EEA1

EEA1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1HYI, 1HYJ, 1JOC, 3MJH
Identifiers
Aliases	EEA1 , MST105, MSTP105, ZFYVE2, early endosome antigen 1
External IDs	OMIM: 605070 MGI: 2442192 HomoloGene: 37822 GeneCards: EEA1
Gene location (Human)
Chr.	Chromosome 12 (human)
End	92,929,331 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	95,881,380 bp
RNA expression pattern
	Top expressed in
	Achilles tendon; ; biceps brachii; ; cavity of mouth; ; human penis; ; urethra; ; synovial joint; ; jejunal mucosa; ; lactiferous duct; ; right ventricle; ; vulva;
	Top expressed in
	secondary oocyte; ; plantaris muscle; ; extensor digitorum longus muscle; ; soleus muscle; ; left colon; ; paraventricular nucleus of hypothalamus; ; calvaria; ; left lung lobe; ; dorsomedial hypothalamic nucleus; ; cingulate gyrus;
	More reference expression data
	n/a
Gene ontology
Molecular function	protein homodimerization activity ; zinc ion binding ; metal ion binding ; calmodulin binding ; GTP-dependent protein binding ; 1-phosphatidylinositol binding ; protein binding ; nucleic acid binding ;
Cellular component	cytoplasm ; recycling endosome ; cytosol ; endosome ; early endosome membrane ; membrane ; axonal spine ; serine-pyruvate aminotransferase complex ; early endosome ; extrinsic component of plasma membrane ; extracellular exosome ; cytoplasmic vesicle ; presynapse ; synapse ;
Biological process	endocytosis ; early endosome to late endosome transport ; synaptic vesicle to endosome fusion ; vesicle fusion ;
	Sources:Amigo / QuickGO
Orthologs
	8411
	216238
	ENSG00000102189
	ENSMUSG00000036499
	Q15075
	Q8BL66
	NM_003566
	NM_001001932
	NP_003557
	NP_001001932
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated February 21, 2024

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 morphplogy.

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]

Related Research Articles

<span class="mw-page-title-main">Phagosome</span>

In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs).

<span class="mw-page-title-main">Phosphatidylinositol 3-phosphate</span> Chemical compound

Phosphatidylinositol 3-phosphate (PtdIns3P) is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and III phosphoinositide 3-kinases activity on phosphatidylinositol.

<span class="mw-page-title-main">Phosphatidylinositol 3,5-bisphosphate</span> Chemical compound

Phosphatidylinositol 3,5-bisphosphate is one of the seven phosphoinositides found in eukaryotic cell membranes. In quiescent cells, the PtdIns(3,5)P2 levels, typically quantified by HPLC, are the lowest amongst the constitutively present phosphoinositides. They are approximately 3 to 5-fold lower as compared to PtdIns3P and PtdIns5P levels, and more than 100-fold lower than the abundant PtdIns4P and PtdIns(4,5)P2. PtdIns(3,5)P2 was first reported to occur in mouse fibroblasts and budding yeast S. cerevisiae in 1997. In S. cerevisiae PtdIns(3,5)P2 levels increase dramatically during hyperosmotic shock. The response to hyperosmotic challenge is not conserved in most tested mammalian cells except for differentiated 3T3L1 adipocytes.

<span class="mw-page-title-main">FYVE domain</span>

In molecular biology the FYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1, YOTB, Vac 1, and EEA1, in which it has been found. FYVE domains bind phosphatidylinositol 3-phosphate, in a way dependent on its metal ion coordination and basic amino acids. The FYVE domain inserts into cell membranes in a pH-dependent manner. The FYVE domain has been connected to vacuolar protein sorting and endosome function.

FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) also known as faciogenital dysplasia 1 protein (FGDY), zinc finger FYVE domain-containing protein 3 (ZFYVE3), or Rho/Rac guanine nucleotide exchange factor FGD1 is a protein that in humans is encoded by the FGD1 gene that lies on the X chromosome. Orthologs of the FGD1 gene are found in dog, cow, mouse, rat, and zebrafish, and also budding yeast and C. elegans. It is a member of the FYVE, RhoGEF and PH domain containing family.

Ras-related protein Rab-5A is a protein that in humans is encoded by the RAB5A gene.

Ras-related protein Rab-7a is a protein that in humans is encoded by the RAB7A gene.

Hepatocyte growth factor-regulated tyrosine kinase substrate is an enzyme that in humans is encoded by the HGS gene.

Syntaxin-6 is a protein that in humans is encoded by the STX6 gene.

PIKfyve, a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene.

Rab11 family-interacting protein 5 is a protein that in humans is encoded by the RAB11FIP5 gene.

Ras-related protein Rab-22A is a protein that in humans is encoded by the RAB22A gene.

Phosphatidylinositol 4-kinase 2-alpha is an enzyme that in humans is encoded by the PI4K2A gene.

Ras-related protein Rab-11B is a protein that in humans is encoded by the RAB11B gene. Rab11b is reported as most abundantly expressed in brain, heart and testes.

Zinc finger FYVE domain-containing protein 16 is a protein that in humans is encoded by the ZFYVE16 gene.

Zinc finger FYVE domain-containing protein 1 is a protein that in humans is encoded by the ZFYVE1 gene.

GTPase activating protein and VPS9 domains 1, also known as GAPVD1, Gapex-5 and RME-6 is a protein which in humans is encoded by the GAPVD1 gene.

FYVE, RhoGEF and PH domain-containing protein 2 (FGD2), also known as zinc finger FYVE domain-containing protein 4 (ZFYVE4), is a protein that in humans is encoded by the FGD2 gene.

RUN and FYVE domain containing 2 (RUFY2) is a protein that in humans is encoded by the RUFY2 gene. The RUFY2 gene is named for two of its domains, the RUN domain and FYVE domains. RUFY2 is a member of the RUFY family of proteins that include RUFY1, RUFY2, RUFY3, and RUFY4. RUFY2 protein has a dynamic role in endosomal membrane trafficking.

The SNX8 is a sorting nexin protein involved in intracellular molecular traffic from the early endosomes to the TGN. It is suggested that it acts as an adaptor protein in events related to immune response and cholesterol regulation, for example. As a protein of the SNXs family, the SNX8 is formed of 465 aminoacids and presents a BAR-domain and a PX-domain which are very relevant in relation to its functions. Furthermore, SNX8 study is motivated by its medical significance in relation to diseases such as Alzheimer's Disease, cancer, neurodevelopmental malformations and to its role in fighting against viral infections.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000102189 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000036499 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

External links

early+endosome+antigen+1 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Overview of all the structural information available in the PDB for UniProt : Q15075 (Early endosome antigen 1) at the PDBe-KB .

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000102189 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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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