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P04156

- PRIO_HUMAN

UniProt

P04156 - PRIO_HUMAN

Protein

Major prion protein

Gene

PRNP

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 193 (01 Oct 2014)
      Sequence version 1 (01 Nov 1986)
      Previous versions | rss
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    Functioni

    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). 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 similarity

    Sites

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

    GO - Molecular functioni

    1. copper ion binding Source: UniProtKB
    2. identical protein binding Source: IntAct
    3. microtubule binding Source: UniProtKB
    4. protein binding Source: IntAct
    5. tubulin binding Source: UniProtKB

    GO - Biological processi

    1. axon guidance Source: Reactome
    2. cell cycle arrest Source: UniProtKB-KW
    3. cellular copper ion homeostasis Source: UniProtKB
    4. learning or memory Source: Ensembl
    5. metabolic process Source: ProtInc
    6. negative regulation of activated T cell proliferation Source: BHF-UCL
    7. negative regulation of apoptotic process Source: Ensembl
    8. negative regulation of calcineurin-NFAT signaling cascade Source: BHF-UCL
    9. negative regulation of interferon-gamma production Source: BHF-UCL
    10. negative regulation of interleukin-17 production Source: BHF-UCL
    11. negative regulation of interleukin-2 production Source: BHF-UCL
    12. negative regulation of protein phosphorylation Source: BHF-UCL
    13. negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    14. negative regulation of T cell receptor signaling pathway Source: BHF-UCL
    15. protein homooligomerization Source: InterPro
    16. response to cadmium ion Source: Ensembl
    17. response to copper ion Source: Ensembl
    18. response to oxidative stress Source: UniProtKB

    Keywords - Molecular functioni

    Prion

    Keywords - Biological processi

    Cell cycle, Growth arrest

    Keywords - Ligandi

    Copper, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_18312. 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
    ProteomesiUP000005640: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:9449. PRNP.

    Subcellular locationi

    Cell membrane; Lipid-anchorGPI-anchor. Golgi apparatus
    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.
    Isoform 2 : Cytoplasm. Nucleus
    Note: Accumulates outside the secretory route in the cytoplasm, from where it relocates to the nucleus.

    GO - Cellular componenti

    1. anchored component of membrane Source: UniProtKB-KW
    2. cytoplasm Source: UniProtKB
    3. endoplasmic reticulum Source: UniProtKB
    4. extracellular vesicular exosome Source: UniProt
    5. extrinsic component of membrane Source: UniProtKB
    6. Golgi apparatus Source: UniProtKB
    7. membrane raft Source: UniProtKB
    8. nucleus Source: UniProtKB-SubCell
    9. plasma membrane Source: UniProtKB

    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) [MIM:123400]: 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 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.9 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti129 – 1291M → 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. 1 Publication
    Corresponds to variant rs1799990 [ dbSNP | Ensembl ].
    VAR_006467
    Natural varianti178 – 1781D → N in FFI and CJD. 2 Publications
    VAR_006469
    Natural varianti180 – 1801V → I in CJD. 1 Publication
    VAR_006470
    Natural varianti196 – 1961E → K in CJD. 1 Publication
    VAR_008749
    Natural varianti200 – 2001E → K in CJD. 3 Publications
    VAR_006473
    Natural varianti203 – 2031V → I in CJD; it could be an extremely rare polymorphism. 1 Publication
    VAR_008751
    Natural varianti208 – 2081R → H in CJD. 2 Publications
    VAR_006474
    Natural varianti210 – 2101V → I in CJD. 1 Publication
    VAR_006475
    Natural varianti211 – 2111E → Q in CJD. 1 Publication
    VAR_008752
    Natural varianti232 – 2321M → R in CJD. 1 Publication
    VAR_006478
    Fatal familial insomnia (FFI) [MIM:600072]: Autosomal dominant disorder and is characterized by neuronal degeneration limited to selected thalamic nuclei and progressive insomnia.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti129 – 1291M → 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. 1 Publication
    Corresponds to variant rs1799990 [ dbSNP | Ensembl ].
    VAR_006467
    Natural varianti178 – 1781D → N in FFI and CJD. 2 Publications
    VAR_006469
    Gerstmann-Straussler disease (GSD) [MIM:137440]: A 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.9 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti102 – 1021P → L in GSD and early-onset dementia. 5 Publications
    VAR_006464
    Natural varianti105 – 1051P → L in GSD. 2 Publications
    VAR_006465
    Natural varianti131 – 1311G → V in GSD. 1 Publication
    VAR_014264
    Natural varianti187 – 1871H → R in GSD. 1 Publication
    VAR_008746
    Natural varianti198 – 1981F → S in GSD; atypical form with neurofibrillary tangles.
    VAR_006472
    Natural varianti202 – 2021D → N in GSD. 1 Publication
    VAR_008750
    Natural varianti212 – 2121Q → P in GSD. 1 Publication
    VAR_008753
    Natural varianti217 – 2171Q → R in GSD; with neurofibrillary tangles. 1 Publication
    VAR_006476
    Huntington disease-like 1 (HDL1) [MIM:603218]: Autosomal dominant, early-onset neurodegenerative disorder with prominent psychiatric features.
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Kuru (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.
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Spongiform encephalopathy with neuropsychiatric features (SENF) [MIM:606688]: 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.
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    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

