PRNP

Prion protein (p27-30) (Creutzfeldt-Jakob disease, Gerstmann-Strausler-Scheinker syndrome, fatal familial insomnia)
PDB rendering based on 1ag2.
Available structures: 1ag2, 1dwy, 1dwz, 1dx0, 1dx1, 1e1g, 1e1j, 1e1p, 1e1s, 1e1u, 1e1w, 1fkc, 1fo7, 1h0l, 1hjm, 1hjn, 1i4m, 1oei, 1qlx, 1qlz, 1qm0, 1qm1, 1qm2, 1qm3, 1tpx, 1tqb, 1tqc, 1uw3, 1xyu, 1xyx, 1y15, 1y2s
Identifiers
Symbol(s)	PRNP; GSS; ASCR; CD230; CJD; MGC26679; PRIP; PrP; PrP27-30; PrP33-35C; PrPc
External IDs	OMIM: 176640 MGI: 97769 Homologene: 7904
Gene Ontology Molecular Function: • copper ion binding • protein binding • microtubule binding • GPI anchor binding Cellular Component: • cytoplasm • endoplasmic reticulum • Golgi apparatus • plasma membrane • extrinsic to membrane • lipid raft Biological Process: • cellular copper ion homeostasis • response to oxidative stress • metabolic process
RNA expression pattern
Additional recommended knowledge Weighing the right way Essential Laboratory Skills Guide Daily Sensitivity Test More reference expression data
Orthologs
	Human	Mouse
Entrez	5621	19122
Ensembl	ENSG00000171867	na
Uniprot	P04156	na
Refseq	NM_000311 (mRNA) NP_000302 (protein)	NM_011170 (mRNA) NP_035300 (protein)
Location	Chr 20: 4.61 - 4.63 Mb	na
Pubmed search	[1]	[2]

PRNP (PRioN Protein (Creutzfeld-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia)) is a gene that provides instructions to make a protein called the prion protein (PrP), which is active in the brain and several other tissues. Although the precise function of PrP is not yet known, it is possibly involved in the transport of charged atoms (ions) of copper to cells from the surrounding environment. Researchers have also proposed roles for PrP in cell signaling or in the formation of gaps between nerve cells (synapses) where cell-to-cell communication occurs.

Different forms of PrP have been identified in the nervous system. The usual cellular form is called PrP^C. Another form, PrP^Sc, has a different 3-dimensional structure and has been associated with inherited, sporadic (non-inherited), and infectious disorders of the brain and nervous system. In a process that is not fully understood, PrP^C can transform into the abnormal PrP^Sc. This abnormal protein can further promote the transformation of PrP^C into PrP^Sc, leading to transmissible spongiform encephalopathy.

The PRNP gene is located on the short (p) arm of chromosome 20 between the end (terminus) of the arm and position 12, from base pair 4,615,068 to base pair 4,630,233.

Related conditions

More than 20 mutations in the PRNP gene have been identified in people with inherited prion diseases, which include the following:

• Creutzfeldt-Jakob disease - aspartic acid-178 is replaced by asparagine while valine is present at amino acid 129
• Gerstmann-Sträussler-Scheinker syndrome - usually a change in codon 102 from proline to leucine
• fatal insomnia - aspartic acid-178 is replaced by asparagine while methionine is present at amino acid 129

Some PRNP mutations lead to a change in single amino acids (the building blocks of proteins) in the prion protein. Others insert additional amino acids into the protein or cause an abnormally short protein to be made. These mutations cause the cell to make prion proteins with an abnormal structure. The abnormal protein, PrP^Sc, accumulates in the brain and destroys nerve cells, which leads to the mental and behavioral features of prion diseases. Several other changes in the PRNP gene (called polymorphisms) do not cause prion diseases, but may affect a person's risk of developing these diseases or alter the course of the disorders.

References

• Castilla J, Hetz C, Soto C (2004). "Molecular mechanisms of neurotoxicity of pathological prion protein". Curr Mol Med 4 (4): 397-403. PMID 15354870.
• Collins S, McLean CA, Masters CL (2001). "Gerstmann-Straussler-Scheinker syndrome,fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies". J Clin Neurosci 8 (5): 387-97. PMID 11535002.
• Kovacs GG, Trabattoni G, Hainfellner JA, Ironside JW, Knight RS, Budka H (2002). "Mutations of the prion protein gene phenotypic spectrum". J Neurol 249 (11): 1567-82. PMID 12420099.
• Montagna P, Gambetti P, Cortelli P, Lugaresi E (2003). "Familial and sporadic fatal insomnia". Lancet Neurol 2 (3): 167-76. PMID 12849238.
• Prusiner SB (2001). "Shattuck lecture--neurodegenerative diseases and prions". N Engl J Med 344 (20): 1516-26. PMID 11357156.
• Weissmann C (2004). "The state of the prion". Nat Rev Microbiol 2 (11): 861-71. PMID 15494743.