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Protein

Major prion protein

Gene

PRNP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Its primary physiological function is unclear. Has cytoprotective activity against internal or environmental stresses. 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. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (PubMed:12732622, PubMed:19936054, PubMed:20564047). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu2+ or ZN2+ for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).By similarityCurated3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi61 – 611Copper or zinc 11 Publication
Metal bindingi62 – 621Copper or zinc 1; via amide nitrogen1 Publication
Metal bindingi63 – 631Copper or zinc 1; via amide nitrogen and carbonyl oxygen1 Publication
Metal bindingi69 – 691Copper or zinc 21 Publication
Metal bindingi70 – 701Copper or zinc 2; via amide nitrogen1 Publication
Metal bindingi71 – 711Copper or zinc 2; via amide nitrogen and carbonyl oxygen1 Publication
Metal bindingi77 – 771Copper or zinc 31 Publication
Metal bindingi78 – 781Copper or zinc 3; via amide nitrogen1 Publication
Metal bindingi79 – 791Copper or zinc 3; via amide nitrogen and carbonyl oxygen1 Publication
Metal bindingi85 – 851Copper or zinc 41 Publication
Metal bindingi86 – 861Copper or zinc 4; via amide nitrogen1 Publication
Metal bindingi87 – 871Copper or zinc 4; via amide nitrogen and carbonyl oxygen1 Publication

GO - Molecular functioni

  • copper ion binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • microtubule binding Source: UniProtKB
  • tubulin binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Prion

Keywords - Biological processi

Cell cycle, Growth arrest

Keywords - Ligandi

Copper, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-419037. NCAM1 interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Major prion protein
Short name:
PrP
Alternative name(s):
ASCR
PrP27-30
PrP33-35C
CD_antigen: CD230
Gene namesi
Name:PRNP
Synonyms:ALTPRP, PRIP, PRP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:9449. PRNP.

Subcellular locationi

  • Cell membrane; Lipid-anchorGPI-anchor 1 Publication
  • Golgi apparatus By similarity

  • Note: Targeted to lipid rafts via association with the heparan sulfate chains of GPC1. Colocates, in the presence of Cu2+, to vesicles in para- and perinuclear regions, where both proteins undergo internalization. Heparin displaces PRNP from lipid rafts and promotes endocytosis.1 Publication
Isoform 2 :

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • cell surface Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extrinsic component of membrane Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • membrane raft Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Amyloid, Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.