    MIMi123400. phenotype.
    137440. phenotype.
    245300. phenotype.
    600072. phenotype.
    603218. phenotype.
    606688. phenotype.
    Orphaneti280397. 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.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2222Add
    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...)
    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

    MaxQBiP04156.
    PaxDbiP04156.
    PRIDEiP04156.

    PTM databases

    PhosphoSiteiP04156.

    Miscellaneous databases

    PMAP-CutDBP04156.

    Expressioni

    Gene expression databases

    ArrayExpressiP04156.
    BgeeiP04156.
    GenevestigatoriP04156.

    Organism-specific databases

    HPAiHPA042754.

    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. 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.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
    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.

    Protein-protein interaction databases

    BioGridi111606. 59 interactions.
    DIPiDIP-29933N.
    IntActiP04156. 65 interactions.
    MINTiMINT-1420984.

    Structurei

    Secondary structure

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

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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).
    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.

    Sequence similaritiesi

    Belongs to the prion family.Curated

    Keywords - Domaini

    Repeat, Signal

    Phylogenomic databases

    eggNOGiNOG41716.
    HOVERGENiHBG008260.
    InParanoidiP04156.
    KOiK05634.
    OMAiHNPGYPH.
    OrthoDBiEOG7DRJ4Q.
    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]
    PANTHERiPTHR11522. PTHR11522. 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. Align

    Isoform 1 (identifier: P04156-1) [UniParc]FASTAAdd to Basket

    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

    MANLGCWMLV LFVATWSDLG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP    50
    PQGGGGWGQP HGGGWGQPHG GGWGQPHGGG WGQPHGGGWG QGGGTHSQWN 100
    KPSKPKTNMK HMAGAAAAGA VVGGLGGYML GSAMSRPIIH FGSDYEDRYY 150
    RENMHRYPNQ VYYRPMDEYS NQNNFVHDCV NITIKQHTVT TTTKGENFTE 200
    TDVKMMERVV EQMCITQYER ESQAYYQRGS SMVLFSSPPV ILLISFLIFL 250
    IVG 253
    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. 1 PublicationCurated
    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.

    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
    VAR_006464
    Natural varianti105 – 1051P → L in GSD. 2 Publications
    VAR_006465
    Natural varianti117 – 1171A → V Linked to development of dementing Gerstmann-Straussler disease. 1 Publication
    VAR_006466
    Natural varianti129 – 1291M → 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. 1 Publication
    Corresponds to variant rs1799990 [ dbSNP | Ensembl ].
    VAR_006467
    Natural varianti131 – 1311G → V in GSD. 1 Publication
    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. 2 Publications
    VAR_006469
    Natural varianti180 – 1801V → I in CJD. 1 Publication
    VAR_006470
    Natural varianti183 – 1831T → A in familial spongiform encephalopathy. 1 Publication
    VAR_006471
    Natural varianti187 – 1871H → R in GSD. 1 Publication
    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
    VAR_008747
    Natural varianti196 – 1961E → K in CJD. 1 Publication
    VAR_008749
    Natural varianti198 – 1981F → S in GSD; atypical form with neurofibrillary tangles.
    VAR_006472
    Natural varianti200 – 2001E → K in CJD. 3 Publications
    VAR_006473
    Natural varianti202 – 2021D → N in GSD. 1 Publication
    VAR_008750
    Natural varianti203 – 2031V → I in CJD; it could be an extremely rare polymorphism. 1 Publication
    VAR_008751
    Natural varianti208 – 2081R → H in CJD. 2 Publications
    VAR_006474
    Natural varianti210 – 2101V → I in CJD. 1 Publication
    VAR_006475
    Natural varianti211 – 2111E → Q in CJD. 1 Publication
    VAR_008752
    Natural varianti212 – 2121Q → P in GSD. 1 Publication
    VAR_008753
    Natural varianti217 – 2171Q → R in GSD; with neurofibrillary tangles. 1 Publication
    VAR_006476
    Natural varianti219 – 2191E → K.1 Publication
    Corresponds to variant rs1800014 [ dbSNP | Ensembl ].
    VAR_006477
    Natural varianti232 – 2321M → R in CJD. 1 Publication
    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:
    EMBL
    GenBank
    DDBJ
    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.
    UCSCiuc002wkt.1. human. [P04156-1]

