EEA1

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

8411

216238

Ensembl

ENSG00000102189

ENSMUSG00000036499

UniProt

Q15075

Q8BL66

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

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

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 morphology.

Involvement in pathogenesis

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

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000102189 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036499 – Ensembl, 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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