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Protein

Major prion protein

Gene

PRNP

Organism
Ovis aries (Sheep)
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)DescriptionActionsGraphical viewLength
Metal bindingi64Copper or zinc 1By similarity1
Metal bindingi65Copper or zinc 1; via amide nitrogenBy similarity1
Metal bindingi66Copper or zinc 1; via amide nitrogen and carbonyl oxygenBy similarity1
Metal bindingi72Copper or zinc 2By similarity1
Metal bindingi73Copper or zinc 2; via amide nitrogenBy similarity1
Metal bindingi74Copper or zinc 2; via amide nitrogen and carbonyl oxygenBy similarity1
Metal bindingi80Copper or zinc 3By similarity1
Metal bindingi81Copper or zinc 3; via amide nitrogenBy similarity1
Metal bindingi82Copper or zinc 3; via amide nitrogen and carbonyl oxygenBy similarity1
Metal bindingi88Copper or zinc 4By similarity1
Metal bindingi90Copper or zinc 4; via amide nitrogenBy similarity1
Metal bindingi91Copper or zinc 4; via amide nitrogen and carbonyl oxygenBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Prion

Keywords - Ligandi

Copper, Metal-binding, Zinc

Protein family/group databases

TCDBi1.C.48.1.1. the prion peptide (prp) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Major prion protein
Short name:
PrP
Alternative name(s):
CD_antigen: CD230
Gene namesi
Name:PRNP
Synonyms:PRP, SIP
OrganismiOvis aries (Sheep)
Taxonomic identifieri9940 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis
Proteomesi
  • UP000002356 Componenti: Chromosome 13

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

Polymorphism at position 171 may be related to the alleles of scrapie incubation-control (SIC) gene in this species.

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.

Scrapie is a transmissible neurodegenerative disorder of sheep and goats. Most sheep that contract the disease naturally die between 24 and 50 months of age. The incubation period in sheep depends on the strain(s) of the infecting pathogen, sheep age at exposure, and the sheep genotype. The survival time is mainly determined by a single genetic locus, SIP, which has two alleles, susceptible (sa) and resistant (pa). Short incubation period is conferred by the partially dominant sa allele. Scrapie can be spread between flockmates, or it can be transmitted from an infected ewe to its lamb.

Keywords - Diseasei

Disease mutation

Chemistry databases

ChEMBLiCHEMBL2406893.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Add BLAST24
ChainiPRO_000002572725 – 233Major prion proteinAdd BLAST209
PropeptideiPRO_0000025728234 – 256Removed in mature formSequence analysisAdd BLAST23

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi182 ↔ 217
Glycosylationi184N-linked (GlcNAc...)Curated1
Glycosylationi200N-linked (GlcNAc...)Curated1
Lipidationi233GPI-anchor amidated alanineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Expressioni

Gene expression databases

ExpressionAtlasiP23907. differential.

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
PRNPP041563EBI-7670302,EBI-977302From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-60917N.
IntActiP23907. 1 interactor.
MINTiMINT-8302691.

Chemistry databases

BindingDBiP23907.

Structurei

Secondary structure

1256
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi112 – 114Combined sources3
Helixi123 – 126Combined sources4
Beta strandi128 – 130Combined sources3
Beta strandi131 – 133Combined sources3
Turni144 – 146Combined sources3
Helixi147 – 155Combined sources9
Helixi157 – 159Combined sources3
Beta strandi165 – 167Combined sources3
Helixi169 – 171Combined sources3
Beta strandi173 – 175Combined sources3
Helixi176 – 196Combined sources21
Helixi203 – 229Combined sources27

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1G04NMR-A145-169[»]
1M25NMR-A145-169[»]
1S4TNMR-A138-158[»]
1TPXX-ray2.56A114-234[»]
1TQBX-ray2.55A127-228[»]
1TQCX-ray2.80A127-228[»]
1UW3X-ray2.04A128-233[»]
1XYUNMR-A124-234[»]
1Y2SNMR-A124-234[»]
2KTMNMR-A172-234[»]
2MV8NMR-A103-234[»]
2MV9NMR-A103-234[»]
2N53NMR-A103-234[»]
2RMVNMR-A145-169[»]
2RMWNMR-A145-169[»]
ProteinModelPortaliP23907.
SMRiP23907.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23907.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati54 – 6219
Repeati63 – 7028
Repeati71 – 7838
Repeati79 – 8648
Repeati87 – 9559

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni25 – 233Interaction with GRB2, ERI3 and SYN1By similarityAdd BLAST209
Regioni54 – 955 X 8 AA tandem repeats of P-H-G-G-G-W-G-QAdd BLAST42

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

GeneTreeiENSGT00510000049083.
HOVERGENiHBG008260.
KOiK05634.
OMAiHNPGYPH.
OrthoDBiEOG091G0HMV.

