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Identification
HMDB Protein ID HMDBP02352
Secondary Accession Numbers
  • 7841
Name Major prion protein
Synonyms
  1. ASCR
  2. CD230 antigen
  3. PrP
  4. PrP27-30
  5. PrP33-35C
Gene Name PRNP
Protein Type Enzyme
Biological Properties
General Function Involved in protein homooligomerization
Specific Function The function of PrP is still under debate. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Isoform 2 may act as a growth suppressor by arresting the cell cycle at the G0/G1 phase. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro)
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
Process
cellular component organization or biogenesis
cellular component organization
cellular component assembly
macromolecular complex assembly
protein complex assembly
protein oligomerization
protein homooligomerization
Cellular Location
  1. Nucleus
  2. Isoform 2:Cytoplasm
Gene Properties
Chromosome Location Chromosome:2
Locus 20p13
SNPs PRNP
Gene Sequence
>762 bp
ATGGCGAACCTTGGCTGCTGGATGCTGGTTCTCTTTGTGGCCACATGGAGTGACCTGGGC
CTCTGCAAGAAGCGCCCGAAGCCTGGAGGATGGAACACTGGGGGCAGCCGATACCCGGGG
CAGGGCAGCCCTGGAGGCAACCGCTACCCACCTCAGGGCGGTGGTGGCTGGGGGCAGCCT
CATGGTGGTGGCTGGGGGCAGCCTCATGGTGGTGGCTGGGGGCAGCCCCATGGTGGTGGC
TGGGGACAGCCTCATGGTGGTGGCTGGGGTCAAGGAGGTGGCACCCACAGTCAGTGGAAC
AAGCCGAGTAAGCCAAAAACCAACATGAAGCACATGGCTGGTGCTGCAGCAGCTGGGGCA
GTGGTGGGGGGCCTTGGCGGCTACATGCTGGGAAGTGCCATGAGCAGGCCCATCATACAT
TTCGGCAGTGACTATGAGGACCGTTACTATCGTGAAAACATGCACCGTTACCCCAACCAA
GTGTACTACAGGCCCATGGATGAGTACAGCAACCAGAACAACTTTGTGCACGACTGCGTC
AATATCACAATCAAGCAGCACACGGTCACCACAACCACCAAGGGGGAGAACTTCACCGAG
ACCGACGTTAAGATGATGGAGCGCGTGGTTGAGCAGATGTGTATCACCCAGTACGAGAGG
GAATCTCAGGCCTATTACCAGAGAGGATCGAGCATGGTCCTCTTCTCCTCTCCACCTGTG
ATCCTCCTGATCTCTTTCCTCATCTTCCTGATAGTGGGATGA
Protein Properties
Number of Residues 253
Molecular Weight 27661.2
Theoretical pI 9.23
Pfam Domain Function
Signals
  • 1-22
Transmembrane Regions
  • None
Protein Sequence
>Major prion protein
MANLGCWMLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQP
HGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHSQWNKPSKPKTNMKHMAGAAAAGA
VVGGLGGYMLGSAMSRPIIHFGSDYEDRYYRENMHRYPNQVYYRPMDEYSNQNNFVHDCV
NITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYERESQAYYQRGSSMVLFSSPPV
ILLISFLIFLIVG
GenBank ID Protein 190468
UniProtKB/Swiss-Prot ID P04156
UniProtKB/Swiss-Prot Entry Name PRIO_HUMAN
PDB IDs
GenBank Gene ID M13899
GeneCard ID PRNP
GenAtlas ID PRNP
HGNC ID HGNC:9449
References
General References
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  4. Finckh U, Muller-Thomsen T, Mann U, Eggers C, Marksteiner J, Meins W, Binetti G, Alberici A, Hock C, Nitsch RM, Gal A: High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet. 2000 Jan;66(1):110-7. [PubMed:10631141 ]
  5. Kretzschmar HA, Stowring LE, Westaway D, Stubblebine WH, Prusiner SB, Dearmond SJ: Molecular cloning of a human prion protein cDNA. DNA. 1986 Aug;5(4):315-24. [PubMed:3755672 ]
  6. Puckett C, Concannon P, Casey C, Hood L: Genomic structure of the human prion protein gene. Am J Hum Genet. 1991 Aug;49(2):320-9. [PubMed:1678248 ]
  7. Lee IY, Westaway D, Smit AF, Wang K, Seto J, Chen L, Acharya C, Ankener M, Baskin D, Cooper C, Yao H, Prusiner SB, Hood LE: Complete genomic sequence and analysis of the prion protein gene region from three mammalian species. Genome Res. 1998 Oct;8(10):1022-37. [PubMed:9799790 ]
  8. Cervenakova L, Buetefisch C, Lee HS, Taller I, Stone G, Gibbs CJ Jr, Brown P, Hallett M, Goldfarb LG: Novel PRNP sequence variant associated with familial encephalopathy. Am J Med Genet. 1999 Dec 15;88(6):653-6. [PubMed:10581485 ]
