EEA1

EEA1
Available structures
PDB	Ortholog search:PDBeRCSB
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;OMA:EEA1 - orthologs
Gene location (Human)
Chr.	Chromosome 12 (human)
End	92,929,331bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	95,881,380bp
RNA expressionpattern
	Top expressed in
	Achilles tendon; ; skin of thigh; ; biceps brachii; ; oral cavity; ; gingival epithelium; ; Skeletal muscle tissue of rectus abdominis; ; tail of epididymis; ; human penis; ; skin of hip; ; Skeletal muscle tissue of biceps brachii;
	Top expressed in
	zygote; ; stroma of bone marrow; ; secondary oocyte; ; skin of external ear; ; cardiac muscle tissue of left ventricle; ; plantaris muscle; ; extensor digitorum longus muscle; ; soleus muscle; ; left colon; ; paraventricular nucleus of hypothalamus;
	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

The geneEEA1encodes for the 1400 amino acidprotein,EarlyEndosome Antigen1.

EEA1 localizes exclusively to earlyendosomesand has an important role in endosomal trafficking. EEA1 binds directly to thephospholipid phosphatidylinositol 3-phosphatethrough its C-terminalFYVE domainand forms ahomodimerthrough acoiled coil.EEA1 acts as a tethering molecule that couples vesicle docking withSNAREssuch asN-ethylmaleimide sensitive fusion protein,bringing the endosomes physically closer and ultimately resulting in the fusion and delivery of endosomal cargo.

Function

EEA1 is aRAB5Aeffector protein which binds via an N-terminalzinc fingerdomain 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 tuberculosisis known to inhibit the recruitment of EEA1 to the phagosomal membrane throughCamKII.^[9]Legionella pneumophilaalso prevents EEA1 recruitment through a currently unknown mechanism.^[10]The related pathogenLegionella longbeachaerecruits EEA1 and appears to replicate within a modified early endosome.^[11]

References

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000102189–Ensembl,May 2017
^^a ^b ^cGRCm38: 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.PMC2890723.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.PMC2691687.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.PMC3673817.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+1at the U.S. National Library of MedicineMedical Subject Headings(MeSH)
Overview of all the structural information available in thePDBforUniProt:Q15075(Early endosome antigen 1) at thePDBe-KB.

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

[refGRCm38Ensembl-2] 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.PMC2890723.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.PMC2691687.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.PMC3673817.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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Function

Involvement in pathogenesis

See also

References

External links