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9.B.37 The Huntington-interacting Protein 14 (HIP14) Family

The Huntington-interacting protein 14 (HIP14) is reported to be a palmitoyltransferase required for exocytosis and targeting of the palmitoylated cysteine string protein (CSP) and the SNAP25 protein which are mislocalized in a HIP14 mutant (Ohyama et al., 2007). HIP14 also palmitoylates CSP. HIP14 may be necessary for presynaptic function including neurotransmitter release by regulating the trafficking of CSP to synapses (Ducker et al., 2004; Ohyama et al., 2007; Stowers and Isacoff, 2007; Yanai et al., 2006).

HIP14 is reported to be a divalent cation transporter capable of transporting Mg2+ found only in eukaryotes (Quamme, 2009). It has up to eight N-terminal Ankyrin repeats (residues 25-270) followed by the transmembrane domain (residues 300-560; The zfDHHC domain superfamily). As of 2018, the function of this protein as a Mg2+ transporter was under debate (Schäffers et al. 2018).

The reaction proposed for HIP14 is:

M2+(in) ⇌ M2+(out)

References associated with 9.B.37 family:

and Quamme GA. (2010). Molecular identification of ancient and modern mammalian magnesium transporters. Am J Physiol Cell Physiol. 298(3):C407-29. 19940067
Ducker, C.E., E.M. Stettler, K.J. French, J.J. Upson, and C.D. Smith. (2004). Huntingtin interacting protein 14 is an oncogenic human protein: palmitoyl acyltransferase. Oncogene 23: 9230-9237. 15489887
Goytain, A., R.M. Hines, and G.A. Quamme. (2008). Huntingtin-interacting proteins, HIP14 and HIP14L, mediate dual functions, palmitoyl acyltransferase and Mg2+ transport. J. Biol. Chem. 283: 33365-33374. 18794299
Hines, R.M., R. Kang, A. Goytain, and G.A. Quamme. (2010). Golgi-specific DHHC zinc finger protein GODZ mediates membrane Ca2+ transport. J. Biol. Chem. 285: 4621-4628. 19955568
Ohyama, T., P. Verstreken, C.V. Ly, T. Rosenmund, A. Rajan, A.C. Tien, C. Haueter, K.L. Schulze, and H.J. Bellen. (2007). Huntingtin-interacting protein 14, a palmitoyl transferase required for exocytosis and targeting of CSP to synaptic vesicles. J. Cell Biol. 179: 1481-1496. 18158335
Rana, M.S., P. Kumar, C.J. Lee, R. Verardi, K.R. Rajashankar, and A. Banerjee. (2018). Fatty acyl recognition and transfer by an integral membrane-acyltransferase. Science 359:. 29326245
Schäffers, O.J.M., J.G.J. Hoenderop, R.J.M. Bindels, and J.H.F. de Baaij. (2018). The rise and fall of novel renal magnesium transporters. Am. J. Physiol. Renal Physiol 314: F1027-F1033. 29412701
Stowers, R.S. and E.Y. Isacoff. (2007). Drosophila huntingtin-interacting protein 14 is a presynaptic protein required for photoreceptor synaptic transmission and expression of the palmitoylated proteins synaptosome-associated protein 25 and cysteine string protein. J. Neurosci. 27: 12874-12883. 18032660
Swarthout, J.T., S. Lobo, L. Farh, M.R. Croke, W.K. Greentree, R.J. Deschenes, and M.E. Linder. (2005). DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras. J. Biol. Chem. 280: 31141-31148. 16000296
Yanai, A., K. Huang, R. Kang, R.R. Singaraja, P. Arstikaitis, L. Gan, P.C. Orban, A. Mullard, C.M. Cowan, L.A. Raymond, R.C. Drisdel, W.N. Green, B. Ravikumar, D.C. Rubinsztein, A. El-Husseini, and M.R. Hayden. (2006). Palmitoylation of huntingtin by HIP14 is essential for its trafficking and function. Nat Neurosci 9: 824-831. 16699508