PRND_MOUSE
ID PRND_MOUSE Reviewed; 179 AA.
AC Q9QUG3; Q9QZT5;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Prion-like protein doppel;
DE AltName: Full=Doppelganger;
DE Short=Dpl {ECO:0000303|PubMed:12110578};
DE AltName: Full=PrPLP;
DE Flags: Precursor;
GN Name=Prnd;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], DEVELOPMENTAL STAGE, AND TISSUE
RP SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=10525406; DOI=10.1006/jmbi.1999.3108;
RA Moore R.C., Lee I.Y., Silverman G.L., Harrison P.M., Strome R.,
RA Heinrich C., Karunaratne A., Pasternak S.H., Chishti M.A., Liang Y.,
RA Mastrangelo P., Wang K., Smit A.F.A., Katamine S., Carlson G.A.,
RA Cohen F.E., Prusiner S.B., Melton D.W., Tremblay P., Hood L.E.,
RA Westaway D.;
RT "Ataxia in prion protein (PrP)-deficient mice is associated with
RT upregulation of the novel PrP-like protein doppel.";
RL J. Mol. Biol. 292:797-817(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/Sv, and C57BL/6J;
RX PubMed=10930132; DOI=10.1023/a:1007059827541;
RA Li A., Sakaguchi S., Atarashi R., Roy B.C., Nakaoke R., Arima K.,
RA Okimura N., Kopacek J., Shigematu K.;
RT "Identification of a novel gene encoding a PrP-like protein expressed as
RT chimeric transcripts fused to PrP exon1/2 in ataxic mouse line with a
RT disrupted PrP gene.";
RL Cell. Mol. Neurobiol. 20:553-567(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DISULFIDE BOND, GPI-ANCHOR AT GLY-155, GLYCOSYLATION, SUBCELLULAR LOCATION,
RP TOPOLOGY, AND TISSUE SPECIFICITY.
RX PubMed=10842180; DOI=10.1074/jbc.m003888200;
RA Silverman G.L., Qin K., Moore R.C., Yang Y., Mastrangelo P., Tremblay P.,
RA Prusiner S.B., Cohen F.E., Westaway D.;
RT "Doppel is an N-glycosylated, glycosylphosphatidylinositol-anchored
RT protein: expression in testis and ectopic production in the brains of
RT Prnp(0/0) mice predisposed to Purkinje cell loss.";
RL J. Biol. Chem. 275:26834-26841(2000).
RN [5]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12110578; DOI=10.1093/emboj/cdf386;
RA Behrens A., Genoud N., Naumann H., Ruelicke T., Janett F., Heppner F.L.,
RA Ledermann B., Aguzzi A.;
RT "Absence of the prion protein homologue Doppel causes male sterility.";
RL EMBO J. 21:3652-3658(2002).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15161660; DOI=10.1016/s0002-9440(10)63784-4;
RA Paisley D., Banks S., Selfridge J., McLennan N.F., Ritchie A.M., McEwan C.,
RA Irvine D.S., Saunders P.T., Manson J.C., Melton D.W.;
RT "Male infertility and DNA damage in Doppel knockout and prion
RT protein/Doppel double-knockout mice.";
RL Am. J. Pathol. 164:2279-2288(2004).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=15007175; DOI=10.1073/pnas.0400131101;
RA Genoud N., Behrens A., Miele G., Robay D., Heppner F.L., Freigang S.,
RA Aguzzi A.;
RT "Disruption of Doppel prevents neurodegeneration in mice with extensive
RT Prnp deletions.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4198-4203(2004).
RN [8]
RP STRUCTURE BY NMR OF 51-157, AND DISULFIDE BONDS.
RX PubMed=11226243; DOI=10.1073/pnas.051627998;
RA Mo H., Moore R.C., Cohen F.E., Westaway D., Prusiner S.B., Wright P.E.,
RA Dyson H.J.;
RT "Two different neurodegenerative diseases caused by proteins with similar
RT structures.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2352-2357(2001).
