title: Primary structure of alpha 2-macroglobulin receptor-associated protein. Human homologue of a Heymann nephritis antigen.
abstract: The alpha 2-macroglobulin (alpha 2M) receptor complex as purified by affinity chromatography contains three polypeptides: a 515-kDa heavy chain, an 85-kDa light chain, and a 39-kDa associated protein. Previous studies have established that the 515/85-kDa components are derived from a 600-kDa precursor whose complete sequence has been determined by cDNA cloning (Herz, J., Hamann, U., Rogne, S., Myklebost, O., Gassepohl, H., and Stanley, K. (1988) EMBO J. 7,4119-4127). We have now determined the primary structure of the human 39-kDa polypeptide, termed alpha 2M receptor-associated protein, by cDNA cloning. The deduced amino acid sequence contains a putative signal sequence that precedes the 323-residue mature protein. Comparative sequence analysis revealed that alpha 2M receptor-associated protein has 73% identity with a rat protein reported to be a pathogenic domain of Heymann nephritis antigen gp 330 and 77% identity to a mouse heparin-binding protein termed HBP-44. The high overall identity suggests that these molecules are interspecies homologues and indicates that the pathogenic domain, previously thought to be a portion of gp 330, is in fact a distinct protein. Further, the 120-residue carboxyl-terminal region of alpha 2M receptor-associated protein has 26% identity with a region of apolipoprotein E containing the low density lipoprotein receptor binding domain. Pulse-chase experiments revealed that the newly formed alpha 2M receptor-associated protein remains cell-associated, while surface labeling experiments followed by immunoprecipitation suggest that this protein is present on the cell surface forming a complex with the alpha 2M receptor heavy and light chains.
authors.affiliation: Biochemistry Laboratory, American Red Cross, Rockville, Maryland 20855.
authors.forename: D K
authors.initials: DK
authors.lastname: Strickland
authors.forename: J D
authors.initials: JD
authors.lastname: Ashcom
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: F
authors.initials: F
authors.lastname: Battey
authors.forename: E
authors.initials: E
authors.lastname: Behre
authors.forename: K
authors.initials: K
authors.lastname: McTigue
authors.forename: J F
authors.initials: JF
authors.lastname: Battey
authors.forename: W S
authors.initials: WS
authors.lastname: Argraves
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D015723:Gene Library; D026541:Heymann Nephritis Antigenic Complex; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010920:Placenta / Q000276:immunology; D011247:Pregnancy; D011487:Protein Conformation; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics* / Q000302:isolation & purification; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: D026541:Heymann Nephritis Antigenic Complex; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; D004247:DNA