Molecular cloning of the cDNA for a human amyloid precursor protein homolog: Evidence for a multigene family

• Published in: Biochemistry (Easton) 1993-05, Vol.32 (17), p.4481-4486
• Main Authors: Sprecher, Cindy A, Grant, Francis J, Grimm, Gloria, O'Hara, Patrick J, Norris, Fanny, Norris, Kjeld, Foster, Donald C
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amyloid beta-Protein Precursor - genetics; Base Sequence; Biological and medical sciences; Blotting, Northern; Brain Chemistry; Cloning, Molecular; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA - chemistry; DNA - genetics; Glycosylation; Humans; Lung - chemistry; Medical sciences; Molecular Sequence Data; Multigene Family; Neurology; Nucleic Acid Hybridization; Oligonucleotide Probes; RNA, Messenger - analysis
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00068a002

Alzheimer's disease is a degenerative neurological disorder characterized by neural loss and brain lesions associated with plaques containing large amounts of the beta/A4 amyloid peptide. Molecular cloning of the cDNA for this peptide from human brain has shown it to be derived by proteolysis from a much larger precursor called the amyloid precursor protein (APP). The biological role of the precursor is unknown, but it has been shown to be transcribed in many human tissues in addition to brain. In the present report, we describe the molecular cloning from a human placental library of a full-length cDNA for a molecule closely related to APP. This novel molecule, which we have called amyloid precursor protein homolog (APPH), shares overall domain organization with APP. It is 763 amino acids in length and appears to encode a signal peptide, a large apparent extracellular domain including a Kunitz inhibitor domain, a transmembrane region, and a short cytoplasmic domain. Northern analysis indicates that it occurs in at least two molecular forms and is transcribed in human brain, heart, lung, liver, and kidney, in addition to placenta. On the basis of its extensive sequence similarity and conservation of domain structure, APPH is the nearest relative of APP yet identified in an emerging multigene family.