PRIO_GORGO
ID PRIO_GORGO Reviewed; 253 AA.
AC P40252; Q28419;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Major prion protein;
DE Short=PrP;
DE AltName: Full=PrP27-30;
DE AltName: Full=PrP33-35C;
DE AltName: CD_antigen=CD230;
DE Flags: Precursor;
GN Name=PRNP; Synonyms=PRP;
OS Gorilla gorilla gorilla (Western lowland gorilla).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Gorilla.
OX NCBI_TaxID=9595;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7837269; DOI=10.1006/jmbi.1994.0030;
RA Schaetzl H.M., Da Costa M., Taylor L., Cohen F.E., Prusiner S.B.;
RT "Prion protein gene variation among primates.";
RL J. Mol. Biol. 245:362-374(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RX PubMed=7991600; DOI=10.1073/pnas.91.25.12159;
RA Cervenakova L., Brown P., Goldfarb L.G., Nagle J., Pettrone K.,
RA Rubenstein R., Dubnick M., Gibbs C.J., Gajdusek D.C.;
RT "Infectious amyloid precursor gene sequences in primates used for
RT experimental transmission of human spongiform encephalopathy.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:12159-12162(1994).
CC -!- FUNCTION: Its primary physiological function is unclear. May play a
CC role in neuronal development and synaptic plasticity. May be required
CC for neuronal myelin sheath maintenance. May promote myelin homeostasis
CC through acting as an agonist for ADGRG6 receptor. May play a role in
CC iron uptake and iron homeostasis. Soluble oligomers are toxic to
CC cultured neuroblastoma cells and induce apoptosis (in vitro) (By
CC similarity). Association with GPC1 (via its heparan sulfate chains)
CC targets PRNP to lipid rafts. Also provides Cu(2+) or Zn(2+) for the
CC ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate
CC side chains (By similarity). {ECO:0000250|UniProtKB:P04156,
CC ECO:0000250|UniProtKB:P04925}.
CC -!- SUBUNIT: Monomer and homodimer. Has a tendency to aggregate into
CC amyloid fibrils containing a cross-beta spine, formed by a steric
CC zipper of superposed beta-strands. Soluble oligomers may represent an
CC intermediate stage on the path to fibril formation. Copper binding may
CC promote oligomerization. Interacts with GRB2, APP, ERI3/PRNPIP and SYN1
CC (By similarity). Mislocalized cytosolically exposed PrP interacts with
CC MGRN1; this interaction alters MGRN1 subcellular location and causes
CC lysosomal enlargement (By similarity). Interacts with APP. Interacts
CC with KIAA1191 (By similarity). Interacts with ADGRG6 (By similarity).
CC {ECO:0000250|UniProtKB:P04156, ECO:0000250|UniProtKB:P04925}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P04156};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P04156}. Golgi
CC apparatus {ECO:0000250|UniProtKB:P04925}. Note=Targeted to lipid rafts
CC via association with the heparan sulfate chains of GPC1. Colocates, in
CC the presence of Cu(2+), to vesicles in para- and perinuclear regions,
CC where both proteins undergo internalization. Heparin displaces PRNP
CC from lipid rafts and promotes endocytosis.
CC {ECO:0000250|UniProtKB:P04156}.
CC -!- DOMAIN: The normal, monomeric form has a mainly alpha-helical
CC structure. The disease-associated, protease-resistant form forms
CC amyloid fibrils containing a cross-beta spine, formed by a steric
CC zipper of superposed beta-strands. Disease mutations may favor
CC intermolecular contacts via short beta strands, and may thereby trigger
CC oligomerization. {ECO:0000250|UniProtKB:P04156}.
CC -!- DOMAIN: Contains an N-terminal region composed of octamer repeats. At
CC low copper concentrations, the sidechains of His residues from three or
CC four repeats contribute to the binding of a single copper ion.
CC Alternatively, a copper ion can be bound by interaction with the
CC sidechain and backbone amide nitrogen of a single His residue. The
CC observed copper binding stoichiometry suggests that two repeat regions
CC cooperate to stabilize the binding of a single copper ion. At higher
CC copper concentrations, each octamer can bind one copper ion by
CC interactions with the His sidechain and Gly backbone atoms. A mixture
CC of binding types may occur, especially in the case of octamer repeat
CC expansion. Copper binding may stabilize the conformation of this region
CC and may promote oligomerization. {ECO:0000250|UniProtKB:P04156}.
CC -!- DISEASE: Note=PrP is found in high quantity in the brain of humans and
CC animals infected with the degenerative neurological diseases kuru,
CC Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS),
CC scrapie, bovine spongiform encephalopathy (BSE), transmissible mink
CC encephalopathy (TME), etc. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the prion family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U08300; AAC50089.1; -; Genomic_DNA.
DR EMBL; U15166; AAA68633.1; -; Genomic_DNA.
DR PIR; I37032; I37032.
DR PIR; S53614; S53614.
DR RefSeq; XP_004061812.1; XM_004061764.2.
