ID JUNO_HUMAN Reviewed; 250 AA. AC A6ND01; DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 3. DT 24-JAN-2024, entry version 108. DE RecName: Full=Sperm-egg fusion protein Juno {ECO:0000305}; DE AltName: Full=Folate receptor 4; DE AltName: Full=Folate receptor delta {ECO:0000250|UniProtKB:Q9EQF4}; DE Short=FR-delta {ECO:0000250|UniProtKB:Q9EQF4}; DE AltName: Full=IZUMO1 receptor protein JUNO {ECO:0000303|PubMed:24739963}; DE Flags: Precursor; GN Name=IZUMO1R {ECO:0000312|HGNC:HGNC:32565}; GN Synonyms=FOLR4, JUNO {ECO:0000303|PubMed:24739963}; 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 [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [2] RP 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 [3] RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 20-228 IN COMPLEX WITH IZUMO1, RP INTERACTION WITH IZUMO1, DISULFIDE BONDS, AND MUTAGENESIS OF GLU-45; RP TRP-62; LEU-81 AND LYS-163. RX PubMed=27309818; DOI=10.1038/nature18595; RA Aydin H., Sultana A., Li S., Thavalingam A., Lee J.E.; RT "Molecular architecture of the human sperm IZUMO1 and egg JUNO RT fertilization complex."; RL Nature 534:562-565(2016). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 20-228 IN COMPLEX WITH IZUMO1, RP INTERACTION WITH IZUMO1, SUBUNIT, DISULFIDE BONDS, AND MUTAGENESIS OF RP TRP-62 AND LEU-81. 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 [5] RP INTERACTION WITH FCRL3/MAIA, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=36070373; DOI=10.1126/sciadv.abn0047; RA Vondrakova J., Frolikova M., Ded L., Cerny J., Postlerova P., RA Palenikova V., Simonik O., Nahacka Z., Basus K., Valaskova E., Machan R., RA Pacey A., Holubcova Z., Koubek P., Ezrova Z., Park S., Liu R., Partha R., RA Clark N., Neuzil J., Ikawa M., Erickson K., Lam K.S., Moore H., RA Komrskova K.; RT "MAIA, Fc receptor-like 3, supersedes JUNO as IZUMO1 receptor during human RT fertilization."; RL Sci. Adv. 8:eabn0047-eabn0047(2022). 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. 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. The ligand-receptor interaction CC probably does not act as a membrane 'fusogen'. Does not bind folate. CC {ECO:0000250|UniProtKB:Q9EQF4}. CC -!- SUBUNIT: Monomer (PubMed:27309808). Interacts with IZUMO1; the CC interaction is direct. IZUMO1 and IZUMO1R/JUNO form a complex with 1:1 CC stoichiometry (PubMed:24739963, PubMed:27309818, PubMed:27309808). CC Interacts with FCRL3/MAIA; FCRL3/MAIA replaces IZUMO1R/JUNO as IZUMO1 CC receptor after sperm-egg adhesion, thereby permitting species-specific CC gamete fusion (PubMed:36070373). {ECO:0000269|PubMed:24739963, CC ECO:0000269|PubMed:27309808, ECO:0000269|PubMed:27309818, CC ECO:0000269|PubMed:36070373}. CC -!