Hap1

Summary

Gene Symbol: Hap1
Description: huntingtin-associated protein 1
Alias: HAP1-A, HAP1-B, huntingtin-associated protein 1, HAP-1
Species: rat
Products:     Hap1

Top Publications

  1. Rong J, Li S, Sheng G, Wu M, Coblitz B, Li M, et al. 14-3-3 protein interacts with Huntingtin-associated protein 1 and regulates its trafficking. J Biol Chem. 2007;282:4748-56 pubmed
    b>HAP1 (Huntingtin-associated protein 1) consists of two alternately spliced isoforms (HAP1A and HAP1B, which have unique C-terminal sequences) and participates in intracellular trafficking...
  2. Yang M, Lim Y, Li X, Zhong J, Zhou X. Precursor of brain-derived neurotrophic factor (proBDNF) forms a complex with Huntingtin-associated protein-1 (HAP1) and sortilin that modulates proBDNF trafficking, degradation, and processing. J Biol Chem. 2011;286:16272-84 pubmed publisher
    ..In this study, we report that proBDNF forms a complex with Huntingtin associated protein-1 (HAP1) and sortilin, which plays an important role in proBDNF intracellular trafficking and stabilization...
  3. Tang T, Tu H, Chan E, Maximov A, Wang Z, Wellington C, et al. Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1. Neuron. 2003;39:227-39 pubmed
    ..Our findings identify a novel molecular link between Htt and InsP3R1-mediated neuronal Ca2+ signaling and provide an explanation for the derangement of cytosolic Ca2+ signaling in HD patients and mouse models. ..
  4. Tang T, Tu H, Orban P, Chan E, Hayden M, Bezprozvanny I. HAP1 facilitates effects of mutant huntingtin on inositol 1,4,5-trisphosphate-induced Ca release in primary culture of striatal medium spiny neurons. Eur J Neurosci. 2004;20:1779-87 pubmed
    Huntington's disease is caused by polyglutamine expansion (exp) in huntingtin (Htt). Htt-associated protein-1 (HAP1) was the first identified Htt-binding partner...
  5. Li S, Hosseini S, Gutekunst C, Hersch S, Ferrante R, Li X. A human HAP1 homologue. Cloning, expression, and interaction with huntingtin. J Biol Chem. 1998;273:19220-7 pubmed
    ..We previously identified a rat huntingtin-associated protein (HAP1) that binds to huntingtin; HAP1 binds more tightly to huntingtin with an expanded glutamine repeat than to wild ..
  6. Li X, Li S, Sharp A, Nucifora F, Schilling G, Lanahan A, et al. A huntingtin-associated protein enriched in brain with implications for pathology. Nature. 1995;378:398-402 pubmed
    ..The HAP-1 protein is enriched in the brain, suggesting a possible basis for the selective brain pathology of HD. ..
  7. Islam M, Takeshita Y, Yanai A, Imagawa A, Jahan M, Wroblewski G, et al. Immunohistochemical analysis of huntingtin-associated protein 1 in adult rat spinal cord and its regional relationship with androgen receptor. Neuroscience. 2017;340:201-217 pubmed publisher
    Huntingtin-associated protein 1 (HAP1) is a neuronal interactor with causatively polyglutamine (polyQ)-expanded huntingtin in Huntington's disease and also associated with pathologically polyQ-expanded androgen receptor (AR) in ..
  8. Liao M, Chen X, Han J, Yang S, Peng T, Li H. Selective expression of Huntingtin-associated protein 1 in {beta}-cells of the rat pancreatic islets. J Histochem Cytochem. 2010;58:255-63 pubmed publisher
    Huntingtin-associated protein-1 (HAP1) was initially identified as a binding partner of huntingtin, the Huntington's disease protein...
  9. Mele M, Aspromonte M, Duarte C. Downregulation of GABAA Receptor Recycling Mediated by HAP1 Contributes to Neuronal Death in In Vitro Brain Ischemia. Mol Neurobiol. 2017;54:45-57 pubmed publisher
    ..decreased the rate of GABAAR β3 subunit recycling and reduced the interaction of the receptors with HAP1, a protein involved in the recycling of the receptors. Furthermore, OGD induced a calpain-mediated cleavage of HAP1...

