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    GAPDH glyceraldehyde-3-phosphate dehydrogenase [ Homo sapiens (human) ]

    Gene ID: 2597, updated on 12-Nov-2024

    Summary

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    Official Symbol
    GAPDHprovided by HGNC
    Official Full Name
    glyceraldehyde-3-phosphate dehydrogenaseprovided by HGNC
    Primary source
    HGNC:HGNC:4141
    See related
    Ensembl:ENSG00000111640 MIM:138400; AllianceGenome:HGNC:4141
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    G3PD; GAPD; HEL-S-162eP
    Summary
    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]
    Expression
    Ubiquitous expression in bone marrow (RPKM 1203.9), heart (RPKM 1083.8) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GAPDH in Genome Data Viewer
    Location:
    12p13.31
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (6534517..6538371)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (6544873..6548727)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (6643683..6647537)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene non-SMC condensin I complex subunit D2 Neighboring gene small Cajal body-specific RNA 10 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:6641915-6642688 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:6642689-6643462 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:6643463-6644236 Neighboring gene GAPDH divergent transcript Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:6645785-6646558 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5864 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5865 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5866 Neighboring gene intermediate filament family orphan 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:6658582-6659082 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:6659083-6659583 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:6660263-6660762 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:6661035-6661552 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:6663184-6663684 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:6663685-6664185 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4169 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4170 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4171 Neighboring gene NOP2 nucleolar protein Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:6677307-6677928

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The tumor suppressor Parkin exerts anticancer effects through regulating mitochondrial GAPDH activity.
      Title: The tumor suppressor Parkin exerts anticancer effects through regulating mitochondrial GAPDH activity.
    2. Regulation of AMPK and GAPDH by Transglutaminase 2 Plays a Pivotal Role in Microvascular Leakage in Diabetic Retinas.
      Title: Regulation of AMPK and GAPDH by Transglutaminase 2 Plays a Pivotal Role in Microvascular Leakage in Diabetic Retinas.
    3. Modification of Glyceraldehyde-3-Phosphate Dehydrogenase with Nitric Oxide: Role in Signal Transduction and Development of Apoptosis.
      Title: Modification of Glyceraldehyde-3-Phosphate Dehydrogenase with Nitric Oxide: Role in Signal Transduction and Development of Apoptosis.
    4. Glyceraldehyde-3-Phosphate Dehydrogenase Binds with Spike Protein and Inhibits the Entry of SARS-CoV-2 into Host Cells.
      Title: Glyceraldehyde-3-Phosphate Dehydrogenase Binds with Spike Protein and Inhibits the Entry of SARS-CoV-2 into Host Cells.
    5. Exploring the Role of Glycolytic Enzymes PFKFB3 and GAPDH in the Modulation of Abeta and Neurodegeneration and Their Potential of Therapeutic Targets in Alzheimer's Disease.
      Title: Exploring the Role of Glycolytic Enzymes PFKFB3 and GAPDH in the Modulation of Aβ and Neurodegeneration and Their Potential of Therapeutic Targets in Alzheimer's Disease.
    6. Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation.
      Title: Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation.
    7. Uncoupled glycerol-3-phosphate shuttle in kidney cancer reveals that cytosolic GPD is essential to support lipid synthesis.
      Title: Uncoupled glycerol-3-phosphate shuttle in kidney cancer reveals that cytosolic GPD is essential to support lipid synthesis.
    8. Glyceraldehyde-3-phosphate dehydrogenase regulates activation of c-Jun N-terminal kinase under oxidative stress.
      Title: Glyceraldehyde-3-phosphate dehydrogenase regulates activation of c-Jun N-terminal kinase under oxidative stress.
    9. Crotonylation of GAPDH regulates human embryonic stem cell endodermal lineage differentiation and metabolic switch.
      Title: Crotonylation of GAPDH regulates human embryonic stem cell endodermal lineage differentiation and metabolic switch.
    10. Combined thioredoxin reductase and glutaminase inhibition exerts synergistic anti-tumor activity in MYC-high high-grade serous ovarian carcinoma.
      Title: Combined thioredoxin reductase and glutaminase inhibition exerts synergistic anti-tumor activity in MYC-high high-grade serous ovarian carcinoma.
    Submit: New GeneRIF Correction See all GeneRIFs (168)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of GAPDH by siRNA enhances HIV-1 infectivity in TZM-bl cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Tandem affinity purification and mass spectrometry analysis identify glyceraldehyde-3-phosphate dehydrogenase (GAPDH), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Gag-Pol gag-pol Immunoprecipitation assay shows that GAPDH directly interacts with HIV-1 Gag and Gag-Pol. Packaging of LysRS and tRNA-Lys3 into virions is negatively regulated by GAPDH, leading to decreased viral infectivity PubMed
    gag-pol Tandem affinity purification and mass spectrometry analysis identify glyceraldehyde-3-phosphate dehydrogenase (GAPDH), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Nef nef Tandem affinity purification and mass spectrometry analysis identify glyceraldehyde-3-phosphate dehydrogenase (GAPDH), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Pr55(Gag) gag Immunoprecipitation assay shows that GAPDH directly interacts with HIV-1 Gag and Gag-Pol. Packaging of LysRS and tRNA-Lys3 into virions is negatively regulated by GAPDH, leading to decreased viral infectivity PubMed
    gag Tandem affinity purification and mass spectrometry analysis identify glyceraldehyde-3-phosphate dehydrogenase (GAPDH), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Rev rev HIV-1 Rev interacting protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells. The interaction of Rev with GAPDH is increased by RRE PubMed
    Tat tat Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is identified to interact with HIV-1 Tat mutant Nullbasic in HeLa cells by LC MS/MS PubMed
    Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed
    vpr Treatment of human primary astrocytes with HIV-1 Vpr downregulates expression of mRNA GAPDH and GAPDH activity PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC88685

