JUNO_MOUSE
ID JUNO_MOUSE Reviewed; 244 AA.
AC Q9EQF4; B0FFS5;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Sperm-egg fusion protein Juno {ECO:0000305};
DE AltName: Full=Folate receptor 4;
DE AltName: Full=Folate receptor delta {ECO:0000303|PubMed:11111049};
DE Short=FR-delta {ECO:0000303|PubMed:11111049};
DE AltName: Full=Folate-binding protein 3 {ECO:0000303|PubMed:11111049};
DE AltName: Full=IZUMO1 receptor protein JUNO {ECO:0000303|PubMed:24739963, ECO:0000303|PubMed:27416963};
DE Flags: Precursor;
GN Name=Izumo1r {ECO:0000250|UniProtKB:A6ND01};
GN Synonyms=Folbp3 {ECO:0000303|PubMed:11111049}, Folr4,
GN Juno {ECO:0000303|PubMed:24739963, ECO:0000303|PubMed:27416963};
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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=11111049; DOI=10.1016/s0378-1119(00)00418-2;
RA Spiegelstein O., Eudy J.D., Finnell R.H.;
RT "Identification of two putative novel folate receptor genes in humans and
RT mouse.";
RL Gene 258:117-125(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=BALB/cJ, and C57BL/6J; TISSUE=Spleen;
RA Ni B., Jia Z.-C., Tian Y., Zhao R.;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Thymus;
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 FUNCTION, SUBCELLULAR LOCATION, GPI-ANCHOR, DISRUPTION PHENOTYPE,
RP PROTEOLYTIC PROCESSING, AND INTERACTION WITH IZUMO1.
RX PubMed=24739963; DOI=10.1038/nature13203;
RA Bianchi E., Doe B., Goulding D., Wright G.J.;
RT "Juno is the egg Izumo receptor and is essential for mammalian
RT fertilization.";
RL Nature 508:483-487(2014).
RN [5]
RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH IZUMO1.
RX PubMed=27309808; DOI=10.1038/nature18596;
RA Ohto U., Ishida H., Krayukhina E., Uchiyama S., Inoue N., Shimizu T.;
RT "Structure of IZUMO1-JUNO reveals sperm-oocyte recognition during mammalian
RT fertilization.";
RL Nature 534:566-569(2016).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 19-221, FUNCTION, SUBUNIT,
RP TOPOLOGY, DISULFIDE BONDS, GLYCOSYLATION AT ASN-73 AND ASN-185, AND
RP MUTAGENESIS OF ASN-73 AND ASN-185.
RX PubMed=26859261; DOI=10.1016/j.cub.2015.12.034;
RA Han L., Nishimura K., Sadat Al Hosseini H., Bianchi E., Wright G.J.,
RA Jovine L.;
RT "Divergent evolution of vitamin B9 binding underlies Juno-mediated adhesion
RT of mammalian gametes.";
RL Curr. Biol. 26:R100-R101(2016).
RN [7]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH IZUMO1.
RX PubMed=25209248; DOI=10.1242/dev.111534;
RA Chalbi M., Barraud-Lange V., Ravaux B., Howan K., Rodriguez N., Soule P.,
RA Ndzoudi A., Boucheix C., Rubinstein E., Wolf J.P., Ziyyat A., Perez E.,
RA Pincet F., Gourier C.;
RT "Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9
RT accumulation in the intercellular contact area prior to fusion during
RT mammalian fertilization.";
RL Development 141:3732-3739(2014).
RN [8]
RP INTERACTION WITH IZUMO1.
RX PubMed=32484434; DOI=10.7554/elife.53913;
RA Lamas-Toranzo I., Hamze J.G., Bianchi E., Fernandez-Fuertes B.,
RA Perez-Cerezales S., Laguna-Barraza R., Fernandez-Gonzalez R., Lonergan P.,
RA Gutierrez-Adan A., Wright G.J., Jimenez-Movilla M., Bermejo-Alvarez P.;
RT "TMEM95 is a sperm membrane protein essential for mammalian
RT fertilization.";
RL Elife 9:0-0(2020).
RN [9] {ECO:0007744|PDB:5JYJ}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 20-221 OF ASN-73 MUTANT,
RP FUNCTION, INTERACTION WITH IZUMO1, DISULFIDE BONDS, GLYCOSYLATION AT
RP ASN-185, AND MUTAGENESIS OF TRP-62; LEU-66; ASN-73; HIS-97; TRP-184 AND
RP ASN-185.
RX PubMed=27416963; DOI=10.1038/ncomms12198;
RA Kato K., Satouh Y., Nishimasu H., Kurabayashi A., Morita J., Fujihara Y.,
RA Oji A., Ishitani R., Ikawa M., Nureki O.;
RT "Structural and functional insights into IZUMO1 recognition by JUNO in
RT mammalian fertilization.";
RL Nat. Commun. 7:12198-12198(2016).
