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Gene Review

HIP1  -  huntingtin interacting protein 1

Homo sapiens

Synonyms: HIP-1, HIP-I, Huntingtin-interacting protein 1, Huntingtin-interacting protein I, ILWEQ
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Disease relevance of HIP1


Psychiatry related information on HIP1


High impact information on HIP1


Chemical compound and disease context of HIP1


Biological context of HIP1


Anatomical context of HIP1

  • Here we demonstrate that HIP1 colocalizes with markers of clathrin-mediated endocytosis in neuronal cells and is highly enriched on clathrin-coated vesicles (CCVs) purified from brain homogenates [10].
  • HIP1/PDGFbetaR is a 180-kD protein when expressed in the murine hematopoietic cell line, Ba/F3, and is constitutively tyrosine phosphorylated [2].
  • In conclusion, we have discovered that HIP1 is a nucleocytoplasmic protein capable of associating with membranes and DNA response elements and regulating transcription [14].
  • Anti-GP-Ibalpha MoAb (CD42b; HIP1) slightly inhibited megakaryocyte colony formation (P < .05). and strongly inhibited proplatelet formation (after 24 hours incubation, P < .0002; after 48 hours incubation, P < .0007) [15].
  • The repertoire of huntingtin-interacting proteins continues to expand with the identification of HIP1, a protein whose yeast homologues have known functions in regulating events associated with the cytoskeleton [16].

Associations of HIP1 with chemical compounds

  • The consequence of t(5;7)(q33;q11.2) is an HIP1/PDGFbetaR fusion gene that encodes amino acids 1 to 950 of HIP1 joined in-frame to the transmembrane and tyrosine kinase domains of the PDGFbetaR [2].
  • HIP1 is a novel androgen receptor regulator, significantly repressing transcription when knocked down using a silencing RNA approach and activating transcription when overexpressed [14].
  • The 5'-flanking region of the gene contained no TATA-like motif, but a binding motif for HIP1, which is suggested to be important in the transcription of TATA-less housekeeping genes, was identified in a region very close to the initiator methionine codon [17].
  • Flow cytometric analysis revealed that FITC-TMVA bound to human formalin-fixed platelets in a saturable manner, and its binding was specifically blocked by HIP1 in a dose-dependent manner [18].
  • This reaction, earlier interpreted as a HIPIP-type oxidation, is a previously uncharacterized oxidation reaction of [4Fe-4S] clusters [19].

Physical interactions of HIP1

  • Here we demonstrate that both HIP1r and HIP1 bind inositol lipids via their epsin N-terminal homology (ENTH) domains [12].
  • Interestingly, HIP12 does not interact with huntingtin but can interact with HIP1. suggesting a potential interaction in vivo that may influence the function of each respective protein [1].

Other interactions of HIP1

  • Mutants that fail to bind CLC are unable to promote clathrin assembly in vitro but still mediate HIP1 homodimerization and heterodimerization with the family member HIP12/HIP1R [11].
  • This region, which contains consensus clathrin- and AP2-binding sites, functions in conjunction with the coiled-coil domain to target HIP1 to CCVs [10].
  • Localization of the human HIP1 gene close to the elastin (ELN) locus on 7q11.23 [20].
  • Anchored polymerase chain reaction using PDGFbetaR primers identified a chimeric transcript containing the HIP1 gene located at 7q11.2 fused to the PDGFbetaR gene on 5q33 [2].
  • Transcription initiation from the dihydrofolate reductase promoter is positioned by HIP1 binding at the initiation site [21].
  • We report that HIP1 physically associates with EGFR and that this association is independent of the lipid, clathrin, and actin interacting domains of HIP1 [22].

Analytical, diagnostic and therapeutic context of HIP1

  • Another genetic technique, analysis of the HIP1 octameric-palindrome repeated sequence, showed greater heterogeneity among the isolates and appears to be a useful method for distinguishing among isolates of C. raciborskii [23].
  • Partially overlapping distribution of epsin1 and HIP1 at the synapse: analysis by immunoelectron microscopy [24].
  • DNA-microarray hybridization and genomic screening revealed a toxic-strain-specific HIP1 fragment coding for a putative Na(+)-dependent transporter [25].
  • Using immunogold electron microscopy, we examine and compare the synaptic distribution of epsin1 and HIP1 in rat CA1 hippocampal synapse [24].
  • However, it does not give rise to observable paramagnetic magnetic circular dichroism in the visible-near UV spectral region and is therefore neither an oxidized HIPIP [4Fe-4S] cluster nor an oxidized [3Fe-3S] cluster [19].


