Reviewed, UniProtKB/Swiss-Prot P04156 (PRIO_HUMAN)

Names and origin

Protein names

Recommended name:
    Major prion protein
      Short name=PrP
Alternative name(s):
    PrP27-30
    PrP33-35C
    ASCR
    CD_antigen=CD230

Gene names

Name:	PRNP
Synonyms:	PRIP, PRP

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	253 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	The physiological function of PrP is not known.
Subunit structure	PrP has a tendency to aggregate yielding polymers called "rods". Interacts with GRB2, PRNPIP and SYN1 By similarity.
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor. Golgi apparatus By similarity.
Post-translational modification	The glycosylation pattern (the amount of mono-, di- and non-glycosylated forms or glycoforms) seems to differ in normal and CJD prion.
Polymorphism	The five tandem octapeptide repeats region is highly unstable. Insertions or deletions of octapeptide repeat units are associated to prion disease.
Involvement in disease	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 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. Ref.25 Ref.26 Ref.28 Ref.29 Ref.32 Ref.33 Ref.36 Ref.37 Ref.41 Defects in PRNP are the cause of Creutzfeldt-Jakob disease (CJD) [MIM:123400]. CJD occurs primarily as a sporadic disorder (1 per million), while 10-15% are familial. Accidental transmission of CJD to humans appears to be iatrogenic (contaminated human growth hormone (HGH), corneal transplantation, electroencephalographic electrode implantation, etc.). Epidemiologic studies have failed to implicate the ingestion of infected annimal meat in the pathogenesis of CJD in human. The triad of microscopic features that characterize the prion diseases consists of (1) spongiform degeneration of neurons, (2) severe astrocytic gliosis that often appears to be out of proportion to the degree of nerve cell loss, and (3) amyloid plaque formation. CJD is characterized by progressive dementia and myoclonic seizures, affecting adults in mid-life. Some patients present sleep disorders, abnormalities of high cortical function, cerebellar and corticospinal disturbances. The disease ends in death after a 3-12 months illness. Ref.25 Ref.26 Ref.28 Ref.29 Ref.32 Ref.33 Ref.36 Ref.37 Ref.41 Defects in PRNP are the cause of fatal familial insomnia (FFI) [MIM:600072]. FFI is an autosomal dominant disorder and is characterized by neuronal degeneration limited to selected thalamic nuclei and progressive insomnia. Ref.24 Defects in PRNP are the cause of Gerstmann-Straussler disease (GSD) [MIM:137440]. GSD is a heterogeneous disorder and was defined as a spinocerebellar ataxia with dementia and plaquelike deposits. GSD incidence is less than 2 per 100 million live births. Ref.4 Ref.22 Ref.27 Ref.30 Ref.31 Ref.34 Ref.35 Ref.38 Ref.42 Defects in PRNP are the cause of Huntington disease-like 1 (HDL1) [MIM:603218]. HDL1 is an autosomal dominant, early onset neurodegenerative disorder with prominent psychiatric features. Defects in PRNP are the cause of kuru [MIM:245300]. Kuru is transmitted during ritualistic cannibalism, among natives of the New Guinea highlands. Patients exhibit various movement disorders like cerebellar abnormalities, rigidity of the limbs, and clonus. Emotional lability is present, and dementia is conspicuously absent. Death usually occurs from 3 to 12 month after onset. Defects in PRNP are the cause of prion disease with protracted course [MIM:606688]; an autosomal dominant presenile dementia with a rapidly progressive and protracted clinical course. The dementia was characterized clinically by frontotemporal features, including early personality changes. Some patients had memory loss, several showed aggressiveness, hyperorality and verbal stereotypy, others had parkinsonian symptoms.
Sequence similarities	Belongs to the prion family.