Creutzfeldt-Jakob disease (CJD)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionOccurs 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 animal 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.
See also OMIM:123400
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti127 – 1271G → V Polymorphism; variant that 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; 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. Always associated with M-129 variant. 2 Publications
Corresponds to variant rs267606980 [ dbSNP | Ensembl ].
VAR_073722
Natural varianti129 – 1291M → V Polymorphism; confers relative protection against acquired, sporadic and some inherited prion diseases in the heterozygous state, possibly by preventing homodimerization; 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. 4 Publications
Corresponds to variant rs1799990 [ dbSNP | Ensembl ].
VAR_006467
Natural varianti178 – 1781D → N in FFI and CJD. 4 Publications
Corresponds to variant rs74315403 [ dbSNP | Ensembl ].
VAR_006469
Natural varianti180 – 1801V → I in CJD. 3 Publications
Corresponds to variant rs74315408 [ dbSNP | Ensembl ].
VAR_006470
Natural varianti196 – 1961E → K in CJD. 1 Publication
VAR_008749
Natural varianti200 – 2001E → K in CJD. 3 Publications
Corresponds to variant rs28933385 [ dbSNP | Ensembl ].
VAR_006473
Natural varianti203 – 2031V → I in CJD; unknown pathological significance. 1 Publication
Corresponds to variant rs776593792 [ dbSNP | Ensembl ].
VAR_008751
Natural varianti208 – 2081R → H in CJD. 1 Publication
Corresponds to variant rs74315412 [ dbSNP | Ensembl ].
VAR_006474
Natural varianti210 – 2101V → I in CJD. 1 Publication
Corresponds to variant rs74315407 [ dbSNP | Ensembl ].
VAR_006475
Natural varianti211 – 2111E → Q in CJD. 1 Publication
Corresponds to variant rs398122370 [ dbSNP | Ensembl ].
VAR_008752
Natural varianti219 – 2191E → K Polymorphism; confers relative protection against sporadic Creutzfeldt-Jakob disease (CJD) in the heterozygous state. 2 Publications
Corresponds to variant rs1800014 [ dbSNP | Ensembl ].
VAR_006477
Natural varianti232 – 2321M → R in CJD. 1 Publication
Corresponds to variant rs74315409 [ dbSNP | Ensembl ].
VAR_006478
Fatal familial insomnia (FFI)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal dominant disorder and is characterized by neuronal degeneration limited to selected thalamic nuclei and progressive insomnia.
See also OMIM:600072
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti129 – 1291M → V Polymorphism; confers relative protection against acquired, sporadic and some inherited prion diseases in the heterozygous state, possibly by preventing homodimerization; 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. 4 Publications
Corresponds to variant rs1799990 [ dbSNP | Ensembl ].
VAR_006467
Natural varianti178 – 1781D → N in FFI and CJD. 4 Publications
Corresponds to variant rs74315403 [ dbSNP | Ensembl ].
VAR_006469
Gerstmann-Straussler disease (GSD)11 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare inherited prion disease characterized by adult onset of memory loss, dementia, ataxia, and pathologic deposition of amyloid-like plaques in the brain. GSD presents with progressive limb and truncal ataxia, dysarthria, and cognitive decline in the thirties and forties, and the average disease duration is 7 years.
See also OMIM:137440
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti102 – 1021P → L in GSD and early-onset dementia. 5 Publications
Corresponds to variant rs74315401 [ dbSNP | Ensembl ].
VAR_006464
Natural varianti105 – 1051P → L in GSD. 2 Publications
Corresponds to variant rs11538758 [ dbSNP | Ensembl ].
VAR_006465
Natural varianti131 – 1311G → V in GSD. 1 Publication
Corresponds to variant rs74315410 [ dbSNP | Ensembl ].
VAR_014264
Natural varianti187 – 1871H → R in GSD. 1 Publication
Corresponds to variant rs74315413 [ dbSNP | Ensembl ].
VAR_008746
Natural varianti198 – 1981F → S in GSD; atypical form with neurofibrillary tangles. 1 Publication
Corresponds to variant rs74315405 [ dbSNP | Ensembl ].
VAR_006472
Natural varianti202 – 2021D → N in GSD. 1 Publication
Corresponds to variant rs761807915 [ dbSNP | Ensembl ].
VAR_008750
Natural varianti212 – 2121Q → P in GSD. 1 Publication
Corresponds to variant rs751882709 [ dbSNP | Ensembl ].
VAR_008753
Natural varianti217 – 2171Q → R in GSD; with neurofibrillary tangles. 1 Publication
Corresponds to variant rs74315406 [ dbSNP | Ensembl ].
VAR_006476
Huntington disease-like 1 (HDL1)
The disease is caused by mutations affecting the gene represented in this entry.1 Publication
Disease descriptionAutosomal dominant, early-onset neurodegenerative disorder with prominent psychiatric features.
See also OMIM:603218
Kuru (KURU)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionKuru 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.
See also OMIM:245300
Spongiform encephalopathy with neuropsychiatric features (SENF)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal 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.
See also OMIM:606688
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti183 – 1831T → A in SENF and early-onset dementia; induces loss of glycosylation at N-181. 3 Publications
Corresponds to variant rs74315411 [ dbSNP | Ensembl ].
VAR_006471

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1 – 11M → S: Protein detected. No protein detected; when associated with S-8. 1 Publication
Mutagenesisi8 – 81M → S: No protein detected; when associated with S-1. 1 Publication