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]
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]

Sequencei

Sequence statusi: Complete.

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

P23907-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVKSHIGSWI LVLFVAMWSD VGLCKKRPKP GGGWNTGGSR YPGQGSPGGN
60 70 80 90 100
RYPPQGGGGW GQPHGGGWGQ PHGGGWGQPH GGGWGQPHGG GGWGQGGSHS
110 120 130 140 150
QWNKPSKPKT NMKHVAGAAA AGAVVGGLGG YMLGSAMSRP LIHFGNDYED
160 170 180 190 200
RYYRENMYRY PNQVYYRPVD RYSNQNNFVH DCVNITVKQH TVTTTTKGEN
210 220 230 240 250
FTETDIKIME RVVEQMCITQ YQRESQAYYQ RGASVILFSS PPVILLISFL

IFLIVG
Length:256
Mass (Da):27,915
Last modified:November 1, 1991 - v1
Checksum:i7FFBEA6C6FDBF8BB
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti112M → T.1 Publication1
Natural varianti136A → V in scrapie; short incubation; sA allele. 3 Publications1
Natural varianti137M → T.1 Publication1
Natural varianti141L → F.3 Publications1
Natural varianti154R → H.3 Publications1
Natural varianti171R → H in scrapie; low incidence. 1 Publication1
Natural varianti171R → Q Linked to susceptibility to scrapie. 9 Publications1
Natural varianti211R → Q.2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31313 Genomic DNA. Translation: AAB97765.1.
X79912 Genomic DNA. Translation: CAA56283.1.
U67922 Genomic DNA. Translation: AAC78726.1.
AJ223072 Genomic DNA. Translation: CAA11073.1.
AY350241 Genomic DNA. Translation: AAR14214.1.
AY350242 Genomic DNA. Translation: AAR14215.1.
AY350243 Genomic DNA. Translation: AAR14216.1.
AY350245 Genomic DNA. Translation: AAR14218.1.
AY350246 Genomic DNA. Translation: AAR14219.1.
AY350248 Genomic DNA. Translation: AAR14221.1.
AY350249 Genomic DNA. Translation: AAR14222.1.
AY350250 Genomic DNA. Translation: AAR14223.1.
AY350254 Genomic DNA. Translation: AAR14227.1.
AY350256 Genomic DNA. Translation: AAR14229.1.
AY350257 Genomic DNA. Translation: AAR14230.1.
AY350261 Genomic DNA. Translation: AAR14234.1.
AY350264 Genomic DNA. Translation: AAR14237.1.
AY350267 Genomic DNA. Translation: AAR14240.1.
AY350268 Genomic DNA. Translation: AAR14241.1.
AY350271 Genomic DNA. Translation: AAR14244.1.
AY350272 Genomic DNA. Translation: AAR14245.1.
AY350273 Genomic DNA. Translation: AAR14246.1.
AY350275 Genomic DNA. Translation: AAR14248.1.
AJ567984 Genomic DNA. Translation: CAE00186.1.
AJ567985 Genomic DNA. Translation: CAE00187.1.
AJ567986 Genomic DNA. Translation: CAE00188.2.
D38179 Genomic DNA. Translation: BAA07376.1.
AJ000680 Genomic DNA. Translation: CAA04235.1.
AJ000681 Genomic DNA. Translation: CAA04236.1.
AJ000736 Genomic DNA. Translation: CAA04274.1.
AJ000739 Genomic DNA. Translation: CAA04277.1.
AY907689 Genomic DNA. Translation: AAW88336.1.
AY907690 Genomic DNA. Translation: AAW88337.1.
AY907691 Genomic DNA. Translation: AAW88338.1.
RefSeqiNP_001009481.1. NM_001009481.1.
XP_012043480.1. XM_012188090.2.
UniGeneiOar.765.

