PRND_HUMAN
ID PRND_HUMAN Reviewed; 176 AA.
AC Q9UKY0; A7U7M5; Q9H311; Q9H312; Q9NTM4;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Prion-like protein doppel;
DE AltName: Full=PrPLP;
DE AltName: Full=Prion protein 2;
DE Flags: Precursor;
GN Name=PRND; Synonyms=DPL; ORFNames=UNQ1830/PRO3443;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-174.
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], AND VARIANT MET-174.
RC TISSUE=Brain cortex, and Testis;
RA Lee I.Y., Wang K., Westaway D., Hood L.E.;
RT "Human mRNA sequence for a novel Prion-like gene, prnd.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RA Chen H.T.;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-174.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-174.
RC TISSUE=Testis;
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 [7]
RP DISULFIDE BONDS, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11063595; DOI=10.1021/bi001523m;
RA Lu K., Wang W., Xie Z., Wong B.-S., Li R., Petersen R.B., Sy M.-S.,
RA Chen S.G.;
RT "Expression and structural characterization of the recombinant human doppel
RT protein.";
RL Biochemistry 39:13575-13583(2000).
RN [8]
RP PROTEIN SEQUENCE OF 26-36, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR
RP LOCATION, TOPOLOGY, TISSUE SPECIFICITY, AND GLYCOSYLATION AT THR-43.
RX PubMed=12200435; DOI=10.1074/jbc.m206357200;
RA Peoc'h K., Serres C., Frobert Y., Martin C., Lehmann S., Chasseigneaux S.,
RA Sazdovitch V., Grassi J., Jouannet P., Launay J.M., Laplanche J.L.;
RT "The human 'prion-like' protein Doppel is expressed in both Sertoli cells
RT and spermatozoa.";
RL J. Biol. Chem. 277:43071-43078(2002).
RN [9]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=15218028; DOI=10.1074/jbc.m404341200;
RA Cereghetti G.M., Negro A., Vinck E., Massimino M.L., Sorgato M.C.,
RA Van Doorslaer S.;
RT "Copper(II) binding to the human Doppel protein may mark its functional
RT diversity from the prion protein.";
RL J. Biol. Chem. 279:36497-36503(2004).
RN [10]
RP FUNCTION, AND DOMAIN.
RX PubMed=20411530; DOI=10.1002/chem.200902405;
RA La Mendola D., Magri A., Campagna T., Campitiello M.A., Raiola L.,
RA Isernia C., Hansson O., Bonomo R.P., Rizzarelli E.;
RT "A doppel alpha-helix peptide fragment mimics the copper(II) interactions
RT with the whole protein.";
RL Chemistry 16:6212-6223(2010).
RN [11]
RP STRUCTURE BY NMR, AND DISULFIDE BOND.
RX PubMed=12595265; DOI=10.1016/s0022-2836(02)01471-7;
RA Luhrs T., Riek R., Guntert P., Wuethrich K.;
RT "NMR structure of the human doppel protein.";
RL J. Mol. Biol. 326:1549-1557(2003).
RN [12]
RP VARIANTS PRO-26; LEU-56 AND MET-174.
RX PubMed=10825657; DOI=10.1016/s0304-3940(00)01100-9;
RA Peoc'h K., Guerin C., Brandel J.-P., Launay J.-M., Laplanche J.-L.;
RT "First report of polymorphisms in the prion-like protein gene (PRND):
RT implications for human prion diseases.";
RL Neurosci. Lett. 286:144-148(2000).
RN [13]
RP VARIANTS ILE-6; PRO-22; ARG-31; LEU-70; SER-149 AND MET-174.
RX PubMed=11702213; DOI=10.1007/s004390100591;
RA Schroeder B., Franz B., Hempfling P., Selbert M., Juergens T.,
RA Kretzschmar H.A., Bodemer M., Poser S., Zerr I.;
RT "Polymorphisms within the prion-like protein gene (Prnd) and their
RT implications in human prion diseases, Alzheimer's disease and other
RT neurological disorders.";
RL Hum. Genet. 109:319-325(2001).
