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Protein

Major prion protein

Gene

PRNP

Organism
Mesocricetus auratus (Golden hamster)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Its primary physiological function is unclear. 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 2
Metal bindingi70 – 701Copper or zinc 2; via amide nitrogen
Metal bindingi71 – 711Copper or zinc 2; via amide nitrogen and carbonyl
Metal bindingi71 – 711Copper or zinc 2; via amide nitrogen and carbonyl oxygenBy similarity
Metal bindingi77 – 771Copper or zinc 3
Metal bindingi78 – 781Copper or zinc 3; via amide nitrogen
Metal bindingi79 – 791Copper or zinc 3; via amide nitrogen and carbonyl oxygen
Metal bindingi85 – 851Copper or zinc 4
Metal bindingi86 – 861Copper or zinc 4; via amide nitrogen
Metal bindingi87 – 871Copper or zinc 4; via amide nitrogen and carbonyl oxygen

GO - Molecular functioni

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Prion

Keywords - Biological processi

Cell cycle, Growth arrest

Keywords - Ligandi

Copper, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Major prion protein
Short name:
PrP
Alternative name(s):
PrP27-30
PrP33-35C
CD_antigen: CD230
Gene namesi
Name:PRNP
Synonyms:PRP
OrganismiMesocricetus auratus (Golden hamster)
Taxonomic identifieri10036 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeMesocricetus

Subcellular locationi

Isoform 2 :
  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: Accumulates outside the secretory route in the cytoplasm, from where it relocates to the nucleus.1 Publication
  • Cell membrane By similarity; Lipid-anchorGPI-anchor By similarity
  • 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.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1 – 11M → S: Protein detected. No protein detected; when associated with S-15. 1 Publication
Mutagenesisi15 – 151M → S: No protein detected; when associated with S-1. 1 Publication
Mutagenesisi183 – 1831T → A: Accumulates intracellularly. 1 Publication
Mutagenesisi199 – 1991T → A: Accumulates intracellularly. 1 Publication

Chemistry

ChEMBLiCHEMBL1293203.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Add
BLAST
Chaini23 – 231209Major prion proteinPRO_0000025695Add
BLAST
Propeptidei232 – 25423Removed in mature form1 PublicationPRO_0000025696Add
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
Lipidationi231 – 2311GPI-anchor amidated serine1 Publication

Post-translational modificationi

Isoform 2 is sumoylated with SUMO1.1 Publication

Keywords - PTMi

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

PTM databases

UniCarbKBiP04273.

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. Interacts with KIAA1191.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-986426,EBI-986426

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

DIPiDIP-1081N.

Structurei

Secondary structure

1
254
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi61 – 633Combined sources
Beta strandi69 – 713Combined sources
Beta strandi73 – 753Combined sources
Beta strandi77 – 793Combined sources
Beta strandi81 – 833Combined sources
Beta strandi85 – 873Combined sources
Beta strandi129 – 1335Combined sources
Beta strandi139 – 1413Combined sources
Helixi144 – 15310Combined sources
Helixi154 – 1563Combined sources
Beta strandi160 – 1634Combined sources
Helixi166 – 1683Combined sources
Helixi172 – 19322Combined sources
Helixi200 – 22223Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1B10NMR-A90-231[»]
2KKGNMR-A23-106[»]
2LH8NMR-A125-228[»]
3NVEX-ray1.70A/B138-143[»]
4YXLX-ray2.60A90-232[»]
DisProtiDP00187.
ProteinModelPortaliP04273.
SMRiP04273. Positions 2-28, 125-228.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04273.

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 – 231209Interaction with GRB2, ERI3 and SYN1By similarityAdd
BLAST
Regioni51 – 91415 X 8 AA tandem repeats of P-H-G-G-G-W-G-QAdd
BLAST
Regioni90 – 231142PrP27-30 (protease resistant core)Add
BLAST

Domaini

The normal, monomeric form has a mainly alpha-helical structure. The disease-associated, protease-resistant form forms amyloid fibrils containing 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.By similarity
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.By similarity

Sequence similaritiesi

Belongs to the prion family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

HOVERGENiHBG008260.