RN [9] {ECO:0007744|PDB:1Z65}
RP STRUCTURE BY NMR OF 1-30.
RX PubMed=16388591; DOI=10.1021/bi051313f;
RA Papadopoulos E., Oglecka K., Maler L., Jarvet J., Wright P.E., Dyson H.J.,
RA Graslund A.;
RT "NMR solution structure of the peptide fragment 1-30, derived from
RT unprocessed mouse Doppel protein, in DHPC micelles.";
RL Biochemistry 45:159-166(2006).
CC -!- FUNCTION: Required for normal acrosome reaction and for normal male
CC fertility (PubMed:12110578, PubMed:15161660, PubMed:15007175). Can bind
CC Cu(2+) (By similarity). {ECO:0000250|UniProtKB:Q9UKY0,
CC ECO:0000269|PubMed:12110578, ECO:0000269|PubMed:15007175,
CC ECO:0000269|PubMed:15161660}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10842180};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:10842180}.
CC -!- TISSUE SPECIFICITY: Detected in testis (PubMed:10842180,
CC PubMed:12110578, PubMed:15161660). Detected within seminiferous
CC tubules, on round and elongated spermatids (at protein level)
CC (PubMed:12110578). Not detected in brain (at protein level)
CC (PubMed:10842180, PubMed:15161660). Detected in testis, and at low
CC levels in heart (PubMed:10525406, PubMed:12110578). Expression in brain
CC is very low and barely detectable (PubMed:10525406).
CC {ECO:0000269|PubMed:10525406, ECO:0000269|PubMed:10842180,
CC ECO:0000269|PubMed:12110578, ECO:0000269|PubMed:15161660}.
CC -!- DEVELOPMENTAL STAGE: Expressed during embryogenesis.
CC {ECO:0000269|PubMed:10525406}.
CC -!- DOMAIN: A short helical region is required and sufficient for Cu(2+)
CC binding. {ECO:0000250|UniProtKB:Q9UKY0}.
CC -!- PTM: N-glycosylated (PubMed:10525406, PubMed:10842180). N-glycosylated
CC at two distinct sites (PubMed:10842180). {ECO:0000269|PubMed:10525406,
CC ECO:0000269|PubMed:10842180}.
CC -!- PTM: O-glycosylated. {ECO:0000250|UniProtKB:Q9UKY0}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate and
CC appear grossly normal and healthy. Females are fertile, but males are
CC almost completely sterile, in spite of normal mating behavior
CC (PubMed:12110578, PubMed:15161660). Two independent studies conclude
CC that male sterility is due to impaired acrosome reaction, but describe
CC contradictory effects on spermatogenesis, possibly due to the use of
CC different mouse strains (PubMed:12110578, PubMed:15161660).
CC Spermatogenesis is normal, with normal sperm counts, normal sperm
CC motility, and no malformation of the sperm head or tail
CC (PubMed:15161660). Late stages of spermiogenesis are impaired, leading
CC to reduced numbers of mature spermatozoa in seminiferous tubules;
CC mutant sperm present morphological abnormalities of the flagellum and
CC sperm head, and decreased motility (PubMed:12110578). Mutant sperm are
CC able to fertilize oocytes in vitro, but many of the resulting embryos
CC die before the morula stage (PubMed:15161660). Mutant sperm cells have
CC elevated levels of DNA damage and DNA strand breaks, and this may be
CC the cause for embryonic lethality (PubMed:15161660). Mice deficient for
CC both Prnd and Prnp have the same phenotype as mice lacking Prnd; they
CC are born at the expected Mendelian rate and appear grossly normal and
CC healthy (PubMed:15161660, PubMed:15007175). Females are fertile, but
CC males deficient for both Prnd and Prnp are sterile, in spite of normal
CC mating behavior (PubMed:15161660, PubMed:15007175). Again, findings
CC about spermatogenesis are contradictory: spermatogenesis is normal,
CC with normal sperm counts, normal sperm motility, and no malformation of
CC the sperm head or tail (PubMed:15161660). Sperm cells display various
CC malformations (PubMed:15007175). Male sterility is due to impaired
CC acrosome reaction (PubMed:15161660). Mutant sperm are able to fertilize
CC oocytes in vitro, but many of the resulting embryos die before the
CC morula stage (PubMed:15161660). Mutant sperm cells have elevated levels
CC of DNA damage and DNA strand breaks, and this may be the cause for
CC embryonic lethality (PubMed:15161660). Aging mice deficient for both
CC Prnd and Prnp do not display loss of cerebellar Purkinje cells or
CC develop ataxia, and do not develop neurological defects
CC (PubMed:15007175). {ECO:0000269|PubMed:12110578,
CC ECO:0000269|PubMed:15007175, ECO:0000269|PubMed:15161660}.
