PRIO_FELCA
ID PRIO_FELCA Reviewed; 256 AA.
AC O18754; O19016; Q5YCW7;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 3.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Major prion protein;
DE Short=PrP;
DE AltName: CD_antigen=CD230;
DE Flags: Precursor;
GN Name=PRNP; Synonyms=PRP;
OS Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood, and Brain;
RA Rohwer R.G., Edelman D., Protzman J.L.;
RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 25-234.
RX PubMed=15474307; DOI=10.1016/j.gene.2004.07.002;
RA Lysek D.A., Nivon L.G., Wuethrich K.;
RT "Amino acid sequence of the Felis catus prion protein.";
RL Gene 341:249-253(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 112-235.
RA Taylor M.S., Newton D.J., Flanagan B.F., Christmas S.E.;
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP STRUCTURE BY NMR OF 104-214.
RX PubMed=15647367; DOI=10.1073/pnas.0408937102;
RA Lysek D.A., Schorn C., Nivon L.G., Esteve-Moya V., Christen B.,
RA Calzolai L., von Schroetter C., Fiorito F., Herrmann T., Guentert P.,
RA Wuethrich K.;
RT "Prion protein NMR structures of cats, dogs, pigs, and sheep.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:640-645(2005).
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 -!- WEB RESOURCE: Name=Cat PRP; Note=Web page on cat sequence problems;
CC URL="http://www.mad-cow.org/cat_prion.html";
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DR EMBL; AF003087; AAB70468.1; -; Genomic_DNA.
DR EMBL; AY573555; AAS94127.1; -; Genomic_DNA.
DR EMBL; Y13698; CAA74032.1; -; Genomic_DNA.
DR PDB; 1XYJ; NMR; -; A=124-234.
DR PDBsum; 1XYJ; -.
DR AlphaFoldDB; O18754; -.
DR BMRB; O18754; -.
DR SMR; O18754; -.
DR InParanoid; O18754; -.
DR EvolutionaryTrace; O18754; -.
DR Proteomes; UP000011712; Unplaced.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
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 1: Evidence at protein level;
KW 3D-structure; 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..24
FT /evidence="ECO:0000250"
FT CHAIN 25..233
FT /note="Major prion protein"
FT /id="PRO_0000025671"
FT PROPEP 234..256
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000025672"
FT REPEAT 54..62
FT /note="1"
FT REPEAT 63..70
FT /note="2"
FT REPEAT 71..78
FT /note="3"
FT REPEAT 79..86
FT /note="4"
FT REPEAT 87..95
FT /note="5"
FT REGION 25..233
FT /note="Interaction with GRB2, ERI3 and SYN1"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 25..41
FT /note="Interaction with ADGRG6"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 28..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 54..95
FT /note="5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q"
FT BINDING 64
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 65
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 66
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 72
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 73
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 74
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 80
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 81
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 82
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 88
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 90
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 91
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT LIPID 233
FT /note="GPI-anchor amidated alanine"
FT /evidence="ECO:0000255"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 182..217
FT /evidence="ECO:0000250|UniProtKB:P04273"
FT CONFLICT 64
FT /note="H -> HA (in Ref. 2; AAS94127)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="H -> HA (in Ref. 2; AAS94127)"
FT /evidence="ECO:0000305"
FT CONFLICT 80
FT /note="H -> HA (in Ref. 2; AAS94127)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="G -> A (in Ref. 2; AAS94127)"
FT /evidence="ECO:0000305"
FT CONFLICT 98..103
FT /note="SHSQWN -> GTHGQWG (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="M -> V (in Ref. 1 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="N -> D (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="H -> R (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="K -> R (in Ref. 2; AAS94127)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="H -> R (in Ref. 1 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="M -> I (in Ref. 1; AAB70468)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="V -> I (in Ref. 1; AAB70468)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="K -> R (in Ref. 1; AAB70468)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="R -> G (in Ref. 1; AAB70468)"
FT /evidence="ECO:0000305"
FT CONFLICT 235
FT /note="A -> V (in Ref. 1; AAB70468)"
FT /evidence="ECO:0000305"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:1XYJ"
FT HELIX 148..154
FT /evidence="ECO:0007829|PDB:1XYJ"
FT HELIX 155..159
FT /evidence="ECO:0007829|PDB:1XYJ"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:1XYJ"
FT HELIX 180..195
FT /evidence="ECO:0007829|PDB:1XYJ"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:1XYJ"
FT HELIX 203..230
FT /evidence="ECO:0007829|PDB:1XYJ"
SQ SEQUENCE 256 AA; 27968 MW; 09CCE931336C50E2 CRC64;
MVKSHIGSWI LVLFVAMWSD VGLCKKRPKP GGGWNTGGSR YPGQGSPGGN RYPPQGGGGW
GQPHGGGWGQ PHGGGWGQPH GGGWGQPHGG GGWGQGGSHS QWNKPSKPKT NMKHMAGAAA
AGAVVGGLGG YMLGSAMSRP LIHFGNDYED RYYRENMYRY PNQVYYRPVD QYSNQNNFVH
DCVNITVKQH TVTTTTKGEN FTETDMKIME RVVEQMCVTQ YQKESEAYYQ RRASAILFSS
PPVILLISFL IFLIVG