Keywords - Diseasei

Amyloidosis, Disease mutation

Organism-specific databases

MalaCardsiPRNP.
MIMi123400. phenotype.
137440. phenotype.
245300. phenotype.
600072. phenotype.
603218. phenotype.
606688. phenotype.
Orphaneti397606. Chronic diarrhea with hereditary sensory and autonomic neuropathy.
280397. Familial Alzheimer-like prion disease.
466. Fatal familial insomnia.
356. Gerstmann-Straussler-Scheinker syndrome.
157941. Huntington disease-like 1.
282166. Inherited Creutzfeldt-Jakob disease.
PharmGKBiPA33796.

Chemistry

ChEMBLiCHEMBL4869.
DrugBankiDB00759. Tetracycline.

Polymorphism and mutation databases

BioMutaiPRNP.
DMDMi130912.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222By similarityAdd
BLAST
Chaini23 – 230208Major prion proteinPRO_0000025675Add
BLAST
Propeptidei231 – 25323Removed in mature formBy similarityPRO_0000025676Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi179 ↔ 2141 Publication
Glycosylationi181 – 1811N-linked (GlcNAc...)1 Publication
Glycosylationi197 – 1971N-linked (GlcNAc...)1 Publication
Lipidationi230 – 2301GPI-anchor amidated serineBy similarity

Post-translational modificationi

The glycosylation pattern (the amount of mono-, di- and non-glycosylated forms or glycoforms) seems to differ in normal and CJD prion.1 Publication
Isoform 2 is sumoylated with SUMO1.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein, Ubl conjugation

Proteomic databases

EPDiP04156.
PaxDbiP04156.
PeptideAtlasiP04156.
PRIDEiP04156.

PTM databases

iPTMnetiP04156.
PhosphoSiteiP04156.
SwissPalmiP04156.

Miscellaneous databases

PMAP-CutDBP04156.

Expressioni

Gene expression databases

BgeeiENSG00000171867.
ExpressionAtlasiP04156. baseline and differential.
GenevisibleiP04156. HS.

Organism-specific databases

HPAiHPA042754.
HPA043398.

Interactioni

Subunit structurei

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).By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself17EBI-977302,EBI-977302
APPP050673EBI-977302,EBI-77613
APPP05067-42EBI-977302,EBI-302641
FAM64AQ9BSJ65EBI-977302,EBI-2568609
Grm5P31424-24EBI-8830282,EBI-8830305From a different organism.
HOXA1P496394EBI-977302,EBI-740785
MAPTP106362EBI-977302,EBI-366182
MPGP293724EBI-977302,EBI-1043398
PkmP524805EBI-8830282,EBI-647785From a different organism.
PLK3Q9H4B44EBI-977302,EBI-751877
PRNPP102795EBI-977302,EBI-7430632From a different organism.
PRNPP239073EBI-977302,EBI-7670302From a different organism.
PrnpP049253EBI-977302,EBI-768613From a different organism.

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • microtubule binding Source: UniProtKB
  • tubulin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111606. 59 interactions.
DIPiDIP-29933N.
IntActiP04156. 88 interactions.
MINTiMINT-1420984.
STRINGi9606.ENSP00000368752.

Chemistry

BindingDBiP04156.