    Polymorphism databases

    DMDMi130912.

    Keywords - Coding sequence diversityi

    Alternative initiation, Polymorphism

    Cross-referencesi

    Web resourcesi

    The Official Mad Cow Disease Home Page
    Wikipedia

    PRNP entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS13080.1. [P04156-1 ]
    PIRi A24173. UJHU.
    RefSeqi NP_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 ]
    UniGenei Hs.472010.
    Hs.610285.
    Hs.721670.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 77-84 [» ]
    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 [» ]
    2IV4 NMR - A 180-195 [» ]
    2IV5 NMR - A 173-195 [» ]
    2IV6 NMR - A 173-195 [» ]
    2K1D NMR - A 90-231 [» ]
    2KUN NMR - A 90-231 [» ]
    2LBG NMR - A 110-136 [» ]
    2LEJ NMR - A 90-231 [» ]
    2LFT NMR - A 90-231 [» ]
    2LSB NMR - A 90-231 [» ]
    2LV1 NMR - A 90-231 [» ]
    2M8T NMR - A 90-231 [» ]
    2OL9 X-ray 0.85 A 170-175 [» ]
    2W9E X-ray 2.90 A 119-231 [» ]
    3HAF X-ray 2.26 A 90-231 [» ]
    3HAK X-ray 1.80 A 125-227 [» ]
    3HEQ X-ray 1.80 A/B 90-231 [» ]
    3HER X-ray 1.85 A/B 90-231 [» ]
    3HES X-ray 2.00 A/B 90-231 [» ]
    3HJ5 X-ray 3.10 A/B 90-231 [» ]
    3HJX X-ray 2.00 A 126-231 [» ]
    3MD4 X-ray 1.15 A/B 127-132 [» ]
    3MD5 X-ray 1.40 A/B 127-132 [» ]
    3NHC X-ray 1.57 A/B 127-132 [» ]
    3NHD X-ray 1.92 A/B 127-132 [» ]
    3NVF X-ray 1.80 A 138-143 [» ]
    4DGI X-ray 2.40 A 120-230 [» ]
    4E1H X-ray 1.40 A/C/E/G/I/K 177-182 [» ]
    B/D/F/H/J/L 211-216 [» ]
    4E1I X-ray 2.03 A/C/E/G/I/K 177-182 [» ]
    B/D/F/H/J/L 211-216 [» ]
    4KML X-ray 1.50 A 24-231 [» ]
    4N9O X-ray 1.50 A 90-231 [» ]
    DisProti DP00466.
    ProteinModelPortali P04156.
    SMRi P04156. Positions 2-28, 90-231.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111606. 59 interactions.
    DIPi DIP-29933N.
    IntActi P04156. 65 interactions.
    MINTi MINT-1420984.

    Chemistry

    BindingDBi P04156.
    ChEMBLi CHEMBL4869.
    DrugBanki DB00759. Tetracycline.

    PTM databases

    PhosphoSitei P04156.

    Polymorphism databases

    DMDMi 130912.

    Proteomic databases

    MaxQBi P04156.
    PaxDbi P04156.
    PRIDEi P04156.

