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Protein

Major prion protein

Gene

Prnp

Organism
Mus musculus (Mouse)
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 promote myelin homeostasis through acting as a agonist for ADGRG6 receptor. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (By similarity). 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 (PubMed:12732622, PubMed:16492732, PubMed:19242475, PubMed:19568430).By similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi60Copper or zinc 1By similarity1
Metal bindingi61Copper or zinc 1; via amide nitrogenBy similarity1
Metal bindingi62Copper or zinc 1; via amide nitrogen and carbonyl oxygenBy similarity1
Metal bindingi68Copper or zinc 2By similarity1
Metal bindingi69Copper or zinc 2; via amide nitrogenBy similarity1
Metal bindingi70Copper or zinc 2; via amide nitrogen and carbonyl oxygenBy similarity1
Metal bindingi76Copper or zinc 3By similarity1
Metal bindingi77Copper or zinc 3; via amide nitrogenBy similarity1
Metal bindingi78Copper or zinc 3; via amide nitrogen and carbonyl oxygenBy similarity1
Metal bindingi84Copper or zinc 4By similarity1
Metal bindingi85Copper or zinc 4; via amide nitrogenBy similarity1
Metal bindingi86Copper or zinc 4; via amide nitrogen and carbonyl oxygenBy similarity1

GO - Molecular functioni

GO - Biological processi

  • cellular copper ion homeostasis Source: MGI
  • cellular response to copper ion Source: MGI
  • cellular response to drug Source: MGI
  • learning or memory Source: Ensembl
  • negative regulation of activated T cell proliferation Source: BHF-UCL
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of calcineurin-NFAT signaling cascade Source: BHF-UCL
  • negative regulation of interferon-gamma production Source: BHF-UCL
  • negative regulation of interleukin-17 production Source: BHF-UCL
  • negative regulation of interleukin-2 production Source: BHF-UCL
  • negative regulation of protein phosphorylation Source: BHF-UCL
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • negative regulation of T cell receptor signaling pathway Source: BHF-UCL
  • nucleobase-containing compound metabolic process Source: MGI
  • protein homooligomerization Source: InterPro
  • regulation of potassium ion transmembrane transport Source: MGI
  • regulation of protein localization Source: MGI
  • response to cadmium ion Source: Ensembl
  • response to oxidative stress Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Prion

Keywords - Ligandi

Copper, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-419037. NCAM1 interactions.

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:Prn-p, Prp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:97769. Prnp.

Subcellular locationi

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • cell surface Source: MGI
  • endoplasmic reticulum Source: MGI
  • extracellular exosome Source: MGI
  • Golgi apparatus Source: MGI
  • membrane Source: MGI
  • membrane raft Source: MGI
  • mitochondrial outer membrane Source: MGI
  • plasma membrane Source: UniProtKB
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.

Disruption phenotypei

No obvious phenotype. Mice develop chronic demyelinating polyneuropathy after 60 weeks. Mice show abnormally low iron levels throughout the body, and are mildly anemic. Iron accumulates in duodenum enterocytes, suggesting impaired transport from the intestine to the blood.6 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi101P → L: No effect on interaction with GRB2. 1 Publication1
Mutagenesisi104P → L: No effect on interaction with GRB2. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL3698.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 221 PublicationAdd BLAST22
ChainiPRO_000002569723 – 230Major prion proteinAdd BLAST208
PropeptideiPRO_0000025698231 – 254Removed in mature formBy similarityAdd BLAST24

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei44Hydroxyproline1 Publication1
Disulfide bondi178 ↔ 213
Glycosylationi180N-linked (GlcNAc...)Curated1
Glycosylationi196N-linked (GlcNAc...)1 Publication1
Lipidationi230GPI-anchor amidated serineBy similarity1

Post-translational modificationi

N-glycosylated.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Hydroxylation, Lipoprotein

Proteomic databases

EPDiP04925.
PaxDbiP04925.
PeptideAtlasiP04925.
PRIDEiP04925.

PTM databases

iPTMnetiP04925.
PhosphoSitePlusiP04925.
UniCarbKBiP04925.

Miscellaneous databases

PMAP-CutDBP04925.