Genome annotation databases

EnsembliENSOART00000005076; ENSOARP00000004991; ENSOARG00000004668.
GeneIDi493887.
KEGGioas:493887.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31313 Genomic DNA. Translation: AAB97765.1.
X79912 Genomic DNA. Translation: CAA56283.1.
U67922 Genomic DNA. Translation: AAC78726.1.
AJ223072 Genomic DNA. Translation: CAA11073.1.
AY350241 Genomic DNA. Translation: AAR14214.1.
AY350242 Genomic DNA. Translation: AAR14215.1.
AY350243 Genomic DNA. Translation: AAR14216.1.
AY350245 Genomic DNA. Translation: AAR14218.1.
AY350246 Genomic DNA. Translation: AAR14219.1.
AY350248 Genomic DNA. Translation: AAR14221.1.
AY350249 Genomic DNA. Translation: AAR14222.1.
AY350250 Genomic DNA. Translation: AAR14223.1.
AY350254 Genomic DNA. Translation: AAR14227.1.
AY350256 Genomic DNA. Translation: AAR14229.1.
AY350257 Genomic DNA. Translation: AAR14230.1.
AY350261 Genomic DNA. Translation: AAR14234.1.
AY350264 Genomic DNA. Translation: AAR14237.1.
AY350267 Genomic DNA. Translation: AAR14240.1.
AY350268 Genomic DNA. Translation: AAR14241.1.
AY350271 Genomic DNA. Translation: AAR14244.1.
AY350272 Genomic DNA. Translation: AAR14245.1.
AY350273 Genomic DNA. Translation: AAR14246.1.
AY350275 Genomic DNA. Translation: AAR14248.1.
AJ567984 Genomic DNA. Translation: CAE00186.1.
AJ567985 Genomic DNA. Translation: CAE00187.1.
AJ567986 Genomic DNA. Translation: CAE00188.2.
D38179 Genomic DNA. Translation: BAA07376.1.
AJ000680 Genomic DNA. Translation: CAA04235.1.
AJ000681 Genomic DNA. Translation: CAA04236.1.
AJ000736 Genomic DNA. Translation: CAA04274.1.
AJ000739 Genomic DNA. Translation: CAA04277.1.
AY907689 Genomic DNA. Translation: AAW88336.1.
AY907690 Genomic DNA. Translation: AAW88337.1.
AY907691 Genomic DNA. Translation: AAW88338.1.
RefSeqiNP_001009481.1. NM_001009481.1.
XP_012043480.1. XM_012188090.2.
UniGeneiOar.765.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1G04NMR-A145-169[»]
1M25NMR-A145-169[»]
1S4TNMR-A138-158[»]
1TPXX-ray2.56A114-234[»]
1TQBX-ray2.55A127-228[»]
1TQCX-ray2.80A127-228[»]
1UW3X-ray2.04A128-233[»]
1XYUNMR-A124-234[»]
1Y2SNMR-A124-234[»]
2KTMNMR-A172-234[»]
2MV8NMR-A103-234[»]
2MV9NMR-A103-234[»]
2N53NMR-A103-234[»]
2RMVNMR-A145-169[»]
2RMWNMR-A145-169[»]
ProteinModelPortaliP23907.
SMRiP23907.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60917N.
IntActiP23907. 1 interactor.
MINTiMINT-8302691.

Chemistry databases

BindingDBiP23907.
ChEMBLiCHEMBL2406893.

Protein family/group databases

TCDBi1.C.48.1.1. the prion peptide (prp) family.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSOART00000005076; ENSOARP00000004991; ENSOARG00000004668.
GeneIDi493887.
KEGGioas:493887.

Organism-specific databases

CTDi5621.

Phylogenomic databases

GeneTreeiENSGT00510000049083.
HOVERGENiHBG008260.
KOiK05634.
OMAiHNPGYPH.
OrthoDBiEOG091G0HMV.

Miscellaneous databases

EvolutionaryTraceiP23907.
PROiP23907.

Gene expression databases

ExpressionAtlasiP23907. differential.

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]
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_SHEEP
AccessioniPrimary (citable) accession number: P23907
Secondary accession number(s): Q5ECG0
, Q6V638, Q6V654, Q712W2, Q712W3, Q7JGT4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: November 30, 2016
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

This protein is produced by a bicistronic gene which also produces the major prion protein/PRNP from an overlapping reading frame.
The alternative prion protein/AltPrP (AC F7VJQ3) 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 (By similarity). In mouse and hamster, the alternative initiation AUG codon is absent and is replaced by a GUG codon.By similarity

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.