Description: Homo sapiens glyceraldehyde-3-phosphate dehydrogenase (GAPDH), transcript variant 1, mRNA. RefSeq Summary (NM_002046): This gene encodes a member of the glyceraldehyde-3-phosphate dehydrogenase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. 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 encoded protein has additionally been identified to have uracil DNA glycosylase activity in the nucleus. Also, this protein contains a peptide that has antimicrobial activity against E. coli, P. aeruginosa, and C. albicans. Studies of a similar protein in mouse have assigned a variety of additional functions including nitrosylation of nuclear proteins, the regulation of mRNA stability, and acting as a transferrin receptor on the cell surface of macrophage. Many pseudogenes similar to this locus are present in the human genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]. Transcript (Including UTRs) Position: hg19 chr12:6,643,585-6,647,537 Size: 3,953 Total Exon Count: 9 Strand: + Coding Region Position: hg19 chr12:6,643,999-6,647,336 Size: 3,338 Coding Exon Count: 8
ID:G3P_HUMAN DESCRIPTION: RecName: Full=Glyceraldehyde-3-phosphate dehydrogenase; Short=GAPDH; EC=1.2.1.12; AltName: Full=Peptidyl-cysteine S-nitrosylase GAPDH; EC=2.6.99.-; FUNCTION: 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. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (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. CATALYTIC ACTIVITY: D-glyceraldehyde 3-phosphate + phosphate + NAD(+) = 3-phospho-D-glyceroyl phosphate + NADH. PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D- glyceraldehyde 3-phosphate: step 1/5. SUBUNIT: 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 CHP1; the interaction increases the binding of CHP1 with microtubules. Associates with microtubules (By similarity). Interacts with EIF1AD, USP25, PRKCI and WARS. INTERACTION: P00533:EGFR; NbExp=4; IntAct=EBI-354056, EBI-297353; P15927:RPA2; NbExp=2; IntAct=EBI-354056, EBI-621404; SUBCELLULAR LOCATION: Cytoplasm, cytosol. Nucleus (By similarity). Cytoplasm, perinuclear region. Membrane. Cytoplasm, cytoskeleton (By similarity). Note=Translocates to the nucleus following S- nitrosylation and interaction with SIAH1, which contains a nuclear localization signal (By similarity). Postnuclear and Perinuclear regions. PTM: S-nitrosylation of Cys-152 leads to interaction with SIAH1, followed by translocation to the nucleus (By similarity). PTM: ISGylated (Probable). PTM: Sulfhydration at Cys-152 increases catalytic activity (By similarity). SIMILARITY: Belongs to the glyceraldehyde-3-phosphate dehydrogenase family. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/gapd/"; WEB RESOURCE: Name=Wikipedia; Note=Glyceraldehyde 3-phosphate dehydrogenase entry; URL="http://en.wikipedia.org/wiki/Glyceraldehyde_3-phosphate_dehydrogenase";
To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): GAPDH CDC HuGE Published Literature: GAPDH Positive Disease Associations: Alzheimer's Disease Related Studies:
Alzheimer's Disease Li Y et al 2004, Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family., Proceedings of the National Academy of Sciences of the United States of America. 2004 Nov;101(44):15688-93.
[PubMed 15507493]
Alzheimer's Disease Li, Y. et al. 2004, Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family., Proceedings of the National Academy of Sciences of the United States of America. 2004 Nov;101(44):15688-93.
[PubMed 15507493]
Individually, these SNPs make differential contributions to disease risk in each of the case-control series, suggesting that variants in functionally similar genes may account for series-to-series heterogeneity of disease risk. Our observations raise the possibility that GAPD genes are AD risk factors, a hypothesis that is consistent with the role of GAPD in neuronal apoptosis.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P04406
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004365 glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity GO:0005515 protein binding GO:0008017 microtubule binding GO:0016491 oxidoreductase activity GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor GO:0016740 transferase activity GO:0019828 aspartic-type endopeptidase inhibitor activity GO:0035605 peptidyl-cysteine S-nitrosylase activity GO:0042802 identical protein binding GO:0050661 NADP binding GO:0051287 NAD binding GO:0097718 disordered domain specific binding
Biological Process: GO:0000226 microtubule cytoskeleton organization GO:0006006 glucose metabolic process GO:0006094 gluconeogenesis GO:0006096 glycolytic process GO:0006417 regulation of translation GO:0006915 apoptotic process GO:0010951 negative regulation of endopeptidase activity GO:0016241 regulation of macroautophagy GO:0017148 negative regulation of translation GO:0031640 killing of cells of other organism GO:0035606 peptidyl-cysteine S-trans-nitrosylation GO:0050715 positive regulation of cytokine secretion GO:0050821 protein stabilization GO:0050832 defense response to fungus GO:0051402 neuron apoptotic process GO:0051873 killing by host of symbiont cells GO:0052501 positive regulation by organism of apoptotic process in other organism involved in symbiotic interaction GO:0055114 oxidation-reduction process GO:0061621 canonical glycolysis GO:0071346 cellular response to interferon-gamma
BioCarta from NCI Cancer Genome Anatomy Project h_mta3Pathway - Downregulated of MTA-3 in ER-negative Breast Tumors h_glycolysisPathway - Glycolysis Pathway
Reactome (by CSHL, EBI, and GO)
Protein P04406 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