  9. Liao YC, Lebo RV, Clawson GA, Smuckler EA: Human prion protein cDNA: molecular cloning, chromosomal mapping, and biological implications. Science. 1986 Jul 18;233(4761):364-7. [PubMed:3014653 ]
  10. Diedrich JF, Knopman DS, List JF, Olson K, Frey WH 2nd, Emory CR, Sung JH, Haase AT: Deletion in the prion protein gene in a demented patient. Hum Mol Genet. 1992 Sep;1(6):443-4. [PubMed:1363802 ]
  11. Samaia HB, Mari JJ, Vallada HP, Moura RP, Simpson AJ, Brentani RR: A prion-linked psychiatric disorder. Nature. 1997 Nov 20;390(6657):241. [PubMed:9384372 ]
  12. Perry RT, Go RC, Harrell LE, Acton RT: SSCP analysis and sequencing of the human prion protein gene (PRNP) detects two different 24 bp deletions in an atypical Alzheimer's disease family. Am J Med Genet. 1995 Feb 27;60(1):12-8. [PubMed:7485229 ]
  13. Tagliavini F, Prelli F, Ghiso J, Bugiani O, Serban D, Prusiner SB, Farlow MR, Ghetti B, Frangione B: Amyloid protein of Gerstmann-Straussler-Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58. EMBO J. 1991 Mar;10(3):513-9. [PubMed:1672107 ]
  14. Goldfarb LG, Brown P, McCombie WR, Goldgaber D, Swergold GD, Wills PR, Cervenakova L, Baron H, Gibbs CJ Jr, Gajdusek DC: Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10926-30. [PubMed:1683708 ]
  15. Chattopadhyay M, Walter ED, Newell DJ, Jackson PJ, Aronoff-Spencer E, Peisach J, Gerfen GJ, Bennett B, Antholine WE, Millhauser GL: The octarepeat domain of the prion protein binds Cu(II) with three distinct coordination modes at pH 7.4. J Am Chem Soc. 2005 Sep 14;127(36):12647-56. [PubMed:16144413 ]
  16. Walter ED, Stevens DJ, Visconte MP, Millhauser GL: The prion protein is a combined zinc and copper binding protein: Zn2+ alters the distribution of Cu2+ coordination modes. J Am Chem Soc. 2007 Dec 19;129(50):15440-1. Epub 2007 Nov 23. [PubMed:18034490 ]
  17. Juanes ME, Elvira G, Garcia-Grande A, Calero M, Gasset M: Biosynthesis of prion protein nucleocytoplasmic isoforms by alternative initiation of translation. J Biol Chem. 2009 Jan 30;284(5):2787-94. doi: 10.1074/jbc.M804051200. Epub 2008 Dec 5. [PubMed:19059915 ]
  18. Stevens DJ, Walter ED, Rodriguez A, Draper D, Davies P, Brown DR, Millhauser GL: Early onset prion disease from octarepeat expansion correlates with copper binding properties. PLoS Pathog. 2009 Apr;5(4):e1000390. doi: 10.1371/journal.ppat.1000390. Epub 2009 Apr 17. [PubMed:19381258 ]
  19. Adrover M, Pauwels K, Prigent S, de Chiara C, Xu Z, Chapuis C, Pastore A, Rezaei H: Prion fibrillization is mediated by a native structural element that comprises helices H2 and H3. J Biol Chem. 2010 Jul 2;285(27):21004-12. doi: 10.1074/jbc.M110.111815. Epub 2010 Apr 7. [PubMed:20375014 ]
  20. Wu D, Zhang W, Luo Q, Luo K, Huang L, Wang W, Huang T, Chen R, Lin Y, Pang D, Xiao G: Copper (II) promotes the formation of soluble neurotoxic PrP oligomers in acidic environment. J Cell Biochem. 2010 Oct 15;111(3):627-33. doi: 10.1002/jcb.22743. [PubMed:20564047 ]
  21. Zhang Y, Swietnicki W, Zagorski MG, Surewicz WK, Sonnichsen FD: Solution structure of the E200K variant of human prion protein. Implications for the mechanism of pathogenesis in familial prion diseases. J Biol Chem. 2000 Oct 27;275(43):33650-4. [PubMed:10954699 ]
  22. Zahn R, Liu A, Luhrs T, Riek R, von Schroetter C, Lopez Garcia F, Billeter M, Calzolai L, Wider G, Wuthrich K: NMR solution structure of the human prion protein. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):145-50. [PubMed:10618385 ]