CC -!- FUNCTION: Required for normal acrosome reaction and for normal male
CC fertility (By similarity). Can bind Cu(2+) (PubMed:15218028,
CC PubMed:20411530). {ECO:0000250|UniProtKB:Q9QUG3,
CC ECO:0000269|PubMed:15218028, ECO:0000269|PubMed:20411530}.
CC -!- INTERACTION:
CC Q9UKY0; Q9NSU2-1: TREX1; NbExp=3; IntAct=EBI-17783836, EBI-16746122;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12200435,
CC ECO:0000269|PubMed:15218028}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:12200435}.
CC -!- TISSUE SPECIFICITY: Expressed in testis, in Sertoli cells, ejaculated
CC spermatozoa and in seminal fluid (at protein level).
CC {ECO:0000269|PubMed:12200435}.
CC -!- DOMAIN: A short helical region is required and sufficient for Cu(2+)
CC binding. {ECO:0000269|PubMed:20411530}.
CC -!- PTM: N-glycosylated. N-glycosylated at two distinct sites.
CC {ECO:0000269|PubMed:12200435}.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:12200435}.
CC -!- SIMILARITY: Belongs to the prion family. {ECO:0000305}.
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DR EMBL; AF106918; AAF02424.1; -; Genomic_DNA.
DR EMBL; AF187843; AAG43448.1; -; mRNA.
DR EMBL; AF187844; AAG43449.1; -; mRNA.
DR EMBL; EU009729; ABU40603.1; -; Genomic_DNA.
DR EMBL; AY358985; AAQ89344.1; -; mRNA.
DR EMBL; AL133396; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043644; AAH43644.1; -; mRNA.
DR CCDS; CCDS13081.1; -.
DR RefSeq; NP_036541.2; NM_012409.3.
DR PDB; 1LG4; NMR; -; A=24-152.
DR PDBsum; 1LG4; -.
DR AlphaFoldDB; Q9UKY0; -.
DR BMRB; Q9UKY0; -.
DR SMR; Q9UKY0; -.
DR BioGRID; 117159; 7.
DR IntAct; Q9UKY0; 2.
DR STRING; 9606.ENSP00000306900; -.
DR TCDB; 1.C.48.1.4; the prion peptide (prp) family.
DR GlyGen; Q9UKY0; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UKY0; -.
DR BioMuta; PRND; -.
DR DMDM; 68067934; -.
DR jPOST; Q9UKY0; -.
DR MassIVE; Q9UKY0; -.
DR PaxDb; Q9UKY0; -.
DR PeptideAtlas; Q9UKY0; -.
DR PRIDE; Q9UKY0; -.
DR ProteomicsDB; 84908; -.
DR Antibodypedia; 57305; 79 antibodies from 17 providers.
DR DNASU; 23627; -.
DR Ensembl; ENST00000305817.3; ENSP00000306900.2; ENSG00000171864.5.
DR GeneID; 23627; -.
DR KEGG; hsa:23627; -.
DR MANE-Select; ENST00000305817.3; ENSP00000306900.2; NM_012409.4; NP_036541.2.
DR UCSC; uc002wkz.5; human.
DR CTD; 23627; -.
DR DisGeNET; 23627; -.
DR GeneCards; PRND; -.
DR HGNC; HGNC:15748; PRND.
DR HPA; ENSG00000171864; Group enriched (choroid plexus, testis).
DR MIM; 604263; gene.
DR neXtProt; NX_Q9UKY0; -.
DR OpenTargets; ENSG00000171864; -.
DR PharmGKB; PA33795; -.
DR VEuPathDB; HostDB:ENSG00000171864; -.
DR eggNOG; ENOG502RAT9; Eukaryota.
DR GeneTree; ENSGT00390000017668; -.
DR HOGENOM; CLU_1524583_0_0_1; -.
DR InParanoid; Q9UKY0; -.
DR OMA; DGIHYDG; -.
DR OrthoDB; 1431300at2759; -.
DR PhylomeDB; Q9UKY0; -.
DR TreeFam; TF337532; -.
DR PathwayCommons; Q9UKY0; -.
DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR SignaLink; Q9UKY0; -.
DR BioGRID-ORCS; 23627; 10 hits in 1058 CRISPR screens.
DR EvolutionaryTrace; Q9UKY0; -.
DR GeneWiki; PRND; -.