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables NAD binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables NADP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables aspartic-type endopeptidase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables disordered domain specific binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables microtubule binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables peptidyl-cysteine S-nitrosylase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in antimicrobial humoral immune response mediated by antimicrobial peptide IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to type II interferon IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in defense response to fungus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in glucose metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in glycolytic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glycolytic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in killing by host of symbiont cells IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in killing of cells of another organism IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in microtubule cytoskeleton organization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of translation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of translation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in neuron apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in peptidyl-cysteine S-trans-nitrosylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of canonical NF-kappaB signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of cytokine production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of type I interferon production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein stabilization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of macroautophagy TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of GAIT complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in lipid droplet IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    located_in microtubule cytoskeleton ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in nuclear membrane IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus HDA PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  
    part_of ribonucleoprotein complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in vesicle HDA PubMed 

    General protein information

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    Preferred Names
    glyceraldehyde-3-phosphate dehydrogenase
    Names
    OCAS, p38 component
    Oct1 coactivator in S phase, 38 Kd component
    aging-associated gene 9 protein
    epididymis secretory sperm binding protein Li 162eP
    peptidyl-cysteine S-nitrosylase GAPDH
    NP_001243728.1
    NP_001276674.1
    NP_001276675.1
    NP_001344872.1
    NP_002037.2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007073.2 RefSeqGene

      Range
      5027..8881
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001256799.3 → NP_001243728.1  glyceraldehyde-3-phosphate dehydrogenase isoform 2

      See identical proteins and their annotated locations for NP_001243728.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and lacks a portion of the 5' coding region compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (2) with a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AF261085, BE893087, HY000136
      Consensus CDS
      CCDS58201.1
      UniProtKB/TrEMBL
      Q2TSD0
      Related
      ENSP00000380067.1, ENST00000396858.5
      Conserved Domains (1) summary
      cl27764
      Location:1 → 290
      Gp_dh_N; Glyceraldehyde 3-phosphate dehydrogenase, NAD binding domain

    2. NM_001289745.3 → NP_001276674.1  glyceraldehyde-3-phosphate dehydrogenase isoform 1

      See identical proteins and their annotated locations for NP_001276674.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1, 3, and 4 encode the same isoform (1).
      Source sequence(s)
      AK308198, BE893087, BM763361, M33197
      Consensus CDS
      CCDS8549.1
      UniProtKB/Swiss-Prot
      E7EUT4, P00354, P04406, Q53X65
      UniProtKB/TrEMBL
      Q2TSD0, V9HVZ4
      Related
      ENSP00000380070.1, ENST00000396861.5
      Conserved Domains (1) summary
      PLN02272
      Location:2 → 332
      PLN02272; glyceraldehyde-3-phosphate dehydrogenase

    3. NM_001289746.2 → NP_001276675.1  glyceraldehyde-3-phosphate dehydrogenase isoform 1

      See identical proteins and their annotated locations for NP_001276675.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, compared to variant 1. Variants 1, 3, and 4 encode the same isoform (1).
      Source sequence(s)
      AC006064, BC023632, HY004110, HY022295
      Consensus CDS
      CCDS8549.1
      UniProtKB/Swiss-Prot
      E7EUT4, P00354, P04406, Q53X65
      UniProtKB/TrEMBL
      Q2TSD0, V9HVZ4
      Related
      ENSP00000380068.1, ENST00000396859.5
      Conserved Domains (1) summary
      PLN02272
      Location:2 → 332
      PLN02272; glyceraldehyde-3-phosphate dehydrogenase

    4. NM_001357943.2 → NP_001344872.1  glyceraldehyde-3-phosphate dehydrogenase isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) uses an alternate splice site but retains the reading frame compared to variant 1. The encoded isoform (4) is shorter than isoform 1.
      Source sequence(s)
      AC006064
      UniProtKB/TrEMBL
      Q2TSD0
      Conserved Domains (1) summary
      cl27764
      Location:2 → 314
      Gp_dh_N; Glyceraldehyde 3-phosphate dehydrogenase, NAD binding domain

    5. NM_002046.7 → NP_002037.2  glyceraldehyde-3-phosphate dehydrogenase isoform 1

      See identical proteins and their annotated locations for NP_002037.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AK308198, BC009081
      Consensus CDS
      CCDS8549.1
      UniProtKB/Swiss-Prot
      E7EUT4, P00354, P04406, Q53X65
      UniProtKB/TrEMBL
      Q2TSD0, V9HVZ4
      Related
      ENSP00000229239.5, ENST00000229239.10
      Conserved Domains (1) summary
      PLN02272
      Location:2 → 332
      PLN02272; glyceraldehyde-3-phosphate dehydrogenase

    RNA

    1. NR_152150.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) uses an alternate splice site and lacks two exons compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region found in variant 1.
      Source sequence(s)
      AC006064

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      6534517..6538371
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      6544873..6548727
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001357938.1: Suppressed sequence

      Description
      NM_001357938.1: This RefSeq was removed because currently there is insufficient support for the transcript and protein.

    2. NM_001357944.1: Suppressed sequence

      Description
      NM_001357944.1: This RefSeq has been removed because there is insufficient support for the transcript and protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P04406.3 GenPept UniProtKB/Swiss-Prot:P04406

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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