HAP1

Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with huntingtin, with two cytoskeletal proteins (dynactin and pericentriolar autoantigen protein 1), and with a hepatocyte growth factor-regulated tyrosine kinase substrate. The interactions with cytoskeletal proteins and a kinase substrate suggest a role for this protein in vesicular trafficking or organelle transport. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Huntingtin Associated Protein 1

Originally identified as neuronal protein that specifically associates with HTT/huntingtin and the binding is enhanced by an expanded polyglutamine repeat within HTT possibly affecting HAP1 interaction properties. Both HTT and HAP1 are involved in intracellular trafficking and HAP1 is proposed to link HTT to motor proteins and/or transport cargos. Seems to play a role in vesicular transport within neurons and axons such as from early endosomes to late endocytic compartments and to promote neurite outgrowth. The vesicular transport function via association with microtubule-dependent transporters can be attenuated by association with mutant HTT. Involved in the axonal transport of BDNF and its activity-dependent secretion; the function seems to involve HTT, DCTN1 and a complex with SORT1. Involved in APP trafficking and seems to facilitate APP anterograde transport and membrane insertion thereby possibly reducing processing into amyloid beta. Involved in delivery of gamma-aminobutyric acid (GABA(A)) receptors to synapses; the function is dependent on kinesin motor protein KIF5 and is disrupted by HTT with expanded polyglutamine repeat. Involved in regulation of autophagosome motility by promoting efficient retrograde axonal transport. Seems to be involved in regulation of membrane receptor recycling and degradation, and respective signal transduction, including GABA(A) receptors, tyrosine kinase receptors, EGFR, IP3 receptor and androgen receptor. Among others suggested to be involved in control of feeding behavior (involving hypothalamic GABA(A) receptors), cerebellar and brainstem development (involving AHI1 and NTRK1/TrkA), postnatal neurogenesis (involving hypothalamic NTRK2/TrkB), and ITPR1/InsP3R1-mediated Ca2+ release (involving HTT and possibly the effect of mutant HTT). Via association with DCTN1/dynactin p150-glued and HTT/huntingtin involved in cytoplasmic retention of REST in neurons. May be involved in ciliogenesis. Involved in regulation of exocytosis. Seems to be involved in formation of cytoplasmic inclusion bodies (STBs). In case of anomalous expression of TBP, can sequester a subset of TBP into STBs; sequestration is enhanced by an expanded polyglutamine repeat within TBP. HAP1-containing STBs have been proposed to play a protective role against neurodegeneration in Huntigton disease (HD) and spinocerebellar ataxia 17 (SCA17).

Anterograde axonal transport Source: UniProtKB
Anterograde axonal transport of mitochondrion Source: GO_Central
Autophagy Source: UniProtKB-KW
Brain development Source: UniProtKB
Cell projection organization Source: UniProtKB-KW
Cerebellum development Source: Ensembl
Chemical synaptic transmission Source: ProtInc
Exocytosis Source: UniProtKB-KW
Hypothalamus cell differentiation Source: Ensembl
Mitochondrion distribution Source: GO_Central
Negative regulation of amyloid-beta formation Source: UniProtKB
Neurogenesis Source: GO_Central
Neurotrophin TRK receptor signaling pathway Source: UniProtKB
Positive regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
Positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity Source: UniProtKB
Positive regulation of neurogenesis Source: Ensembl
Positive regulation of neurotrophin production Source: UniProtKB
Positive regulation of non-motile cilium assembly Source: UniProtKB
Positive regulation of synaptic transmission, GABAergic Source: UniProtKB
Protein localization Source: UniProtKB
Protein targeting Source: GO_Central
Regulation of exocytosis Source: UniProtKB
Regulation of organelle transport along microtubule Source: UniProtKB
Retrograde axonal transport Source: UniProtKB
Vesicle transport along microtubule Source: GO_Central

Cytoskeleton; Mitochondrion; Cytoplasm; Early endosome; Endoplasmic reticulum; Lysosome; Nucleus; Axon; Presynapse; Dendritic spine; Dendrite; Autophagosome; Growth cone; Neuron projection; Synaptic vesicle. Localizes to large nonmembrane-bound cytoplasmic bodies found in various types of neurons, called stigmoid bodies (STBs). Localization to neuronal processes and neurite tips is decreased by YWHAZ. In the nucleus localizes to nuclear rods.