title: MAp44, a human protein associated with pattern recognition molecules of the complement system and regulating the lectin pathway of complement activation.
abstract: Essential effector functions of innate immunity are mediated by complement activation initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL) and the ficolins. We present a novel, phylogenetically conserved protein, MAp44, which is found in human serum at 1.4 microg/ml in Ca(2+)-dependent complexes with the soluble pattern recognition molecules. The affinity for MBL is in the nanomolar range (K(D) = 0.6 nM) as determined by surface plasmon resonance. The first eight exons of the gene for MAp44 encode four domains shared with MBL-associated serine protease (MASP)-1 and MASP-3 (CUB1-EGF-CUB2-CCP1), and a ninth exon encodes C-terminal 17 aa unique to MAp44. mRNA profiling in human tissues shows high expression in the heart. MAp44 competes with MASP-2 for binding to MBL and ficolins, resulting in inhibition of complement activation. Our results add a novel mechanism to those known to control the innate immune system.
authors.affiliation: Departments of Medical Microbiology and Immunology, University of Aarhus, Arhus, Denmark.
authors.forename: Søren E
authors.initials: SE
authors.lastname: Degn
authors.forename: Annette G
authors.initials: AG
authors.lastname: Hansen
authors.forename: Rudi
authors.initials: R
authors.lastname: Steffensen
authors.forename: Christian
authors.initials: C
authors.lastname: Jacobsen
authors.forename: Jens C
authors.initials: JC
authors.lastname: Jensenius
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003167:Complement Activation; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020349:Surface Plasmon Resonance; D000097604:Ficolins
chemical_list: D007527:Isoenzymes; D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012333:RNA, Messenger; D000097604:Ficolins; C084067:MASP1 protein, human