- INTERACTION: CC A6ND01-1; Q8IYV9-1: IZUMO1; NbExp=13; IntAct=EBI-16208304, EBI-16208297; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9EQF4}; CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:Q9EQF4}. Cell CC projection, microvillus membrane {ECO:0000269|PubMed:36070373}; Lipid- CC anchor, GPI-anchor {ECO:0000250|UniProtKB:Q9EQF4}. Note=GPI-anchored at CC the oolemma microvilli. {ECO:0000250|UniProtKB:Q9EQF4}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=A6ND01-1; Sequence=Displayed; CC Name=2; CC IsoId=A6ND01-2; Sequence=VSP_040470; CC -!- TISSUE SPECIFICITY: Expressed in unfertilized oocytes (at protein CC level). {ECO:0000269|PubMed:36070373}. 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. Sheding is probably required to CC block to polyspermy and ensuring egg fusion with a single sperm. CC {ECO:0000250|UniProtKB:Q9EQF4}. CC -!- MISCELLANEOUS: [Isoform 2]: Gene prediction based on similarity to CC orthologs. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the folate receptor 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; AP002784; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS81615.1; -. [A6ND01-1] DR RefSeq; NP_001186135.1; NM_001199206.1. [A6ND01-1] DR PDB; 5F4E; X-ray; 2.40 A; B=20-228. DR PDB; 5F4Q; X-ray; 1.80 A; A/B/C/D=20-228. DR PDB; 5JKA; X-ray; 2.00 A; A/B=20-228. DR PDB; 5JKB; X-ray; 3.23 A; A/B/C/D=20-228. DR PDB; 5JKC; X-ray; 2.90 A; B=20-228. DR PDB; 5JKD; X-ray; 2.90 A; B=20-228. DR PDB; 5JKE; X-ray; 2.86 A; B/D=20-228. DR PDBsum; 5F4E; -. DR PDBsum; 5F4Q; -. DR PDBsum; 5JKA; -. DR PDBsum; 5JKB; -. DR PDBsum; 5JKC; -. DR PDBsum; 5JKD; -. DR PDBsum; 5JKE; -. DR AlphaFoldDB; A6ND01; -. DR SMR; A6ND01; -. DR DIP; DIP-62034N; -. DR IntAct; A6ND01; 1. DR STRING; 9606.ENSP00000332963; -. DR TCDB; 9.B.92.1.2; the folate receptor (fr) family. DR GlyCosmos; A6ND01; 1 site, No reported glycans. DR GlyGen; A6ND01; 1 site. DR BioMuta; IZUMO1R; -. DR MassIVE; A6ND01; -. DR PaxDb; 9606-ENSP00000332963; -. DR PeptideAtlas; A6ND01; -. DR Antibodypedia; 45349; 302 antibodies from 19 providers. DR DNASU; 390243; -. DR Ensembl; ENST00000328458.6; ENSP00000332963.5; ENSG00000183560.10. [A6ND01-1] DR Ensembl; ENST00000440961.6; ENSP00000416935.2; ENSG00000183560.10. [A6ND01-2] DR Ensembl; ENST00000687084.1; ENSP00000510041.1; ENSG00000183560.10. [A6ND01-1] DR GeneID; 390243; -. DR KEGG; hsa:390243; -. DR MANE-Select; ENST00000687084.1; ENSP00000510041.1; NM_001199206.4; NP_001186135.1. DR UCSC; uc058gou.1; human. [A6ND01-1] DR AGR; HGNC:32565; -. DR CTD; 390243; -. DR DisGeNET; 390243; -. DR GeneCards; IZUMO1R; -. DR HGNC; HGNC:32565; IZUMO1R. DR HPA; ENSG00000183560; Not detected. DR MIM; 615737; gene. DR neXtProt; NX_A6ND01; -. DR OpenTargets; ENSG00000183560; -. DR VEuPathDB; HostDB:ENSG00000183560; -. DR eggNOG; ENOG502RYYP; Eukaryota. DR GeneTree; ENSGT00950000183144; -. DR InParanoid; A6ND01; -. DR OMA; NAPLCQE; -. DR OrthoDB; 2905009at2759; -. DR PhylomeDB; A6ND01; -. DR TreeFam; TF328532; -. DR PathwayCommons; A6ND01; -. DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins. DR SignaLink; A6ND01; -. DR BioGRID-ORCS; 390243; 2 hits in 300 CRISPR screens. DR GenomeRNAi; 390243; -. DR Pharos; A6ND01; Tbio. DR PRO; PR:A6ND01; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; A6ND01; Protein. DR Bgee; ENSG00000183560; Expressed in lymph node and 39 other cell types or tissues. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0038023; F:signaling receptor activity; IPI:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl. DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB. DR GO; GO:0007342; P:fusion of sperm to egg plasma membrane involved in single fertilization; ISS:UniProtKB. DR GO; GO:0007338; P:single fertilization; ISS:UniProtKB. DR GO; GO:0035036; P:sperm-egg recognition; ISS:UniProtKB. DR InterPro; IPR004269; Folate_rcpt. DR InterPro; IPR018143; Folate_rcpt-like. DR PANTHER; PTHR10517; FOLATE RECEPTOR; 1. DR PANTHER; PTHR10517:SF10; SPERM-EGG FUSION PROTEIN JUNO; 1. DR Pfam; PF03024; Folate_rec; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cell projection; KW Disulfide bond; Fertilization; Glycoprotein; GPI-anchor; Lipoprotein; KW Membrane; Receptor; Reference proteome; Signal. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT CHAIN 20..228 FT /note="Sperm-egg fusion protein Juno" FT /id="PRO_0000332987" FT PROPEP 229..250 FT /evidence="ECO:0000255" FT /id="PRO_0000429472" FT REGION 62..81 FT /note="Important for interaction with IZUMO1" FT /evidence="ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818" FT LIPID 228 FT /note="GPI-anchor amidated serine" FT /evidence="ECO:0000255" FT CARBOHYD 73 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 27..55 FT /evidence="ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818, ECO:0007744|PDB:5F4E, FT ECO:0007744|PDB:5F4Q, ECO:0007744|PDB:5JKA, FT ECO:0007744|PDB:5JKB, ECO:0007744|PDB:5JKC, FT ECO:0007744|PDB:5JKD, ECO:0007744|PDB:5JKE" FT DISULFID 47..95 FT /evidence="ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818, ECO:0007744|PDB:5F4E, FT ECO:0007744|PDB:5F4Q, ECO:0007744|PDB:5JKA, FT ECO:0007744|PDB:5JKB, ECO:0007744|PDB:5JKC, FT ECO:0007744|PDB:5JKD, ECO:0007744|PDB:5JKE" FT DISULFID 56..99 FT /evidence="ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818, ECO:0007744|PDB:5F4E, FT ECO:0007744|PDB:5F4Q, ECO:0007744|PDB:5JKA, FT ECO:0007744|PDB:5JKB, ECO:0007744|PDB:5JKC, FT ECO:0007744|PDB:5JKD, ECO:0007744|PDB:5JKE" FT DISULFID 79..172 FT /evidence="ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818, ECO:0007744|PDB:5F4E, FT ECO:0007744|PDB:5F4Q, ECO:0007744|PDB:5JKA, FT ECO:0007744|PDB:5JKB, ECO:0007744|PDB:5JKC, FT ECO:0007744|PDB:5JKD, ECO:0007744|PDB:5JKE" FT DISULFID 86..143 FT /evidence="ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818, ECO:0007744|PDB:5F4E, FT ECO:0007744|PDB:5F4Q, ECO:0007744|PDB:5JKA, FT ECO:0007744|PDB:5JKB, ECO:0007744|PDB:5JKC, FT ECO:0007744|PDB:5JKD, ECO:0007744|PDB:5JKE" FT DISULFID 132..206 FT /evidence="ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818, ECO:0007744|PDB:5F4E, FT ECO:0007744|PDB:5F4Q, ECO:0007744|PDB:5JKA, FT