More Information

Publications44

  1. Yuen E, Wei J, Zhong P, Yan Z. Disrupted GABAAR trafficking and synaptic inhibition in a mouse model of Huntington's disease. Neurobiol Dis. 2012;46:497-502 pubmed publisher
    ..receptors, the key determinant of the strength of synaptic inhibition, have been found to bind to the huntingtin associated protein 1 (HAP1)...
  2. Chan E, Nasir J, Gutekunst C, Coleman S, Maclean A, Maas A, et al. Targeted disruption of Huntingtin-associated protein-1 (Hap1) results in postnatal death due to depressed feeding behavior. Hum Mol Genet. 2002;11:945-59 pubmed
    ..To gain insight into the normal physiological role of HAP-1, mice were generated with homozygous disruption at the Hap1 locus...
  3. Rong J, McGuire J, Fang Z, Sheng G, Shin J, Li S, et al. Regulation of intracellular trafficking of huntingtin-associated protein-1 is critical for TrkA protein levels and neurite outgrowth. J Neurosci. 2006;26:6019-30 pubmed
    ..There is growing evidence that huntingtin-associated protein-1 (HAP1) also interacts with microtubule-dependent transporters and is involved in intracellular trafficking...
  4. Gutekunst C, Li S, Yi H, Ferrante R, Li X, Hersch S. The cellular and subcellular localization of huntingtin-associated protein 1 (HAP1): comparison with huntingtin in rat and human. J Neurosci. 1998;18:7674-86 pubmed
    The cellular and subcellular distribution of HAP1 was examined in rat brain by light and electron microscopic immunocytochemistry and subcellular fractionation...
  5. Li S, Li H, Torre E, Li X. Expression of huntingtin-associated protein-1 in neuronal cells implicates a role in neuritic growth. Mol Cell Neurosci. 2000;16:168-83 pubmed
    Huntingtin-associated protein-1 (HAP1) binds more tightly to mutant huntingtin, but its function and distribution in neurites are not clear...
  6. Taherzadeh Fard E, Saft C, Wieczorek S, Epplen J, Arning L. Age at onset in Huntington's disease: replication study on the associations of ADORA2A, HAP1 and OGG1. Neurogenetics. 2010;11:435-9 pubmed publisher
    ..variations in the genes encoding adenosinergic A(2A) receptor (ADORA2A), human huntingtin-associated protein-1 (HAP1) and the single base excision repair enzyme, 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1)...
  7. Li S, Yu Z, Li C, Nguyen H, Zhou Y, Deng C, et al. Lack of huntingtin-associated protein-1 causes neuronal death resembling hypothalamic degeneration in Huntington's disease. J Neurosci. 2003;23:6956-64 pubmed
    ..Here, we show that huntingtin-associated protein-1 (HAP1), which is involved in intracellular trafficking of epidermal growth factor receptor (EGFR), is highly expressed in ..
  8. Li S, Gutekunst C, Hersch S, Li X. Association of HAP1 isoforms with a unique cytoplasmic structure. J Neurochem. 1998;71:2178-85 pubmed
    b>HAP1 is a neural protein and interacts with the Huntington's disease protein huntingtin. There are at least two HAP1 isoforms, HAP1-A and HAP1-B, which have different C-terminal amino acid sequences...
  9. Zimdahl H, Gosele C, Lütjens G, Grutzner F, Kreitler T, Voss K, et al. Assignment of the huntingtin (Hdh) gene, the huntingtin associated protein (Hap1) gene, and the huntingtin interacting protein (Hip1) gene to rat chromosomes 14, 10, and 12 by radiation hybrid mapping and fluorescent in situ hybridization. Cytogenet Cell Genet. 2001;94:101-4 pubmed
  10. McGuire J, Rong J, Li S, Li X. Interaction of Huntingtin-associated protein-1 with kinesin light chain: implications in intracellular trafficking in neurons. J Biol Chem. 2006;281:3552-9 pubmed
    Huntingtin-associated protein-1 (HAP1) was initially identified as an interacting partner of huntingtin, the Huntington disease protein...
  11. Li S, Gutekunst C, Hersch S, Li X. Interaction of huntingtin-associated protein with dynactin P150Glued. J Neurosci. 1998;18:1261-9 pubmed
    ..Huntingtin-associated protein (HAP1) is a neuronal protein and binds to huntingtin in association with the polyglutamine repeat...
  12. Mackenzie K, Duffield M, Peiris H, Phillips L, Zanin M, Teo E, et al. Huntingtin-associated protein 1 regulates exocytosis, vesicle docking, readily releasable pool size and fusion pore stability in mouse chromaffin cells. J Physiol. 2014;592:1505-18 pubmed publisher
    Huntingtin-associated protein 1 (HAP1) was initially established as a neuronal binding partner of huntingtin, mutations in which underlie Huntington's disease...
  13. Metzger S, Rong J, Nguyen H, Cape A, Tomiuk J, Soehn A, et al. Huntingtin-associated protein-1 is a modifier of the age-at-onset of Huntington's disease. Hum Mol Genet. 2008;17:1137-46 pubmed publisher