CC -!- FUNCTION: Receptor for IZUMO1 present at the cell surface of oocytes
CC (oolemma), which is essential for species-specific gamete recognition
CC and fertilization (PubMed:24739963, PubMed:26859261, PubMed:27309808,
CC PubMed:27416963). The IZUMO1:IZUMO1R/JUNO interaction is a necessary
CC adhesion event between sperm and egg that is required for fertilization
CC but is not sufficient for cell fusion (PubMed:24739963,
CC PubMed:26859261, PubMed:27309808). The ligand-receptor interaction
CC probably does not act as a membrane 'fusogen' (PubMed:24739963,
CC PubMed:26859261, PubMed:27309808). Does not bind folate
CC (PubMed:24739963). {ECO:0000269|PubMed:24739963,
CC ECO:0000269|PubMed:26859261, ECO:0000269|PubMed:27309808,
CC ECO:0000269|PubMed:27416963}.
CC -!- SUBUNIT: Monomer (PubMed:26859261). Interacts with IZUMO1; the
CC interaction is direct (PubMed:24739963, PubMed:26859261,
CC PubMed:27309808, PubMed:25209248, PubMed:27416963, PubMed:32484434).
CC IZUMO1 and IZUMO1R/JUNO form a complex with 1:1 stoichiometry (By
CC similarity). {ECO:0000250|UniProtKB:A6ND01,
CC ECO:0000269|PubMed:24739963, ECO:0000269|PubMed:25209248,
CC ECO:0000269|PubMed:26859261, ECO:0000269|PubMed:27309808,
CC ECO:0000269|PubMed:27416963}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24739963,
CC ECO:0000269|PubMed:25209248, ECO:0000269|PubMed:27309808}; Lipid-
CC anchor, GPI-anchor {ECO:0000269|PubMed:24739963}. Note=GPI-anchored at
CC the oolemma. {ECO:0000269|PubMed:24739963}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9EQF4-1; Sequence=Displayed;
CC Name=2; Synonyms=FR4v3;
CC IsoId=Q9EQF4-2; Sequence=VSP_033414;
CC -!- TISSUE SPECIFICITY: Widely expressed with higher expression in thymus,
CC spleen and lung (PubMed:11111049). Present at the cell surface of
CC unfertilized oocytes, while it is barely detectable 30 to 40 minutes
CC after fertilization (at protein level) (PubMed:24739963).
CC {ECO:0000269|PubMed:11111049, ECO:0000269|PubMed:24739963}.
CC -!- PTM: The protein is rapidly cleaved following fertilization, being only
CC weakly detectable in zona-intact fertilized eggs at telophase II and
CC undetectable at the pronuclear stage (PubMed:24739963). Sheding is
CC probably required to block to polyspermy and ensuring egg fusion with a
CC single sperm (PubMed:24739963). {ECO:0000269|PubMed:24739963}.
CC -!- DISRUPTION PHENOTYPE: Female mice are infertile and eggs do not fuse
CC with normal sperm (PubMed:24739963). Both male and female mice develop
CC normally and are overtly healthy (PubMed:24739963). Male mice are
CC fertile (PubMed:24739963). Despite infertility, female mice display
CC natural mating behaviors, as assessed by vaginal plug formation and the
CC presence of motile sperm in the reproductive tract when paired with
CC fertile males (PubMed:24739963). They respond to hormone treatment by
CC ovulating morphologically normal eggs at numbers that do not
CC significantly differ from wild-type (PubMed:24739963). However, eggs
CC are not fertilized and have more sperm within their perivitelline space
CC compared to wild-type eggs, demonstrating that the zona pellucida of
CC eggs cannot be penetrated by sperm in vivo (PubMed:24739963).
CC {ECO:0000269|PubMed:24739963}.
CC -!- MISCELLANEOUS: Was named 'Juno' after the Roman goddess of fertility
CC and marriage. {ECO:0000305|PubMed:24739963}.
CC -!- SIMILARITY: Belongs to the folate receptor family. {ECO:0000305}.
CC -!- CAUTION: In contrast to FOLR1 and FOLR2, unable to bind folate.
CC {ECO:0000269|PubMed:26859261, ECO:0000305|PubMed:24739963}.
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DR EMBL; AF250145; AAG36877.1; -; mRNA.
DR EMBL; EU326437; ABY56297.1; -; mRNA.
DR EMBL; EU326438; ABY56298.1; -; mRNA.
DR EMBL; BC028431; AAH28431.1; -; mRNA.