  1. HIP12 is a non-proapoptotic member of a gene family including HIP1, an interacting protein with huntingtin. Chopra, V.S., Metzler, M., Rasper, D.M., Engqvist-Goldstein, A.E., Singaraja, R., Gan, L., Fichter, K.M., McCutcheon, K., Drubin, D., Nicholson, D.W., Hayden, M.R. Mamm. Genome (2000) [Pubmed]
  2. Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor beta receptor (PDGFbetaR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2). Ross, T.S., Bernard, O.A., Berger, R., Gilliland, D.G. Blood (1998) [Pubmed]
  3. Huntingtin-interacting protein 1 is overexpressed in prostate and colon cancer and is critical for cellular survival. Rao, D.S., Hyun, T.S., Kumar, P.D., Mizukami, I.F., Rubin, M.A., Lucas, P.C., Sanda, M.G., Ross, T.S. J. Clin. Invest. (2002) [Pubmed]
  4. HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain. Kalchman, M.A., Koide, H.B., McCutcheon, K., Graham, R.K., Nichol, K., Nishiyama, K., Kazemi-Esfarjani, P., Lynn, F.C., Wellington, C., Metzler, M., Goldberg, Y.P., Kanazawa, I., Gietz, R.D., Hayden, M.R. Nat. Genet. (1997) [Pubmed]
  5. Chromatin differences between active and inactive X chromosomes revealed by genomic footprinting of permeabilized cells using DNase I and ligation-mediated PCR. Pfeifer, G.P., Riggs, A.D. Genes Dev. (1991) [Pubmed]
  6. Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins. Huang, K., Yanai, A., Kang, R., Arstikaitis, P., Singaraja, R.R., Metzler, M., Mullard, A., Haigh, B., Gauthier-Campbell, C., Gutekunst, C.A., Hayden, M.R., El-Husseini, A. Neuron (2004) [Pubmed]
  7. Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain. Hackam, A.S., Yassa, A.S., Singaraja, R., Metzler, M., Gutekunst, C.A., Gan, L., Warby, S., Wellington, C.L., Vaillancourt, J., Chen, N., Gervais, F.G., Raymond, L., Nicholson, D.W., Hayden, M.R. J. Biol. Chem. (2000) [Pubmed]
  8. Oxidation-reduction properties of Chromatium vinosum high potential iron-sulfur protein. Mizrahi, I.A., Wood, F.E., Cusanovich, M.A. Biochemistry (1976) [Pubmed]
  9. Molecular properties of high potential iron sulfur protein of Chromatium warmingii. Wermter, U., Fischer, U. Z. Naturforsch., C, Biosci. (1983) [Pubmed]
  10. HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and adaptor protein 2. Metzler, M., Legendre-Guillemin, V., Gan, L., Chopra, V., Kwok, A., McPherson, P.S., Hayden, M.R. J. Biol. Chem. (2001) [Pubmed]
  11. Huntingtin interacting protein 1 (HIP1) regulates clathrin assembly through direct binding to the regulatory region of the clathrin light chain. Legendre-Guillemin, V., Metzler, M., Lemaire, J.F., Philie, J., Gan, L., Hayden, M.R., McPherson, P.S. J. Biol. Chem. (2005) [Pubmed]
  12. HIP1 and HIP1r stabilize receptor tyrosine kinases and bind 3-phosphoinositides via epsin N-terminal homology domains. Hyun, T.S., Rao, D.S., Saint-Dic, D., Michael, L.E., Kumar, P.D., Bradley, S.V., Mizukami, I.F., Oravecz-Wilson, K.I., Ross, T.S. J. Biol. Chem. (2004) [Pubmed]
  13. IRS-PCR-based genetic mapping of the huntingtin interacting protein gene (HIP1) on mouse chromosome 5. Himmelbauer, H., Wedemeyer, N., Haaf, T., Wanker, E.E., Schalkwyk, L.C., Lehrach, H. Mamm. Genome (1998) [Pubmed]
  14. Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors. Mills, I.G., Gaughan, L., Robson, C., Ross, T., McCracken, S., Kelly, J., Neal, D.E. J. Cell Biol. (2005) [Pubmed]
  15. Influence of monoclonal antiplatelet glycoprotein antibodies on in vitro human megakaryocyte colony formation and proplatelet formation. Takahashi, R., Sekine, N., Nakatake, T. Blood (1999) [Pubmed]
  16. Toward understanding the molecular pathology of Huntington's disease. Wellington, C.L., Brinkman, R.R., O'Kusky, J.R., Hayden, M.R. Brain Pathol. (1997) [Pubmed]
  17. Genomic structure of human transcobalamin II: comparison to human intrinsic factor and transcobalamin I. Li, N., Seetharam, S., Seetharam, B. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  18. TMVA, a snake C-type lectin-like protein from Trimeresurus mucrosquamatus venom, activates platelet via GPIb. Tai, H., Wei, Q., Jin, Y., Su, M., Song, J.X., Zhou, X.D., Ouyang, H.M., Wang, W.Y., Xiong, Y.L., Zhang, Y. Toxicon (2004) [Pubmed]
  19. Spectroscopic studies of ferricyanide oxidation of Azotobacter vinelandii ferredoxin I. Morgan, T.V., Stephens, P.J., Devlin, F., Stout, C.D., Melis, K.A., Burgess, B.K. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  20. Localization of the human HIP1 gene close to the elastin (ELN) locus on 7q11.23. Wedemeyer, N., Peoples, R., Himmelbauer, H., Lehrach, H., Francke, U., Wanker, E.E. Genomics (1997) [Pubmed]
  21. Transcription initiation from the dihydrofolate reductase promoter is positioned by HIP1 binding at the initiation site. Means, A.L., Farnham, P.J. Mol. Cell. Biol. (1990) [Pubmed]
  22. Huntingtin interacting protein 1 is a novel brain tumor marker that associates with epidermal growth factor receptor. Bradley, S.V., Holland, E.C., Liu, G.Y., Thomas, D., Hyun, T.S., Ross, T.S. Cancer Res. (2007) [Pubmed]
  23. Varied diazotrophies, morphologies, and toxicities of genetically similar isolates of Cylindrospermopsis raciborskii (nostocales, cyanophyceae) from Northern Australia. Saker, M.L., Neilan, B.A. Appl. Environ. Microbiol. (2001) [Pubmed]
  24. Partially overlapping distribution of epsin1 and HIP1 at the synapse: analysis by immunoelectron microscopy. Yao, P.J., Bushlin, I., Petralia, R.S. J. Comp. Neurol. (2006) [Pubmed]
  25. Identification of an Na(+)-dependent transporter associated with saxitoxin-producing strains of the cyanobacterium Anabaena circinalis. Pomati, F., Burns, B.P., Neilan, B.A. Appl. Environ. Microbiol. (2004) [Pubmed]
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