PRNP

PRNP (PRioN Protein (Creutzfeld-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia)) is a genecite journal | author = Kretzschmar HA, Stowring LE, Westaway D, Stubblebine WH, Prusiner SB, Dearmond SJ | title = Molecular cloning of a human prion protein cDNA | journal = DNA | volume = 5 | issue = 4 | pages = 315–24 | year = 1986 | month = August | pmid = 3755672 | doi = | url = | issn = ] cite journal | author = Sparkes RS, Simon M, Cohn VH, "et al" | title = Assignment of the human and mouse prion protein genes to homologous chromosomes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 83 | issue = 19 | pages = 7358–62 | year = 1986 | month = October | pmid = 3094007 | pmc = 386716 | url = http://www.pnas.org/cgi/pmidlookup?view=long&pmid=3094007 | issn = ] cite journal | author = Liao YC, Lebo RV, Clawson GA, Smuckler EA | title = Human prion protein cDNA: molecular cloning, chromosomal mapping, and biological implications | journal = Science (journal) | volume = 233 | issue = 4761 | pages = 364–7 | year = 1986 | month = July | pmid = 3014653 | url = http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=3014653 | issn = ] cite journal | author = Robakis NK, Devine-Gage EA, Jenkins EC, "et al" | title = Localization of a human gene homologous to the PrP gene on the p arm of chromosome 20 and detection of PrP-related antigens in normal human brain | journal = Biochem. Biophys. Res. Commun. | volume = 140 | issue = 2 | pages = 758–65 | year = 1986 | month = October | pmid = 2877664 | url = http://linkinghub.elsevier.com/retrieve/pii/0006-291X(86)90796-5 | issn = ] that provides instructions to make a protein called the prion protein (PrP), which is expressed in the brain and several other tissues.cite journal | author=Prusiner SB | title=Shattuck lecture--neurodegenerative diseases and prions | journal=N Engl J Med | year=2001 | pages=1516–26 | volume=344 | issue=20 | pmid=11357156] cite journal | author=Weissmann C | title=The state of the prion | journal=Nat Rev Microbiol | year=2004 | pages=861–71 | volume=2 | issue=11 | pmid=15494743 | doi=10.1038/nrmicro1025]

The human 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.

PRNP has also recently been designated CD230 (cluster of differentiation 230).

Function

Although the precise function of PrP is not yet known, it is possibly involved in the transport of ionic 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, 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.

Disease linkage

More than 20 mutations in the PRNP gene have been identified in people with inherited prion diseases, which include the following:cite journal | author=Castilla J, Hetz C, Soto C | title=Molecular mechanisms of neurotoxicity of pathological prion protein | journal=Curr Mol Med | year=2004 | pages=397–403 | volume=4 | issue=4 | pmid=15354870 | doi=10.2174/1566524043360654] cite journal | author=Kovacs GG, Trabattoni G, Hainfellner JA, Ironside JW, Knight RS, Budka H | title=Mutations of the prion protein gene phenotypic spectrum | journal=J Neurol | year=2002 | pages=1567–82 | volume=249 | issue=11 | pmid=12420099 | doi=10.1007/s00415-002-0896-9]

* 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 leucinecite journal | author=Collins S, McLean CA, Masters CL | title=Gerstmann-Straussler-Scheinker syndrome,fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies | journal=J Clin Neurosci | year=2001 | pages=387–97 | volume=8 | issue=5 | pmid=11535002 | doi=10.1054/jocn.2001.0919]
* fatal insomnia - aspartic acid-178 is replaced by asparagine while methionine is present at amino acid 129cite journal | author=Montagna P, Gambetti P, Cortelli P, Lugaresi E | title=Familial and sporadic fatal insomnia | journal=Lancet Neurol | year=2003 | pages=167–76 | volume=2 | issue=3 | pmid=12849238 | doi=10.1016/S1474-4422(03)00323-5]

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

External links

* [http://www.genecards.org/cgi-bin/carddisp?PRNP GeneCard]

External links

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