HIP1 (Huntingtin Interacting Protein 1)

Page updated 27/5/02

Related to Sla2 from Saccharomyces cerevisae, HIP1 is so called as it binds to huntingtin (Kalchman et al, 1997), a protein that contains a stretch of glutamic acids that are variable in number due to a tendency for increased repeats to be inserted in this part of the gene.  Beyond 35 glutamines, results in the failure of HIP1 to bind, and this is at least partly responsible for the neuronal degeneration  that is a hall mark of the disease.  HIP1 is implicated in endocytosis (Engqvist-Goldstein et al, 1999) being a component of the clathrin coated vesicle system.  HIP1 binds PIP₂ by the ENTH domain (epsin N-terminal homology), clathrin and AP2  (Metzler et al, 2001) through the central coiled-coil domain (Engqvist-Goldstein et al, 2000), and actin through a talin-like domain at the C-terminus (Engqvist-Goldstein et al, 1999).

HIP1 is a 120Kda protein that forms a 60nm, rod-shaped dimer with globular ends of 7-10nm diameter.

See Endocytosis

References:-

Engqvist-Goldstein, A.E.Y., Kessels, M.M., Chopra, V.S., Hayden, M.R. & Drubin, D.G. (1999). "An actin binding protein of the Sla2/Huntington Interacting Protein 1 family is a novel component of clatherin-coated pits and vesicles." J.Cell Biol. 147(7), 1503-1518.

Engqvist-Goldstein, A. E. Y., Warren, R. A., Kessels, M. M., Keen, J. H., Heuser, J. & Drubin, D. G. (2001) The actin-binding protein Hip1R associates with clathrin during early stages of endocytosis and promotes clathrin assembly in vitro., J.Cell Biol. 154, 1209-1223.

Kalchman, M.A., Koide, K., McCutcheon, K., Graham, R.K., Nichol, K., Nishiyama, K., Kazemi-Esfarjani, P., Lynn, F.C., Wellington, C., Metzler, M. et al. (1997). HIP1, a human homolog of S. cerevisiae Sla2p, interacts with membrane associated huntingtin in the brain. Nature Genetics 16, 44-53.

Legendre-Guillemin, V., Metzler, M., Charbonneau, M., Gan, L., Chopra, V., Phillie, J., Hayden, M. R. & McPherson, P. S. (2002) HIP1 and HIP12 display differential binding to F-actin, AP2, and clathrin., J.Biol.Chem. 277, 19897-19904.

Metzler, M., Legendre-Guillemin, V., Gan, L., Chopra, V., Kwok, A., McPherson, P. S. & Hayden, M. R. (2001) HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and adaptor protein 2., J.Biol.Chem. 276, 39271-39276.