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
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.
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.
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.
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.
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,