Ontologies

Keywords
Cellular component	Cell membrane Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Prion
Domain	Repeat Signal
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	cellular copper ion homeostasis Non-traceable author statement. Source: UniProtKB metabolic process Ref.1 Traceable author statement. Source: ProtInc protein homooligomerization Inferred from electronic annotation. Source: InterPro response to oxidative stress Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from sequence or structural similarity. Source: UniProtKB anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum Inferred from sequence or structural similarity. Source: UniProtKB extrinsic to membrane Traceable author statement. Source: UniProtKB membrane raft Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	copper ion binding Traceable author statement. Source: UniProtKB identical protein binding Inferred from physical interaction. Source: IntAct microtubule binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-977302,EBI-977302
Aldoc	P05063	1	EBI-977302,EBI-444845	From a different organism.
APP	P05067	1	EBI-977302,EBI-77613
Hnrnpa2b1	O88569	1	EBI-977302,EBI-299636	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Chain

23 – 230

208

Major prion protein

PRO_0000025675

Propeptide

231 – 253

23

Removed in mature form By similarity

PRO_0000025676

Regions

Repeat

51 – 59

9

1

Repeat

60 – 67

8

2

Repeat

68 – 75

8

3

Repeat

76 – 83

8

4

Repeat

84 – 91

8

5

Region

23 – 230

208

Interaction with GRB2, PRNPIP and SYN1 By similarity

Region

51 – 91

41

5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q

Amino acid modifications

Lipidation

230

1

GPI-anchor amidated serine By similarity

Glycosylation

181

1

N-linked (GlcNAc...)

Glycosylation

197

1

N-linked (GlcNAc...)

Disulfide bond

179 ↔ 214

Natural variations

Natural variant

56 – 63

8

Missing Ref.2 Ref.10 Ref.12

VAR_013763

Natural variant

102

1

P → L in GSD and early-onset dementia.

VAR_006464

Natural variant

105

1

P → L in GSD. Ref.30 Ref.31

VAR_006465

Natural variant

117

1

A → V Linked to development of dementing Gerstmann-Straussler disease. Ref.23

VAR_006466

Natural variant

129

1

M → V Polymorphism; determines the disease phenotype in patients who have a PrP mutation at position 178. Patients with M-129 develop FFI, those with V-129 develop CJD. dbSNP rs1799990. Ref.23

VAR_006467

Natural variant

131

1

G → V in GSD. Ref.42

VAR_014264

Natural variant

171

1

N → S in schizoaffective disorder. dbSNP rs16990018. Ref.11

VAR_006468

Natural variant

178

1

D → N in FFI and CJD.

VAR_006469

Natural variant

180

1

V → I in CJD. Ref.28

VAR_006470

Natural variant

183

1

T → A in familial spongiform encephalopathy. Ref.40

VAR_006471

Natural variant

187

1

H → R in GSD. Ref.4

VAR_008746

Natural variant

188

1

T → K in early-onset dementia; dementia associated to prion diseases. Ref.40 Ref.39

VAR_008748

Natural variant

188

1

T → R Ref.40 Ref.39

VAR_008747

Natural variant

196

1

E → K in CJD. Ref.41

VAR_008749

Natural variant

198

1

F → S in GSD; atypical form with neurofibrillary tangles.

VAR_006472

Natural variant

200

1

E → K in CJD. Ref.26 Ref.32 Ref.33

VAR_006473

Natural variant

202

1

D → N in GSD. Ref.38

VAR_008750

Natural variant

203

1

V → I in CJD; it could be an extremely rare polymorphism. Ref.41

VAR_008751

Natural variant

208

1

R → H in CJD. Ref.36 Ref.37

VAR_006474

Natural variant

210

1

V → I in CJD. Ref.29

VAR_006475

Natural variant

211

1

E → Q in CJD. Ref.41

VAR_008752

Natural variant

212

1

Q → P in GSD. Ref.38

VAR_008753

Natural variant

217

1

Q → R in GSD; with neurofibrillary tangles. Ref.27

VAR_006476

Natural variant

219

1

E → K: dbSNP rs1800014. Ref.35

VAR_006477

Natural variant

232

1

M → R in CJD. Ref.28

VAR_006478

Natural variant

238

1

P → S Ref.39

VAR_008754

Experimental info

Sequence conflict

118

1

Missing in AAA19664. Ref.9

Sequence conflict

118

1

Missing in BAA00011. Ref.9

Sequence conflict

169

1

Y → H in ABD63004. Ref.6

Sequence conflict

227

1

Q → K in AAH22532. Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

253

Helix Strand Turn

Details...

