ADP-ribosylation factor GTPase-activating protein 1 is an enzyme that in humans is encoded by the ARFGAP1 gene. [5] [6] Two transcript variants encoding different isoforms have been found for this gene.
The protein encoded by this gene is a GTPase-activating protein (GAP) which associates with the Golgi apparatus and which interacts with ADP-ribosylation factor 1 (ARF1). The encoded protein promotes hydrolysis of ARF1-bound GTP and is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. The activity of this protein is stimulated by phosphoinositides and inhibited by phosphatidylcholine. [6]
The protein has two amphipathic lipid packing sensor motifs (ALPS), that let the protein sense the curvature of the membrane (<30 nm) or lipid packing defects, and in this way evaluate if the vesicle is mature and ready for coat disassembly. [7] [8]
ARFGAP1 has been shown to interact with KDELR1 and LRRK2. [9] [10] [11]
The Golgi apparatus, also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles inside the cell before the vesicles are sent to their destination. It resides at the intersection of the secretory, lysosomal, and endocytic pathways. It is of particular importance in processing proteins for secretion, containing a set of glycosylation enzymes that attach various sugar monomers to proteins as the proteins move through the apparatus.
GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a protein domain common to many GTPases.
COPI is a coatomer, a protein complex that coats vesicles transporting proteins from the cis end of the Golgi complex back to the rough endoplasmic reticulum (ER), where they were originally synthesized, and between Golgi compartments. This type of transport is retrograde transport, in contrast to the anterograde transport associated with the COPII protein. The name "COPI" refers to the specific coat protein complex that initiates the budding process on the cis-Golgi membrane. The coat consists of large protein subcomplexes that are made of seven different protein subunits, namely α, β, β', γ, δ, ε and ζ.
ADP-ribosylation factor 6 (ARF6) is a member of the ADP ribosylation factor family of GTP-binding proteins. ARF6 has a variety of cellular functions that are frequently involved in trafficking of biological membranes and transmembrane protein cargo. ARF6 has specifically been implicated in endocytosis of plasma membrane proteins and also, to a lesser extent, plasma membrane protein recycling.
ADP ribosylation factors (ARFs) are members of the ARF family of GTP-binding proteins of the Ras superfamily. ARF family proteins are ubiquitous in eukaryotic cells, and six highly conserved members of the family have been identified in mammalian cells. Although ARFs are soluble, they generally associate with membranes because of N-terminus myristoylation. They function as regulators of vesicular traffic and actin remodelling.
The coatomer is a protein complex that coats membrane-bound transport vesicles. Two types of coatomers are known:
ADP-ribosylation factor 1 is a protein that in humans is encoded by the ARF1 gene.
Coatomer subunit beta is a protein that in humans is encoded by the COPB1 gene.
Cytohesin-2 is a protein that in humans is encoded by the CYTH2 gene.
Cytohesin-1 formerly known as Pleckstrin homology, Sec7 and coiled/coil domains 1 (PSCD1) is a protein that in humans is encoded by the CYTH1 gene.
ADP-ribosylation factor 3 is a protein that in humans is encoded by the ARF3 gene.
ADP-ribosylation factor 5 is a protein that in humans is encoded by the ARF5 gene.
ADP-ribosylation factor 4 is a protein that in humans is encoded by the ARF4 gene.
KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 1, also known as KDELR1, is a protein which in humans is encoded by the KDELR1 gene.
Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 is a protein that in humans is encoded by the ASAP2 gene.
ADP-ribosylation factor-related protein 1 is a protein that in humans is encoded by the ARFRP1 gene.
GTP-binding protein ARD-1 is a protein that in humans is encoded by the TRIM23 gene.
ADP-ribosylation factor GTPase-activating protein 3 is a protein that in humans is encoded by the ARFGAP3 gene.
IQ motif and SEC7 domain-containing protein 1 also known as ARF-GEP100 (ADP-Ribosylation Factor - Guanine nucleotide-Exchange Protein - 100-kDa) is a protein that in humans is encoded by the IQSEC1 gene.
Exomer is a heterotetrameric protein complex similar to COPI and other adaptins. It was first described in the yeast Saccharomyces cerevisiae. Exomer is a cargo adaptor important in transporting molecules from the Golgi apparatus toward the cell membrane. The vesicles it is found on are different from COPI vesicles in that they do not appear to have a "coat" or "scaffold" around them.