The gene EEA1 encodes for the 1400 amino acid

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

, Early

Endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of the endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membra ...

Antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

1. EEA1 localizes exclusively to early

endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of the endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membra ...

s and has an important role in endosomal trafficking. EEA1 binds directly to the

phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

phosphatidylinositol 3-phosphate Phosphatidylinositol 3-phosphate (PI3P) 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 phosph ...

through its C-terminal

FYVE domain In molecular biology the FYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1 (yeast orthologue of PIKfyve), YOTB, Vac 1 (vesicle transport protein), and EEA1, in which it has been found. FYVE domains bind phosphatidyli ...

and forms a

homodimer In biochemistry, a protein dimer is a macromolecular complex or protein multimer, multimer formed by two protein monomers, or single proteins, which are usually Non-covalent interaction, non-covalently bound. Many macromolecules, such as proteins ...

through a

coiled coil A coiled coil is a structural motif in proteins in which two to seven alpha-helices are coiled together like the strands of a rope. ( Dimers and trimers are the most common types.) They have been found in roughly 5-10% of proteins and have a ...

. EEA1 acts as a tethering molecule that couples vesicle docking with

SNARE SNARE proteins – "Soluble NSF attachment protein, SNAP REceptors" – are a large protein family consisting of at least 24 members in yeasts and more than 60 members in mammalian and plant cells. The primary role of SNARE proteins is to m ...

s such as

N-ethylmaleimide sensitive fusion protein ''N''-ethylmaleimide-sensitive factor, also known as NSF or ''N''-ethylmaleimide sensitive fusion proteins, is an enzyme which in humans is encoded by the ''NSF'' gene. Function NSF is a homohexameric AAA ATPase involved in membrane fusion. ...

, bringing the endosomes physically closer and ultimately resulting in the fusion and delivery of endosomal cargo.

Function

EEA1 is a

RAB5A Ras-related protein Rab-5A is a protein that in humans is encoded by the ''RAB5A'' gene. Function RAB5A localizes to early endosomes where it is involved in the recruitment of RAB7A and the maturation of these compartments to early endosomes. ...

effector protein which binds via an N-terminal

zinc finger A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) which stabilizes the fold. The term ''zinc finger'' was originally coined to describe the finger-like appearance of a ...

domain and is required for fusion of early and late endosomes and for sorting at the early endosome level. EEA1 plays a role in endocytosis and is recruited by Rab5-GTP to endosomal membranes. EEA1 may be regulated through monoubiquination, affecting endosome fusion and trafficking. 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 ''Mycobacterium tuberculosis'' (M. tb), also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' ha ...

'' is known to inhibit the recruitment of EEA1 to the phagosomal membrane through

CamKII /calmodulin-dependent protein kinase II (CaM kinase II or CaMKII) is a serine/threonine-specific protein kinase that is regulated by the /calmodulin complex. CaMKII is involved in many signaling cascades and is thought to be an important mediat ...

. ''

Legionella pneumophila ''Legionella pneumophila'', the primary causative agent for Legionnaires' disease, Legionnaire's disease, is an Aerobic organism, aerobic, pleomorphic, Flagellum, flagellated, non-spore-forming, Gram-negative bacteria, Gram-negative bacterium. ' ...

'' also prevents EEA1 recruitment through a currently unknown mechanism. The related pathogen ''

Legionella longbeachae ''Legionella longbeachae'' is one species of the family Legionellaceae. It was first isolated from a patient in Long Beach, California. It is found predominantly in potting soil and compost. Human infection from ''L. longbeachae'' is particularl ...

'' recruits EEA1 and appears to replicate within a modified early endosome.

References

External links

* * {{PDBe-KB2, Q15075, Early endosome antigen 1 Peripheral membrane proteins

Function

Involvement in pathogenesis

See also

References

External links