Expressioni

Tissue specificityi

Highly expressed in the brain, lung, kidney and heart. Expressed at low levels in the liver and spleen.2 Publications

Gene expression databases

BgeeiENSMUSG00000079037.
CleanExiMM_PRNP.
ExpressionAtlasiP04925. baseline and differential.
GenevisibleiP04925. MM.

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 (PubMed:11571277). Mislocalized cytosolically exposed PrP interacts with MGRN1; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement (By similarity). Interacts with APP. Interacts with KIAA1191 (By similarity). Interacts with ADGRG6 (PubMed:27501152).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself9EBI-768613,EBI-768613
Cacna2d1O085323EBI-768613,EBI-770939
Grb2Q606317EBI-768613,EBI-1688
PRNPP041563EBI-768613,EBI-977302From a different organism.

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi202389. 38 interactors.
DIPiDIP-4N.
IntActiP04925. 13 interactors.
MINTiMINT-214988.
STRINGi10090.ENSMUSP00000088833.

Chemistry databases

BindingDBiP04925.

Structurei

Secondary structure

1254
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni121 – 123Combined sources3
Beta strandi124 – 126Combined sources3
Beta strandi127 – 129Combined sources3
Helixi143 – 152Combined sources10
Helixi153 – 155Combined sources3
Beta strandi160 – 162Combined sources3
Helixi165 – 167Combined sources3
Beta strandi168 – 170Combined sources3
Helixi171 – 192Combined sources22
Helixi199 – 222Combined sources24
Turni224 – 228Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AG2NMR-A123-225[»]
1XYXNMR-A120-231[»]
1Y15NMR-A120-231[»]
1Y16NMR-A120-231[»]
2K5ONMR-A120-231[»]
2KFMNMR-A120-231[»]
2KFONMR-A120-231[»]
2KU5NMR-A120-231[»]
2KU6NMR-A120-231[»]
2L1DNMR-A120-231[»]
2L1ENMR-A120-231[»]
2L1HNMR-A120-231[»]
2L1KNMR-A120-231[»]
2L39NMR-A118-231[»]
2L40NMR-A120-231[»]
3NVGX-ray1.48A137-142[»]
3NVHX-ray1.61A137-143[»]
4H88X-ray1.90A120-230[»]
4J8RX-ray2.30I/J67-82[»]
4MA7X-ray1.97A116-229[»]
4MA8X-ray2.20C116-229[»]
DisProtiDP00265.
ProteinModelPortaliP04925.
SMRiP04925.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04925.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati51 – 5818
Repeati59 – 6628
Repeati67 – 7438
Repeati75 – 8248
Repeati83 – 9058

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni23 – 231Interaction with GRB2, ERI3 and SYN11 PublicationAdd BLAST209
Regioni23 – 38Interaction with ADGRG61 PublicationAdd BLAST16
Regioni51 – 905 X 8 AA tandem repeats of P-H-G-G-G-W-G-QAdd BLAST40

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.
HOGENOMiHOG000232077.
HOVERGENiHBG008260.
InParanoidiP04925.
KOiK05634.
OMAiHNPGYPH.
OrthoDBiEOG091G0HMV.
PhylomeDBiP04925.
TreeFamiTF105188.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

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

P04925-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANLGYWLLA LFVTMWTDVG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP
60 70 80 90 100
PQGGTWGQPH GGGWGQPHGG SWGQPHGGSW GQPHGGGWGQ GGGTHNQWNK
110 120 130 140 150
PSKPKTNLKH VAGAAAAGAV VGGLGGYMLG SAMSRPMIHF GNDWEDRYYR
160 170 180 190 200
ENMYRYPNQV YYRPVDQYSN QNNFVHDCVN ITIKQHTVTT TTKGENFTET
210 220 230 240 250
DVKMMERVVE QMCVTQYQKE SQAYYDGRRS SSTVLFSSPP VILLISFLIF

LIVG
Length:254
Mass (Da):27,977
Last modified:January 1, 1990 - v2
Checksum:iD5331E6321826CC0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti133M → V in AAA39996 (PubMed:3462700).Curated1
Sequence conflicti133M → V in AAA39999 (PubMed:3923361).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti108L → F Linked to long incubation time. 1
Natural varianti189T → V Linked to long incubation time; requires 2 nucleotide substitutions. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M18070 Genomic DNA. Translation: AAA39997.1.
M18071 Genomic DNA. Translation: AAA39998.1.
M13685 mRNA. Translation: AAA39996.1.
U29186 Genomic DNA. Translation: AAC02804.1.
BC006703 mRNA. Translation: AAH06703.1.
M30384 mRNA. Translation: AAA39999.1.
CCDSiCCDS16766.1.
PIRiA29669. A23544.
RefSeqiNP_001265185.1. NM_001278256.1.
NP_035300.1. NM_011170.3.
UniGeneiMm.648.