Beta strand

63 – 66

4

Beta strand

70 – 73

4

Turn

74 – 76

3

Beta strand

78 – 82

5

Helix

144 – 153

10

Helix

154 – 156

3

Helix

166 – 168

3

Helix

172 – 189

18

Beta strand

191 – 193

3

Helix

194 – 197

4

Helix

200 – 223

24

Sequences

	Sequence		Length	Mass (Da)
	P04156-1 [UniParc]. Last modified November 1, 1986. Version 1. Checksum: 43DB596BAAA66484	FASTA	253	27,661
	10 20 30 40 50 60 MANLGCWMLV LFVATWSDLG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP PQGGGGWGQP 70 80 90 100 110 120 HGGGWGQPHG GGWGQPHGGG WGQPHGGGWG QGGGTHSQWN KPSKPKTNMK HMAGAAAAGA 130 140 150 160 170 180 VVGGLGGYML GSAMSRPIIH FGSDYEDRYY RENMHRYPNQ VYYRPMDEYS NQNNFVHDCV 190 200 210 220 230 240 NITIKQHTVT TTTKGENFTE TDVKMMERVV EQMCITQYER ESQAYYQRGS SMVLFSSPPV 250 ILLISFLIFL IVG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a human prion protein cDNA." Kretzschmar H.A., Stowring L.E., Westaway D., Stubblebine W.H., Prusiner S.B., Dearmond S.J. DNA 5:315-324(1986) [PubMed: 3755672] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Genomic structure of the human prion protein gene." Puckett C., Concannon P., Casey C., Hood L.E. Am. J. Hum. Genet. 49:320-329(1991) [PubMed: 1678248] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT 56-GLY--GLY-63 DEL. Tissue: Brain.
[3]	"Complete genomic sequence and analysis of the prion protein gene region from three mammalian species." Lee I.Y., Westaway D., Smit A.F.A., Wang K., Seto J., Chen L., Acharya C., Ankener M., Baskin D., Cooper C., Yao H., Prusiner S.B., Hood L.E. Genome Res. 8:1022-1037(1998) [PubMed: 9799790] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Novel PRNP sequence variant associated with familial encephalopathy." Cervenakova L., Buetefisch C., Lee H.S., Taller I., Stone G., Gibbs C.J. Jr., Brown P., Hallett M., Goldfarb L.G. Am. J. Med. Genet. 88:653-656(1999) [PubMed: 10581485] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GSD ARG-187. Tissue: Blood.
[5]	"Cloning of human prostate prion protein cDNA." Hryb D.J., Reynolds T.A., Nakhla A.M., Kahn S.M., Khan S.M., Romas N.A., Rosner W. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Prostate.
[6]	"Analysis and comparison of several mammalian prion protein genes Prnp." Zhang J., Liu Y., Chen H., Jiang H., Lu W., Zhu X., Xie Q., Cai X., Liu X. Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Ovary.
[9]	"Human prion protein cDNA: molecular cloning, chromosomal mapping, and biological implications." Liao Y.-C.J., Lebo R.V., Clawson G.A., Smuckler E.A. Science 233:364-367(1986) [PubMed: 3014653] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-253.
[10]	"Deletion in the prion protein gene in a demented patient." Diedrich J.F., Knopman D.S., List J.F., Olson K., Frey W.H., Emory C.R., Sung J.H., Haase A.T. Hum. Mol. Genet. 1:443-444(1992) [PubMed: 1363802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 9-232, VARIANT 56-GLY--GLY-63 DEL. Tissue: Brain.
[11]	"A prion-linked psychiatric disorder." Samaia H.B., Mari J.J., Vallada H.P., Moura R.P., Simpson A.J.G., Brentani R.R. Nature 390:241-241(1997) [PubMed: 9384372] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 8-253, VARIANT SCHIZOAFFECTIVE DISORDER SER-171.
