Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Major prion protein

Gene

PRNP

Organism
Oryctolagus cuniculus (Rabbit)
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). 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 1By similarity
Metal bindingi62 – 621Copper or zinc 1; via amide nitrogenBy similarity
Metal bindingi63 – 631Copper or zinc 1; via amide nitrogen and carbonyl oxygenBy similarity
Metal bindingi69 – 691Copper or zinc 2By similarity
Metal bindingi70 – 701Copper or zinc 2; via amide nitrogenBy similarity
Metal bindingi71 – 711Copper or zinc 2; via amide nitrogen and carbonyl oxygenBy similarity
Metal bindingi77 – 771Copper or zinc 3By similarity
Metal bindingi78 – 781Copper or zinc 3; via amide nitrogenBy similarity
Metal bindingi79 – 791Copper or zinc 3; via amide nitrogen and carbonyl oxygenBy similarity
Metal bindingi85 – 851Copper or zinc 4By similarity
Metal bindingi86 – 861Copper or zinc 4; via amide nitrogenBy similarity
Metal bindingi87 – 871Copper or zinc 4; via amide nitrogen and carbonyl oxygenBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Prion

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
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Chromosome 4

Subcellular locationi

  • 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, Golgi apparatus, Membrane

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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2828Sequence analysisAdd
BLAST
Chaini29 – 229201Major prion proteinPRO_0000025721Add
BLAST
Propeptidei230 – 25223Removed in mature formSequence analysisPRO_0000025722Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi178 ↔ 2131 Publication
Glycosylationi180 – 1801N-linked (GlcNAc...)Sequence analysis
Glycosylationi196 – 1961N-linked (GlcNAc...)Sequence analysis
Lipidationi229 – 2291GPI-anchor amidated alanineSequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

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

Protein-protein interaction databases

DIPiDIP-59794N.
STRINGi9986.ENSOCUP00000001797.

Structurei

Secondary structure

1
252
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi128 – 1303Combined sources
Turni131 – 1344Combined sources
Helixi143 – 15210Combined sources
Helixi153 – 1553Combined sources
Beta strandi161 – 1633Combined sources
Helixi165 – 1673Combined sources
Helixi171 – 19121Combined sources
Turni192 – 1943Combined sources
Helixi199 – 22022Combined sources
Helixi222 – 2287Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2FJ3NMR-A91-228[»]
2JOHNMR-A91-228[»]
2JOMNMR-A91-228[»]
4HLSX-ray1.45A/B119-229[»]
4HMMX-ray1.50A/B119-229[»]
4HMRX-ray1.60A/B119-229[»]
ProteinModelPortaliQ95211.
SMRiQ95211. Positions 2-28, 124-227.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ95211.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati51 – 5991
Repeati60 – 6782
Repeati68 – 7583
Repeati76 – 8384
Repeati84 – 9295

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni23 – 229207Interaction with GRB2, ERI3 and SYN1By similarityAdd
BLAST
Regioni51 – 92425 X 8 AA tandem repeats of P-H-G-G-G-W-G-QAdd
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

eggNOGiENOG410IJMM. Eukaryota.
ENOG410YXUU. LUCA.
GeneTreeiENSGT00510000049083.
HOVERGENiHBG008260.
InParanoidiQ95211.
OMAiHNPGYPH.
OrthoDBiEOG7DRJ4Q.
TreeFamiTF105188.

Family and domain databases

Gene3Di1.10.790.10. 1 hit.
InterProiIPR000817. Prion.
IPR022416. Prion/Doppel_prot_b-ribbon_dom.
IPR020949. Prion_copper_b_octapeptide.
IPR025860. Prion_N_dom.
[Graphical view]
PANTHERiPTHR10502:SF11. PTHR10502:SF11. 1 hit.
PfamiPF00377. Prion. 1 hit.
PF11587. Prion_bPrPp. 1 hit.
PF03991. Prion_octapep. 5 hits.
[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]

Sequencei

Sequence statusi: Complete.

