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 12-APR-2017, entry version 71. DE RecName: Full=Sperm-egg fusion protein Juno; DE AltName: Full=Folate receptor 4; DE AltName: Full=Folate receptor delta; DE Short=FR-delta; DE AltName: Full=IZUMO1 receptor protein JUNO {ECO:0000303|PubMed:24739963}; DE Flags: Precursor; GN Name=IZUMO1R {ECO:0000312|HGNC:HGNC:32565}; Synonyms=FOLR4, JUNO; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA 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 RP IZUMO1, INTERACTION WITH IZUMO1, DISULFIDE BONDS, AND MUTAGENESIS OF RP GLU-45; 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 RP IZUMO1, INTERACTION WITH IZUMO1, SUBUNIT, DISULFIDE BONDS, AND RP MUTAGENESIS OF 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 RT mammalian fertilization."; RL Nature 534:566-569(2016). CC -!- FUNCTION: Receptor for IZUMO1 present at the cell surface of CC oocytes (oolemma), which is essential for species-specific gamete CC recognition and fertilization. The IZUMO1:IZUMO1R/JUNO interaction CC is a necessary adhesion event between sperm and egg that is CC required for fertilization but is not sufficient for cell fusion. CC The ligand-receptor interaction probably does not act as a CC 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 CC 1:1 stoichiometry (PubMed:24739963, PubMed:27309818, CC PubMed:27309808). {ECO:0000269|PubMed:24739963, CC ECO:0000269|PubMed:27309808, ECO:0000269|PubMed:27309818}. CC -!- SUBCELLULAR LOCATION: Cell membrane CC {ECO:0000250|UniProtKB:Q9EQF4}; Lipid-anchor, GPI-anchor CC {ECO:0000250|UniProtKB:Q9EQF4}. Note=GPI-anchored at the oolemma. CC {ECO:0000250|UniProtKB:Q9EQF4}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=A6ND01-1; Sequence=Displayed; CC Note=No experimental confirmation available. Gene prediction CC based on EST data.; CC Name=2; CC IsoId=A6ND01-2; Sequence=VSP_040470; CC Note=No experimental confirmation available. Gene prediction CC based on similarity to orthologs.; CC -!- PTM: The protein is rapidly cleaved following fertilization, being CC only weakly detectable in zona-intact fertilized eggs at telophase CC II and undetectable at the pronuclear stage. Sheding is probably CC required to block to polyspermy and ensuring egg fusion with a CC single sperm. {ECO:0000250|UniProtKB:Q9EQF4}. 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 UniGene; Hs.553758; -. 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 ProteinModelPortal; A6ND01; -. DR SMR; A6ND01; -. DR DIP; DIP-62034N; -. DR STRING; 9606.ENSP00000416935; -. DR TCDB; 9.B.92.1.2; the folate receptor (fr) family. DR BioMuta; FOLR4; -. DR PaxDb; A6ND01; -. DR PRIDE; A6ND01; -. DR Ensembl; ENST00000328458; ENSP00000332963; ENSG00000183560. [A6ND01-1] DR Ensembl; ENST00000440961; ENSP00000416935; ENSG00000183560. [A6ND01-2] DR GeneID; 390243; -. DR KEGG; hsa:390243; -. DR UCSC; uc058gou.1; human. [A6ND01-1] DR CTD; 390243; -. DR GeneCards; IZUMO1R; -. DR HGNC; HGNC:32565; IZUMO1R. DR MIM; 615737; gene. DR neXtProt; NX_A6ND01; -. DR OpenTargets; ENSG00000183560; -. DR eggNOG; ENOG410IFFP; Eukaryota. DR eggNOG; ENOG4111IU4; LUCA. DR GeneTree; ENSGT00390000010470; -. DR HOGENOM; HOG000006539; -. DR HOVERGEN; HBG039612; -. DR InParanoid; A6ND01; -. DR KO; K13649; -. DR OMA; GRCLQKW; -. DR OrthoDB; EOG091G0GIA; -. DR PhylomeDB; A6ND01; -. DR TreeFam; TF328532; -. DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins. DR GenomeRNAi; 390243; -. DR PRO; PR:A6ND01; -. DR Proteomes; UP000005640; Chromosome 11. DR ExpressionAtlas; A6ND01; baseline and differential. DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0004872; F:receptor activity; IPI:UniProtKB. DR GO; GO:0006501; P:C-terminal protein lipidation; TAS:Reactome. DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB. DR GO; GO:0007342; P:fusion of sperm to egg plasma membrane; 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; PTHR10517; 1. DR Pfam; PF03024; Folate_rec; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Complete proteome; KW Disulfide bond; Fertilization; Glycoprotein; GPI-anchor; Lipoprotein; KW