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9.B.17 The VAMP-associated protein (VAP) Family

The VAMP-associated proteins (VAPs) are highly conserved integral endoplasmic reticulum membrane proteins implicated in diverse cellular functions, including the regulation of lipid transport and homeostasis, membrane trafficking, neurotransmitter release, stabilization of presynaptic microtubules, and the unfolded protein response. A single missense mutation within the human VAP-B gene was identified in three forms of familial motor neuron disease. Yeast, flies and mammals have VAPs. There is a network of VAP-interacting proteins. Their mechanisms of action are not well understood (Lev et al., 2008). However, VAPs form a network with a reticulophagy receptor and Atg8 (Yang and Klionsky 2020).

The endoplasmic reticulum transmembrane protein vesicle-associated membrane protein-associated protein (VAP) plays a central role in the formation and function of membrane contact sites (MCS) through its interactions with proteins. The major sperm protein (MSP) domain of VAP binds to a variety of sequences which are referred to as FFAT-like motifs. Furuita et al. 2021 investigated the interactions of eight peptides containing FFAT-like motifs with the VAP-A MSP domain (VAP-AMSP ) by solution NMR. Six of eight peptides were specifically bound to VAP-A. The RNA-dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2 has an FFAT-like motif which specifically binds to VAP-AMSP as well as other FFAT-like motifs. 

References associated with 9.B.17 family:

Furuita, K., M. Hiraoka, K. Hanada, T. Fujiwara, and C. Kojima. (2021). Sequence requirements of the FFAT-like motif for specific binding to VAP-A are revealed by NMR. FEBS Lett. 595: 2248-2256. 34312846
Lev, S., D. Ben Halevy, D. Peretti, and N. Dahan. (2008). The VAP protein family: from cellular functions to motor neuron disease. Trends Cell Biol. 18: 282-290. 18468439
Li, M.T., W. Di, H. Xu, Y.K. Yang, H.W. Chen, F.X. Zhang, Z.H. Zhai, and D.Y. Chen. (2013). Negative regulation of RIG-I-mediated innate antiviral signaling by SEC14L1. J. Virol. 87: 10037-10046. 23843640
Mendes, L.F.S. and A.J. Costa-Filho. (2022). A gold revision of the Golgi Dynamics (GOLD) domain structure and associated cell functionalities. FEBS Lett. 596: 973-990. 35099811
Ribeiro, F.M., L.T. Ferreira, S. Marion, S. Fontes, M. Gomez, S.S. Ferguson, M.A. Prado, and V.F. Prado. (2007). SEC14-like protein 1 interacts with cholinergic transporters. Neurochem Int 50: 356-364. 17092608
Sohda, M., Y. Misumi, A. Yamamoto, A. Yano, N. Nakamura, and Y. Ikehara. (2001). Identification and characterization of a novel Golgi protein, GCP60, that interacts with the integral membrane protein giantin. J. Biol. Chem. 276: 45298-45306. 11590181
Yamanaka, T., R. Nishiyama, T. Shimogori, and N. Nukina. (2020). Proteomics-Based Approach Identifies Altered ER Domain Properties by ALS-Linked VAPB Mutation. Sci Rep 10: 7610. 32376919
Yang, Y. and D.J. Klionsky. (2020). A novel reticulophagy receptor, Epr1: a bridge between the phagophore protein Atg8 and ER transmembrane VAP proteins. Autophagy 1-2. [Epub: Ahead of Print] 33121335