GAPDH

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH or G3PDH) is an enzyme of about 37kDa that is consisdered as a cellular enzyme involved in glycolysis. It catelyzes the sixth step of glycolysis. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a pleiotropic enzyme that is overexpressed in apoptosis and in several human chronic pathologies. Its role as a mediator for cell death has also been highlighted. A recent report suggests that GAPDH may be genetically associated with late-onset of Alzheimer's disease. Besides, deprenyl, which has originally been used as a monoamine oxidase inhibitor for Parkinson's disease, binds to GAPDH and displays neuroprotective actions.

GAPDH Related Areas

Signal Transduction>>Adaptor Protein>> GAPDH

GAPDH Alternative Names

CDABP0047, G3PD, GAPD, MGC88685 [Homo sapiens]
Gapd, MGC102544, MGC102546, MGC103190, MGC103191, MGC105239 [Mus musculus]

Summaries for GAPDH

Entrez Gene summary for GAPDH :

The product of this gene catalyzes an important energy-yielding step in carbohydrate metabolism, the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate in the presence of inorganic phosphate and nicotinamide adenine dinucleotide (NAD). The enzyme exists as a tetramer of identical chains. Many pseudogenes similar to this locus are present in the human genome. Two transcript variants encoding different isoforms have been found for this gene.

OMIM - description for GAPDH :

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes an important energy-yielding step in carbohydrate metabolism, the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate in the presence of inorganic phosphate and nicotinamide adenine dinucleotide (NAD). The enzyme is thought to be a tetramer of identical chains.

Wikipedia summary for GAPDH :

Glyceraldehyde 3-phosphate dehydrogenase (abbreviated as GAPDH or less commonly as GAPDH) (EC 1.2.1.12) is an enzyme of ~37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long established metabolic function, GAPDH has recently been implicated in several non-metabolic processes, including transcription activation, initiation of apoptosis,[1] and ER to Golgi vesicle shuttling.

Human GAPDH Protein General Information

 

• Protein names: Recommended name: Glyceraldehyde-3-phosphate dehydrogenase
  Short name: GAPDH
• Sequence length: 335 AA
• Sequence similarities: Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.
• Post-translational modification: S-nitrosylation of Cys-152 leads to interaction with SIAH1, followed by translocation to the nucleus By similarity. ISGylated
• Subunit structure: Homotetramer. Interacts with TPPP; the interaction is direct. Interacts (when S-nitrosylated) with SIAH1; leading to nuclear translocation. Interacts with RILPL1/GOSPEL, leading to prevent the interaction between GAPDH and SIAH1 and prevent nuclear translocation Interacts with EIF1AD, USP25, PRKCI and WARS.
• Subcellular location: Cytoplasm › cytosol. Nucleus. Cytoplasm › perinuclear region. Membrane. Note: Translocates to the nucleus following S-nitrosylation and interaction with SIAH1, which contains a nuclear localization signal. Postnuclear and Perinuclear regions.

General information above from UniProt

Function for GAPDH Protein

UniProtKB:

Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC By similarity. Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate.

Genatlas:

• GAPDH catalyzing the reversible oxidative phosphorylation of G3P in the presence of Pi and NAD (glycolysis and gluconeogenesis)
• GAPDH is involved exclusively in cytosolic energy production
• GAPDH isinvolved in neuronal disease and in programmed cell death
• GAPDH may play a role in P. gingivalis adherence and colonization of the oral cavity
• GAPDH 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
• GAPDH 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
• GAPDH accumulates in mitochondria during apoptosis, and induces the pro-apoptotic mitochondrial membrane permeabilization, a decisive event of the intrinsic pathway of apoptosis (Pubmed 17597534)
• glycolytic enzyme playing an essential role in the phosphorelay signaling, where its redox-sensitive cysteine residue may provide additional input signals (Pubmed 18406331)
• GAPDH may participates in oxidative stress-induced cell death via an alternative mechanism in which aggregation but not nuclear translocation of GAPDH plays a role (Pubmed 19837666)

Homology for human GAPDH

• ortholog to gapdh, Danio rerio
• ortholog to Gapdh, Rattus norvegicus
• ortholog to Gapdh, Mus musculus

Phenotype Information for GAPDH

• Gene/Locus: Huntingtin
• Phenotype: Huntington disease

Phenotype Information for GAPDH from OMIM (Online Mendelian Inheritance in Man)

Drugs for GAPDH

Drugs for GAPDH from TTD (Therapeutic Targets Database)