[12]	"SSCP analysis and sequencing of the human prion protein gene (PRNP) detects two different 24 bp deletions in an atypical Alzheimer's disease family." Perry R.T., Go R.C., Harrell L.E., Acton R.T. Am. J. Med. Genet. 60:12-18(1995) [PubMed: 7485229] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-85, VARIANT 56-GLY--GLY-63 DEL.
[13]	"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." Tagliavini F., Prelli F., Ghiso J., Bugiani O., Serban D., Prusiner S.B., Farlow M.R., Ghetti B., Frangione B. EMBO J. 10:513-519(1991) [PubMed: 1672107] [Abstract] Cited for: PROTEIN SEQUENCE OF 58-85 AND 111-150.
[14]	"Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene." Goldfarb L.G., Brown P., McCombie W.R., Goldgaber D., Swergold G.D., Wills P.R., Cervenakova L., Baron H., Gibbs C.J. Jr., Gajdusek D.C. Proc. Natl. Acad. Sci. U.S.A. 88:10926-10930(1991) [PubMed: 1683708] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 84-91.
[15]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-197, MASS SPECTROMETRY.
[16]	"Solution structure of the E200K variant of human prion protein. Implications for the mechanism of pathogenesis in familial prion diseases." Zhang Y., Swietnicki W., Zagorski M.G., Surewicz W.K., Soennichsen F.D. J. Biol. Chem. 275:33650-33654(2000) [PubMed: 10954699] [Abstract] Cited for: STRUCTURE BY NMR OF 90-231 OF MUTANT LYS-200.
[17]	"NMR solution structure of the human prion protein." Zahn R., Liu A., Luhrs T., Riek R., von Schroetter C., Lopez Garcia F., Billeter M., Calzolai L., Wider G., Wuethrich K. Proc. Natl. Acad. Sci. U.S.A. 97:145-150(2000) [PubMed: 10618385] [Abstract] Cited for: STRUCTURE BY NMR OF 23-230.
[18]	"NMR structures of three single-residue variants of the human prion protein." Calzolai L., Lysek D.A., Guntert P., von Schroetter C., Riek R., Zahn R., Wuethrich K. Proc. Natl. Acad. Sci. U.S.A. 97:8340-8345(2000) [PubMed: 10900000] [Abstract] Cited for: STRUCTURE BY NMR OF 118-221.
[19]	"The octapeptide repeats in mammalian prion protein constitute a pH-dependent folding and aggregation site." Zahn R. J. Mol. Biol. 334:477-488(2003) [PubMed: 14623188] [Abstract] Cited for: STRUCTURE BY NMR OF 61-68.
[20]	"Mutations and polymorphisms in the prion protein gene." Palmer M.S., Collinge J. Hum. Mutat. 2:168-173(1993) [PubMed: 8364585] [Abstract] Cited for: REVIEW ON VARIANTS.
[21]	"Genetic and infectious prion diseases." Prusiner S.B. Arch. Neurol. 50:1129-1153(1993) [PubMed: 8105771] [Abstract] Cited for: REVIEW ON VARIANTS.
[22]	"Linkage of a prion protein missense variant to Gerstmann-Straussler syndrome." Hsiao K., Baker H.F., Crow T.J., Poulter M., Owen F., Terwilliger J.D., Westaway D., Ott J., Pursiner S.B. Nature 338:342-345(1989) [PubMed: 2564168] [Abstract] Cited for: VARIANT GSD LEU-102.
[23]	"Pro-->Leu change at position 102 of prion protein is the most common but not the sole mutation related to Gerstmann-Straussler syndrome." Doh-Ura K., Tateishi J., Sasaki H., Kitamoto T., Sakaki Y. Biochem. Biophys. Res. Commun. 163:974-979(1989) [PubMed: 2783132] [Abstract] Cited for: VARIANTS LEU-102; VAL-117 AND VAL-129.