CC -!- MISCELLANEOUS: Loss of cerebellar Purkinje cells and ataxia has been
CC observed in mice with mutations that cause Prnd overexpression in the
CC brain, suggesting that aberrant overexpression of Prnd causes
CC neurotoxicity. {ECO:0000269|PubMed:10525406,
CC ECO:0000269|PubMed:15007175}.
CC -!- SIMILARITY: Belongs to the prion family. {ECO:0000305}.
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DR EMBL; U29187; AAD52000.1; -; Genomic_DNA.
DR EMBL; AF165165; AAF02544.1; -; mRNA.
DR EMBL; AF165166; AAF02545.1; -; mRNA.
DR EMBL; AF192382; AAF09196.1; -; mRNA.
DR EMBL; AF192383; AAF09197.1; -; mRNA.
DR EMBL; AF192384; AAF09198.1; -; mRNA.
DR EMBL; AF192385; AAF09199.1; -; mRNA.
DR EMBL; BC025140; AAH25140.1; -; mRNA.
DR CCDS; CCDS16767.1; -.
DR RefSeq; NP_001119810.1; NM_001126338.2.
DR RefSeq; NP_001265186.1; NM_001278257.1.
DR RefSeq; NP_001265449.1; NM_001278520.1.
DR RefSeq; NP_075530.1; NM_023043.3.
DR PDB; 1I17; NMR; -; A=51-157.
DR PDB; 1Z65; NMR; -; A=1-30.
DR PDBsum; 1I17; -.
DR PDBsum; 1Z65; -.
DR AlphaFoldDB; Q9QUG3; -.
DR BMRB; Q9QUG3; -.
DR SMR; Q9QUG3; -.
DR BioGRID; 204986; 1.
DR IntAct; Q9QUG3; 1.
DR STRING; 10090.ENSMUSP00000105801; -.
DR GlyGen; Q9QUG3; 2 sites.
DR iPTMnet; Q9QUG3; -.
DR PaxDb; Q9QUG3; -.
DR PRIDE; Q9QUG3; -.
DR DNASU; 26434; -.
DR Ensembl; ENSMUST00000110169; ENSMUSP00000105798; ENSMUSG00000027338.
DR Ensembl; ENSMUST00000110170; ENSMUSP00000105799; ENSMUSG00000027338.
DR Ensembl; ENSMUST00000110171; ENSMUSP00000105800; ENSMUSG00000027338.
DR Ensembl; ENSMUST00000110172; ENSMUSP00000105801; ENSMUSG00000027338.
DR GeneID; 26434; -.
DR KEGG; mmu:26434; -.
DR UCSC; uc008mmd.3; mouse.
DR CTD; 23627; -.
DR MGI; MGI:1346999; Prnd.
DR VEuPathDB; HostDB:ENSMUSG00000027338; -.
DR eggNOG; ENOG502RAT9; Eukaryota.
DR GeneTree; ENSGT00390000017668; -.
