GAPDH

Description

The GAPDH (glyceraldehyde-3-phosphate dehydrogenase) is a protein-coding gene located on chromosome 12.

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is an enzyme of about 37 kDa that catalyzes the sixth step of glycolysis, breaking down glucose for energy and carbon molecules. Beyond this metabolic role, GAPDH is involved in various non-metabolic processes, including transcription activation, initiation of apoptosis, ER-to-Golgi vesicle shuttling, and fast axonal, or axoplasmic transport. A testis-specific isoenzyme GAPDHS is expressed in sperm. GAPDH exists mainly as a tetramer under normal cellular conditions, composed of four identical 37-kDa subunits, each containing a single catalytic thiol group crucial for its function. Nuclear GAPDH exhibits an increased isoelectric point (pI) of pH 8.3–8.7. The cysteine residue C152 in the enzyme's active site is required for apoptosis induction by oxidative stress. Post-translational modifications of cytoplasmic GAPDH contribute to its functions outside of glycolysis. GAPDH is encoded by a single gene producing a single mRNA transcript with 8 splice variants, although an isoform exists as a separate gene expressed only in spermatozoa.

GAPDH, also known as Peptidyl-cysteine S-nitrosylase GAPDH, exhibits both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities. It plays a key role in glycolysis by catalyzing the conversion of D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. GAPDH also influences the organization and assembly of the cytoskeleton by facilitating CHP1-dependent microtubule and membrane associations. It is a component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition during inflammatory processes. Upon interferon-gamma treatment, GAPDH assembles into the GAIT complex and binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs, suppressing their translation. GAPDH is also involved in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production through its interaction with TRAF2 and TRAF3, respectively. GAPDH participates in nuclear events including transcription, RNA transport, DNA replication, and apoptosis. Its nuclear functions are likely due to its nitrosylase activity, which mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2, and PRKDC.

GAPDH is also known as G3PD, GAPD, HEL-S-162eP.

Associated Diseases

WES Whole Exome Sequencing