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FLASH GENE
Symbol HAP1 contributors: mct/npt - updated : 02-11-2016
HGNC name huntingtin-associated protein 1
HGNC id 4812
Location 17q21.2      Physical location : 39.878.890 - 39.890.898
Synonym name
  • neuroan 1
  • huntingtin-associated protein 2
  • Synonym symbol(s) HLP, HAP2, HLP1, HIP5
    DNA
    TYPE functioning gene
    STRUCTURE 12.01 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    KRTHA3A 17q12-q21 keratin, hair, acidic, 3A KRTHA3B 17q12-q21 keratin, hair, acidic, 3B KRTHA4 17q12-q21 keratin, hair, acidic, 4 KRTHA1 17q12-q21 keratin, hair, acidic, 1 KRTHAP1 17q12-q21 keratin, hair, acidic, pseudogene 1 KRTHA7 17q12-q21 keratin, hair, acidic, 7 KRTHA8 17q12-q21 keratin, hair, acidic, 8 KRTHA2 17q12-q21 keratin, hair, acidic, 2 KRTHA5 17q12-q21 keratin, hair, acidic, 5 KRTHA6 17q12-q21 keratin, hair, acidic, 6 KRT13 17q21-q22 keratin 13 KRT15 17q21.2 keratin 15 KRT19 17q21 keratin 19 KRT9 17q21.1-q21.2 keratin 9 (epidermolytic palmoplantar keratoderma) KRT14 17q21-q22 keratin 14 (epidermolysis bullosa simplex, Dowling-Meara, Koebner) KRT16 17q21-q22 keratin 16 (focal non-epidermolytic palmoplantar keratoderma) KRT17 17q21-q22 keratin 17 LOC388385 17 LOC388385 SUI1 17q21.31 putative translation initiation factor GAS 17q21-q21.2 gastrin HAP1 17q21.2-q21.3 huntingtin-associated protein 1 (neuroan 1) JUP 17q21 junction plakoglobin SC65 17q21.31 synaptonemal complex protein SC65 FKBP10 17q21.1 FK506 binding protein 10, 65 kDa MGC20781 17q21.31 hypothetical protein MGC20781 KLHL10 17q21.2 kelch-like 10 (Drosophila) FLJ10572 17q21.31 hypothetical protein FLJ10572 ACLY 17q21-q22 ATP citrate lyase DKFZP434H0115 17q21.31 hypothetical protein DKFZp434H0115 CNP 17q21 2',3'-cyclic nucleotide 3' phosphodiesterase DNAJC7 17q11.2 DnaJ (Hsp40) homolog, subfamily C, member 7 KBRAS2 17q21.31 I-kappa-B-interacting Ras-like protein 2
    regionally located mapped to a region implicated in a variety of neurological conditions
    RNA
    TRANSCRIPTS type messenger
    text protein alternatively spliced HAP1A, HAP1B, HAP1C, other minor transcripts detected in some brain regions (Li, 98)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 splicing 3944 69 619 . detected in pancreatic beta cells 2000 10974549
  • lacking an alternate in-frame exon in the 5' coding region compared to variant 1
  • HAP1A
  • co-localizes and co-migrates with insulin-containing vesicles and actin-based MYO5A motor protein in the INS1 pancreatic beta cell line
  • 10 - 3893 - 602 . detected in pancreatic beta cells 2000 10974549
  • HAP1B
  • 10 - 3869 - 594 - 2000 10974549
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine     Homo sapiens
    Endocrine      Homo sapiens
    Nervousbraindiencephalonhypothalamus highly
     brainbasal nucleicaudate nucleus  
     brainforebraincerebral cortex  
     spinal cord    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveenterocyte Homo sapiens
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text predominantly, in the brain, present during early embryogenesis
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a HAP1 N-terminal
  • a leucine zipper motif
  • a putative tyrosine kinase phosphorylation site
  • a coiled coil domains
  • HOMOLOGY
    interspecies ortholog to C.elegans Trak1
    homolog to rattus Hap1 (68pc)
    homolog to murine Hap1 (68.7pc)
    Homologene
    FAMILY
    CATEGORY adaptor , transport
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    text
  • actin-cytoskeleton associated
  • colocalized in perinuclear inclusion bodies
  • basic FUNCTION
  • likely to play a role in neural development
  • mediating interactions among cytoskeletal, vascular and motor proteins
  • may play a role as a trafficking protein or as an adaptor between cargos and intracellular transporters
  • regulating inhibitory synaptic transmission by modulating gamma-aminobutyric acid type A receptor membrane trafficking
  • playing an essential role in regulating post natal feeding
  • playing an essential role in the stimulatory effect of HD on BDNF trafficking
  • involved in intracellular trafficking of the GABA(A) receptor
  • acting as a mediator of feeding behavior
  • with HTT, participate in intracellular trafficking and polyglutamine expansion affects vesicular transport (Wu 2009)
  • may participate in axonal transport and activity-dependent release of pro-BDNF by interacting with the BDNF prodomain (Wu 2010)
  • involved in axonal transport of BDNF (Wu 2010)
  • may play a role in the transport and release of pro-BDNF and the reduced association of HAP1 with the prodomain may underlie the decreased transport and release of BDNF in HD (Wu 2010)
  • may be involved in the regulation of cellular trafficking and secretion of insulin (Liao 2010)
  • HAP1-associated intracellular trafficking that plays in maintaining neuronal process integrity and normal animal behavior (Lin 2010)
