http://purl.uniprot.org/citations/11463336 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/11463336 | http://www.w3.org/2000/01/rdf-schema#comment | "Anosmin-1, the gene product of the KAL gene, is implicated in the pathogenesis of X-linked Kallmann's syndrome. Anosmin-1 protein expression is restricted to the basement membrane and interstitial matrix of tissues affected in this syndrome during development. The anosmin-1 sequence indicates an N-terminal cysteine-rich domain, a whey acidic protein (WAP) domain, four fibronectin type III (FnIII) domains and a C-terminal histidine-rich region, and shows similarity with cell-adhesion molecules, such as neural cell-adhesion molecule, TAG-1 and L1. We investigated the structural and functional significance of three loss-of-function missense mutations of anosmin-1 using comparative modelling of the four FnIII and the WAP domains based on known NMR and crystal structures. Three missense mutation-encoded amino acid substitutions, N267K, E514K and F517L, were mapped to structurally defined positions on the GFCC' beta-sheet face of the first and third FnIII domains. Electrostatic maps demonstrated large basic surfaces containing clusters of conserved predicted heparan sulphate-binding residues adjacent to these mutation sites. To examine these modelling results anosmin-1 was expressed in insect cells. The incorporation of the three mutations into recombinant anosmin-1 had no effect on its secretion. The removal of two dibasic motifs that may constitute potential physiological cleavage sites for anosmin-1 had no effect on cleavage. Peptides based on the anosmin-1 sequences R254--K285 and P504--K527 were then synthesized in order to assess the effect of the three mutations on cellular adhesion, using cell lines that represented potential functional targets of anosmin-1. Peptides (10 microg/ml) incorporating the N267K and E514K substitutions promoted enhanced adhesion to 13.S.1.24 rat olfactory epithelial cells and canine MDCK1 kidney epithelial cells (P<0.01) compared with the wild-type peptides. This result was attributed to the introduction of a lysine residue adjacent to the large basic surfaces. We predict that two of the three missense mutants increase the binding of anosmin-1 to an extracellular target, possibly by enhancing heparan sulphate binding, and that this critically affects the function of anosmin-1."xsd:string |
http://purl.uniprot.org/citations/11463336 | http://purl.org/dc/terms/identifier | "doi:10.1042/0264-6021:3570647"xsd:string |
http://purl.uniprot.org/citations/11463336 | http://purl.uniprot.org/core/author | "Robertson A."xsd:string |
http://purl.uniprot.org/citations/11463336 | http://purl.uniprot.org/core/author | "Boehm M.K."xsd:string |
http://purl.uniprot.org/citations/11463336 | http://purl.uniprot.org/core/author | "Perkins S.J."xsd:string |
http://purl.uniprot.org/citations/11463336 | http://purl.uniprot.org/core/author | "Bouloux P.M."xsd:string |
http://purl.uniprot.org/citations/11463336 | http://purl.uniprot.org/core/author | "MacColl G.S."xsd:string |
http://purl.uniprot.org/citations/11463336 | http://purl.uniprot.org/core/author | "Nash J.A."xsd:string |
http://purl.uniprot.org/citations/11463336 | http://purl.uniprot.org/core/date | "2001"xsd:gYear |
http://purl.uniprot.org/citations/11463336 | http://purl.uniprot.org/core/name | "Biochem J"xsd:string |
http://purl.uniprot.org/citations/11463336 | http://purl.uniprot.org/core/pages | "647-659"xsd:string |
http://purl.uniprot.org/citations/11463336 | http://purl.uniprot.org/core/title | "Molecular modelling and experimental studies of mutation and cell-adhesion sites in the fibronectin type III and whey acidic protein domains of human anosmin-1."xsd:string |
http://purl.uniprot.org/citations/11463336 | http://purl.uniprot.org/core/volume | "357"xsd:string |
http://purl.uniprot.org/citations/11463336 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/11463336 |
http://purl.uniprot.org/citations/11463336 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/11463336 |
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http://purl.uniprot.org/uniprot/P11362 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/11463336 |
http://purl.uniprot.org/uniprot/P23352 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/11463336 |