Structurei

Secondary structure

1
253
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi63 – 675Combined sources
Beta strandi70 – 734Combined sources
Turni74 – 763Combined sources
Beta strandi79 – 824Combined sources
Beta strandi118 – 1225Combined sources
Beta strandi125 – 1273Combined sources
Beta strandi128 – 1314Combined sources
Beta strandi141 – 1433Combined sources
Helixi144 – 15310Combined sources
Helixi154 – 1563Combined sources
Beta strandi159 – 1635Combined sources
Helixi166 – 1683Combined sources
Turni171 – 1733Combined sources
Beta strandi178 – 1814Combined sources
Helixi185 – 1873Combined sources
Turni188 – 1903Combined sources
Turni193 – 1953Combined sources
Beta strandi212 – 2154Combined sources
Turni223 – 2253Combined sources
Turni228 – 2303Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1E1GNMR-A125-228[»]
1E1JNMR-A125-228[»]
1E1PNMR-A125-228[»]
1E1SNMR-A125-228[»]
1E1UNMR-A125-228[»]
1E1WNMR-A125-228[»]
1FKCNMR-A90-231[»]
1FO7NMR-A90-231[»]
1H0LNMR-A121-230[»]
1HJMNMR-A125-228[»]
1HJNNMR-A125-228[»]
1I4MX-ray2.00A119-226[»]
1OEHNMR-A77-84[»]
1OEINMR-A61-84[»]
1QLXNMR-A23-230[»]
1QLZNMR-A23-230[»]
1QM0NMR-A90-230[»]
1QM1NMR-A90-230[»]
1QM2NMR-A121-230[»]
1QM3NMR-A121-230[»]
2IV4NMR-A180-195[»]
2IV5NMR-A173-195[»]
2IV6NMR-A173-195[»]
2K1DNMR-A90-231[»]
2KUNNMR-A90-231[»]
2LBGNMR-A110-136[»]
2LEJNMR-A90-231[»]
2LFTNMR-A90-231[»]
2LSBNMR-A90-231[»]
2LV1NMR-A90-231[»]
2M8TNMR-A90-231[»]
2OL9X-ray0.85A170-175[»]
2W9EX-ray2.90A119-231[»]
3HAFX-ray2.26A90-231[»]
3HAKX-ray1.80A125-227[»]
3HEQX-ray1.80A/B90-231[»]
3HERX-ray1.85A/B90-231[»]
3HESX-ray2.00A/B90-231[»]
3HJ5X-ray3.10A/B90-231[»]
3HJXX-ray2.00A126-231[»]
3MD4X-ray1.15A/B127-132[»]
3MD5X-ray1.40A/B127-132[»]
3NHCX-ray1.57A/B127-132[»]
3NHDX-ray1.92A/B127-132[»]
3NVFX-ray1.80A138-143[»]
4DGIX-ray2.40A120-230[»]
4E1HX-ray1.40A/C/E/G/I/K177-182[»]
B/D/F/H/J/L211-216[»]
4E1IX-ray2.03A/C/E/G/I/K177-182[»]
B/D/F/H/J/L211-216[»]
4KMLX-ray1.50A24-231[»]
4N9OX-ray1.50A90-231[»]
DisProtiDP00466.
ProteinModelPortaliP04156.
SMRiP04156. Positions 2-28, 90-231.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04156.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati51 – 5991
Repeati60 – 6782
Repeati68 – 7583
Repeati76 – 8384
Repeati84 – 9185

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni23 – 230208Interaction with GRB2, ERI3 and SYN1By similarityAdd
BLAST
Regioni51 – 91415 X 8 AA tandem repeats of P-H-G-G-G-W-G-QAdd
BLAST

Domaini

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).3 Publications
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.3 Publications

Sequence similaritiesi

Belongs to the prion family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IJMM. Eukaryota.
ENOG410YXUU. LUCA.
GeneTreeiENSGT00510000049083.
HOVERGENiHBG008260.
InParanoidiP04156.
KOiK05634.
OMAiHNPGYPH.
OrthoDBiEOG091G0HMV.
PhylomeDBiP04156.
TreeFamiTF105188.