  23. Calzolai L, Lysek DA, Guntert P, von Schroetter C, Riek R, Zahn R, Wuthrich K: NMR structures of three single-residue variants of the human prion protein. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8340-5. [PubMed:10900000 ]
  24. Knaus KJ, Morillas M, Swietnicki W, Malone M, Surewicz WK, Yee VC: Crystal structure of the human prion protein reveals a mechanism for oligomerization. Nat Struct Biol. 2001 Sep;8(9):770-4. [PubMed:11524679 ]
  25. Burns CS, Aronoff-Spencer E, Dunham CM, Lario P, Avdievich NI, Antholine WE, Olmstead MM, Vrielink A, Gerfen GJ, Peisach J, Scott WG, Millhauser GL: Molecular features of the copper binding sites in the octarepeat domain of the prion protein. Biochemistry. 2002 Mar 26;41(12):3991-4001. [PubMed:11900542 ]
  26. Zahn R: The octapeptide repeats in mammalian prion protein constitute a pH-dependent folding and aggregation site. J Mol Biol. 2003 Nov 28;334(3):477-88. [PubMed:14623188 ]
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  29. Sawaya MR, Sambashivan S, Nelson R, Ivanova MI, Sievers SA, Apostol MI, Thompson MJ, Balbirnie M, Wiltzius JJ, McFarlane HT, Madsen AO, Riekel C, Eisenberg D: Atomic structures of amyloid cross-beta spines reveal varied steric zippers. Nature. 2007 May 24;447(7143):453-7. Epub 2007 Apr 29. [PubMed:17468747 ]
  30. Antonyuk SV, Trevitt CR, Strange RW, Jackson GS, Sangar D, Batchelor M, Cooper S, Fraser C, Jones S, Georgiou T, Khalili-Shirazi A, Clarke AR, Hasnain SS, Collinge J: Crystal structure of human prion protein bound to a therapeutic antibody. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2554-8. doi: 10.1073/pnas.0809170106. Epub 2009 Feb 9. [PubMed:19204296 ]
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  32. Hsiao K, Baker HF, Crow TJ, Poulter M, Owen F, Terwilliger JD, Westaway D, Ott J, Prusiner SB: Linkage of a prion protein missense variant to Gerstmann-Straussler syndrome. Nature. 1989 Mar 23;338(6213):342-5. [PubMed:2564168 ]
  33. Doh-ura K, Tateishi J, Sasaki H, Kitamoto T, Sakaki Y: Pro----leu change at position 102 of prion protein is the most common but not the sole mutation related to Gerstmann-Straussler syndrome. Biochem Biophys Res Commun. 1989 Sep 15;163(2):974-9. [PubMed:2783132 ]
  34. Medori R, Montagna P, Tritschler HJ, LeBlanc A, Cortelli P, Tinuper P, Lugaresi E, Gambetti P: Fatal familial insomnia: a second kindred with mutation of prion protein gene at codon 178. Neurology. 1992 Mar;42(3 Pt 1):669-70. [PubMed:1347910 ]
  35. Goldfarb LG, Haltia M, Brown P, Nieto A, Kovanen J, McCombie WR, Trapp S, Gajdusek DC: New mutation in scrapie amyloid precursor gene (at codon 178) in Finnish Creutzfeldt-Jakob kindred. Lancet. 1991 Feb 16;337(8738):425. [PubMed:1671440 ]
  36. Goldfarb LG, Mitrova E, Brown P, Toh BK, Gajdusek DC: Mutation in codon 200 of scrapie amyloid protein gene in two clusters of Creutzfeldt-Jakob disease in Slovakia. Lancet. 1990 Aug 25;336(8713):514-5. [PubMed:1975028 ]
  37. Hsiao K, Dlouhy SR, Farlow MR, Cass C, Da Costa M, Conneally PM, Hodes ME, Ghetti B, Prusiner SB: Mutant prion proteins in Gerstmann-Straussler-Scheinker disease with neurofibrillary tangles. Nat Genet. 1992 Apr;1(1):68-71. [PubMed:1363810 ]
  38. Kitamoto T, Ohta M, Doh-ura K, Hitoshi S, Terao Y, Tateishi J: Novel missense variants of prion protein in Creutzfeldt-Jakob disease or Gerstmann-Straussler syndrome. Biochem Biophys Res Commun. 1993 Mar 15;191(2):709-14. [PubMed:8461023 ]
  39. Pocchiari M, Salvatore M, Cutruzzola F, Genuardi M, Allocatelli CT, Masullo C, Macchi G, Alema G, Galgani S, Xi YG, et al.: A new point mutation of the prion protein gene in Creutzfeldt-Jakob disease. Ann Neurol. 1993 Dec;34(6):802-7. [PubMed:7902693 ]
