huntingtin-interacting protein 1 huntingtin-interacting protein 1 huntingtin-interacting protein 1 also known as hip-1 is a protein that in humans is encoded by the hip1 gene. hip1available structurespdbortholog search: pdbe rcsb list of pdb id codes2no2, 2qa7, 3i00identifiersaliaseship1, hip-i, ilweq, shon, shonbeta, shongamma, huntingtin interacting protein 1external idsomim: 601767 mgi: 1099804 homologene: 68463 genecards: hip1 gene location (human)chr.chromosome 7 (human)band7q11.23start75,533,298 bpend75,738,962 bpgene location (mouse)chr.chromosome 5 (mouse)band5 g2|5 75.18 cmstart135,406,531 bpend135,545,120 bprna expression patternbgeehumanmouse (ortholog)top expressed incorpus callosumsural nerveinferior ganglion of vagus nerverenal medullaachilles tendonsubthalamic nucleuslower lobe of lungpopliteal arteryright coronary arteryvisceral pleuratop expressed insacculeascending aortatrigeminal ganglionaortic valveexternal carotid arteryinternal carotid arterymirrorotic placodeinterventricular septumblastocystmore reference expression databiogpsn/agene ontologymolecular function clathrin binding structural constituent of cytoskeleton protein binding phosphatidylinositol binding actin binding phospholipid binding epidermal growth factor receptor binding phosphatidylinositol-4,5-bisphosphate binding clathrin light chain binding phosphatidylinositol-3-phosphate binding glutamate receptor binding ap-2 adaptor complex binding clathrin adaptor activity protein homodimerization activity phosphatidylinositol-3,4-bisphosphate binding protein heterodimerization activity actin filament binding phosphatidylinositol-3,5-bisphosphate binding cellular component cytoplasm golgi apparatus membrane intracellular membrane-bounded organelle clathrin-coated vesicle membrane cytoskeleton cytoplasmic vesicle endomembrane system clathrin-coated vesicle nucleus cytosol ap-2 adaptor complex extrinsic component of cytoplasmic side of plasma membrane extrinsic component of presynaptic membrane extrinsic component of postsynaptic membrane presynapse postsynapse postsynaptic membrane glutamatergic synapse actin cortical patch biological process regulation of apoptotic process cell differentiation positive regulation of receptor-mediated endocytosis regulation of transcription, dna-templated endocytosis transcription, dna-templated clathrin-dependent endocytosis clathrin coat assembly apoptotic signaling pathway activation of cysteine-type endopeptidase activity involved in apoptotic process apoptotic process cytoskeleton organization regulation of endocytosis positive regulation of epidermal growth factor receptor signaling pathway protein stabilization positive regulation of protein kinase b signaling membrane organization neurotransmitter receptor transport positive regulation of platelet-derived growth factor receptor-beta signaling pathway actin filament organization sources:amigo / quickgoorthologsspecieshumanmouseentrez3092215114ensemblensg00000127946ensmusg00000039959uniproto00291q8vd75refseq (mrna)nm_001243198nm_005338nm_001382444nm_001382445nm_146001nm_001382848refseq (protein)np_001230127np_005329np_001369373np_001369374np_666113np_001369777location (ucsc)chr 7: 75.53 – 75.74 mbchr 5: 135.41 – 135.55 mbpubmed searchwikidataview/edit humanview/edit mouse hip-1 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. discovery huntingtin interacting protein 1 (hip1) was first identified by wanker et al. in 1997. function 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’s pro apoptotic effect may involve activation of caspase-8 and a novel hip1 protein interactor hippi. hip1’s non-pathological activity includes clathrin assembly via interaction with clathrin light chains. hip1 is the human homologue of sla2p, a membrane protein in the periphery. sla2p is an actin-binding protein involved in endocytosis, thus indicating hip1 in this role. further details suggesting an important role for hip-1 in endocytosis comes from binding studies looking at hip-1 binding to actin. actin binding by hip-1 is altered depending on whether clathrin is also bound to hip-1. clinical significance hip1 has also been found to be overexpressed in some cancers including a subset of colorectal and prostate cancers. this is of specific interest because prostate cancer disease progression involves altered transcription/expression of the androgen receptor (ar). the ar is a nuclear hormone receptor transcription factor that contains polyglutamine repeats. in 2005 mills and colleagues showed that hip1 is able to regulate transcription of hormone receptors via the androgen response element (are) and also alters the rate of degradation of the ar. it is likely that hip1 is also able to regulate, or at least interact with proteins that also possess the are.