Family and domain databases

Gene3Di1.10.790.10. 1 hit.
InterProiIPR000817. Prion.
IPR022416. Prion/Doppel_prot_b-ribbon_dom.
IPR025860. Prion_N_dom.
[Graphical view]
PANTHERiPTHR10502:SF11. PTHR10502:SF11. 1 hit.
PfamiPF00377. Prion. 1 hit.
PF11587. Prion_bPrPp. 1 hit.
[Graphical view]
PRINTSiPR00341. PRION.
SMARTiSM00157. PRP. 1 hit.
[Graphical view]
SUPFAMiSSF54098. SSF54098. 1 hit.
PROSITEiPS00291. PRION_1. 1 hit.
PS00706. PRION_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P04156-1) [UniParc]FASTAAdd to basket
Also known as: PrP

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MANLGCWMLV LFVATWSDLG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP
60 70 80 90 100
PQGGGGWGQP HGGGWGQPHG GGWGQPHGGG WGQPHGGGWG QGGGTHSQWN
110 120 130 140 150
KPSKPKTNMK HMAGAAAAGA VVGGLGGYML GSAMSRPIIH FGSDYEDRYY
160 170 180 190 200
RENMHRYPNQ VYYRPMDEYS NQNNFVHDCV NITIKQHTVT TTTKGENFTE
210 220 230 240 250
TDVKMMERVV EQMCITQYER ESQAYYQRGS SMVLFSSPPV ILLISFLIFL

IVG
Length:253
Mass (Da):27,661
Last modified:November 1, 1986 - v1
Checksum:i43DB596BAAA66484
GO
Isoform 2 (identifier: P04156-2) [UniParc]FASTAAdd to basket
Also known as: PrP(M8)

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: Missing.

Show »
Length:246
Mass (Da):26,885
Checksum:i309B13B142A41566
GO
Isoform 3 (identifier: F7VJQ1-1) [UniParc]FASTAAdd to basket
Also known as: AltPrP
The sequence of this isoform can be found in the external entry F7VJQ1.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:73
Mass (Da):8,691
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti118 – 1181Missing in AAA19664 (PubMed:3014653).Curated
Sequence conflicti118 – 1181Missing in BAA00011 (PubMed:3014653).Curated
Sequence conflicti169 – 1691Y → H in ABD63004 (Ref. 6) Curated
Sequence conflicti227 – 2271Q → K in AAH22532 (PubMed:15489334).Curated

Polymorphismi

The five tandem octapeptide repeats region is highly unstable. Insertions or deletions of octapeptide repeat units are associated to prion disease.1 Publication
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).3 Publications