    ..interacting proteins might contribute to this variation in the AAO and investigated human htt-associated protein-1 (HAP1) using genetic and functional assays...
  14. Sheng G, Xu X, Lin Y, Wang C, Rong J, Cheng D, et al. Huntingtin-associated protein 1 interacts with Ahi1 to regulate cerebellar and brainstem development in mice. J Clin Invest. 2008;118:2785-95 pubmed publisher
    ..In this study, we found that mouse Ahi1 formed a stable complex with huntingtin-associated protein 1 (Hap1), which is critical for neonatal development and involved in intracellular trafficking...
  15. Wong Y, Holzbaur E. The regulation of autophagosome dynamics by huntingtin and HAP1 is disrupted by expression of mutant huntingtin, leading to defective cargo degradation. J Neurosci. 2014;34:1293-305 pubmed publisher
    ..Here, we show that both huntingtin (htt) and its adaptor protein huntingtin-associated protein-1 (HAP1) copurify and colocalize with autophagosomes in neurons...
  16. Takeshita Y, Fujinaga R, Zhao C, Yanai A, Shinoda K. Huntingtin-associated protein 1 (HAP1) interacts with androgen receptor (AR) and suppresses SBMA-mutant-AR-induced apoptosis. Hum Mol Genet. 2006;15:2298-312 pubmed
    Huntingtin-associated protein 1 (HAP1), an interactor of huntingtin, has been known as an essential component of the stigmoid body (STB) and recently reported to play a protective role against neurodegeneration in Huntington's disease (HD)..
  17. Fujinaga R, Yanai A, Nakatsuka H, Yoshida K, Takeshita Y, Uozumi K, et al. Anti-human placental antigen complex X-P2 (hPAX-P2) anti-serum recognizes C-terminus of huntingtin-associated protein 1A common to 1B as a determinant marker for the stigmoid body. Histochem Cell Biol. 2007;128:335-48 pubmed
    ..The STBs also contain huntingtin-associated protein 1 (HAP1), and the HAP1-cDNA transfection induces STB-like inclusions in cultured cells...
  18. Vital M, Bidegain E, Raggio V, Esperón P. Molecular characterization of genes modifying the age at onset in Huntington's disease in Uruguayan patients. Int J Neurosci. 2016;126:510-513 pubmed publisher
    ..influence of genetic modifiers of the AAO of HD including: (CAG)n and del2642 in the IT15 gene, ADORA2A rs5751876, HAP1 rs4523977, PGC1-? rs7665116 and UCH-L1 rs5030732...
  19. Yang G, Yang M, Lim Y, Lu J, Wang T, Qi J, et al. Huntingtin associated protein 1 regulates trafficking of the amyloid precursor protein and modulates amyloid beta levels in neurons. J Neurochem. 2012;122:1010-22 pubmed publisher
    ..However, the mechanism of APP trafficking remains unclear. We present evidence that huntingtin associated protein 1 (HAP1) may reduce A? production by regulating APP trafficking to the non-amyloidogenic pathway...
  20. Colomer V, Engelender S, Sharp A, Duan K, Cooper J, Lanahan A, et al. Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide, with a rac1 guanine nucleotide exchange factor domain. Hum Mol Genet. 1997;6:1519-25 pubmed
    ..neuronal morphologic abnormalities of HD may involve interactions with proteins that bind to huntingtin, such as HAP1. The biological significance of this interaction is unclear because neither HAP1 nor huntingtin have significant ..
  21. Wang Z, Peng T, Wu H, He J, Li H. HAP1 helps to regulate actin-based transport of insulin-containing granules in pancreatic β cells. Histochem Cell Biol. 2015;144:39-48 pubmed publisher
    Huntingtin-associated protein 1 (HAP1) is enriched in neurons and binds to polyglutamine-expanded huntingtin. It consists of two alternatively spliced isoforms, HAP1A and HAP1B, which differ only in their short C-terminal sequences...
  22. Page K, Potter L, Aronni S, Everitt B, Dunnett S. The expression of Huntingtin-associated protein (HAP1) mRNA in developing, adult and ageing rat CNS: implications for Huntington's disease neuropathology. Eur J Neurosci. 1998;10:1835-45 pubmed
    Using radioactive in situ hybridization, we have mapped the expression of Huntingtin-associated protein (HAP1) mRNA in rat brain at developmental stages (E12-E19, PO-P21), in adult rats (3 months) and in 'aged' (19-21 months) rats...
  23. Wu L, Fan Y, Li S, Li X, Zhou X. Huntingtin-associated protein-1 interacts with pro-brain-derived neurotrophic factor and mediates its transport and release. J Biol Chem. 2010;285:5614-23 pubmed publisher
    ..Here, we report that Huntingtin-associated protein-1 (HAP1) interacts with the prodomain of BDNF and that the interaction was reduced in the presence of polyQ-expanded ..