[24]	"Fatal familial insomnia: a second kindred with mutation of prion protein gene at codon 178." Medori R., Montagna P., Tritschler H.J., Leblanc A., Cortelli P., Tinuper P., Lugaresi E., Gambetti P. Neurology 42:669-670(1992) [PubMed: 1347910] [Abstract] Cited for: VARIANT FFI ASN-178.
[25]	"New mutation in scrapie amyloid precursor gene (at codon 178) in Finnish Creutzfeldt-Jakob kindred." Goldfarb L.G., Haltia M., Brown P., Nieto A., Kovanen J., McCombie W.R., Trapp S., Gajdusek D.C. Lancet 337:425-425(1991) [PubMed: 1671440] [Abstract] Cited for: VARIANT CJD ASN-178.
[26]	"Mutation in codon 200 of scrapie amyloid protein gene in two clusters of Creutzfeldt-Jakob disease in Slovakia." Goldfarb L., Mitrova E., Brown P., Toh B.K., Gajdusek D.C. Lancet 336:514-515(1990) [PubMed: 1975028] [Abstract] Cited for: VARIANT CJD LYS-200.
[27]	"Mutant prion proteins in Gerstmann-Straussler-Scheinker disease with neurofibrillary tangles." Hsiao K., Dlouhy S.R., Farlow M.R., Cass C., da Costa M., Conneally P.M., Hodes M.E., Ghetti B., Prusiner S.B. Nat. Genet. 1:68-71(1992) [PubMed: 1363810] [Abstract] Cited for: VARIANT GSD ARG-217.
[28]	"Novel missense variants of prion protein in Creutzfeldt-Jakob disease or Gerstmann-Straussler syndrome." Kitamoto T., Ohta M., Doh-Ura K., Hitoshi S., Terao Y., Tateishi J. Biochem. Biophys. Res. Commun. 191:709-714(1993) [PubMed: 8461023] [Abstract] Cited for: VARIANTS CJD ILE-180 AND ARG-232.
[29]	"A new point mutation of the prion protein gene in Creutzfeldt-Jakob disease." Pocchiari M., Salvatore M., Cutruzzola F., Genuardi M., Allcatelli C.T., Masullo C., Macchi G., Alema G., Galgani S., Xi Y.G., Petraroli R., Silvestrini M.C., Brunori M. Ann. Neurol. 34:802-807(1993) [PubMed: 7902693] [Abstract] Cited for: VARIANT CJD ILE-210.
[30]	"A missense mutation at codon 105 with codon 129 polymorphism of the prion protein gene in a new variant of Gerstmann-Straussler-Scheinker disease." Yamada M., Itoh Y., Fujigasaki H., Naruse S., Kaneko K., Kitamoto T., Tateishi J., Otomo E., Hayakawa M., Tanaka J., Matsushita M., Miyatake T. Neurology 43:2723-2724(1993) [PubMed: 7902972] [Abstract] Cited for: VARIANT GSD LEU-105.
[31]	"A variant of Gerstmann-Straussler-Scheinker disease carrying codon 105 mutation with codon 129 polymorphism of the prion protein gene: a clinicopathological study." Itoh Y., Yamada M., Hayakawa M., Shozawa T., Tanaka J., Matsushita M., Kitamoto T., Tateishi J., Otomo E. J. Neurol. Sci. 127:77-86(1994) [PubMed: 7699395] [Abstract] Cited for: VARIANT GSD LEU-105.
[32]	"Japanese family with Creutzfeldt-Jakob disease with codon 200 point mutation of the prion protein gene." Inoue I., Kitamoto T., Doh-Ura K., Shii H., Goto I., Tateishi J. Neurology 44:299-301(1994) [PubMed: 7906019] [Abstract] Cited for: VARIANT CJD LYS-200.
[33]	"Mutation in codon 200 and polymorphism in codon 129 of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease." Gabizon R., Rosenman H., Meiner Z., Kahana I., Kahana E., Shugart Y., Ott J., Prusiner S.B. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 343:385-390(1994) [PubMed: 7913755] [Abstract] Cited for: VARIANT CJD LYS-200.