Genome annotation databases

EnsembliENSMUST00000091288; ENSMUSP00000088833; ENSMUSG00000079037.
GeneIDi19122.
KEGGimmu:19122.
UCSCiuc008mly.3. mouse.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M18070 Genomic DNA. Translation: AAA39997.1.
M18071 Genomic DNA. Translation: AAA39998.1.
M13685 mRNA. Translation: AAA39996.1.
U29186 Genomic DNA. Translation: AAC02804.1.
BC006703 mRNA. Translation: AAH06703.1.
M30384 mRNA. Translation: AAA39999.1.
CCDSiCCDS16766.1.
PIRiA29669. A23544.
RefSeqiNP_001265185.1. NM_001278256.1.
NP_035300.1. NM_011170.3.
UniGeneiMm.648.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AG2NMR-A123-225[»]
1XYXNMR-A120-231[»]
1Y15NMR-A120-231[»]
1Y16NMR-A120-231[»]
2K5ONMR-A120-231[»]
2KFMNMR-A120-231[»]
2KFONMR-A120-231[»]
2KU5NMR-A120-231[»]
2KU6NMR-A120-231[»]
2L1DNMR-A120-231[»]
2L1ENMR-A120-231[»]
2L1HNMR-A120-231[»]
2L1KNMR-A120-231[»]
2L39NMR-A118-231[»]
2L40NMR-A120-231[»]
3NVGX-ray1.48A137-142[»]
3NVHX-ray1.61A137-143[»]
4H88X-ray1.90A120-230[»]
4J8RX-ray2.30I/J67-82[»]
4MA7X-ray1.97A116-229[»]
4MA8X-ray2.20C116-229[»]
DisProtiDP00265.
ProteinModelPortaliP04925.
SMRiP04925.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202389. 38 interactors.
DIPiDIP-4N.
IntActiP04925. 13 interactors.
MINTiMINT-214988.
STRINGi10090.ENSMUSP00000088833.

Chemistry databases

BindingDBiP04925.
ChEMBLiCHEMBL3698.

PTM databases

iPTMnetiP04925.
PhosphoSitePlusiP04925.
UniCarbKBiP04925.

Proteomic databases

EPDiP04925.
PaxDbiP04925.
PeptideAtlasiP04925.
PRIDEiP04925.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000091288; ENSMUSP00000088833; ENSMUSG00000079037.
GeneIDi19122.
KEGGimmu:19122.
UCSCiuc008mly.3. mouse.

Organism-specific databases

CTDi5621.
MGIiMGI:97769. Prnp.

Phylogenomic databases

eggNOGiENOG410IJMM. Eukaryota.
ENOG410YXUU. LUCA.
GeneTreeiENSGT00510000049083.
HOGENOMiHOG000232077.
HOVERGENiHBG008260.
InParanoidiP04925.
KOiK05634.
OMAiHNPGYPH.
OrthoDBiEOG091G0HMV.
PhylomeDBiP04925.
TreeFamiTF105188.

Enzyme and pathway databases

ReactomeiR-MMU-419037. NCAM1 interactions.

Miscellaneous databases

ChiTaRSiPrnp. mouse.
EvolutionaryTraceiP04925.
PMAP-CutDBP04925.
PROiP04925.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000079037.
CleanExiMM_PRNP.
ExpressionAtlasiP04925. baseline and differential.
GenevisibleiP04925. MM.

Family and domain databases

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

Entry informationi

Entry nameiPRIO_MOUSE
AccessioniPrimary (citable) accession number: P04925
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 1, 1990
Last modified: November 30, 2016
This is version 184 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.