HIP1

The product of this gene is a membrane-associated protein that functions in clathrin-mediated endocytosis and protein trafficking within the cell. The encoded protein binds to the huntingtin protein in the brain; this interaction is lost in Huntington's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Full Name

Huntingtin Interacting Protein 1

Function

Plays a role in clathrin-mediated endocytosis and trafficking (PubMed:11532990, PubMed:11577110, PubMed:11889126).

Involved in regulating AMPA receptor trafficking in the central nervous system in an NMDA-dependent manner (By similarity).

Regulates presynaptic nerve terminal activity (By similarity).

Enhances androgen receptor (AR)-mediated transcription (PubMed:16027218).

May act as a proapoptotic protein that induces cell death by acting through the intrinsic apoptosis pathway (PubMed:11007801).

Binds 3-phosphoinositides (via ENTH domain) (PubMed:14732715).

May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis (PubMed:14732715).

May play a functional role in the cell filament networks (PubMed:18790740).

May be required for differentiation, proliferation, and/or survival of somatic and germline progenitors (PubMed:11007801, PubMed:12163454).

Biological Process

Actin filament organization Source: GO_Central
Activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
Apoptotic process Source: MGI
Apoptotic signaling pathway Source: UniProtKB
Cell differentiation Source: UniProtKB-KW
Clathrin coat assembly Source: UniProtKB
Clathrin-dependent endocytosis Source: InterPro
Endocytosis Source: GO_Central
Neurotransmitter receptor transport Source: ParkinsonsUK-UCL
Positive regulation of epidermal growth factor receptor signaling pathway Source: ParkinsonsUK-UCL
Positive regulation of platelet-derived growth factor receptor-beta signaling pathway Source: ParkinsonsUK-UCL
Positive regulation of protein kinase B signaling Source: ParkinsonsUK-UCL
Positive regulation of receptor-mediated endocytosis Source: UniProtKB
Protein stabilization Source: ParkinsonsUK-UCL
Regulation of apoptotic process Source: MGI
Regulation of endocytosis Source: ParkinsonsUK-UCL

Cellular Location

Nucleus; Cytoplasm; Endomembrane system; Clathrin-coated vesicle membrane. Shuttles between cytoplasm and nucleus. Nuclear translocation can be induced by AR.

Involvement in disease

A chromosomal aberration involving HIP1 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;7)(q33;q11.2) with PDGFRB (PubMed:9616134). The chimeric HIP1-PDGFRB transcript results from an in-frame fusion of the two genes (PubMed:9616134). The reciprocal PDGFRB-HIP1 transcript is not expressed (PubMed:9616134).