Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol GAPDH contributors: mct/shn - updated : 22-08-2015
HGNC name glyceraldehyde-3-phosphate dehydrogenase
HGNC id 4141
Location 12p13.31      Physical location : 6.643.656 - 6.647.536
Synonym name aging-associated gene 9 protein
Synonym symbol(s) G3PD, GAPD, MGC88685, OK/SW-cl.12, CDABP0047
EC.number 1.2.1.12
DNA
TYPE functioning gene
STRUCTURE 3.88 kb     9 Exon(s)
regulatory sequence Promoter (TATA box)
Binding site   enhancer   HRE
text structure
  • containing a hypoxia responsive element (HRE) consisting of a hypoxia inducible factor-1 (HIF-1) consensus binding site plus adjacent sequence
  • a gln-responsive element
  • MAPPING cloned Y linked N status confirmed
    Map pter - D12S356 - D12S374 - GAPDH - D12S1623 - D12S1625 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 1310 - 335 - 2002 11955624
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
     salivary gland   highly
    Lymphoid/Immunetonsils   highly
    Reproductivefemale systemovary  highly
     female systemuteruscervix highly
    Respiratoryrespiratory tractlarynx  highly
    Skin/Tegumentskin   highly
    Visualeyeanterior segmentcornea  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Muscular    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticerthrocyte
    cell lineage
    cell lines lung cancer cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a NAD-binding domain
  • conjugated PhosphoP
    mono polymer homomer , tetramer
    HOMOLOGY
    interspecies ortholog to gapdh, Danio rerio
    ortholog to Gapdh, Rattus norvegicus
    ortholog to Gapdh, Mus musculus
    Homologene
    FAMILY
  • glyceraldehyde 3-phosphate dehydrogenase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • triggering apoptosis when translocated to the nucleus
  • nuclear localization is regulated by ceramide in a cell cycle-dependent manner
  • exact function of GAPDH in the nucleus is largely unknown but nuclear GAPDH seems to be involved in the regulation of TP53 activation
  • nuclear translocation of GAPDH might be regulated by the PI3K signaling pathway acting mainly as a nuclear export signal and the AMPK signaling pathway acting as a nuclear import signal
  • association between AIRE-induced apoptosis and GAPDH nuclear translocation
  • basic FUNCTION
  • catalyzing the reversible oxidative phosphorylation of G3P in the presence of Pi and NAD (glycolysis and gluconeogenesis)
  • involved exclusively in cytosolic energy production
  • involved in neuronal disease and in programmed cell death
  • may play a role in P. gingivalis adherence and colonization of the oral cavity
  • is required for membrane transport between the endoplasmic reticulum and the Golgi complex
  • nuclear GAPDH isoform is involved in the maintenance and/or protection of telomeres
  • is a target for insulin regulation
  • general mediator initiating one or more apoptotic cascades, may be involved in the Lewy body formation and probably associated with the apoptotic death pathway
  • accumulates in mitochondria during apoptosis, and induces the pro-apoptotic mitochondrial membrane permeabilization, a decisive event of the intrinsic pathway of apoptosis
  • glycolytic enzyme playing an essential role in the phosphorelay signaling, where its redox-sensitive cysteine residue may provide additional input signals
  • may participates in oxidative stress-induced cell death via an alternative mechanism in which aggregation but not nuclear translocation of GAPDH plays a role
  • critical role of GAPDH aggregates in oxidative stress-induced brain damage
  • exerts other functions beyond glycolysis, and oxidatively modified GAPDH regulates its cellular functions by changing its interacting proteins
  • GAPDH-dependent phosphorylation of L1CAM is a novel mechanism in regulating L1CAM-mediated neurite outgrowth
  • displays multiple functions, such as nuclear RNA export, DNA replication and repair, and apoptotic cell death
  • Nitrosylated-GAPDH physiologically transnitrosylates nuclear proteins such as sirtuin-1, histone deacetylase-2 and DNA-activated protein kinase
  • AIRE-induced cellular stress and apoptosis are associated with GAPDH translocation into the nuclei
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate , energetic
    signaling
    a component
    INTERACTION
    DNA
    RNA binding
    small molecule cofactor, nucleotide,
  • Pi
  • NAD
  • ATP
  • protein
  • C-terminus of amyloid precursor protein
  • Huntingtin and dentatorubral-pallidoluysian atrophy protein, DRPLA
  • Spinocerebellar ataxia type1, SCA1 and androgen receptor, AR
  • 2,3-DPGM and 3-PGK
  • protein disulfide isomerase, PDI
  • phospholipase D2, PLD2
  • muscle specific Ca(2)+/calmodulin-dependent protein kinase, CaMKIIbeta(M)
  • N-myristoylated p22
  • Rab2
  • Ca(2+)/calmodulin-dependent protein kinase phosphatase, CaMKP
  • even in absentia homolog 1 (Drosophila), SIAH1
  • myocilin, MYOC
  • protein SET
  • TPPP/p25 protein
  • FKBP6
  • ISYNA1
  • NLS-bearing SIAH1
  • Nitrosylated GAPDH (SNO-GAPDH) binds to Siah1
  • AIRE-induced apoptosis pathway is associated with GAPDH nuclear translocation and induction of NO-induced cellular stress in AIRE-expressing cells
  • NPM1 physiologically bound to both SIAH1 and GAPDH, disrupting the SIAH1–GAPDH complex in the nucleus in response to nitrosative stress
  • GAPDH–SIAH1 interaction is augmented by S-nitrosylation of GAPDH
  • NPM1 did not compete with RILPL1 for GAPDH binding in the cytoplasm, although a small amount of NPM1 protein was able to reside in the cytoplasm
  • MZF1 regulates GAPDH, indicating a role for GAPDH in calcitriol-mediated signaling
  • MAP3K5 a representative stress kinase, interacts with both GAPDH and SIAH1 and is likely able to phosphorylate Siah1 at specific amino acid residues
  • dissociation of the GAPDH/SIAH1 pro-apoptotic complex can block high glucose-induced pericyte apoptosis, widely considered a hallmark feature of Diabetic retinopathy (DR)
  • cell & other
  • actin filaments
  • REGULATION
    activated by hypoxia
    induced by thioredoxin
    glutamine
    inhibited by binding to the cell membrane
    lipid peroxidation products such as HNE and HHE
    Other disulfide bonding due to oxidant exposure leads to a reduced enzymatic activity
    upregulated with proliferation, activation, and differentiation
    phosphorylated by protein kinase Ciota /lambda
    regulated by RILP1 (binds GAPDH, in competition with SIAH1, retaining GAPDH in the cytosol and preventing its nuclear translocation)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   amplification    
    in Huntington disease (high molecular weight protein)
    tumoral     --over  
    in gastric cancer
    tumoral   translocation    
    with BCL6 in primary diffuse large B-cell lymphomas of the central nervous system
    tumoral     --over  
    overexpressed in renal cell carcinoma
    constitutional     --over  
    in apoptosis and in several chronic pathologies
    Susceptibility to late-onset Alzheimer disease
    Variant & Polymorphism SNP SNP increasing the risk of late-onset Alzheimer disease
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabete  
    agents that can directly target modification of GAPDH have potential in inhibiting the development and in arresting the progression of diabetic retinopathy
    ANIMAL & CELL MODELS