DR HOGENOM; CLU_1524583_0_0_1; -.
DR InParanoid; Q9QUG3; -.
DR OrthoDB; 1431300at2759; -.
DR PhylomeDB; Q9QUG3; -.
DR TreeFam; TF337532; -.
DR Reactome; R-MMU-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR BioGRID-ORCS; 26434; 0 hits in 38 CRISPR screens.
DR EvolutionaryTrace; Q9QUG3; -.
DR PRO; PR:Q9QUG3; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9QUG3; protein.
DR Bgee; ENSMUSG00000027338; Expressed in mesenchyme of tongue and 49 other tissues.
DR ExpressionAtlas; Q9QUG3; baseline.
DR Genevisible; Q9QUG3; MM.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; IDA:MGI.
DR GO; GO:0007340; P:acrosome reaction; IMP:UniProtKB.
DR GO; GO:0006878; P:cellular copper ion homeostasis; IDA:MGI.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0007338; P:single fertilization; IMP:UniProtKB.
DR Gene3D; 1.10.790.10; -; 1.
DR InterPro; IPR021566; Doppel.
DR InterPro; IPR036924; Prion/Doppel_b-ribbon_dom_sf.
DR InterPro; IPR022416; Prion/Doppel_prot_b-ribbon_dom.
DR Pfam; PF11466; Doppel; 1.
DR Pfam; PF00377; Prion; 1.
DR SUPFAM; SSF54098; SSF54098; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amyloid; Cell membrane; Copper; Disulfide bond;
KW Fertilization; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW Metal-binding; Prion; Reference proteome; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000250|UniProtKB:Q9UKY0"
FT CHAIN 26..155
FT /note="Prion-like protein doppel"
FT /id="PRO_0000025747"
FT PROPEP 156..179
FT /note="Removed in mature form"
FT /evidence="ECO:0000305|PubMed:10842180"
FT /id="PRO_0000025748"
FT REGION 27..50
FT /note="Flexible tail"
FT REGION 51..155
FT /note="Globular"
FT REGION 125..142
FT /note="Cu(2+) binding"
FT /evidence="ECO:0000250|UniProtKB:Q9UKY0"
FT LIPID 155
FT /note="GPI-anchor amidated glycine"
FT /evidence="ECO:0000305|PubMed:10842180"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:10842180"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:10842180"
FT DISULFID 95..148
FT /evidence="ECO:0000269|PubMed:10842180,
FT ECO:0000269|PubMed:11226243, ECO:0007744|PDB:1I17"
FT DISULFID 109..143
FT /evidence="ECO:0000269|PubMed:10842180,
FT ECO:0000269|PubMed:11226243, ECO:0007744|PDB:1I17"
FT CONFLICT 156
FT /note="A -> P (in Ref. 1; AAF02545)"
FT /evidence="ECO:0000305"
FT HELIX 8..20
FT /evidence="ECO:0007829|PDB:1Z65"
FT TURN 21..24
FT /evidence="ECO:0007829|PDB:1Z65"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:1I17"
FT HELIX 73..82
FT /evidence="ECO:0007829|PDB:1I17"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:1I17"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:1I17"
FT HELIX 102..116
FT /evidence="ECO:0007829|PDB:1I17"
FT HELIX 118..125
FT /evidence="ECO:0007829|PDB:1I17"
FT HELIX 129..145
FT /evidence="ECO:0007829|PDB:1I17"
SQ SEQUENCE 179 AA; 20442 MW; FC8B788259EE40F2 CRC64;
MKNRLGTWWV AILCMLLASH LSTVKARGIK HRFKWNRKVL PSSGGQITEA RVAENRPGAF
IKQGRKLDID FGAEGNRYYA ANYWQFPDGI YYEGCSEANV TKEMLVTSCV NATQAANQAE
FSREKQDSKL HQRVLWRLIK EICSAKHCDF WLERGAALRV AVDQPAMVCL LGFVWFIVK