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

Q95211-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAHLGYWMLL LFVATWSDVG LCKKRPKPGG GWNTGGSRYP GQSSPGGNRY
60 70 80 90 100
PPQGGGWGQP HGGGWGQPHG GGWGQPHGGG WGQPHGGGWG QGGTHNQWGK
110 120 130 140 150
PSKPKTSMKH VAGAAAAGAV VGGLGGYMLG SAMSRPLIHF GNDYEDRYYR
160 170 180 190 200
ENMYRYPNQV YYRPVDQYSN QNSFVHDCVN ITVKQHTVTT TTKGENFTET
210 220 230 240 250
DIKIMERVVE QMCITQYQQE SQAAYQRAAG VLLFSSPPVI LLISFLIFLI

VG
Length:252
Mass (Da):27,432
Last modified:February 1, 1997 - v1
Checksum:i2E177AAF38B23A54
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28334 Genomic DNA. Translation: AAC48697.1.
PIRiJC6175.
RefSeqiXP_008254357.1. XM_008256135.1.
XP_008254358.1. XM_008256136.1.
UniGeneiOcu.6364.

Genome annotation databases

EnsembliENSOCUT00000002082; ENSOCUP00000001797; ENSOCUG00000002086.
GeneIDi100008658.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28334 Genomic DNA. Translation: AAC48697.1.
PIRiJC6175.
RefSeqiXP_008254357.1. XM_008256135.1.
XP_008254358.1. XM_008256136.1.
UniGeneiOcu.6364.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2FJ3NMR-A91-228[»]
2JOHNMR-A91-228[»]
2JOMNMR-A91-228[»]
4HLSX-ray1.45A/B119-229[»]
4HMMX-ray1.50A/B119-229[»]
4HMRX-ray1.60A/B119-229[»]
ProteinModelPortaliQ95211.
SMRiQ95211. Positions 2-28, 124-227.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59794N.
STRINGi9986.ENSOCUP00000001797.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSOCUT00000002082; ENSOCUP00000001797; ENSOCUG00000002086.
GeneIDi100008658.

Organism-specific databases

CTDi5621.

Phylogenomic databases

eggNOGiENOG410IJMM. Eukaryota.
ENOG410YXUU. LUCA.
GeneTreeiENSGT00510000049083.
HOVERGENiHBG008260.
InParanoidiQ95211.
OMAiHNPGYPH.
OrthoDBiEOG7DRJ4Q.
TreeFamiTF105188.

Miscellaneous databases

EvolutionaryTraceiQ95211.

Family and domain databases

Gene3Di1.10.790.10. 1 hit.
InterProiIPR000817. Prion.
IPR022416. Prion/Doppel_prot_b-ribbon_dom.
IPR020949. Prion_copper_b_octapeptide.
IPR025860. Prion_N_dom.
[Graphical view]
PANTHERiPTHR10502:SF11. PTHR10502:SF11. 1 hit.
PfamiPF00377. Prion. 1 hit.
PF11587. Prion_bPrPp. 1 hit.
PF03991. Prion_octapep. 5 hits.
[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. "Characterization of a prion protein (PrP) gene from rabbit; a species with apparent resistance to infection by prions."
    Loftus B., Rogers M.
    Gene 184:215-219(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: New Zealand white.
  2. "Unique structural characteristics of the rabbit prion protein."
    Wen Y., Li J., Yao W., Xiong M., Hong J., Peng Y., Xiao G., Lin D.
    J. Biol. Chem. 285:31682-31693(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 91-228 OF WILD TYPE AND MUTANT ASN-173, DISULFIDE BOND.

Entry informationi

Entry nameiPRIO_RABIT
AccessioniPrimary (citable) accession number: Q95211
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: April 13, 2016
This is version 114 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, Complete proteome, Reference proteome

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.