HIP1

Description

The HIP1 (huntingtin interacting protein 1) is a protein-coding gene located on chromosome 7.

HIP1 is a protein that interacts with the huntingtin protein. It is known to contain a domain homologous to the death effector domains (DED) found on proteins involved in apoptosis. It is believed that accumulation of high levels of the free form of this protein (free as in dissociated from the huntingtin and free to bind other key protein(s)) in the cell is one of the mechanisms by which neuron cell death is caused in Huntington‘s disease (via the caspase-3 route). The role of Hip-1 in caspase mediated cell death remains unclear. HIP1 was first identified by Wanker et al. in 1997. HIP1 was found to bind to Htt in an N-terminal dependent manner, and co-localise with Htt in the CNS although the nature of this interaction with respect to muHtt was not identified. It has since been found that the CAG expansion seen with muHtt results in decreased binding affinity for HIP1, thus causing disruption of HIP1’s usual function, and also an increase in free HIP1. It is likely that this decreased affinity plays a role in mediating HD pathogenesis, due to loss of cytoskeletal integrity and induction of apoptosis.

HIP1 plays a critical role in clathrin-mediated endocytosis and trafficking. It regulates AMPA receptor trafficking in the central nervous system in an NMDA-dependent manner. Additionally, HIP1 regulates presynaptic nerve terminal activity and enhances androgen receptor-mediated transcription. While HIP1 may act as a proapoptotic protein inducing cell death through the intrinsic apoptosis pathway, it can also promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis through its ENTH domain. HIP1 interacts with various proteins, including those involved in clathrin-mediated endocytosis, cytoskeleton organization, and signaling pathways. It also plays a role in cell differentiation, proliferation, and survival.

HIP1 is also known as HIP-I, ILWEQ, SHON, SHONbeta, SHONgamma.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing