Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
The protein contains 335 amino acids for an estimated molecular weight of 36053 Da.
Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:3170585, PubMed:11724794). 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 (PubMed:3170585, PubMed:11724794). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates (updated: June 2, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs45541435 | |
| dbSNP:rs1062429 |
Biological Process
Antimicrobial humoral immune response mediated by antimicrobial peptide
Canonical glycolysis
Cellular response to interferon-gamma
Defense response to fungus
Gluconeogenesis
Glycolytic process
Killing by host of symbiont cells
Killing of cells of other organism
Microtubule cytoskeleton organization
Negative regulation of endopeptidase activity
Negative regulation of translation
Neuron apoptotic process
Peptidyl-cysteine S-trans-nitrosylation
Positive regulation by organism of apoptotic process in other organism involved in symbiotic interaction
Positive regulation of cytokine production
Positive regulation of cytokine secretion
Protein stabilization
Regulation of macroautophagy
The reference OMIM entry for this protein is 138400
Glyceraldehyde-3-phosphate dehydrogenase; gapdh
Gapd; g3pd
Oct1 coactivator in s phase, 38-kd component
Ocas, p38 component
DESCRIPTION
Glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) 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) (Dayhoff, 1972).CLONING
Sequence data for GAPD were published in the atlas of Dayhoff (1972). The enzyme is present in such widely separated forms as man, lobster, and E. coli. Its rate of evolutionary change is one of the slowest known. In the cytoplasm GAPDH exists primarily as a tetrameric isoform composed of 4 identical 37-kD subunits. GAPDH is also found in the particulate fractions, such as the nucleus, the mitochondria, and the small vesicular fractions (review by Tristan et al., 2011). Variants have been found in a number of phyletically diverse organisms (Lebherz and Rutter, 1967). as in lactic acid dehydrogenase. Variants were found in man by Charlesworth (1972).GENE FUNCTION
Burke et al. (1996) demonstrated that synthetic polyglutamine peptides, DRPLA protein (607462) and huntingtin (HTT; 613004) from unaffected individuals with normal-sized polyglutamine tracts bind to GAPD. They noted that GAPD has also been shown to bind to RNA, ATP, calcyclin (114110), actin (see 102610), tubulin (see 191130) and amyloid precursor protein (104760). On the basis of their findings, Burke et al.(1996) postulated that the diseases characterized by the presence of an expanded CAG repeat may share a common metabolic pathogenesis involving GAPD as a functional component. Roses (1996) and Barinaga (1996) reviewed the findings. Using human embryonic kidney and mouse neuroblastoma cell lines, Bae et al. (2006) showed that nuclear translocation and associated neurotoxicity of mutant huntingtin was mediated by a ternary complex of huntingtin, GAPDH, and SIAH1 (602212), a ubiquitin E3 ligase that provided the nuclear translocation signal. Overexpression of GAPDH or SIAH1 enhanced nuclear translocation of mutant huntingtin and cytotoxicity, whereas GAPDH mutants unable to bind SIAH1 prevented translocation. Depletion of GAPDH or SIAH1 by RNA interference diminished nuclear translocation of mutant huntingtin. Zheng et al. (2003) isolated and functionally characterized a multicomponent OCT1 (164175) coactivator, OCAS, that is essential for S phase-dependent histone H2B (see 609904) transcription. The p38 component of OCAS, which the authors identified as GADPH, bound directly to OCT1, exhibited potent transactivation potential, was selectively recruited to the H2B promoter in S phase, and was essential for S phase-specific H2B transcription in vivo and in vitro. Binding to OCT1, as well as OCAS function, was stimulated by NAD+, but inhibited by NADH. OCAS also interacted with NPAT (601448), a cyclin E (123837)/CDK2 (116953) substrate broadly involved in histone gene transcription. These studies linked the H2B transcriptional machinery to cell cycle regulators, and possibly to cellular metabolic state (redox status), and set the stage for studies of the underlying mechanisms and the basis for coordinated histone gene expression and coupling to DNA replication. Meyer-Siegler et al. (1991) isolated a cDNA for uracil-DNA glycosylase (see UNG; 191525) that, to their surprise, was completely homologous to the 37-kD subunit of GAPD. They showed that the 37-kD subunit of commercially obtained erythrocyte GAPD possessed uracil-DNA glycosylas ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 138400 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).