  24. Shimojo M. Huntingtin regulates RE1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) nuclear trafficking indirectly through a complex with REST/NRSF-interacting LIM domain protein (RILP) and dynactin p150 Glued. J Biol Chem. 2008;283:34880-6 pubmed publisher
    ..We further show that HAP1 (huntingtin-associated protein-1) prevents this complex from translocating REST/NRSF to the nucleus...
  25. Karadima G, Dimovasili C, Koutsis G, Vassilopoulos D, Panas M. Age at onset in Huntington's disease: replication study on the association of HAP1. Parkinsonism Relat Disord. 2012;18:1027-8 pubmed publisher
    In recent years two association studies investigating the HAP1 T441M (rs4523977) polymorphism as a potential modifying factor of the age at onset (AAO) of Huntington's disease (HD), have been reported...
  26. Weng L, Lin Y, Li A, Wang C, Yan S, Sun M, et al. Loss of Ahi1 affects early development by impairing BM88/Cend1-mediated neuronal differentiation. J Neurosci. 2013;33:8172-84 pubmed publisher
    ..Here we report that full-length, but not N-terminal, Ahi1 binds Hap1, a huntingtin-associated protein that is essential for the postnatal survival of mice and that this binding is ..
  27. Engelender S, Sharp A, Colomer V, Tokito M, Lanahan A, Worley P, et al. Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin. Hum Mol Genet. 1997;6:2205-12 pubmed
    ..We previously identified a protein (HAP1) which binds to huntingtin in a glutamine repeat length-dependent manner...
  28. Gauthier L, Charrin B, Borrell Pages M, Dompierre J, Rangone H, Cordelières F, et al. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell. 2004;118:127-38 pubmed
    ..Huntingtin-mediated transport involves huntingtin-associated protein-1 (HAP1) and the p150(Glued) subunit of dynactin, an essential component of molecular motors...
  29. Li Y, Chin L, Levey A, Li L. Huntingtin-associated protein 1 interacts with hepatocyte growth factor-regulated tyrosine kinase substrate and functions in endosomal trafficking. J Biol Chem. 2002;277:28212-21 pubmed
    Huntingtin-associated protein 1 (HAP1) is a novel protein of unknown function with a higher binding affinity for the mutant form of Huntington's disease protein huntingtin...
  30. Czeredys M, Gruszczynska Biegala J, Schacht T, Methner A, Kuznicki J. Expression of genes encoding the calcium signalosome in cellular and transgenic models of Huntington's disease. Front Mol Neurosci. 2013;6:42 pubmed publisher
    ..These changes, however, differed in the two models of HD used in this study. Our results indicate that each HD model exhibits distinct features that may only partially resemble the human disease. ..
  31. Twelvetrees A, Yuen E, Arancibia Carcamo I, Macaskill A, Rostaing P, Lumb M, et al. Delivery of GABAARs to synapses is mediated by HAP1-KIF5 and disrupted by mutant huntingtin. Neuron. 2010;65:53-65 pubmed publisher
    ..We identify the adaptor linking the receptors to KIF5 as the huntingtin-associated protein 1 (HAP1)...
  32. Takeshita Y, Fujinaga R, Kokubu K, Islam M, Jahan M, Yanai A, et al. Interaction of ataxin-3 with huntingtin-associated protein 1 through Josephin domain. Neuroreport. 2011;22:232-8 pubmed publisher
    Huntingtin-associated protein 1 (HAP1) is an essential component of the stigmoid body (STB) and known as a possible neuroprotective interactor with causative proteins for Huntington's disease, spinal and bulbar muscular atrophy, ..
  33. Keryer G, Pineda J, Liot G, Kim J, Dietrich P, Benstaali C, et al. Ciliogenesis is regulated by a huntingtin-HAP1-PCM1 pathway and is altered in Huntington disease. J Clin Invest. 2011;121:4372-82 pubmed publisher
    ..Here, we demonstrate that WT HTT regulates ciliogenesis by interacting through huntingtin-associated protein 1 (HAP1) with pericentriolar material 1 protein (PCM1)...
  34. Colin E, Zala D, Liot G, Rangone H, Borrell Pages M, Li X, et al. Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons. EMBO J. 2008;27:2124-34 pubmed publisher
    ..This also applies to other vesicles suggesting an essential role for huntingtin in the control of vesicular directionality in neurons. ..
  35. Xiang J, Yang H, Zhao T, Sun M, Xu X, Zhou X, et al. Huntingtin-associated protein 1 regulates postnatal neurogenesis and neurotrophin receptor sorting. J Clin Invest. 2014;124:85-98 pubmed publisher
    ..Huntingtin-associated protein 1 (HAP1) participates in intracellular trafficking in neurons, and its absence leads to postnatal death in mice...