    Protocols and materials databases

    DNASUi 5621.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000379440 ; ENSP00000368752 ; ENSG00000171867 . [P04156-1 ]
    ENST00000430350 ; ENSP00000399376 ; ENSG00000171867 . [P04156-1 ]
    GeneIDi 5621.
    KEGGi hsa:5621.
    UCSCi uc002wkt.1. human. [P04156-1 ]

    Organism-specific databases

    CTDi 5621.
    GeneCardsi GC20P004615.
    GeneReviewsi PRNP.
    HGNCi HGNC:9449. PRNP.
    HPAi HPA042754.
    MIMi 123400. phenotype.
    137440. phenotype.
    176640. gene.
    245300. phenotype.
    600072. phenotype.
    603218. phenotype.
    606688. phenotype.
    neXtProti NX_P04156.
    Orphaneti 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.
    PharmGKBi PA33796.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG41716.
    HOVERGENi HBG008260.
    InParanoidi P04156.
    KOi K05634.
    OMAi HNPGYPH.
    OrthoDBi EOG7DRJ4Q.
    PhylomeDBi P04156.
    TreeFami TF105188.

    Enzyme and pathway databases

    Reactomei REACT_18312. NCAM1 interactions.

    Miscellaneous databases

    ChiTaRSi PRNP. human.
    EvolutionaryTracei P04156.
    GenomeRNAii 5621.
    NextBioi 21844.
    PMAP-CutDB P04156.
    PROi P04156.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P04156.
    Bgeei P04156.
    Genevestigatori P04156.