[34]	"Gerstmann-Straussler-Scheinker disease with mutation at codon 102 and methionine at codon 129 of PRNP in previously unreported patients." Young K., Jones C.K., Piccardo P., Lazzarini A., Golbe L.I., Zimmerman T.R., Dickson D.W., McLachlan D.C., St George-Hyslop P.H., Lennox A. Neurology 45:1127-1134(1995) [PubMed: 7783876] [Abstract] Cited for: VARIANT GSD LEU-102.
[35]	"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)." Barbanti P., Fabbrini G., Salvatore M., Petraroli R., Cardone F., Maras B., Equestre M., Macchi G., Lenzi G.L., Pocchiari M. Neurology 47:734-741(1996) [PubMed: 8797472] [Abstract] Cited for: VARIANT GSD LEU-102, VARIANT LYS-219.
[36]	"Mutation of the prion protein gene at codon 208 in familial Creutzfeldt-Jakob disease." Mastrianni J.A., Iannicola C., Myers R.M., Dearmond S., Prusiner S.B. Neurology 47:1305-1312(1996) [PubMed: 8909447] [Abstract] Cited for: VARIANT CJD HIS-208.
[37]	"Familial spongiform encephalopathy associated with a novel prion protein gene mutation." Nitrini R., Rosemberg S., Passos-Bueno M.R., da Silva L.S., Iughetti P., Papadopoulos M., Carrilho P.M., Caramelli P., Albrecht S., Zatz M., Leblanc A. Ann. Neurol. 42:138-146(1997) [PubMed: 9266722] [Abstract] Cited for: VARIANT CJD HIS-208.
[38]	"Phenotypic variability of Gerstmann-Straussler-Scheinker disease is associated with prion protein heterogeneity." Piccardo P., Dlouhy S.R., Lievens P.M., Young K., Bird T.D., Nochlin D., Dickson D.W., Vinters H.V., Zimmerman T.R., Mackenzie I.R., Kish S.J., Ang L.C., De Carli C., Pocchiari M., Brown P., Gibbs C.J. Jr., Gajdusek D.C., Bugiani O. , Ironside J., Tagliavini F., Ghetti B. J. Neuropathol. Exp. Neurol. 57:979-988(1998) [PubMed: 9786248] [Abstract] Cited for: VARIANTS GSD ASN-202 AND PRO-212.
[39]	"Molecular genetics of human prion diseases in Germany." Windl O., Giese A., Schulz-Schaeffer W., Zerr I., Skworc K., Arendt S., Oberdieck C., Bodemer M., Poser S., Kretzschmar H.A. Hum. Genet. 105:244-252(1999) [PubMed: 10987652] [Abstract] Cited for: VARIANTS ARG-188 AND SER-238.
[40]	"High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes." Finckh U., Mueller-Thomsen T., Mann U., Eggers C., Marksteiner J., Meins W., Binetti G., Alberici A., Hock C., Nitsch R.M., Gal A. Am. J. Hum. Genet. 66:110-117(2000) [PubMed: 10631141] [Abstract] Cited for: VARIANTS EARLY-ONSET DEMENTIA LEU-102; ALA-183 AND LYS-188.
[41]	"Identification of three novel mutations (E196K, V203I, E211Q) in the prion protein gene (PRNP) in inherited prion diseases with Creutzfeldt-Jakob disease phenotype." Peoc'h K., Manivet P., Beaudry P., Attane F., Besson G., Didier H., Delasnerie-Laupretre N., Laplanche J.-L. Hum. Mutat. 15:482-482(2000) [PubMed: 10790216] [Abstract] Cited for: VARIANTS CJD LYS-196; ILE-203 AND GLN-211.
[42]	"A new PRNP mutation (G131V) associated with Gerstmann-Straussler-Scheinker disease." Panegyres P.K., Toufexis K., Kakulas B.A., Cernevakova L., Brown P., Ghetti B., Piccardo P., Dlouhy S.R. Arch. Neurol. 58:1899-1902(2001) [PubMed: 11709001] [Abstract] Cited for: VARIANT GSD VAL-131.
+	Additional computationally mapped references.

