9.A.49 The Prenylated Rab Acceptor Protein 1 (PRA1) Family PRA1 domain family, member 2 (PRAF2) is a 19-kDa protein with a prenylated Rab acceptor 1 (PRA1) motif and four TMSs. PRAF2 is highly expressed in the brain and serves as a candidate prognostic marker in neuroblastoma (NB). PRAF2 is related to proteins PRAF1 (PRA1, prenylin, Yip3) and PRAF3 (GTRAP3-18, JWA, Arl6-IP5), both of which are enriched in the brain and implicated in cellular transport and endo/exocytic vesicle trafficking. The distribution and localization of PRAF2 in the mature human brain revealed that in the human cerebellum, the PRAF2 protein is strongly expressed in Purkinje cells and, more moderately, in cells of the molecular and the granular layers (Koomoa et al. 2008; ). In the cerebral cortex, hippocampus and lateral ventricles, PRAF2 can be detected in neuronal cells but not non-neuronal cells. PRAF2 is enriched in synaptic vesicles prepared from rat brains. The expression of PRAF2 in specific regions of the brain including synaptic vesicles suggest a physiological function in participatioin of multiple aspects of synaptic vesicle maturation, transport and signal transmission. Di-arginine and FFAT-like motifs retain a subpopulation of PRA1 at ER-mitochondria membrane contact sites, suggesting that it has a functional role within the ER (Abu Irqeba and Ogilvie 2020).
References:
Abu Irqeba, A. and J.M. Ogilvie. (2020). Di-arginine and FFAT-like motifs retain a subpopulation of PRA1 at ER-mitochondria membrane contact sites. PLoS One 15: e0243075.
Da Silva, E., M.G.H. Scott, H. Enslen, and S. Marullo. (2023). Control of CCR5 Cell-Surface Targeting by the PRAF2 Gatekeeper. Int J Mol Sci 24:.
Dickison, V.M., A.M. Richmond, A. Abu Irqeba, J.G. Martak, S.C. Hoge, M.J. Brooks, M.I. Othman, R. Khanna, A.J. Mears, A.Y. Chowdhury, A. Swaroop, and J.M. Ogilvie. (2012). A role for prenylated rab acceptor 1 in vertebrate photoreceptor development. BMC Neurosci 13: 152.
Fo, C.S., C.S. Coleman, C.J. Wallick, A.L. Vine, and A.S. Bachmann. (2006). Genomic organization, expression profile, and characterization of the new protein PRA1 domain family, member 2 (PRAF2). Gene 371: 154-165.
Geerts, D., C.J. Wallick, D.L. Koomoa, J. Koster, R. Versteeg, R.C. Go, and A.S. Bachmann. (2007). Expression of prenylated Rab acceptor 1 domain family, member 2 (PRAF2) in neuroblastoma: correlation with clinical features, cellular localization, and cerulenin-mediated apoptosis regulation. Clin Cancer Res 13: 6312-6319.
Kitta, S., T. Kaminishi, M. Higashi, T. Shima, K. Nishino, N. Nakamura, H. Kosako, T. Yoshimori, and A. Kuma. (2024). YIPF3 and YIPF4 regulate autophagic turnover of the Golgi apparatus. EMBO. J. 43: 2954-2978.
Koomoa, D.L., R.C. Go, K. Wester, and A.S. Bachmann. (2008). Expression profile of PRAF2 in the human brain and enrichment in synaptic vesicles. Neurosci Lett 436: 171-176.
Liang, Z., H. Veeraprame, N. Bayan, and G. Li. (2004). The C-terminus of prenylin is important in forming a dimer conformation necessary for endoplasmic-reticulum-to-Golgi transport. Biochem. J. 380: 43-49.
Schweneker, M., A.S. Bachmann, and K. Moelling. (2005). JM4 is a four-transmembrane protein binding to the CCR5 receptor. FEBS Lett. 579: 1751-1758.
Tanimoto, K., K. Suzuki, E. Jokitalo, N. Sakai, T. Sakaguchi, D. Tamura, G. Fujii, K. Aoki, S. Takada, R. Ishida, M. Tanabe, H. Itoh, Y. Yoneda, M. Sohda, Y. Misumi, and N. Nakamura. (2011). Characterization of YIPF3 and YIPF4, cis-Golgi Localizing Yip domain family proteins. Cell Struct Funct 36: 171-185.
Examples:
TC#	Name	Organismal Type	Example
9.A.49.1.1	Prenylated Rab acceptor protein 1 (PRA1, prenylin, yip3) of 185 aas and 3 - 4 putative TMSs. The C-terminus of prenylin is important in forming a dimer conformation necessary for endoplasmic-reticulum-to-Golgi transport (Liang et al. 2004). It may play a role in postnatal development of the inner retina (Dickison et al. 2012).		PRA1 of Homo sapiens

