VAPA
Description
The VAPA (VAMP associated protein A) is a protein-coding gene located on chromosome 18.
VAPA, or Vesicle-Associated Membrane Protein-Associated Protein A, is a protein encoded by the VAPA gene in humans. It belongs to the VAP protein family, which also includes VAPB and VAPC. These proteins are integral endoplasmic reticulum membrane proteins of type II and are widespread among eukaryotes. VAPA is expressed in all human tissues and is believed to be involved in membrane trafficking through interactions with SNAREs, lipid transport and metabolism regulation, and the Unfolded Protein Response (UPR). The protein has three domains: an N-terminal beta-sheet with an immunoglobulin-like fold, a central coiled-coil domain, and a C-terminal transmembrane domain (TMD) commonly found in t-SNARE proteins and other proteins associated with vesicular transport. VAPA can form homodimers and heterodimers with VAPB through interactions involving their TMDs. Due to its widespread expression, the intracellular localization and function of VAPA can vary between cell types.
VAPA is an endoplasmic reticulum (ER)-anchored protein that facilitates the formation of contact sites between the ER and endosomes. It achieves this by interacting with FFAT motif-containing proteins like STARD3 and WDR44. The interaction with STARD3 allows for cholesterol transfer from the ER to endosomes, while the interaction with WDR44 participates in the export of newly synthesized proteins. Additionally, VAPA can be recruited to the plasma membrane through binding with OSBPL3. The OSBPL3-VAPA complex stimulates RRAS signaling, which in turn decreases the activation of integrin beta-1 (ITGB1) at the cell surface. Moreover, VAPA may contribute to regulating ER morphology in collaboration with OSBPL3. It is believed to play a role in vesicle trafficking.
VAPA is also known as VAMP-A, VAP-33, VAP-A, VAP33, hVAP-33.
