Protein structure
The EHD protein family is a relatively small group of proteins which have been shown to play a role in several physiological functions, the most notable being the regulation of endocytotic vesicles. This family is recognized by its highly conserved EH (Eps15 homology) domain, a structural motif that has been shown to facilitate specificity and interaction between protein and effector. The four mammalian EHD proteins that have been classified are: EHD1, EHD2, EHD3, and EHD4.
During the late 20th century, several advances were made regarding the identification of proteins involved in endocytotic recycling and other mechanisms of intracellular trafficking. This period of research led to the discovery of over 60 proteins which collectively make up the Rab family. Rab proteins have been found to play a major role in endocytotic recycling via SNARE-based vesicle fusion and transport. When bound to GTP, Rab proteins have a large affinity for their respective effectors which then work to carry out a specific function.
Some years later after the identification of the Rab family, the EHD family was discovered and was found to be associated with the same effectors that interact with Rab proteins. This mutual interaction insinuated that the EHD proteins must be somehow cooperatively involved in the endocytotic recycling pathway.
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell. The area in the axon that holds groups of vesicles is an axon terminal or "terminal bouton". Up to 130 vesicles can be released per bouton over a ten-minute period of stimulation at 0.2 Hz. In the visual cortex of the human brain, synaptic vesicles have an average diameter of 39.5 nanometers (nm) with a standard deviation of 5.1 nm.
The Rab family of proteins is a member of the Ras superfamily of small G proteins. Approximately 70 types of Rabs have now been identified in humans. Rab proteins generally possess a GTPase fold, which consists of a six-stranded beta sheet which is flanked by five alpha helices. Rab GTPases regulate many steps of membrane trafficking, including vesicle formation, vesicle movement along actin and tubulin networks, and membrane fusion. These processes make up the route through which cell surface proteins are trafficked from the Golgi to the plasma membrane and are recycled. Surface protein recycling returns proteins to the surface whose function involves carrying another protein or substance inside the cell, such as the transferrin receptor, or serves as a means of regulating the number of a certain type of protein molecules on the surface.
Annexin is a common name for a group of cellular proteins. They are mostly found in eukaryotic organisms.
Retromer is a complex of proteins that has been shown to be important in recycling transmembrane receptors from endosomes to the trans-Golgi network (TGN).
Class III PI 3-kinase is a subgroup of the enzyme family, phosphoinositide 3-kinase that share a common protein domain structure, substrate specificity and method of activation.
Adenylylation, more commonly known as AMPylation, is a process in which an adenosine monophosphate (AMP) molecule is covalently attached to the amino acid side chain of a protein. This covalent addition of AMP to a hydroxyl side chain of the protein is a posttranslational modification. Adenylylation involves a phosphodiester bond between a hydroxyl group of the molecule undergoing adenylylation, and the phosphate group of the adenosine monophosphate nucleotide. Enzymes that are capable of catalyzing this process are called AMPylators.
Ras-related protein Rab-7a is a protein that in humans is encoded by the RAB7A gene.
Ras-related protein Rab-11A is a protein that in humans is encoded by the RAB11A gene.
Golgin subfamily A member 2 is a protein that in humans is encoded by the GOLGA2 gene.
Ras-related protein Rab-3A is a protein that in humans is encoded by the RAB3A gene. It is involved in calcium-triggered exocytosis in neurons.
Syntaxin-6 is a protein that in humans is encoded by the STX6 gene.
Vesicle-associated membrane protein 3 is a protein that in humans is encoded by the VAMP3 gene.
Ras-related protein Rab-9A is a protein that in humans is encoded by the RAB9A gene.
EH domain-containing protein 1, also known as testilin or PAST homolog 1 (PAST1), is a protein that in humans is encoded by the EHD1 gene belonging to the EHD protein family.
Rab11 family-interacting protein 2 is a protein that in humans is encoded by the RAB11FIP2 gene.
Rab11 family-interacting protein 5 is a protein that in humans is encoded by the RAB11FIP5 gene.
Blood vessel epicardial substance (BVES) also known as popeye domain-containing protein 1 (POPDC1) is a protein that in humans is encoded by the BVES gene.
Kinesin-like protein KIF1A, also known as axonal transporter of synaptic vesicles or microtubule-based motor KIF1A, is a protein that in humans is encoded by the KIF1A gene.
Ras and EF-hand domain-containing protein also known as Ras-related protein Rab-45 is a protein that in humans is encoded by the RASEF gene.
Eps15 homology domain-containing protein 3, abbreviated as EHD3 and also known as PAST3, is a protein encoded by the EHD3 gene. It has been observed in humans, mice and rats. It belongs to the EHD protein family, a group of four membrane remodeling proteins related to the Dynamin superfamily of large GTPases. Although the four of them are 70-80% amino acid identical, they all have different locations. Its main function is related to endocytic transport.
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