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti56 – 638Missing .3 Publications
VAR_013763
Natural varianti102 – 1021P → L in GSD and early-onset dementia. 5 Publications
Corresponds to variant rs74315401 [ dbSNP | Ensembl ].
VAR_006464
Natural varianti105 – 1051P → L in GSD. 2 Publications
Corresponds to variant rs11538758 [ dbSNP | Ensembl ].
VAR_006465
Natural varianti117 – 1171A → V Linked to development of dementing Gerstmann-Straussler disease. 1 Publication
Corresponds to variant rs74315402 [ dbSNP | Ensembl ].
VAR_006466
Natural varianti127 – 1271G → V Polymorphism; variant that 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; 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. Always associated with M-129 variant. 2 Publications
Corresponds to variant rs267606980 [ dbSNP | Ensembl ].
VAR_073722
Natural varianti129 – 1291M → V Polymorphism; confers relative protection against acquired, sporadic and some inherited prion diseases in the heterozygous state, possibly by preventing homodimerization; 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. 4 Publications
Corresponds to variant rs1799990 [ dbSNP | Ensembl ].
VAR_006467
Natural varianti131 – 1311G → V in GSD. 1 Publication
Corresponds to variant rs74315410 [ dbSNP | Ensembl ].
VAR_014264
Natural varianti171 – 1711N → S in schizoaffective disorder. 1 Publication
Corresponds to variant rs16990018 [ dbSNP | Ensembl ].
VAR_006468
Natural varianti178 – 1781D → N in FFI and CJD. 4 Publications
Corresponds to variant rs74315403 [ dbSNP | Ensembl ].
VAR_006469
Natural varianti180 – 1801V → I in CJD. 3 Publications
Corresponds to variant rs74315408 [ dbSNP | Ensembl ].
VAR_006470
Natural varianti183 – 1831T → A in SENF and early-onset dementia; induces loss of glycosylation at N-181. 3 Publications
Corresponds to variant rs74315411 [ dbSNP | Ensembl ].
VAR_006471
Natural varianti187 – 1871H → R in GSD. 1 Publication
Corresponds to variant rs74315413 [ dbSNP | Ensembl ].
VAR_008746
Natural varianti188 – 1881T → K in early-onset dementia; dementia associated to prion diseases. 1 Publication
VAR_008748
Natural varianti188 – 1881T → R.1 Publication
Corresponds to variant rs372878791 [ dbSNP | Ensembl ].
VAR_008747
Natural varianti196 – 1961E → K in CJD. 1 Publication
VAR_008749
Natural varianti198 – 1981F → S in GSD; atypical form with neurofibrillary tangles. 1 Publication
Corresponds to variant rs74315405 [ dbSNP | Ensembl ].
VAR_006472
Natural varianti200 – 2001E → K in CJD. 3 Publications
Corresponds to variant rs28933385 [ dbSNP | Ensembl ].
VAR_006473
Natural varianti202 – 2021D → N in GSD. 1 Publication
Corresponds to variant rs761807915 [ dbSNP | Ensembl ].
VAR_008750
Natural varianti203 – 2031V → I in CJD; unknown pathological significance. 1 Publication
Corresponds to variant rs776593792 [ dbSNP | Ensembl ].
VAR_008751
Natural varianti208 – 2081R → H in CJD. 1 Publication
Corresponds to variant rs74315412 [ dbSNP | Ensembl ].
VAR_006474
Natural varianti210 – 2101V → I in CJD. 1 Publication
Corresponds to variant rs74315407 [ dbSNP | Ensembl ].
VAR_006475
Natural varianti211 – 2111E → Q in CJD. 1 Publication
Corresponds to variant rs398122370 [ dbSNP | Ensembl ].
VAR_008752
Natural varianti212 – 2121Q → P in GSD. 1 Publication
Corresponds to variant rs751882709 [ dbSNP | Ensembl ].
VAR_008753
Natural varianti217 – 2171Q → R in GSD; with neurofibrillary tangles. 1 Publication
Corresponds to variant rs74315406 [ dbSNP | Ensembl ].
VAR_006476
Natural varianti219 – 2191E → K Polymorphism; confers relative protection against sporadic Creutzfeldt-Jakob disease (CJD) in the heterozygous state. 2 Publications
Corresponds to variant rs1800014 [ dbSNP | Ensembl ].
VAR_006477
Natural varianti232 – 2321M → R in CJD. 1 Publication
Corresponds to variant rs74315409 [ dbSNP | Ensembl ].
VAR_006478
Natural varianti238 – 2381P → S.1 Publication
VAR_008754

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 77Missing in isoform 2. CuratedVSP_039045

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13899 mRNA. Translation: AAA60182.1.
X83416 Genomic DNA. Translation: CAA58442.1.
U29185 Genomic DNA. Translation: AAC78725.1.
AF076976 Genomic DNA. Translation: AAD46098.1.
AY008282 mRNA. Translation: AAG21693.1.
DQ408531 Genomic DNA. Translation: ABD63004.1.
AL133396 Genomic DNA. Translation: CAB75503.1.
AL133396 Genomic DNA. Translation: CAI19053.1.
BC012844 mRNA. Translation: AAH12844.1.
BC022532 mRNA. Translation: AAH22532.1.
D00015 mRNA. Translation: BAA00011.1.
M13667 mRNA. Translation: AAA19664.1.
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.
CCDSiCCDS13080.1. [P04156-1]
PIRiA24173. UJHU.
RefSeqiNP_000302.1. NM_000311.3. [P04156-1]
NP_001073590.1. NM_001080121.1. [P04156-1]
NP_001073591.1. NM_001080122.1. [P04156-1]
NP_001073592.1. NM_001080123.1. [P04156-1]
NP_898902.1. NM_183079.2. [P04156-1]
UniGeneiHs.472010.
Hs.610285.
Hs.721670.