9.A.49.1.10	PRA1 family protein 2, Praf2 of 158 aas		*Praf2 of Dictyostelium discoideum* (Slime mold)**

9.A.49.1.11	RAB acceptor of 226 aas, Cgd8		Cgd8 of Cryptosporidium parvum

9.A.49.1.12	Yip3 or PRA3 of 176 aas and 2 or 3 TMSs (Tanimoto et al. 2011). YIPF3 and YIPF4 regulate autophagic turnover of the Golgi apparatus (Kitta et al. 2024). Expression of the YIPF3 gene encoding the protein containing a mutated LIR motif caused an elongated Golgi morphology, indicating the importance of Golgi turnover via selective autophagy.		*Yip3 of Saccharomyces cerevisiae* (Baker's yeast)**

9.A.49.1.2	Prenylated Rab acceptor protein 2 (PRAF2; JM4) of 178 aas and 4 TMSs in a 2 + 2 TMS arrangement. Its expression profiles and characteristics have been described (Fo et al. 2006; Koomoa et al. 2008). JM4 interacts with the CC chemokine receptor 5 (CCR5), a major co-receptor for human immunodeficiency virus (HIV); CCR5 mutants lacking the carboxy (C)-terminus interfere with HIV infection (Schweneker et al. 2005). JM4, JWA (TC# 9.A.49.1.3), and GTRAP3-18 co-localise and heterodimerise indicating a functional relationship. JM4 co-localizes with calnexin in the endoplasmic reticulum and with the mannose 6-phosphate receptor in the Golgi. JM4 and GTRAP3-18 harbor a Rab-acceptor motif, indicating a function in vesicle formation in the Golgi. The cinokex may function in trafficking and membrane localization of CCR5 receptor, and possibly other receptors or amino acid transporters (Schweneker et al. 2005). It may be involved in ER/Golgi transport and vesicular traffic, and it plays a proapoptotic role in cerulenin-induced neuroblastoma apoptosis (Geerts et al. 2007). It is involved in control of CCR5 cell-surface targeting (Da Silva et al. 2023).		PRAF2 of Homo sapiens

9.A.49.1.3	PRAF3 of 188 aas and 4 TMSs. It is also called PRA2, GTRAP3-18, JWA, ARL6IP5, DERP11, and Ar16-IP5. JWA, like JM4 (TC# 9.A.49.1.2), is a four TMS protein, which binds to the CCR5 receptor (Schweneker et al. 2005). JM4, JWA, and GTRAP3-18 co-localize and heterodimerize, indicating a functional relationship. JM4 co-localises with calnexin in the endoplasmic reticulum and with the mannose 6-phosphate receptor in the Golgi. JM4 and GTRAP3-18 harbor a Rab-acceptor motif, indicating a function in vesicle formation in the Golgi complex.Thus, Schweneker et al. 2005 demonstrated CCR5-interacting proteins, suggesting a function in trafficking and membrane localization of the receptor, possibly as well as other receptors and amino acid transporters.		PRAF3 of Homo sapiens

9.A.49.1.4	PRA1 family protein B1		*Protein B1 of Arabidopsis thaliana* (Mouse-ear cress)**

9.A.49.1.5	PrafB of 158 aas and 4 TMSs.		*PrafB of Polysphondylium pallidum* (Cellular slime mold)**

9.A.49.1.6	RAB interacting protein of 206 aas		Pro1 family member of Trypanosoma vivax

9.A.49.1.7	Uncharacterized protein of 197 aas		UP of Leishmania braziliensis

9.A.49.1.8	Prenylated rab acceptor 1 of 230 aas		Prenylated rab acceptor 1 of Acanthamoeba castellanii

9.A.49.1.9	Uncharacterized protein of 177 aas		UP of Micromonas pusilla (Picoplanktonic green alga)

Examples:
TC#	Name	Organismal Type	Example