Membrane; Receptor; Reference proteome; Signal. FT SIGNAL 1 19 {ECO:0000255}. FT CHAIN 20 228 Sperm-egg fusion protein Juno. FT /FTId=PRO_0000332987. FT PROPEP 229 250 {ECO:0000255}. FT /FTId=PRO_0000429472. FT REGION 62 81 Important for interaction with IZUMO1. FT {ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818}. FT LIPID 228 228 GPI-anchor amidated serine. FT {ECO:0000255}. FT CARBOHYD 73 73 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 27 55 {ECO:0000244|PDB:5F4E, FT ECO:0000244|PDB:5F4Q, FT ECO:0000244|PDB:5JKA, FT ECO:0000244|PDB:5JKB, FT ECO:0000244|PDB:5JKC, FT ECO:0000244|PDB:5JKD, FT ECO:0000244|PDB:5JKE, FT ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818}. FT DISULFID 47 95 {ECO:0000244|PDB:5F4E, FT ECO:0000244|PDB:5F4Q, FT ECO:0000244|PDB:5JKA, FT ECO:0000244|PDB:5JKB, FT ECO:0000244|PDB:5JKC, FT ECO:0000244|PDB:5JKD, FT ECO:0000244|PDB:5JKE, FT ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818}. FT DISULFID 56 99 {ECO:0000244|PDB:5F4E, FT ECO:0000244|PDB:5F4Q, FT ECO:0000244|PDB:5JKA, FT ECO:0000244|PDB:5JKB, FT ECO:0000244|PDB:5JKC, FT ECO:0000244|PDB:5JKD, FT ECO:0000244|PDB:5JKE, FT ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818}. FT DISULFID 79 172 {ECO:0000244|PDB:5F4E, FT ECO:0000244|PDB:5F4Q, FT ECO:0000244|PDB:5JKA, FT ECO:0000244|PDB:5JKB, FT ECO:0000244|PDB:5JKC, FT ECO:0000244|PDB:5JKD, FT ECO:0000244|PDB:5JKE, FT ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818}. FT DISULFID 86 143 {ECO:0000244|PDB:5F4E, FT ECO:0000244|PDB:5F4Q, FT ECO:0000244|PDB:5JKA, FT ECO:0000244|PDB:5JKB, FT ECO:0000244|PDB:5JKC, FT ECO:0000244|PDB:5JKD, FT ECO:0000244|PDB:5JKE, FT ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818}. FT DISULFID 132 206 {ECO:0000244|PDB:5F4E, FT ECO:0000244|PDB:5F4Q, FT ECO:0000244|PDB:5JKA, FT ECO:0000244|PDB:5JKB, FT ECO:0000244|PDB:5JKC, FT ECO:0000244|PDB:5JKD, FT ECO:0000244|PDB:5JKE, FT ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818}. FT DISULFID 136 186 {ECO:0000244|PDB:5F4E, FT ECO:0000244|PDB:5F4Q, FT ECO:0000244|PDB:5JKA, FT ECO:0000244|PDB:5JKB, FT ECO:0000244|PDB:5JKC, FT ECO:0000244|PDB:5JKD, FT ECO:0000244|PDB:5JKE, FT ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818}. FT DISULFID 149 166 {ECO:0000244|PDB:5F4E, FT ECO:0000244|PDB:5F4Q, FT ECO:0000244|PDB:5JKA, FT ECO:0000244|PDB:5JKB, FT ECO:0000244|PDB:5JKC, FT ECO:0000244|PDB:5JKD, FT ECO:0000244|PDB:5JKE, FT ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818}. FT VAR_SEQ 110 116 Missing (in isoform 2). {ECO:0000305}. FT /FTId=VSP_040470. FT MUTAGEN 45 45 E->A: Nearly abolishes interaction with FT IZUMO1. {ECO:0000269|PubMed:27309818}. FT MUTAGEN 45 45 E->K: Abolishes interaction with IZUMO1. FT {ECO:0000269|PubMed:27309818}. FT MUTAGEN 62 62 W->A: Nearly abolishes interaction with FT IZUMO1. {ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818}. FT MUTAGEN 81 81 L->A: Abolishes interaction with IZUMO1. FT {ECO:0000269|PubMed:27309808, FT ECO:0000269|PubMed:27309818}. FT MUTAGEN 163 163 K->E: Mildly decreases interaction with FT IZUMO1. {ECO:0000269|PubMed:27309818}. FT HELIX 21 23 {ECO:0000244|PDB:5JKA}. FT STRAND 24 26 {ECO:0000244|PDB:5JKC}. FT STRAND 30 32 {ECO:0000244|PDB:5JKA}. FT HELIX 45 50 {ECO:0000244|PDB:5F4Q}. FT STRAND 53 56 {ECO:0000244|PDB:5F4Q}. FT HELIX 58 63 {ECO:0000244|PDB:5F4Q}. FT STRAND 66 68 {ECO:0000244|PDB:5F4Q}. FT TURN 70 72 {ECO:0000244|PDB:5F4Q}. FT TURN 76 79 {ECO:0000244|PDB:5F4Q}. FT HELIX 84 99 {ECO:0000244|PDB:5F4Q}. FT HELIX 104 106 {ECO:0000244|PDB:5F4Q}. FT STRAND 107 109 {ECO:0000244|PDB:5F4Q}. FT STRAND 124 126 {ECO:0000244|PDB:5F4Q}. FT STRAND 129 131 {ECO:0000244|PDB:5F4Q}. FT HELIX 133 143 {ECO:0000244|PDB:5F4Q}. FT STRAND 146 149 {ECO:0000244|PDB:5F4Q}. FT STRAND 153 155 {ECO:0000244|PDB:5F4E}. FT HELIX 175 178 {ECO:0000244|PDB:5F4Q}. FT HELIX 182 189 {ECO:0000244|PDB:5F4Q}. FT TURN 190 192 {ECO:0000244|PDB:5F4Q}. FT STRAND 193 196 {ECO:0000244|PDB:5F4Q}. FT STRAND 203 207 {ECO:0000244|PDB:5F4Q}. FT HELIX 213 215 {ECO:0000244|PDB:5F4Q}. FT HELIX 220 227 {ECO:0000244|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 //