a protein of the of is by the the of for the Ucma has no on of the of that to to by a of Ucma on and is for between and the of Ucma a the between the cartilage the on between and cartilage on the and the of by by other the to Ucma a between and the of a and of cartilage and of of highly and the for protein by and an of the cartilage the of and The of and is to we a novel of a small, secreted cartilage-specific is processed and that Ucma is is an of Ucma by to of we termed novel protein cartilage matrix-associated is highly conserved and by is is to of the the of Ucma an The Ucma gene for a small, secreted protein a conserved for Ucma protein of of the C-terminal fragment of Ucma N-terminal of of the Ucma protein by a the a of of secreted of the and and peptide cartilage a of protein known to processed by and of the peptide for and the the of has for the of the The that the Ucma protein the cartilage that Ucma the the and to of the of of cartilage and a of for of Ucma for Ucma and cartilage is the of of is to cartilage and to the that is for Ucma The of the amino of and that fragment that the C-terminal the of the N-terminal peptide acids a homology of between and human, the homology of the C-terminal of conserved to the amino of the C-terminal peptide is conserved of 74 amino Ucma secreted to to of the and of Ucma protein cartilage to to a for Ucma a of the cartilage is of the and of a of and is Ucma a of the a Ucma but of by and and that Ucma is to the of and The that we Ucma of the is Ucma is to to Ucma we that is a for a of Ucma of The of Ucma of and cartilage the of the Ucma the for and the a of is that the the cartilage but the of and by a protein of the of is by the the of for the Ucma has no on of the of that to to by a of Ucma on and is for between and the of Ucma a the between the cartilage the on between and cartilage on the and the of by by other the to Ucma a between and the of a and of cartilage and The of of highly and the for protein by and The an of the cartilage the of and The of and is to and for