DR CCDS; CCDS22831.1; -. [Q9EQF4-1]
DR RefSeq; NP_075026.1; NM_022888.2. [Q9EQF4-1]
DR RefSeq; XP_006510593.1; XM_006510530.2. [Q9EQF4-2]
DR RefSeq; XP_006510594.1; XM_006510531.3. [Q9EQF4-2]
DR PDB; 5EJN; X-ray; 2.70 A; A/B=19-221.
DR PDB; 5JYJ; X-ray; 2.30 A; A=20-221.
DR PDBsum; 5EJN; -.
DR PDBsum; 5JYJ; -.
DR AlphaFoldDB; Q9EQF4; -.
DR SMR; Q9EQF4; -.
DR STRING; 10090.ENSMUSP00000034409; -.
DR GlyGen; Q9EQF4; 2 sites.
DR iPTMnet; Q9EQF4; -.
DR EPD; Q9EQF4; -.
DR PaxDb; Q9EQF4; -.
DR PRIDE; Q9EQF4; -.
DR Antibodypedia; 45349; 281 antibodies from 19 providers.
DR DNASU; 64931; -.
DR Ensembl; ENSMUST00000034409; ENSMUSP00000034409; ENSMUSG00000031933. [Q9EQF4-1]
DR GeneID; 64931; -.
DR KEGG; mmu:64931; -.
DR UCSC; uc009ofh.2; mouse. [Q9EQF4-1]
DR UCSC; uc012gom.1; mouse. [Q9EQF4-2]
DR CTD; 390243; -.
DR MGI; MGI:1929185; Izumo1r.
DR VEuPathDB; HostDB:ENSMUSG00000031933; -.
DR eggNOG; ENOG502RYYP; Eukaryota.
DR GeneTree; ENSGT00950000183144; -.
DR InParanoid; Q9EQF4; -.
DR OMA; NAPLCQE; -.
DR OrthoDB; 1224404at2759; -.
DR PhylomeDB; Q9EQF4; -.
DR TreeFam; TF328532; -.
DR Reactome; R-MMU-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR BioGRID-ORCS; 64931; 2 hits in 70 CRISPR screens.
DR ChiTaRS; Izumo1r; mouse.
DR PRO; PR:Q9EQF4; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9EQF4; protein.
DR Bgee; ENSMUSG00000031933; Expressed in animal zygote and 30 other tissues.
DR ExpressionAtlas; Q9EQF4; baseline and differential.
DR Genevisible; Q9EQF4; MM.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; TAS:MGI.
DR GO; GO:0038023; F:signaling receptor activity; IPI:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IDA:UniProtKB.
DR GO; GO:0007342; P:fusion of sperm to egg plasma membrane involved in single fertilization; IDA:UniProtKB.
DR GO; GO:0007338; P:single fertilization; IDA:UniProtKB.
DR GO; GO:0035036; P:sperm-egg recognition; IDA:UniProtKB.
DR InterPro; IPR004269; Folate_rcpt.
DR InterPro; IPR018143; Folate_rcpt-like.
DR PANTHER; PTHR10517; PTHR10517; 1.
DR Pfam; PF03024; Folate_rec; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW Fertilization; Glycoprotein; GPI-anchor; Lipoprotein; Membrane; Receptor;
KW Reference proteome; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..222
FT /note="Sperm-egg fusion protein Juno"
FT /id="PRO_0000332988"
FT PROPEP 223..244
FT /evidence="ECO:0000255"
FT /id="PRO_0000429473"
FT REGION 62..81
FT /note="Important for interaction with IZUMO1"
FT /evidence="ECO:0000250|UniProtKB:A6ND01"
FT LIPID 222
FT /note="GPI-anchor amidated glycine"
FT /evidence="ECO:0000255"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:26859261"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26859261,
FT ECO:0000269|PubMed:27416963, ECO:0007744|PDB:5EJN,
FT ECO:0007744|PDB:5JYJ"
FT DISULFID 27..55
FT /evidence="ECO:0000269|PubMed:26859261,
FT ECO:0000269|PubMed:27416963, ECO:0007744|PDB:5EJN,
FT ECO:0007744|PDB:5JYJ"
FT DISULFID 47..95
FT /evidence="ECO:0000269|PubMed:26859261,
FT ECO:0000269|PubMed:27416963, ECO:0007744|PDB:5EJN,
FT ECO:0007744|PDB:5JYJ"
FT DISULFID 56..99
FT /evidence="ECO:0000269|PubMed:26859261,
FT ECO:0000269|PubMed:27416963, ECO:0007744|PDB:5EJN,
FT ECO:0007744|PDB:5JYJ"
FT DISULFID 79..166
FT /evidence="ECO:0000269|PubMed:26859261,
FT ECO:0000269|PubMed:27416963, ECO:0007744|PDB:5EJN,
FT ECO:0007744|PDB:5JYJ"
FT DISULFID 86..137
FT /evidence="ECO:0000269|PubMed:26859261,
FT ECO:0000269|PubMed:27416963, ECO:0007744|PDB:5EJN,
FT ECO:0007744|PDB:5JYJ"
FT DISULFID 126..200
FT /evidence="ECO:0000269|PubMed:26859261,
FT ECO:0000269|PubMed:27416963, ECO:0007744|PDB:5EJN,
FT ECO:0007744|PDB:5JYJ"
FT DISULFID 130..180
FT /evidence="ECO:0000269|PubMed:26859261,
FT ECO:0000269|PubMed:27416963, ECO:0007744|PDB:5EJN,
FT ECO:0007744|PDB:5JYJ"
FT DISULFID 143..160
FT /evidence="ECO:0000269|PubMed:27416963,
FT ECO:0007744|PDB:5JYJ"
FT VAR_SEQ 155
FT /note="E -> EGEWINYALVALRLGEAARGSEGKGQWKVRSPFSIPT (in
FT isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_033414"
FT MUTAGEN 62
FT /note="W->A: Impaired ability to promote sperm-egg
FT interaction due to reduced interaction with IZUMO1."
