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FLASH GENE
Symbol GAP43 contributors: mct/pgu - updated : 05-10-2018
HGNC name growth associated protein 43
HGNC id 4140
Location 3q13.31      Physical location : 115.342.150 - 115.440.334
Synonym name
  • neuromodulin
  • neuron growth associated protein 43
  • nerve growth-related peptide GAP43
  • axonal membrane protein GAP-43
  • protein F1
  • calmodulin-binding protein P-57
  • neural phosphoprotein B-50
  • GDNF-induced neuronal phenotype
  • Synonym symbol(s) B50, PP46, GAP-43
    DNA
    TYPE functioning gene
    STRUCTURE 98.18 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure proximal promoter provides a relatively compact and neuron-specific model to investigate the transcriptional machinery and chromatin context required for axon outgrowth in developing and regenerating neurons
    MAPPING cloned Y linked N status confirmed
    Map cen - POU1F1 - GAP43 - DRD3 - RHO - TF - CP - SI - SST - qter
    Physical map
    MAK3P 3q13.31 likely ortholog of mouse Mak3p homolog (S. cerevisiae) ATP6V1A 3q13.31 ATPase, H+ transporting, lysosomal 70kDa, V1 subunit A DKFZp434C0328 3q13.31 hypothetical protein DKFZp434C0328 MGC42530 3q13.31 hypothetical protein MGC42530 KIAA1407 3q13.31 KIAA1407 protein QTRTD1 3q13.31 queuine tRNA-ribosyltransferase domain containing 1 LOC391566 3 similar to Histone H2B.n (H2B/n) (H2B.2) DRD3 3q13.3 dopamine receptor D3 LOC391567 3 similar to hypothetical protein FLJ11560 ZNF80 3q13.3 zinc finger protein 80 (pT17) FLJ39873 3q13.31 hypothetical protein FLJ39873 ZNF288 3q13.2 zinc finger protein 288 LOC344811 3q13.31 similar to DNA-binding protein B LOC391568 3 similar to EIF4EL3 protein GAP43 3q13.1-q13.2 growth associated protein 43 LSAMP 3q13.2-q21 limbic system-associated membrane protein LOC151579 3q13.31 similar to basic leucine zipper and W2 domains 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 1747 - 238 - 2007 17577668
    4 - 2143 - 274 - 2007 17577668
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainforebrain    Homo sapiens
     brainlimbic systemhippocampus   Homo sapiens
     spinal cordanterior horn  highly Homo sapiens
    Olfactory (smell)olfactory bulb     Homo sapiens
    Visualeye     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscular     Homo sapiens
    Nervousperipherous    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Muscularmyoblast Homo sapiens
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one IQ domain
  • short calmodulin-binding motif containing conserved Ile and Glu residues
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Basp2
    Homologene
    FAMILY
  • neuromodulin family
  • CATEGORY signaling growth factor
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    text
  • granules of anterior horn neurophils
  • membrane of horn cells
  • localized to the axon and growth cones of developing neurons and preferential expression in the forebrain and in highly plastic central nervous system regions such as the olfactory bulb, hippocampus, dorsal root ganglia, and ascending sensory pathways in the spinal cord
  • in myoblasts the localization appeared to be mostly nuclear, whereas with differentiation the protein started to display a sarcomeric-like pattern
  • basic FUNCTION
  • palmitoylated neuronal protein component of neurons regenerative response
  • implicated in axogenesis in several of the same neuronal types
  • presynaptic protein implicated in axonal growth, neuronal differentiation, plasticity, and regeneration
  • involved in neuronal plasticity and neurotransmitter release
  • involved in axon growth and synaptic plasticity
  • DPYSL3 and GAP43 are both involved in neurite outgrowth, a crucial process for the differentiation of neurons
  • BASP1 and GAP43 have overlapping, but not identical, functions in relation to neurite outgrowth
  • potential participation of GAP43 in G-protein cycle by its preferential activation of depalmitoylated GNAO1
  • neurotrophin-dependent membrane-bound phosphoprotein highly expressed during the development of the nervous system
  • expression of GAP43 in fibroblasts results in lengthening of the cell cycle compared to control fibroblasts
  • GAP43 and BASP1 participate in the regulation of actin cytoskeleton dynamics in neuronal axon terminals
