Homo sapiens Protein: HAP1
InnateDB Protein IDBP-49697.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol HAP1
Protein Name huntingtin-associated protein 1
Synonyms HAP2; hHLP1; HIP5; HLP;
Species Homo sapiens
Ensembl Protein ENSP00000334002
InnateDB Gene IDBG-49695 (HAP1)
Protein Structure
UniProt Annotation
Function 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 faciltate 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 Ca(2+) 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). {ECO:0000269PubMed:18922795}.
Subcellular Localization Cytoplasm {ECO:0000269PubMed:9742138}. Cell projection, axon {ECO:0000269PubMed:9742138}. Cytoplasm, cytoskeleton {ECO:0000250}. Lysosome {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle {ECO:0000250}. Mitochondrion {ECO:0000305PubMed:9742138}. Nucleus {ECO:0000250}. Cytoplasmic vesicle, autophagosome {ECO:0000250}. Note=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 (By similarity). {ECO:0000250}.
Disease Associations
Tissue Specificity Predominantly expressed in brain. Selectively expressed in neurons.
Number of Interactions This gene and/or its encoded proteins are associated with 82 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.
Experimentally validated
Total 82 [view]
Protein-Protein 82 [view]
Protein-DNA 0
Protein-RNA 0
Predicted by orthology
Total 6 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005515 protein binding
Biological Process
GO:0007268 synaptic transmission
GO:0007420 brain development
GO:0008104 protein localization
GO:0047496 vesicle transport along microtubule
Cellular Component
GO:0005856 cytoskeleton
GO:0015629 actin cytoskeleton
GO:0016023 cytoplasmic membrane-bounded vesicle
Protein Structure and Domains
InterPro IPR006933 HAP1, N-terminal
PFAM PF04849
Post-translational Modifications
SwissProt P54257
PhosphoSite PhosphoSite-P54257
UniProt Splice Variant
Entrez Gene 9001
UniGene Hs.669865
RefSeq NP_817084
OMIM 600947
HPRD 02972
EMBL AB209105 AC109319 AF040723 AJ012824 AJ224877 AK022007 U38371
GenPept AAC39861 AAC50297 BAB13952 BAD92342 CAB82785 CAC09418