FT /evidence="ECO:0000269|PubMed:27416963"
FT MUTAGEN 66
FT /note="L->A: Does not affect ability to promote sperm-egg
FT interaction."
FT /evidence="ECO:0000269|PubMed:27416963"
FT MUTAGEN 73
FT /note="N->D: Does not affect ability to promote sperm-egg
FT interaction."
FT /evidence="ECO:0000269|PubMed:27416963"
FT MUTAGEN 73
FT /note="N->Q: Reduces apparent molecular weight of the
FT protein, in agreement with the loss of one glycosylation
FT site. Abolishes secretion of the extracellular domain; when
FT associated with G-185."
FT /evidence="ECO:0000269|PubMed:26859261"
FT MUTAGEN 97
FT /note="H->A: Does not affect ability to promote sperm-egg
FT interaction."
FT /evidence="ECO:0000269|PubMed:27416963"
FT MUTAGEN 184
FT /note="W->A: Does not affect ability to promote sperm-egg
FT interaction."
FT /evidence="ECO:0000269|PubMed:27416963"
FT MUTAGEN 185
FT /note="N->D: Reduced stability of the protein."
FT /evidence="ECO:0000269|PubMed:27416963"
FT MUTAGEN 185
FT /note="N->G: Reduces apparent molecular weight of the
FT protein, in agreement with the loss of one glycosylation
FT site. Abolishes secretion of the extracellular domain; when
FT associated with Q-73."
FT /evidence="ECO:0000269|PubMed:26859261"
FT MUTAGEN 185
FT /note="N->S: No effect on interaction with IZUMO1."
FT /evidence="ECO:0000269|PubMed:26859261"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:5JYJ"
FT HELIX 45..50
FT /evidence="ECO:0007829|PDB:5JYJ"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:5JYJ"
FT HELIX 58..63
FT /evidence="ECO:0007829|PDB:5JYJ"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:5JYJ"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:5JYJ"
FT HELIX 84..99
FT /evidence="ECO:0007829|PDB:5JYJ"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:5EJN"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:5JYJ"
FT STRAND 107..113
FT /evidence="ECO:0007829|PDB:5JYJ"
FT STRAND 115..120
FT /evidence="ECO:0007829|PDB:5JYJ"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:5JYJ"
FT HELIX 127..136
FT /evidence="ECO:0007829|PDB:5JYJ"
FT TURN 137..139
FT /evidence="ECO:0007829|PDB:5JYJ"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:5JYJ"
FT HELIX 169..172
FT /evidence="ECO:0007829|PDB:5JYJ"
FT HELIX 176..182
FT /evidence="ECO:0007829|PDB:5JYJ"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:5JYJ"
FT STRAND 186..190
FT /evidence="ECO:0007829|PDB:5JYJ"
FT STRAND 197..201
FT /evidence="ECO:0007829|PDB:5JYJ"
FT HELIX 214..221
FT /evidence="ECO:0007829|PDB:5JYJ"
SQ SEQUENCE 244 AA; 28203 MW; 2940393EF68A52B7 CRC64;
MAQWWQILLG LWAVLPTLAG DKLLSVCMNS KRHKQEPGPE DELYQECRPW EDNACCTRST
SWEAHLEEPL LFNFSMMHCG LLTPACRKHF IQAICFHECS PNLGPWIQPV VPNGQEEQRV
WGVPLCQEDC EDWWRACHSS LTCKSNWLHG WDWSEEKKHC PAHEPCLPFS YHFPTPDDLC
EKIWNNTFKA SPERRNSGRC LQKWFEPTLS NPNVEVALHF AGSALAPQLS YTLPAFSLCL
LFHP