  • during development, this protein plays a crucial role in growth and in branch formation of neurites, while in the adult it is only expressed in a few brain regions
  • neuron-specific phosphoprotein, which plays critical role in axon growth and synapses functions during neurogenesis
  • efficient transcription of the distal promoter of GAP43 is an important mark for the transition of P19 cells from the progenitor stage into neuronal differentiation
  • essential for axon pathfinding in both cortical afferents and efferents
  • in contrast to callosal neurites, in which NTN1 required GAP43 in order to stimulate both outgrowth and guidance, in ventrolateral efferents, NTN1 required GAP43 only to stimulate outgrowth, but not guidance
  • involved in mechanisms controlling pathfinding and branching of neurons during development and regeneration
  • axonal translation of ACTB mRNA supports axon branching and axonal translation of GAP43 mRNA supports elongating growth
  • presynaptic protein that plays key roles in axonal growth and guidance and in modulating synapse formation
  • complex interplay between phosphorylation and lipidation in mediating the localization of GAP43 in neuronal cells
  • also in skeletal muscle, this protein can be a key player in calcium/calmodulin homeostasis
  • involvement of GAP43 in the dynamic intracellular Ca2+ homeostasis, a common conserved role among the different species
  • likely a negative feedback of cooperative action of CALM1, GAP43, and PPP3CA on P/Q and L-type channels activity
  • protein kinase C (PKC)-activated phosphoprotein, that is often implicated in axonal plasticity and regeneration 5)
  • astrocytic GAP43 mediates glial plasticity during astrogliosis, providing beneficial effects for neuronal plasticity and survival and attenuation of microglial activation 5)
  • synapse-related genes showed significant age-related expression change (DLG4, GAP43, SLC17A7)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interact with cytoskeletal and signaling molecules such as actin, calmodulin, rabaptin, G-protein, and PI (4,5)P2 that are involved in secretion and endocytosis
  • interacting with DPYSL3 and MAP2
  • interacting with NCAM1 (play pivotal roles in neuronal development and plasticity and possess interdependent functions)
  • interaction between GAP43 andGNAO1 influences the signal transduction pathways leading to differentiation of neural cells
  • LYPLA2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP43 subcellular distribution
  • LYPLA1, LYPLA2 are cytosolic enzymes that catalyze depalmitoylation of membrane-anchored, palmitoylated HRAS and growth-associated protein-43 (GAP43), respectively
  • KHSRP is an important regulator of mRNA stability and axonal length that works in direct opposition to ELAVL4 to regulate the levels of GAP43 and other AU-rich element (ARE)-containing neuronal mRNAs
  • PKC-dependent phosphorylation of GAP43 plays a critical role in regulating postsynaptic GPHN aggregation in developing GABAergic synapses
  • is involved in the orientation of cell division by interacting with GNAI1 and this should be an important mechanism for neurogenesis in the mammalian brain
  • cell & other
    REGULATION
    repressed by NFATC4 (negative and not a positive regulator of GAP43 during neuronal outgrowth and maturation)
    Other regulated by ARRPP19 (through the nerve growth factor)
    through MEK/ERK pathway, S1P stimulates GAP43 transcription with increased binding of CEBPB to the 5prime-promoter
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in amyotrophic lateral sclerosis
    constitutional     --other  
    altered expression of GAP43 and Rho Kinase in patients with Parkinson disease
    constitutional     --over  
    of GAP43 in skin of patients with early-stage peripheral neuropathie
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • impaired regeneration of intra-epidermal C fibers in the early stages of type 2 diabetes mellitus, as indicated by GAP43, might be a marker of incipient diabetic neuropathy
  • Therapy target
    ANIMAL & CELL MODELS
  • developmental and adult Gap43 deficiency in mice dynamically alters hippocampal neurogenesis and mossy fiber volume