Web resources

The Official Mad Cow Disease Home Page

GeneReviews

Wikipedia

PRNP entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

M13899 mRNA. Translation: AAA60182.1.
X83416 Genomic DNA. Translation: CAA58442.1.
U29185 Genomic DNA. Translation: AAC78725.1.
AY008282 mRNA. Translation: AAG21693.1.
AF076976 Genomic DNA. Translation: AAD46098.1.
DQ408531 Genomic DNA. Translation: ABD63004.1.
AL133396 Genomic DNA. Translation: CAB75503.1.
BC012844 mRNA. Translation: AAH12844.1.
BC022532 mRNA. Translation: AAH22532.1.
M13667 mRNA. Translation: AAA19664.1.
D00015 mRNA. Translation: BAA00011.1.
M81929 Genomic DNA. Translation: AAB59442.1.
M81930 Genomic DNA. Translation: AAB59443.1.
AF030575 Genomic DNA. Translation: AAC05365.1.
S80732 Genomic DNA. Translation: AAB50648.2.
S80743 Genomic DNA. Translation: AAB50649.2.
S71208 Genomic DNA. Translation: AAB20521.1.
S71210 Genomic DNA. Translation: AAB20522.1.
S71212 Genomic DNA. Translation: AAB20523.1.

IPI

IPI00022284.

PIR

UJHU. A24173.

RefSeq

NP_000302.1.
NP_001073590.1.
NP_001073591.1.
NP_001073592.1.
NP_898902.1.

UniGene

Hs.472010
Hs.610285
Hs.714553

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1E1G	NMR	-	A	125-228	[»]
1E1J	NMR	-	A	125-228	[»]
1E1P	NMR	-	A	125-228	[»]
1E1S	NMR	-	A	125-228	[»]
1E1U	NMR	-	A	125-228	[»]
1E1W	NMR	-	A	125-228	[»]
1FKC	NMR	-	A	90-231	[»]
1FO7	NMR	-	A	90-231	[»]
1H0L	NMR	-	A	121-230	[»]
1HJM	NMR	-	A	125-228	[»]
1HJN	NMR	-	A	125-228	[»]
1I4M	X-ray	2.00	A	119-226	[»]
1OEH	NMR	-	A	61-68	[»]
1OEI	NMR	-	A	61-84	[»]
1QLX	NMR	-	A	23-230	[»]
1QLZ	NMR	-	A	23-230	[»]
1QM0	NMR	-	A	90-230	[»]
1QM1	NMR	-	A	90-230	[»]
1QM2	NMR	-	A	121-230	[»]
1QM3	NMR	-	A	121-230	[»]
2K1D	NMR	-	A	90-231	[»]
2W9E	X-ray	2.90	A	119-231	[»]

DisProt

DP00466.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04156. 10 interactions.

Proteomic databases

PRIDE

P04156.

Genome annotation databases

Ensembl

ENSG00000171867. Homo sapiens. [Contig view]

GeneID

5621.

KEGG

hsa:5621.

UCSC

uc002wku.1. human.

Organism-specific databases

GeneCards

GC20P004615.

H-InvDB

HIX0015613.

HGNC

HGNC:9449. PRNP.

MIM

123400. phenotype.
137440. phenotype.
176640. gene.
245300. phenotype.
600072. phenotype.
603218. phenotype.
606688. phenotype.

Orphanet

204. Creutzfeldt-Jakob disease.
356. Gerstmann-Straussler-Scheinker syndrome.
157941. Huntington disease-like 1.
466. Insomnia, familial fatal.

PharmGKB

PA33796.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P04156.

OMA

P04156. PNQVYYR.

Enzyme and pathway databases

Pathway_Interaction_DB

glypican_1pathway. Glypican 1 network.

Gene expression databases

ArrayExpress

P04156.

Bgee

P04156.

GermOnline

ENSG00000171867. Homo sapiens.

Family and domain databases

InterPro

IPR000817. Prion.
[Graphical view]

Gene3D

G3DSA:1.10.790.10. Prion. 1 hit.

PANTHER

PTHR11522. Prion. 1 hit.

Pfam

PF00377. Prion. 1 hit.
PF03991. Prion_octapep. 5 hits.
[Graphical view]

PRINTS

PR00341. PRION.

SMART

SM00157. PRP. 1 hit.
[Graphical view]

PROSITE

PS00291. PRION_1. 1 hit.
PS00706. PRION_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00759. Tetracycline.

NextBio

21844.

PMAP-CutDB

P04156.

SOURCE

Search...

Entry information

Entry name

PRIO_HUMAN

Accession

Primary (citable) accession number: P04156
Secondary accession number(s): O60489 , P78446, Q15216, Q15221, Q27H91, Q8TBG0, Q96E70, Q9UP19

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	November 1, 1986
Last modified:	July 7, 2009
This is version 134 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)