GAPDH
Glyceraldehyde-3-phosphate dehydrogenase
Also known as: G3P_HUMAN, GAPD
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P04406
- Gene
- GAPDH
- Ensembl
- ENSG00000111640
- Chromosome
- 12
- Canonical length
- 335 aa
- Protein class
- Enzymes, FDA approved drug targets, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nuclear membrane,Vesicles,Plasma membrane,Cytosol
- Quaternary structure
- Homotetramer
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
335 residues, UniProt reviewed canonical sequence.
>P04406|GAPDH
1 MGKVKVGVNG FGRIGRLVTR AAFNSGKVDI VAINDPFIDL NYMVYMFQYD STHGKFHGTV
61 KAENGKLVIN GNPITIFQER DPSKIKWGDA GAEYVVESTG VFTTMEKAGA HLQGGAKRVI
121 ISAPSADAPM FVMGVNHEKY DNSLKIISNA SCTTNCLAPL AKVIHDNFGI VEGLMTTVHA
181 ITATQKTVDG PSGKLWRDGR GALQNIIPAS TGAAKAVGKV IPELNGKLTG MAFRVPTANV
241 SVVDLTCRLE KPAKYDDIKK VVKQASEGPL KGILGYTEHQ VVSSDFNSDT HSSTFDAGAG
301 IALNDHFVKL ISWYDNEFGY SNRVVDLMAH MASKELocalizationUniProt · AlphaFold · HPA
Whether an antibody against GAPDH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.24
- Highest tissue expression
- 25,843 nTPM
Expression across tissuesHPA
Tissue
- skeletal muscle: 25,843 nTPM
- tongue: 17,635 nTPM
- heart muscle: 5,081 nTPM
- bone marrow: 4,349 nTPM
- choroid plexus: 3,529 nTPM
- midbrain: 3,176 nTPM
Single-cell type
- esophageal apical cells: 15,050 nCPM
- extravillous trophoblasts: 13,578 nCPM
- esophageal suprabasal cells: 9,710 nCPM
- esophageal basal cells: 8,938 nCPM
- migrating cytotrophoblasts: 8,316 nCPM
- syncytiotrophoblasts: 5,108 nCPM
Immune cell
- total PBMC: 6,810 nTPM
- classical monocyte: 4,299 nTPM
- myeloid DC: 3,258 nTPM
- basophil: 2,588 nTPM
- T-reg: 2,132 nTPM
- intermediate monocyte: 2,013 nTPM
Brain region
- thalamus: 2,646 nTPM
- hypothalamus: 2,372 nTPM
- midbrain: 2,353 nTPM
- cerebellum: 2,340 nTPM
- medulla oblongata: 2,312 nTPM
- pons: 2,289 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about GAPDH.
Disease | ImmuneIEDB
Conditions an epitope on GAPDH was assayed in.
- multiple sclerosis B cell
- rheumatoid arthritis B cell
- autoimmune disease of central nervous system B cell
- onchocerciasis B cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against GAPDH are reported. Each links to that disease's full target list.
ReferencesPubMed · IEDB
Publications for GAPDH from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
9 publications
- Anti-GAPDH Autoantibodies as a Pathogenic Determinant and Potential Biomarker of Neuropsychiatric Diseases.
2016 · Arthritis Rheumatol · RCR 1.2 · 29 citations - Anti-GAPDH Autoantibody Is Associated with Increased Disease Activity and Intracranial Pressure in Systemic Lupus Erythematosus.
2019 · J Immunol Res · RCR 0.8 · 15 citations - Glyceraldehyde 3-phosphate dehydrogenase is a novel autoantigen leading autoimmune responses to proliferating cell nuclear antigen multiprotein complexes in lupus patients.
2004 · Int Immunol · RCR 0.7 · 28 citations - Screening of autoantibodies as biomarkers in the serum of renal cancer patients based on human proteome microarray.
2022 · Acta Biochim Biophys Sin (Shanghai) · RCR 0.5 · 5 citations - EFFECT OF PLASMAPHERESIS AND PASSAGE OF ANTI-RETINAL ANTIBODIES THROUGH THE PLACENTA IN A CASE OF NON-PARANEOPLASTIC AUTOIMMUNE RETINOPATHY.
2017 · Retin Cases Brief Rep · RCR 0.4 · 7 citations
Show 4 more
- Identification of Glyceraldehyde-3-Phosphate and Alcohol Dehydrogenases as Autoantigens in Doberman Hepatitis.
2017 · Scand J Immunol · RCR 0.4 · 5 citations - Seroreactivity against retinal proteins in a case of POC1B gene associated cone dystrophy with normal funduscopic appearance: a systematic approach to diagnosis.
2023 · Ophthalmic Genet · RCR 0.4 · 2 citations - Inhibition of glyceraldehyde-3-phosphate dehydrogenase activity by antibodies present in the cerebrospinal fluid of patients with multiple sclerosis.
2010 · J Immunol · RCR 0.3 · 13 citations - Serum anti-GAPDH autoantibody levels reflect the severity of cervical lesions: A potential serum biomarker for cervical cancer screening.
2019 · Oncol Lett · RCR 0.2 · 5 citations
Reference: B cellIEDB
4 publications
- High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients.
2016 · Mol Cell Proteomics · RCR 2.5 · 66 citations - Disordered Antigens and Epitope Overlap Between Anti-Citrullinated Protein Antibodies and Rheumatoid Factor in Rheumatoid Arthritis.
2020 · Arthritis Rheumatol · RCR 1.7 · 30 citations - Antibody profiling identifies novel antigenic targets in spinal cord injury patients.
2016 · J Neuroinflammation · RCR 0.7 · 18 citations - Linear epitopes in Onchocerca volvulus vaccine candidate proteins and excretory-secretory proteins.
2018 · Parasite Immunol · RCR 0.6 · 10 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.67
- gnomAD pLI
- 0.11
- gnomAD missense Z
- 1.81
- DepMap mean gene effect
- -1.29
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- antimicrobial humoral immune response mediated by antimicrobial peptide
- canonical glycolysis
- cellular response to type II interferon
- defense response to fungus
- glycolytic process
- killing by host of symbiont cells
- killing of cells of another organism
- microtubule cytoskeleton organization
- negative regulation of endopeptidase activity
- negative regulation of translation
- neuron apoptotic process
- peptidyl-cysteine S-trans-nitrosylation
- positive regulation of canonical NF-kappaB signal transduction
- positive regulation of cytokine production
- positive regulation of type I interferon production
- protein stabilization
- regulation of macroautophagy
Molecular functions
- aspartic-type endopeptidase inhibitor activity
- disordered domain specific binding
- glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity
- identical protein binding
- microtubule binding
- NAD binding
- NADP binding
- peptidyl-cysteine S-nitrosylase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Glyceraldehyde-3-phosphate dehydrogenase, type I
- Glyceraldehyde 3-phosphate dehydrogenase, NAD(P) binding domain
- Glyceraldehyde 3-phosphate dehydrogenase, catalytic domain
- Glyceraldehyde 3-phosphate dehydrogenase, active site
- Glyceraldehyde/Erythrose phosphate dehydrogenase family
- NAD(P)-binding domain superfamily
- Glyceraldehyde 3-phosphate dehydrogenase, NAD binding domain
- Glyceraldehyde 3-phosphate dehydrogenase, C-terminal domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of GAPDH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads GAPDH as an antibody target. Whether an autoantibody or antibody against GAPDH could matter depends on whether native GAPDH is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
GAPDH is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label GAPDH as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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