JUNO_HUMAN
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 03-AUG-2022, entry version 100.
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).
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 {ECO:0000269|PubMed:24739963, ECO:0000269|PubMed:27309808,
CC ECO:0000269|PubMed:27309818}.
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}. Note=GPI-
CC anchored at the oolemma. {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 -!- 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}.
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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 GlyGen; A6ND01; 1 site.
DR BioMuta; IZUMO1R; -.
DR MassIVE; A6ND01; -.
DR PaxDb; A6ND01; -.
DR PeptideAtlas; A6ND01; -.
DR PRIDE; A6ND01; -.
DR Antibodypedia; 45349; 281 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 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 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 240 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 tissues.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0038023; F:signaling receptor activity; IPI:UniProtKB.
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; 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..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