  40. Yamada M, Itoh Y, Fujigasaki H, Naruse S, Kaneko K, Kitamoto T, Tateishi J, Otomo E, Hayakawa M, Tanaka J, et al.: A missense mutation at codon 105 with codon 129 polymorphism of the prion protein gene in a new variant of Gerstmann-Straussler-Scheinker disease. Neurology. 1993 Dec;43(12):2723-4. [PubMed:7902972 ]
  41. Itoh Y, Yamada M, Hayakawa M, Shozawa T, Tanaka J, Matsushita M, Kitamoto T, Tateishi J, Otomo E: A variant of Gerstmann-Straussler-Scheinker disease carrying codon 105 mutation with codon 129 polymorphism of the prion protein gene: a clinicopathological study. J Neurol Sci. 1994 Dec 1;127(1):77-86. [PubMed:7699395 ]
  42. Inoue I, Kitamoto T, Doh-ura K, Shii H, Goto I, Tateishi J: Japanese family with Creutzfeldt-Jakob disease with codon 200 point mutation of the prion protein gene. Neurology. 1994 Feb;44(2):299-301. [PubMed:7906019 ]
  43. Gabizon R, Rosenman H, Meiner Z, Kahana I, Kahana E, Shugart Y, Ott J, Prusiner SB: Mutation in codon 200 and polymorphism in codon 129 of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease. Philos Trans R Soc Lond B Biol Sci. 1994 Mar 29;343(1306):385-90. [PubMed:7913755 ]
  44. Young K, Jones CK, Piccardo P, Lazzarini A, Golbe LI, Zimmerman TR Jr, Dickson DW, McLachlan DC, St George-Hyslop P, Lennox A, et al.: Gerstmann-Straussler-Scheinker disease with mutation at codon 102 and methionine at codon 129 of PRNP in previously unreported patients. Neurology. 1995 Jun;45(6):1127-34. [PubMed:7783876 ]
  45. Barbanti P, Fabbrini G, Salvatore M, Petraroli R, Cardone F, Maras B, Equestre M, Macchi G, Lenzi GL, Pocchiari M: Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Straussler-Scheinker disease (PrP-P102L mutation). Neurology. 1996 Sep;47(3):734-41. [PubMed:8797472 ]
  46. Mastrianni JA, Iannicola C, Myers RM, DeArmond S, Prusiner SB: Mutation of the prion protein gene at codon 208 in familial Creutzfeldt-Jakob disease. Neurology. 1996 Nov;47(5):1305-12. [PubMed:8909447 ]
  47. Nitrini R, Rosemberg S, Passos-Bueno MR, da Silva LS, Iughetti P, Papadopoulos M, Carrilho PM, Caramelli P, Albrecht S, Zatz M, LeBlanc A: Familial spongiform encephalopathy associated with a novel prion protein gene mutation. Ann Neurol. 1997 Aug;42(2):138-46. [PubMed:9266722 ]
  48. Piccardo P, Dlouhy SR, Lievens PM, Young K, Bird TD, Nochlin D, Dickson DW, Vinters HV, Zimmerman TR, Mackenzie IR, Kish SJ, Ang LC, De Carli C, Pocchiari M, Brown P, Gibbs CJ Jr, Gajdusek DC, Bugiani O, Ironside J, Tagliavini F, Ghetti B: Phenotypic variability of Gerstmann-Straussler-Scheinker disease is associated with prion protein heterogeneity. J Neuropathol Exp Neurol. 1998 Oct;57(10):979-88. [PubMed:9786248 ]
  49. Windl O, Giese A, Schulz-Schaeffer W, Zerr I, Skworc K, Arendt S, Oberdieck C, Bodemer M, Poser S, Kretzschmar HA: Molecular genetics of human prion diseases in Germany. Hum Genet. 1999 Sep;105(3):244-52. [PubMed:10987652 ]
  50. Peoc'h K, Manivet P, Beaudry P, Attane F, Besson G, Hannequin D, Delasnerie-Laupretre N, Laplanche JL: Identification of three novel mutations (E196K, V203I, E211Q) in the prion protein gene (PRNP) in inherited prion diseases with Creutzfeldt-Jakob disease phenotype. Hum Mutat. 2000 May;15(5):482. [PubMed:10790216 ]
  51. Panegyres PK, Toufexis K, Kakulas BA, Cernevakova L, Brown P, Ghetti B, Piccardo P, Dlouhy SR: A new PRNP mutation (G131V) associated with Gerstmann-Straussler-Scheinker disease. Arch Neurol. 2001 Nov;58(11):1899-902. [PubMed:11709001 ]