GAPDH Rabbit Polyclonal Antibody

功能

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), also called uracil DNA glycosylase, catalyzes the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate in the presence of inorganic phosphate and nicotinamide adenine dinucleotide (NAD), an important energy-yielding step in carbohydrate metabolism. While GAPDH has long been recognized as playing an integral role in glycolysis, additional functions of GAPDH include acting as a uricil DNA glycosylase, activating transcription, binding RNA and involvement in nuclear RNA export, DNA replication and DNA repair. Expression of GAPDH is upregulated in liver, lung and prostate cancers. GAPDH translocates to the nucleus during apoptosis. GAPDH complexes with neuronal proteins implicated in human neuro-degenerative disorders including the β-Amyloid precursor, Huntingtin and other triplet repeat neuronal disorder proteins.

背景文献

1. Tisdale EJ. Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein kinase Ciota /lambda and plays a role in microtubule dynamics in the early secretory pathway. J. Biol. Chem. 277:3334-3341 (2002).

2. Arif A et al. Heterotrimeric GAIT complex drives transcript-selective translation inhibition in murine macrophages. Mol. Cell. Biol. 32:5046-5055 (2012).

序列相似性

Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.

翻译后修饰

S-nitrosylation of Cys-152 leads to interaction with SIAH1, followed by translocation to the nucleus (By similarity). S-nitrosylation of Cys-247 is induced by interferon-gamma and LDL(ox) implicating the iNOS-S100A8/9 transnitrosylase complex and seems to prevent interaction with phosphorylated RPL13A and to interfere with GAIT complex activity.; ISGylated.; Sulfhydration at Cys-152 increases catalytic activity.; Oxidative stress can promote the formation of high molecular weight disulfide-linked GAPDH aggregates, through a process called nucleocytoplasmic coagulation. Such aggregates can be observed in vivo in the affected tissues of patients with Alzheimer disease or alcoholic liver cirrhosis, or in cell cultures during necrosis. Oxidation at Met-46 may play a pivotal role in the formation of these insoluble structures. This modification has been detected in vitro following treatment with free radical donor (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide. It has been proposed to destabilize nearby residues, increasing the likelihood of secondary oxidative damages, including oxidation of Tyr-45 and Met-105. This cascade of oxidations may augment GAPDH misfolding, leading to intermolecular disulfide cross-linking and aggregation.; Succination of Cys-152 and Cys-247 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits glyceraldehyde-3-phosphate dehydrogenase activity. Fumarate concentration as well as succination of cysteine residues in GAPDH is significantly increased in muscle of diabetic mammals. It was proposed that the S-(2-succinyl)cysteine chemical modification may be a useful biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins by fumarate may contribute to the metabolic changes underlying the development of diabetes complications.

亚细胞定位

Cytoskeleton. Cytosol. Nucleus.

UNIPROT #

SwissProt: P04406 Human

SwissProt: P16858 Mouse

SwissProt: P04797 Rat

别名