The gene EEA1 encodes for the 1400 amino acid protein, Early Endosome Antigen 1.

EEA1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesEEA1, MST105, MSTP105, ZFYVE2, early endosome antigen 1
External IDsOMIM: 605070; MGI: 2442192; HomoloGene: 37822; GeneCards: EEA1; OMA:EEA1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003566

NM_001001932

RefSeq (protein)

NP_003557

NP_001001932

Location (UCSC)Chr 12: 92.77 – 92.93 MbChr 10: 95.78 – 95.88 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

EEA1 localizes exclusively to early endosomes and has an important role in endosomal trafficking. EEA1 binds directly to the phospholipid phosphatidylinositol 3-phosphate through its C-terminal FYVE domain and forms a homodimer through a coiled coil. EEA1 acts as a tethering molecule that couples vesicle docking with SNAREs such as N-ethylmaleimide sensitive fusion protein, bringing the endosomes physically closer and ultimately resulting in the fusion and delivery of endosomal cargo.

Function

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EEA1 is a RAB5A effector protein which binds via an N-terminal zinc finger domain and is required for fusion of early and late endosomes and for sorting at the early endosome level.[5][6]

EEA1 plays a role in endocytosis and is recruited by Rab5-GTP to endosomal membranes.[7] EEA1 may be regulated through monoubiquination, affecting endosome fusion and trafficking.[8] Ubiquitin selective segregase p97 may regulate EEA1's tethering ability, affecting its endosome trafficking and morphplogy.

Involvement in pathogenesis

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Due to the proteins importance in vesicular trafficking, a number of intracellular bacteria prevent EEA1 recruitment to the vacuole. Mycobacterium tuberculosis is known to inhibit the recruitment of EEA1 to the phagosomal membrane through CamKII.[9] Legionella pneumophila also prevents EEA1 recruitment through a currently unknown mechanism.[10] The related pathogen Legionella longbeachae recruits EEA1 and appears to replicate within a modified early endosome.[11]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000102189Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036499Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Mishra A, Eathiraj S, Corvera S, Lambright DG (Jun 2010). "Structural basis for Rab GTPase recognition and endosome tethering by the C2H2 zinc finger of Early Endosomal Autoantigen 1 (EEA1)". Proceedings of the National Academy of Sciences of the United States of America. 107 (24): 10866–71. Bibcode:2010PNAS..10710866M. doi:10.1073/pnas.1000843107. PMC 2890723. PMID 20534488.
  6. ^ Barysch SV, Aggarwal S, Jahn R, Rizzoli SO (Jun 2009). "Sorting in early endosomes reveals connections to docking- and fusion-associated factors" (PDF). Proceedings of the National Academy of Sciences of the United States of America. 106 (24): 9697–702. Bibcode:2009PNAS..106.9697B. doi:10.1073/pnas.0901444106. PMC 2691687. PMID 19487677.
  7. ^ Stefan C, Audhya A, Emr SD (January 2010). "Chapter 138 - FYVE Domains in Membrane Trafficking and Cell Signaling". In Bradshaw RA, Dennis EA (eds.). Handbook of Cell Signaling (Second ed.). San Diego: Academic Press. pp. 1111–1121. doi:10.1016/B978-0-12-374145-5.00138-8. ISBN 978-0-12-374145-5.
  8. ^ Ramanathan HN, Zhang G, Ye Y (May 2013). "Monoubiquitination of EEA1 regulates endosome fusion and trafficking". Cell & Bioscience. 3 (1): 24. doi:10.1186/2045-3701-3-24. PMC 3673817. PMID 23701900.
  9. ^ Malik ZA, Thompson CR, Hashimi S, Porter B, Iyer SS, Kusner DJ (Mar 2003). "Cutting edge: Mycobacterium tuberculosis blocks Ca2+ signaling and phagosome maturation in human macrophages via specific inhibition of sphingosine kinase". Journal of Immunology. 170 (6): 2811–5. doi:10.4049/jimmunol.170.6.2811. PMID 12626530.
  10. ^ Urwyler S, Nyfeler Y, Ragaz C, Lee H, Mueller LN, Aebersold R, Hilbi H (Jan 2009). "Proteome analysis of Legionella vacuoles purified by magnetic immunoseparation reveals secretory and endosomal GTPases". Traffic. 10 (1): 76–87. doi:10.1111/j.1600-0854.2008.00851.x. PMID 18980612. S2CID 205840762.
  11. ^ Asare R, Abu Kwaik Y (Jun 2007). "Early trafficking and intracellular replication of Legionella longbeachaea within an ER-derived late endosome-like phagosome". Cellular Microbiology. 9 (6): 1571–87. doi:10.1111/j.1462-5822.2007.00894.x. PMID 17309675. S2CID 11318022.
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