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 (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P04273-1) [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

        10         20         30         40         50
MANLSYWLLA LFVAMWTDVG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP
60 70 80 90 100
PQGGGTWGQP HGGGWGQPHG GGWGQPHGGG WGQPHGGGWG QGGGTHNQWN
110 120 130 140 150
KPSKPKTNMK HMAGAAAAGA VVGGLGGYML GSAMSRPMMH FGNDWEDRYY
160 170 180 190 200
RENMNRYPNQ VYYRPVDQYN NQNNFVHDCV NITIKQHTVT TTTKGENFTE
210 220 230 240 250
TDIKIMERVV EQMCTTQYQK ESQAYYDGRR SSAVLFSSPP VILLISFLIF

LMVG
Length:254
Mass (Da):27,919
Last modified:January 1, 1988 - v1
Checksum:i442C0E3ED4D20672
GO
Isoform 2 (identifier: P04273-2) [UniParc]FASTAAdd to basket

Also known as: PrP(M15)

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.

Show »
Length:240
Mass (Da):26,325
Checksum:i02F8F94C92BC9022
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1414Missing in isoform 2. CuratedVSP_039046Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14054 Genomic DNA. Translation: AAA37091.1.
K02234 mRNA. Translation: AAA37092.1.
PIRiI48168. UJHYIH.
RefSeqiXP_005068717.1. XM_005068660.2. [P04273-1]
XP_012967855.1. XM_013112401.1. [P04273-1]

Genome annotation databases

GeneIDi101829062.

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14054 Genomic DNA. Translation: AAA37091.1.
K02234 mRNA. Translation: AAA37092.1.
PIRiI48168. UJHYIH.
RefSeqiXP_005068717.1. XM_005068660.2. [P04273-1]
XP_012967855.1. XM_013112401.1. [P04273-1]

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1B10NMR-A90-231[»]
2KKGNMR-A23-106[»]
2LH8NMR-A125-228[»]
3NVEX-ray1.70A/B138-143[»]
4YXLX-ray2.60A90-232[»]
DisProtiDP00187.
ProteinModelPortaliP04273.
SMRiP04273. Positions 2-28, 125-228.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-1081N.

Chemistry

ChEMBLiCHEMBL1293203.

PTM databases

UniCarbKBiP04273.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi101829062.

Organism-specific databases

CTDi5621.

Phylogenomic databases

HOVERGENiHBG008260.

Miscellaneous databases

EvolutionaryTraceiP04273.

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...

Publicationsi

  1. "Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene."
    Basler K., Oesch B., Scott M., Westaway D., Waelchli M., Groth D.F., McKinley M.P., Prusiner S.B., Weissmann C.
    Cell 46:417-428(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 15-254.
  3. "Purification and properties of the cellular and scrapie hamster prion proteins."
    Turk E., Teplow D.B., Hood L.E., Prusiner S.B.
    Eur. J. Biochem. 176:21-30(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT ASN-181 AND ASN-197, DISULFIDE BONDS.
  4. "Scrapie prion protein contains a phosphatidylinositol glycolipid."
    Stahl N., Borchelt D.R., Hasiao K., Prusiner S.B.
    Cell 51:229-240(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: GPI-ANCHOR.
  5. "Identification of glycoinositol phospholipid linked and truncated forms of the scrapie prion protein."
    Stahl N., Baldwin M.A., Burlingame A.L., Prusiner S.B.
    Biochemistry 29:8879-8884(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: GPI-ANCHOR AT SER-231.
  6. "Intracellular accumulation of the cellular prion protein after mutagenesis of its Asn-linked glycosylation sites."
    Rogers M., Taraboulos A., Scott M., Groth D., Prusiner S.B.
    Glycobiology 1:101-109(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF THR-183 AND THR-199.
  7. Cited for: COPPER- OR ZINC-BINDING SITES, DOMAIN.
  8. "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.
  9. "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.
  10. "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-15, SUMOYLATION.
  11. "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.
  12. "Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform."
    James T.L., Liu H., Ulyanov N.B., Farr-Jones S., Zhang H., Donne D.G., Kaneko K., Groth D., Mehlhorn I., Prusiner S.B., Cohen F.E.
    Proc. Natl. Acad. Sci. U.S.A. 94:10086-10091(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 90-231.
  13. "Structure of the recombinant full-length hamster prion protein PrP(29-231): the N-terminus is highly flexible."
    Donne D.G., Viles J.H., Groth D., Mehlhorn I., James T.L., Cohen F.E., Prusiner S.B., Wright P.E., Dyson H.J.
    Proc. Natl. Acad. Sci. U.S.A. 94:13452-13457(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 29-231.

Entry informationi

Entry nameiPRIO_MESAU
AccessioniPrimary (citable) accession number: P04273
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: January 1, 1988
Last modified: May 11, 2016
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.