EEA1

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Early endosome antigen 1
1joc.gif
Early endosome antigen 1 C-terminal FYVE domain dimer with lipids. PDB entry 1joc[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols EEA1 ; MST105; MSTP105; ZFYVE2
External IDs OMIM605070 HomoloGene37822 GeneCards: EEA1 Gene
Orthologs
Species Human Mouse
Entrez 8411 216238
Ensembl ENSG00000102189 ENSMUSG00000036499
UniProt Q15075 Q8BL66
RefSeq (mRNA) NM_003566 NM_001001932
RefSeq (protein) NP_003557 NP_001001932
Location (UCSC) Chr 12:
93.16 – 93.32 Mb
Chr 10:
95.94 – 96.05 Mb
PubMed search [1] [2]

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

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[edit]

EEA1 is a RAB5A effector protein which binds via a N-terminal zinc finger domain and is required for fusion of early and late endosomes and for sorting at the early endosome level [2][3]

Involvement in pathogenesis[edit]

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.[4] Legionella pneumophila also prevents EEA1 recruitment through a currently unknown mechanism.[5] Interestingly, the related pathogen Legionella longbeachae recruits EEA1 and appears to replicate within a modified early endosome.[6]

See also[edit]

References[edit]

  1. ^ Dumas, J. J.; Merithew, E.; Sudharshan, E.; Rajamani, D.; Hayes, S.; Lawe, D.; Corvera, S.; Lambright, D. G. (2001). "Multivalent endosome targeting by homodimeric EEA1". Molecular cell 8 (5): 947–958. doi:10.1016/S1097-2765(01)00385-9. PMID 11741531.  edit
  2. ^ Mishra, A.; Eathiraj, S.; Corvera, S.; Lambright, D. G. (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 107 (24): 10866–10871. doi:10.1073/pnas.1000843107. PMC 2890723. PMID 20534488.  edit
  3. ^ Barysch, S. V.; Aggarwal, S.; Jahn, R.; Rizzoli, S. O. (2009). "Sorting in early endosomes reveals connections to docking- and fusion-associated factors". Proceedings of the National Academy of Sciences 106 (24): 9697. doi:10.1073/pnas.0901444106.  edit
  4. ^ Malik, Z. A.; Thompson, C. R.; Hashimi, S.; Porter, B.; Iyer, S. S.; Kusner, D. J. (2003). "Cutting edge: Mycobacterium tuberculosis blocks Ca2+ signaling and phagosome maturation in human macrophages via specific inhibition of sphingosine kinase". Journal of immunology (Baltimore, Md. : 1950) 170 (6): 2811–2815. PMID 12626530.  edit
  5. ^ Urwyler, S.; Nyfeler, Y.; Ragaz, C.; Lee, H.; Mueller, L. N.; Aebersold, R.; Hilbi, H. (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.  edit
  6. ^ Asare, R.; Abu Kwaik, Y. (2007). "Early trafficking and intracellular replication of Legionella longbeachaea within an ER-derived late endosome-like phagosome". Cellular Microbiology 9 (6): 1571–1587. doi:10.1111/j.1462-5822.2007.00894.x. PMID 17309675.  edit

External links[edit]