Genome annotation databases

EnsembliENST00000379440; ENSP00000368752; ENSG00000171867. [P04156-1]
ENST00000430350; ENSP00000399376; ENSG00000171867. [P04156-1]
GeneIDi5621.
KEGGihsa:5621.

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Cross-referencesi

Web resourcesi

The Official Mad Cow Disease Home Page
Wikipedia

PRNP entry

Protein Spotlight

The shape of harm - Issue 179 of May 2016

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13899 mRNA. Translation: AAA60182.1.
X83416 Genomic DNA. Translation: CAA58442.1.
U29185 Genomic DNA. Translation: AAC78725.1.
AF076976 Genomic DNA. Translation: AAD46098.1.
AY008282 mRNA. Translation: AAG21693.1.
DQ408531 Genomic DNA. Translation: ABD63004.1.
AL133396 Genomic DNA. Translation: CAB75503.1.
AL133396 Genomic DNA. Translation: CAI19053.1.
BC012844 mRNA. Translation: AAH12844.1.
BC022532 mRNA. Translation: AAH22532.1.
D00015 mRNA. Translation: BAA00011.1.
M13667 mRNA. Translation: AAA19664.1.
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.
CCDSiCCDS13080.1. [P04156-1]
PIRiA24173. UJHU.
RefSeqiNP_000302.1. NM_000311.3. [P04156-1]
NP_001073590.1. NM_001080121.1. [P04156-1]
NP_001073591.1. NM_001080122.1. [P04156-1]
NP_001073592.1. NM_001080123.1. [P04156-1]
NP_898902.1. NM_183079.2. [P04156-1]
UniGeneiHs.472010.
Hs.610285.
Hs.721670.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1E1GNMR-A125-228[»]
1E1JNMR-A125-228[»]
1E1PNMR-A125-228[»]
1E1SNMR-A125-228[»]
1E1UNMR-A125-228[»]
1E1WNMR-A125-228[»]
1FKCNMR-A90-231[»]
1FO7NMR-A90-231[»]
1H0LNMR-A121-230[»]
1HJMNMR-A125-228[»]
1HJNNMR-A125-228[»]
1I4MX-ray2.00A119-226[»]
1OEHNMR-A77-84[»]
1OEINMR-A61-84[»]
1QLXNMR-A23-230[»]
1QLZNMR-A23-230[»]
1QM0NMR-A90-230[»]
1QM1NMR-A90-230[»]
1QM2NMR-A121-230[»]
1QM3NMR-A121-230[»]
2IV4NMR-A180-195[»]
2IV5NMR-A173-195[»]
2IV6NMR-A173-195[»]
2K1DNMR-A90-231[»]
2KUNNMR-A90-231[»]
2LBGNMR-A110-136[»]
2LEJNMR-A90-231[»]
2LFTNMR-A90-231[»]
2LSBNMR-A90-231[»]
2LV1NMR-A90-231[»]
2M8TNMR-A90-231[»]
2OL9X-ray0.85A170-175[»]
2W9EX-ray2.90A119-231[»]
3HAFX-ray2.26A90-231[»]
3HAKX-ray1.80A125-227[»]
3HEQX-ray1.80A/B90-231[»]
3HERX-ray1.85A/B90-231[»]
3HESX-ray2.00A/B90-231[»]
3HJ5X-ray3.10A/B90-231[»]
3HJXX-ray2.00A126-231[»]
3MD4X-ray1.15A/B127-132[»]
3MD5X-ray1.40A/B127-132[»]
3NHCX-ray1.57A/B127-132[»]
3NHDX-ray1.92A/B127-132[»]
3NVFX-ray1.80A138-143[»]
4DGIX-ray2.40A120-230[»]
4E1HX-ray1.40A/C/E/G/I/K177-182[»]
B/D/F/H/J/L211-216[»]
4E1IX-ray2.03A/C/E/G/I/K177-182[»]
B/D/F/H/J/L211-216[»]
4KMLX-ray1.50A24-231[»]
4N9OX-ray1.50A90-231[»]
DisProtiDP00466.
ProteinModelPortaliP04156.
SMRiP04156. Positions 2-28, 90-231.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111606. 59 interactions.
DIPiDIP-29933N.
IntActiP04156. 88 interactions.
MINTiMINT-1420984.
STRINGi9606.ENSP00000368752.

