Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis through acting as an agonist for ADGRG6 receptor. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (By similarity). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or Zn(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity). Monomer and homodimer. Has a tendency to aggregate into amyloid fibrils containing a cross-beta spine, formed by a steric zipper of superposed beta-strands. Soluble oligomers may represent an intermediate stage on the path to fibril formation. Copper binding may promote oligomerization (PubMed:11524679, PubMed:11900542, PubMed:14623188, PubMed:17468747, PubMed:19204296, PubMed:19927125, PubMed:20375014, PubMed:20564047). Interacts with GRB2, APP, ERI3/PRNPIP and SYN1. Mislocalized cytosolically exposed PrP interacts with MGRN1; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement (By similarity). Interacts with KIAA1191 (PubMed:21153684). Interacts with ADGRG6 (By similarity). Targeted to lipid rafts via association with the heparan sulfate chains of GPC1. Colocates, in the presence of Cu(2+), to vesicles in para- and perinuclear regions, where both proteins undergo internalization. Heparin displaces PRNP from lipid rafts and promotes endocytosis. The normal, monomeric form, PRPN(C), has a mainly alpha-helical structure. Misfolding of this form produces a disease-associated, protease-resistant form, PRPN (Sc), accompanied by a large increase of the beta-sheet content and formation of amyloid fibrils. These fibrils consist of a cross-beta spine, formed by a steric zipper of superposed beta-strands. Disease mutations may favor intermolecular contacts via short beta strands, and may thereby trigger oligomerization. In addition, the heparan-sulfate proteoglycan, GPC1, promotes the association of PRPN (C) to lipid rafts and appears to facilitate the conversion to PRPN (Sc). Contains an N-terminal region composed of octamer repeats. At low copper concentrations, the sidechains of His residues from three or four repeats contribute to the binding of a single copper ion. Alternatively, a copper ion can be bound by interaction with the sidechain and backbone amide nitrogen of a single His residue. The observed copper binding stoichiometry suggests that two repeat regions cooperate to stabilize the binding of a single copper ion. At higher copper concentrations, each octamer can bind one copper ion by interactions with the His sidechain and Gly backbone atoms. A mixture of binding types may occur, especially in the case of octamer repeat expansion. Copper binding may stabilize the conformation of this region and may promote oligomerization. The glycosylation pattern (the amount of mono-, di- and non-glycosylated forms or glycoforms) seems to differ in normal and CJD prion. The five tandem octapeptide repeats region is highly unstable. Insertions or deletions of octapeptide repeat units are associated to prion disease. A number of polymorphisms confer resistance to prion diseases (PubMed:1439789, PubMed:9482303, PubMed:19923577, PubMed:26061765). Val-127 has been selected for in response to the Kuru epidemic and confers resistance to prion disease by acting as a 'dominant negative' inhibitor of prion conversion (PubMed:26061765). Val-127 is not only itself resistant to conformational conversion, but also inhibits conversion of wild-type proteins. Confers protection against classical Creutzfeldt-Jakob disease (CJD) and Kuru in the heterozygous state, but can be infected with variant CJD prions, resulting from exposure to bovine spongiform encephalopathy prions. Confers complete resistance to all prion strains when homozygous (PubMed:26061765). Always associated with M-129 variant (PubMed:26061765). Val-129 confers relative protection against acquired, sporadic and some inherited prion diseases in the heterozygous state, possibly by preventing homodimerization (PubMed:1439789). Lys-219 confers relative protection against sporadic Creutzfeldt-Jakob disease (CJD) in the heterozygous state (PubMed:9482303). PrP is found in high quantity in the brain of humans and animals infected with neurodegenerative diseases known as transmissible spongiform encephalopathies or prion diseases, like: Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI), Gerstmann-Straussler disease (GSD), Huntington disease-like type 1 (HDL1) and kuru in humans; scrapie in sheep and goat; bovine spongiform encephalopathy (BSE) in cattle; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of mule deer and elk; feline spongiform encephalopathy (FSE) in cats and exotic ungulate encephalopathy (EUE) in nyala and greater kudu. The prion diseases illustrate three manifestations of CNS degeneration: (1) infectious (2) sporadic and (3) dominantly inherited forms. TME, CWD, BSE, FSE, EUE are all thought to occur after consumption of prion-infected foodstuffs. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. This protein is produced by a bicistronic gene which also produces the alternative prion protein/AltPrP (AC F7VJQ1) from an overlapping reading frame. The alternative prion protein/AltPrP (AC F7VJQ1) and PRNP have no apparent direct functional relation since a mutation that removes the start codon of the AltPrP has no apparent effect on the biology of PRNP. In mouse and hamster, the alternative initiation AUG codon is absent and is replaced by a GUG codon. Belongs to the prion family. An isoform was shown to be localized to both the cytoplasm and the nucleus and to be sumoylated with SUMO1 (PubMed:19059915). The article has later been withdrawn by the authors. PRNP entry The shape of harm - Issue 179 of May 2016