Primary structure of alpha 2-macroglobulin receptor-associated protein. Human homologue of a Heymann nephritis antigen

J Biol Chem. 1991 Jul 15;266(20):13364-9.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • DNA / genetics
  • DNA / isolation & purification
  • Female
  • Gene Library
  • Heymann Nephritis Antigenic Complex
  • Humans
  • Kidney Glomerulus / immunology
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Membrane Glycoproteins / genetics*
  • Mice
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Placenta / immunology
  • Pregnancy
  • Protein Conformation
  • Rats
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / isolation & purification
  • Sequence Homology, Nucleic Acid
  • Transcription, Genetic
  • alpha-Macroglobulins / metabolism*

Substances

  • Heymann Nephritis Antigenic Complex
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • alpha-Macroglobulins
  • DNA

Associated data

  • GENBANK/D10110
  • GENBANK/D10111
  • GENBANK/M63255
  • GENBANK/M63926
  • GENBANK/M63959
  • GENBANK/M63977
  • GENBANK/M63978
  • GENBANK/M63997
  • GENBANK/M63998
  • GENBANK/M64865