ECO:0007744|PDB:5JKB, ECO:0007744|PDB:5JKC, FT ECO:0007744|PDB:5JKD, ECO:0007744|PDB:5JKE" FT DISULFID 136..186 FT /evidence="ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818, ECO:0007744|PDB:5F4E, FT ECO:0007744|PDB:5F4Q, ECO:0007744|PDB:5JKA, FT ECO:0007744|PDB:5JKB, ECO:0007744|PDB:5JKC, FT ECO:0007744|PDB:5JKD, ECO:0007744|PDB:5JKE" FT DISULFID 149..166 FT /evidence="ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818, ECO:0007744|PDB:5F4E, FT ECO:0007744|PDB:5F4Q, ECO:0007744|PDB:5JKA, FT ECO:0007744|PDB:5JKB, ECO:0007744|PDB:5JKC, FT ECO:0007744|PDB:5JKD, ECO:0007744|PDB:5JKE" FT VAR_SEQ 110..116 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_040470" FT MUTAGEN 45 FT /note="E->A: Nearly abolishes interaction with IZUMO1." FT /evidence="ECO:0000269|PubMed:27309818" FT MUTAGEN 45 FT /note="E->K: Abolishes interaction with IZUMO1." FT /evidence="ECO:0000269|PubMed:27309818" FT MUTAGEN 62 FT /note="W->A: Nearly abolishes interaction with IZUMO1." FT /evidence="ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818" FT MUTAGEN 81 FT /note="L->A: Abolishes interaction with IZUMO1." FT /evidence="ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818" FT MUTAGEN 163 FT /note="K->E: Mildly decreases interaction with IZUMO1." FT /evidence="ECO:0000269|PubMed:27309818" FT HELIX 21..23 FT /evidence="ECO:0007829|PDB:5JKA" FT STRAND 24..26 FT /evidence="ECO:0007829|PDB:5JKC" FT STRAND 30..32 FT /evidence="ECO:0007829|PDB:5JKA" FT HELIX 45..50 FT /evidence="ECO:0007829|PDB:5F4Q" FT STRAND 53..56 FT /evidence="ECO:0007829|PDB:5F4Q" FT HELIX 58..63 FT /evidence="ECO:0007829|PDB:5F4Q" FT STRAND 66..68 FT /evidence="ECO:0007829|PDB:5F4Q" FT TURN 70..72 FT /evidence="ECO:0007829|PDB:5F4Q" FT TURN 76..79 FT /evidence="ECO:0007829|PDB:5F4Q" FT HELIX 84..99 FT /evidence="ECO:0007829|PDB:5F4Q" FT HELIX 104..106 FT /evidence="ECO:0007829|PDB:5F4Q" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:5F4Q" FT STRAND 124..126 FT /evidence="ECO:0007829|PDB:5F4Q" FT STRAND 129..131 FT /evidence="ECO:0007829|PDB:5F4Q" FT HELIX 133..143 FT /evidence="ECO:0007829|PDB:5F4Q" FT STRAND 146..149 FT /evidence="ECO:0007829|PDB:5F4Q" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:5F4E" FT HELIX 175..178 FT /evidence="ECO:0007829|PDB:5F4Q" FT HELIX 182..189 FT /evidence="ECO:0007829|PDB:5F4Q" FT TURN 190..192 FT /evidence="ECO:0007829|PDB:5F4Q" FT STRAND 193..196 FT /evidence="ECO:0007829|PDB:5F4Q" FT STRAND 203..207 FT /evidence="ECO:0007829|PDB:5F4Q" FT HELIX 213..215 FT /evidence="ECO:0007829|PDB:5F4Q" FT HELIX 220..227 FT /evidence="ECO:0007829|PDB:5F4Q" SQ SEQUENCE 250 AA; 28672 MW; CBF2FD967ABAF6E7 CRC64; MACWWPLLLE LWTVMPTWAG DELLNICMNA KHHKRVPSPE DKLYEECIPW KDNACCTLTT SWEAHLDVSP LYNFSLFHCG LLMPGCRKHF IQAICFYECS PNLGPWIQPV GSLGWEVAPS GQGERVVNVP LCQEDCEEWW EDCRMSYTCK SNWRGGWDWS QGKNRCPKGA QCLPFSHYFP TPADLCEKTW SNSFKASPER RNSGRCLQKW FEPAQGNPNV AVARLFASSA PSWELSYTIM VCSLFLPFLS //