DR GenomeRNAi; 23627; -.
DR Pharos; Q9UKY0; Tbio.
DR PRO; PR:Q9UKY0; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9UKY0; protein.
DR Bgee; ENSG00000171864; Expressed in right testis and 83 other tissues.
DR Genevisible; Q9UKY0; HS.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB.
DR GO; GO:0007340; P:acrosome reaction; ISS:UniProtKB.
DR GO; GO:0006878; P:cellular copper ion homeostasis; IBA:GO_Central.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR DisProt; DP02823; -.
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; Direct protein sequencing;
KW Disulfide bond; Fertilization; Glycoprotein; GPI-anchor; Lipoprotein;
KW Membrane; Metal-binding; Prion; Reference proteome; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:12200435"
FT CHAIN 26..152
FT /note="Prion-like protein doppel"
FT /id="PRO_0000025745"
FT PROPEP 153..176
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025746"
FT REGION 27..50
FT /note="Flexible tail"
FT REGION 51..152
FT /note="Globular"
FT REGION 122..139
FT /note="Cu(2+) binding"
FT /evidence="ECO:0000269|PubMed:20411530"
FT LIPID 152
FT /note="GPI-anchor amidated glycine"
FT /evidence="ECO:0000255"
FT CARBOHYD 43
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:12200435"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:12200435"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:12200435"
FT DISULFID 94..145
FT /evidence="ECO:0000269|PubMed:11063595,
FT ECO:0000269|PubMed:12595265, ECO:0007744|PDB:1LG4"
FT DISULFID 108..140
FT /evidence="ECO:0000269|PubMed:11063595,
FT ECO:0000269|PubMed:12595265, ECO:0007744|PDB:1LG4"
FT VARIANT 6
FT /note="S -> I"
FT /evidence="ECO:0000269|PubMed:11702213"
FT /id="VAR_013769"
FT VARIANT 22
FT /note="S -> P"
FT /evidence="ECO:0000269|PubMed:11702213"
FT /id="VAR_013770"
FT VARIANT 26
FT /note="T -> P"
FT /evidence="ECO:0000269|PubMed:10825657"
FT /id="VAR_013765"
FT VARIANT 31
FT /note="H -> R"
FT /evidence="ECO:0000269|PubMed:11702213"
FT /id="VAR_013771"
FT VARIANT 56
FT /note="P -> L (in dbSNP:rs35453518)"
FT /evidence="ECO:0000269|PubMed:10825657"
FT /id="VAR_013766"
FT VARIANT 70
FT /note="F -> L"
FT /evidence="ECO:0000269|PubMed:11702213"
FT /id="VAR_013772"
FT VARIANT 149
FT /note="L -> S"
FT /evidence="ECO:0000269|PubMed:11702213"
FT /id="VAR_013773"
FT VARIANT 174
FT /note="T -> M (in dbSNP:rs2245220)"
FT /evidence="ECO:0000269|PubMed:10525406,
FT ECO:0000269|PubMed:10825657, ECO:0000269|PubMed:11702213,
FT ECO:0000269|PubMed:12975309, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.2"
FT /id="VAR_013767"
FT CONFLICT 143
FT /note="K -> E (in Ref. 2; AAG43448/AAG43449)"
FT /evidence="ECO:0000305"
FT HELIX 72..81
FT /evidence="ECO:0007829|PDB:1LG4"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:1LG4"
FT HELIX 101..115
FT /evidence="ECO:0007829|PDB:1LG4"
FT TURN 117..121
FT /evidence="ECO:0007829|PDB:1LG4"
FT HELIX 126..141
FT /evidence="ECO:0007829|PDB:1LG4"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:1LG4"
SQ SEQUENCE 176 AA; 20293 MW; A0F41EB0DFEED236 CRC64;
MRKHLSWWWL ATVCMLLFSH LSAVQTRGIK HRIKWNRKAL PSTAQITEAQ VAENRPGAFI
KQGRKLDIDF GAEGNRYYEA NYWQFPDGIH YNGCSEANVT KEAFVTGCIN ATQAANQGEF
QKPDNKLHQQ VLWRLVQELC SLKHCEFWLE RGAGLRVTMH QPVLLCLLAL IWLTVK