    Family and domain databases

    Gene3Di 1.10.790.10. 1 hit.
    InterProi IPR000817. Prion.
    IPR022416. Prion/Doppel_prot_b-ribbon_dom.
    IPR025860. Prion_N_dom.
    [Graphical view ]
    PANTHERi PTHR11522. PTHR11522. 1 hit.
    Pfami PF00377. Prion. 1 hit.
    PF11587. Prion_bPrPp. 1 hit.
    [Graphical view ]
    PRINTSi PR00341. PRION.
    SMARTi SM00157. PRP. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54098. SSF54098. 1 hit.
    PROSITEi PS00291. PRION_1. 1 hit.
    PS00706. PRION_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. 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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-253.
    10. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 9-232, VARIANT 56-GLY--GLY-63 DEL.
      Tissue: Brain.
    11. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 84-91.
    15. "Prion, amyloid beta-derived Cu(II) ions, or free Zn(II) ions support S-nitroso-dependent autocleavage of glypican-1 heparan sulfate."
      Mani K., Cheng F., Havsmark B., Jonsson M., Belting M., Fransson L.A.
      J. Biol. Chem. 278:38956-38965(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: COPPER-BINDING, FUNCTION.
    16. "The octarepeat domain of the prion protein binds Cu(II) with three distinct coordination modes at pH 7.4."
      Chattopadhyay M., Walter E.D., Newell D.J., Jackson P.J., Aronoff-Spencer E., Peisach J., Gerfen G.J., Bennett B., Antholine W.E., Millhauser G.L.
      J. Am. Chem. Soc. 127:12647-12656(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: COPPER-BINDING.
    17. "The prion protein is a combined zinc and copper binding protein: Zn2+ alters the distribution of Cu2+ coordination modes."
      Walter E.D., Stevens D.J., Visconte M.P., Millhauser G.L.
      J. Am. Chem. Soc. 129:15440-15441(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: COPPER-BINDING, ZINC-BINDING.
    18. "Biosynthesis of prion protein nucleocytoplasmic isoforms by alternative initiation of translation."
      Juanes M.E., Elvira G., Garcia-Grande A., Calero M., Gasset M.
      J. Biol. Chem. 284:2787-2794(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE INITIATION (ISOFORM 2), SUBCELLULAR LOCATION, MUTAGENESIS OF MET-1 AND MET-8.
    19. "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] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-197.
      Tissue: Leukemic T-cell.
    20. "Glypican-1 mediates both prion protein lipid raft association and disease isoform formation."
      Taylor D.R., Whitehouse I.J., Hooper N.M.
      PLoS Pathog. 5:E1000666-E1000666(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, DISEASE ASSOCIATION.
    21. "Early onset prion disease from octarepeat expansion correlates with copper or zinc binding properties."
      Stevens D.J., Walter E.D., Rodriguez A., Draper D., Davies P., Brown D.R., Millhauser G.L.
      PLoS Pathog. 5:E1000390-E1000390(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: COPPER-BINDING.
    22. "Prion fibrillization is mediated by a native structural element that comprises helices H2 and H3."
      Adrover M., Pauwels K., Prigent S., de Chiara C., Xu Z., Chapuis C., Pastore A., Rezaei H.
      J. Biol. Chem. 285:21004-21012(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT, DOMAIN.
    23. "Copper (II) promotes the formation of soluble neurotoxic PrP oligomers in acidic environment."
      Wu D., Zhang W., Luo Q., Luo K., Huang L., Wang W., Huang T., Chen R., Lin Y., Pang D., Xiao G.
      J. Cell. Biochem. 111:627-633(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: COPPER-BINDING, CIRCULAR DICHROISM, DOMAIN, FUNCTION, SUBUNIT.
    24. Cited for: INTERACTION WITH KIAA1191.
    25. "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] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 90-231 OF MUTANT LYS-200.
    26. Cited for: STRUCTURE BY NMR OF 23-230.
    27. "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] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 118-221.
    28. "Crystal structure of the human prion protein reveals a mechanism for oligomerization."
      Knaus K.J., Morillas M., Swietnicki W., Malone M., Surewicz W.K., Yee V.C.
      Nat. Struct. Biol. 8:770-774(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 119-226, DOMAIN, SUBUNIT.
    29. Cited for: X-RAY CRYSTALLOGRAPHY (0.75 ANGSTROMS) OF 61-65 IN COMPLEX WITH COPPER ION, DOMAIN, SUBUNIT.
    30. "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] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 61-68, DISULFIDE BOND, SUBUNIT.
    31. "Mutations and polymorphisms in the prion protein gene."
      Palmer M.S., Collinge J.
      Hum. Mutat. 2:168-173(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON VARIANTS.
    32. "Genetic and infectious prion diseases."
      Prusiner S.B.
      Arch. Neurol. 50:1129-1153(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON VARIANTS.
    33. Cited for: X-RAY CRYSTALLOGRAPHY (0.85 ANGSTROMS) OF 170-175, SUBUNIT, DOMAIN.
    34. Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 119-231 IN COMPLEX WITH FAB FRAGMENT OF MONOCLONAL ANTIBODY ICSM 18, SUBUNIT.
    35. "Conformational diversity in prion protein variants influences intermolecular beta-sheet formation."
      Lee S., Antony L., Hartmann R., Knaus K.J., Surewicz K., Surewicz W.K., Yee V.C.
      EMBO J. 29:251-262(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 125-227 OF VARIANT VAL-129; VARIANT FFI/CJD ASN-178 AND VARIANT GSD SER-198, SUBUNIT, DOMAIN.
    36. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT GSD LEU-102.
    37. "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] [Europe PMC] [Abstract]
      Cited for: VARIANTS LEU-102; VAL-117 AND VAL-129.
    38. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT FFI ASN-178.
    39. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT CJD ASN-178.
    40. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT CJD LYS-200.
    41. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT GSD ARG-217.
    42. "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] [Europe PMC] [Abstract]
      Cited for: VARIANTS CJD ILE-180 AND ARG-232.
    43. Cited for: VARIANT CJD ILE-210.
    44. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT GSD LEU-105.
    45. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT GSD LEU-105.
    46. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT CJD LYS-200.
    47. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT CJD LYS-200.
    48. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT GSD LEU-102.
    49. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT GSD LEU-102, VARIANT LYS-219.
    50. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT CJD HIS-208.
    51. Cited for: VARIANT CJD HIS-208.
    52. Cited for: VARIANTS GSD ASN-202 AND PRO-212.
    53. Cited for: VARIANTS ARG-188 AND SER-238.
    54. "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] [Europe PMC] [Abstract]
      Cited for: VARIANTS EARLY-ONSET DEMENTIA LEU-102; ALA-183 AND LYS-188.
    55. "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] [Europe PMC] [Abstract]
      Cited for: VARIANTS CJD LYS-196; ILE-203 AND GLN-211.
    56. "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] [Europe PMC] [Abstract]
      Cited for: VARIANT GSD VAL-131.

    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: October 1, 2014
    This is version 193 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 from an overlapping reading frame.
    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.

    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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3