  • critical for the transport of multiple proteins to the nerve terminals to maintain the integrity of neuronal processes and selective disruption of the processes of orexin neurons can cause abnormal feeding and locomotor activity (Lin 2010)
  • is a neural HTT interactor that is widely expressed as a core molecule of the stigmoid body (a neurocytoplasmic inclusion) in the limbic and hypothalamic regions and has putative protective functions against some neurodegenerative diseases
  • HAP1 regulates APP subcellular trafficking to the non-amyloidogenic pathway and may negatively regulate APP production in neurons
  • HTT and HAP1 are regulators of autophagosome transport in neurons, suggesting that misregulation of autophagosome transport in Huntington disease leads to inefficient autophagosome maturation, potentially due to inhibition of autophagosome/lysosome fusion along the axon
  • brain-enriched protein that plays a key role in the trafficking of neuronal surviving and differentiating cargos
  • may help regulate transport of insulin-containing secretory granules along cortical actin filaments, raising the possibility that HAP1 may play an important role in actin-based secretory vesicle trafficking in neurons
  • critical roles for HAP1 and KIT in postnatal neurogenesis and adult depressive behavior
  • involved in intracellular trafficking, vesicle transport, and membrane receptor endocytosis
  • participates in intracellular trafficking via its association with various microtubule- dependent transporters and organelles
  • has emerging roles in starvation response
  • HAP1, TRAK1 and TRAK2 have a degree of common function, particularly regarding intracellular receptor trafficking
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text vesicular transport
    PATHWAY
    metabolism
    signaling neurotransmission
    synaptic transmission
    a component
  • complexing with DCTN1 for association of motor proteins with microtubules
  • REST, DCTN1, HTT, HAP1, and RILP form a complex involved in the translocation of REST into the nucleus and HAP1 controls REST cellular localization in neurons
  • part of HAP1-AHI1 complex in the brainstem working as a sensor for insulin signals in feeding control
  • HAP1 regulates likely APP subcellular trafficking to the non-amyloidogenic pathway and may negatively regulate APP production in neurons
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Huntingtin (HD) (binding enhanced by an expanded polyglutamine repeat)
  • p150 (GLUED) subunit of dynactin and the pericentriolar protein PCM1, NEUROD1 and MAP3K10
  • interacting with AR via the ligand binding domain, in a polyQ-dependent manner, to attenuate or regulate AR function, and forms cytoplasmic aggregations sequestering AR
  • binds microtubule-dependent transporters that engage anterograde or retrograde transport and also associates with a variety of organelles and membrane receptors (Rong 2007)
  • interacting with AHI1 (critical role of the AHI1-HAP1 complex in early brain development) (Sheng 2008)
  • HTT regulates ciliogenesis by interacting through HAP1 with pericentriolar material 1 protein (PCM1)
  • may reduce APP production by regulating APP trafficking to the non-amyloidogenic pathway
  • HAP1 is a regulatory protein that binds AHI1
  • HAP1 is a novel functional partner of TSC1
  • link between HAP1 and TSC1 that regulates neuronal MTOR signaling and neuronal morphogenesis
  • stabilized the association of NTRK2 with the intracellular sorting protein sortilin, prevented NTRK2 degradation, and promoted its anterograde transport
  • HAP1 interacts with BCR on microtubules to regulate neuronal differentiation
  • interacts with synapsin I, an abundant neuronal phosphoprotein that associates with synaptic vesicle (SV) during neurotransmitter release and regulates synaptic plasticity and neuronal development
  • is important for insulin secretion of pancreatic beta-cells via regulating the intracellular trafficking and plasma membrane localization of CACNA1C, providing new insight into the mechanisms that regulate insulin release from pancreatic beta cells
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    enriched in neurons, suggesting that its dysfunction could contribute to the selective neuropathology in HD (Wu 2009)
    constitutional   deletion    
    significantly alters APP endocytosis and reduces the re-insertion of APP into the cytoplasmic membrane
    Susceptibility to Huntington disease (HD) (modifying the age-at-onset)
    Variant & Polymorphism other M441-HAP1 polymorphism modifies the age-at-onset of HD (8-years delayed onset of first symptoms)(Metzger 2008)
    Candidate gene PSP (progressive supranuclear palsy), a late-onset atypical parkinsonian disorder
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • neurogenesis, but not gliogenesis, was affected in Hap1-null neurospheres and mouse brain
  • Hap1 knockout mice had a lower plasma basal insulin level than control mice