Juno (protein)

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External IDsGeneCards: [1]
RefSeq (mRNA)



RefSeq (protein)



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Juno also known as folate receptor 4, folate receptor delta or IZUMO1R is a protein that in humans is encoded by the FOLR4 gene.[1] Juno is a member of the folate receptor family[2] and is GPI-anchored to the plasmalemma of the mammalian egg cell that recognizes its sperm-riding counterpart, IZUMO1, and facilitates fertilization. The protein was named after Juno, the Roman goddess of fertility and marriage.[3]

After the initial fertilisation stage, a sudden decrease of Juno from the egg cell surface occurs and Juno becomes virtually undetectable after just 40 minutes.[3][4] Still, after fertilization via intracytoplasmic sperm injection, the egg cell does not lose cell-surface expression of Juno, which suggests that Juno contributes to the prevention of polyspermy.[4] Mice lacking Juno on the surface of their egg cells are infertile because their egg cells do not fuse with normal sperm, demonstrating Juno's essential role in the fertility of female mice.[3]


Based on a sequence homology search for genes relate to the folate receptor, the gene for folate receptor 4 was first identified in mice and humans in 2000 at the University of Nebraska.[2]

In 2014, the function of folate receptor 4 was discovered by the researchers of the Wellcome Trust Sanger Institute who also proposed that the protein be renamed as Juno.[4] Juno was initially found in murine oocytes, but its interaction with Izumo was subsequently found in other mammalian species, including humans.[4][4][5][6][7] Being previously elusive, Juno was discovered nine years after its male counterpart, Izumo1.[3]

3D structure

The crystal structure of Juno (PDB: 5EJN​) was reported in February 2016 by researchers at Karolinska Institutet, in collaboration with the group at the Wellcome Trust Sanger Institute.[8]

Model organisms

Model organisms have been used in the study of JUNO function. A conditional knockout mouse line called Izumo1rtm2a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[9] Male and female animals underwent a standardized phenotypic screen[10] to determine the effects of deletion.[11][12][13][14] Additional screens performed: - In-depth immunological phenotyping[15]


  1. "Entrez Gene: Folate receptor 4, delta (putative)".
  2. 2.0 2.1 Spiegelstein O, Eudy JD, Finnell RH (Nov 2000). "Identification of two putative novel folate receptor genes in humans and mouse". Gene. 258 (1–2): 117–25. doi:10.1016/S0378-1119(00)00418-2. PMID 11111049.
  3. 3.0 3.1 3.2 3.3 "Sperm meets egg: protein essential for fertilization discovered". Wellcome Trust Sanger Institute. 16 April 2014. Retrieved 16 April 2014.
  4. 4.0 4.1 4.2 4.3 4.4 Mayer K (16 April 2014). "Sperm/Egg Fusion Depends on Pairing of His/Her Proteins". Genetic Engineering & Biotechnology News. Retrieved 16 April 2014.
  5. Bianchi E, Doe B, Goulding D, Wright GJ (Apr 2014). "Juno is the egg Izumo receptor and is essential for mammalian fertilization". Nature. 508 (7497): 483–7. doi:10.1038/nature13203. PMC 3998876. PMID 24739963.
  6. Everts S (16 April 2014). "Sperm Protein Meets Its Match". Chemical & Engineering News. 92 (16).
  7. Anthony Rivas (16 April 2014). "'Juno' Protein Connects Egg To Sperm; Scientists Finally Unravel Mystery Of How The Cells Bond". Medical Daily. Retrieved 16 April 2014.
  8. Han L, Nishimura K, Sadat Al Hosseini H, Bianchi E, Wright GJ, Jovine L (2016). "Divergent evolution of vitamin B9 binding underlies Juno-mediated adhesion of mammalian gametes". Curr. Biol. 26 (3): R100–1. doi:10.1016/j.cub.2015.12.034. PMC 4751342. PMID 26859261. PDB: 5EJN
  9. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  10. 10.0 10.1 "International Mouse Phenotyping Consortium".
  11. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  12. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  13. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  14. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  15. 15.0 15.1 "Infection and Immunity Immunophenotyping (3i) Consortium".