Chemistry

BindingDBiP04156.
ChEMBLiCHEMBL4869.
DrugBankiDB00759. Tetracycline.

PTM databases

iPTMnetiP04156.
PhosphoSiteiP04156.
SwissPalmiP04156.

Polymorphism and mutation databases

BioMutaiPRNP.
DMDMi130912.

Proteomic databases

EPDiP04156.
PaxDbiP04156.
PeptideAtlasiP04156.
PRIDEiP04156.

Protocols and materials databases

DNASUi5621.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000379440; ENSP00000368752; ENSG00000171867. [P04156-1]
ENST00000430350; ENSP00000399376; ENSG00000171867. [P04156-1]
GeneIDi5621.
KEGGihsa:5621.

Organism-specific databases

CTDi5621.
GeneCardsiPRNP.
GeneReviewsiPRNP.
HGNCiHGNC:9449. PRNP.
HPAiHPA042754.
HPA043398.
MalaCardsiPRNP.
MIMi123400. phenotype.
137440. phenotype.
176640. gene.
245300. phenotype.
600072. phenotype.
603218. phenotype.
606688. phenotype.
neXtProtiNX_P04156.
Orphaneti397606. Chronic diarrhea with hereditary sensory and autonomic neuropathy.
280397. Familial Alzheimer-like prion disease.
466. Fatal familial insomnia.
356. Gerstmann-Straussler-Scheinker syndrome.
157941. Huntington disease-like 1.
282166. Inherited Creutzfeldt-Jakob disease.
PharmGKBiPA33796.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJMM. Eukaryota.
ENOG410YXUU. LUCA.
GeneTreeiENSGT00510000049083.
HOVERGENiHBG008260.
InParanoidiP04156.
KOiK05634.
OMAiHNPGYPH.
OrthoDBiEOG091G0HMV.
PhylomeDBiP04156.
TreeFamiTF105188.

Enzyme and pathway databases

ReactomeiR-HSA-419037. NCAM1 interactions.

Miscellaneous databases

ChiTaRSiPRNP. human.
EvolutionaryTraceiP04156.
GenomeRNAii5621.
PMAP-CutDBP04156.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171867.
ExpressionAtlasiP04156. baseline and differential.
GenevisibleiP04156. HS.

Family and domain databases

Gene3Di1.10.790.10. 1 hit.
InterProiIPR000817. Prion.
IPR022416. Prion/Doppel_prot_b-ribbon_dom.
IPR025860. Prion_N_dom.
[Graphical view]
PANTHERiPTHR10502:SF11. PTHR10502:SF11. 1 hit.
PfamiPF00377. Prion. 1 hit.
PF11587. Prion_bPrPp. 1 hit.
[Graphical view]
PRINTSiPR00341. PRION.
SMARTiSM00157. PRP. 1 hit.
[Graphical view]
SUPFAMiSSF54098. SSF54098. 1 hit.
PROSITEiPS00291. PRION_1. 1 hit.
PS00706. PRION_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPRIO_HUMAN
AccessioniPrimary (citable) accession number: P04156
Secondary accession number(s): O60489
, P78446, Q15216, Q15221, Q27H91, Q5QPB4, Q8TBG0, Q96E70, Q9UP19
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: November 1, 1986
Last modified: September 7, 2016
This is version 215 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

This protein is produced by a bicistronic gene which also produces the The alternative prion protein/AltPrP (AC F7VJQ1) from an overlapping reading frame.1 Publication
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.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  8. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.