DR RefSeq; XP_018872663.1; XM_019017118.1.
DR RefSeq; XP_018872664.1; XM_019017119.1.
DR AlphaFoldDB; P40252; -.
DR BMRB; P40252; -.
DR SMR; P40252; -.
DR STRING; 9593.ENSGGOP00000007899; -.
DR Ensembl; ENSGGOT00000044450; ENSGGOP00000034151; ENSGGOG00000036480.
DR GeneID; 101135304; -.
DR KEGG; ggo:101135304; -.
DR CTD; 5621; -.
DR eggNOG; ENOG502S2A8; Eukaryota.
DR GeneTree; ENSGT00510000049083; -.
DR HOGENOM; CLU_094631_0_0_1; -.
DR InParanoid; P40252; -.
DR OMA; HNPGYPH; -.
DR OrthoDB; 1403854at2759; -.
DR Proteomes; UP000001519; Chromosome 20.
DR Bgee; ENSGGOG00000036480; Expressed in prefrontal cortex and 5 other tissues.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016234; C:inclusion body; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl.
DR GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR GO; GO:0019828; F:aspartic-type endopeptidase inhibitor activity; IEA:Ensembl.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:1903135; F:cupric ion binding; IEA:Ensembl.
DR GO; GO:1903136; F:cuprous ion binding; IEA:Ensembl.
DR GO; GO:0005539; F:glycosaminoglycan binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0008017; F:microtubule binding; IEA:Ensembl.
DR GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0038023; F:signaling receptor activity; IEA:Ensembl.
DR GO; GO:0031802; F:type 5 metabotropic glutamate receptor binding; IEA:Ensembl.
DR GO; GO:0032147; P:activation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IEA:Ensembl.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl.
DR GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007611; P:learning or memory; IEA:Ensembl.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; IEA:Ensembl.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IEA:Ensembl.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IEA:Ensembl.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IEA:Ensembl.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IEA:Ensembl.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:1990535; P:neuron projection maintenance; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IEA:Ensembl.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IEA:Ensembl.
DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:1905664; P:regulation of calcium ion import across plasma membrane; IEA:Ensembl.
DR GO; GO:1900449; P:regulation of glutamate receptor signaling pathway; IEA:Ensembl.
DR GO; GO:1902938; P:regulation of intracellular calcium activated chloride channel activity; IEA:Ensembl.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR Gene3D; 1.10.790.10; -; 1.
DR InterPro; IPR000817; Prion.
DR InterPro; IPR036924; Prion/Doppel_b-ribbon_dom_sf.
DR InterPro; IPR022416; Prion/Doppel_prot_b-ribbon_dom.
DR InterPro; IPR025860; Prion_N_dom.
DR Pfam; PF00377; Prion; 1.
DR Pfam; PF11587; Prion_bPrPp; 1.
DR PRINTS; PR00341; PRION.
DR SMART; SM00157; PRP; 1.
DR SUPFAM; SSF54098; SSF54098; 1.
DR PROSITE; PS00291; PRION_1; 1.
DR PROSITE; PS00706; PRION_2; 1.
PE 3: Inferred from homology;
KW Amyloid; Cell membrane; Copper; Disulfide bond; Glycoprotein;
KW Golgi apparatus; GPI-anchor; Lipoprotein; Membrane; Metal-binding; Prion;
KW Reference proteome; Repeat; Signal; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000250"
FT CHAIN 23..230
FT /note="Major prion protein"
FT /id="PRO_0000025673"
FT PROPEP 231..253
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025674"
FT REPEAT 51..59
FT /note="1"
FT REPEAT 60..67
FT /note="2"
FT REPEAT 68..75
FT /note="3"
FT REPEAT 76..83
FT /note="4"
FT REPEAT 84..91
FT /note="5"
FT REGION 23..230
FT /note="Interaction with GRB2, ERI3 and SYN1"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 23..38
FT /note="Interaction with ADGRG6"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 26..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..91
FT /note="5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q"
FT BINDING 61
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 62
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 63
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 69
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 70
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 71
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 77
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 78
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 79
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 85
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 86
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 87
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT LIPID 230
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000250|UniProtKB:P04273"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 179..214
FT /evidence="ECO:0000250|UniProtKB:P04273"
FT CONFLICT 6
FT /note="C -> Y (in Ref. 2; AAA68633)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 253 AA; 27660 MW; E28F4C3FAABCA49E CRC64;
MANLGCWMLV LFVATWSDLG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP PQGGGGWGQP
HGGGWGQPHG GGWGQPHGGG WGQPHGGGWG QGGGTHSQWN KPSKPKTNMK HMAGAAAAGA
VVGGLGGYML GSAMSRPIIH FGSDYEDRYY RENMHRYPNQ VYYRPMDQYS NQNNFVHDCV
NITIKQHTVT TTTKGENFTE TDVKMMERVV EQMCITQYER ESQAYYQRGS SMVLFSSPPV
ILLISFLIFL IVG
