P10096 · G3P_BOVIN
- ProteinGlyceraldehyde-3-phosphate dehydrogenase
- GeneGAPDH
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids333 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. 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 (By similarity).
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).
Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. 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. 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 (By similarity).
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 (By similarity).
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).
Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. 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. 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 (By similarity).
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 (By similarity).
Catalytic activity
- D-glyceraldehyde 3-phosphate + NAD+ + phosphate = (2R)-3-phospho-glyceroyl phosphate + H+ + NADH
- L-cysteinyl-[protein] + S-nitroso-L-cysteinyl-[GAPDH] = L-cysteinyl-[GAPDH] + S-nitroso-L-cysteinyl-[protein]This reaction proceeds in the forward direction.
Activity regulation
Glyceraldehyde-3-phosphate dehydrogenase activity is inhibited by fumarate, via the formation of S-(2-succinyl)cysteine residues.
Pathway
Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5.
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 11-12 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: RI | ||||||
Binding site | 33 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 78 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 120 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 149-151 | D-glyceraldehyde 3-phosphate (UniProtKB | ChEBI) | ||||
Sequence: SCT | ||||||
Active site | 150 | Nucleophile | ||||
Sequence: C | ||||||
Site | 177 | Activates thiol group during catalysis | ||||
Sequence: H | ||||||
Binding site | 180 | D-glyceraldehyde 3-phosphate (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 209-210 | D-glyceraldehyde 3-phosphate (UniProtKB | ChEBI) | ||||
Sequence: TG | ||||||
Binding site | 232 | D-glyceraldehyde 3-phosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 314 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: N |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameGlyceraldehyde-3-phosphate dehydrogenase
- EC number
- Short namesGAPDH
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos
Accessions
- Primary accessionP10096
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Translocates to the nucleus following S-nitrosylation and interaction with SIAH1, which contains a nuclear localization signal. Colocalizes with CHP1 to small punctate structures along the microtubules tracks.
Keywords
- Cellular component
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 81 variants from UniProt as well as other sources including ClinVar and dbSNP.
Protein family/group databases
PTM/Processing
Features
Showing features for initiator methionine, chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Chain | PRO_0000145481 | 2-333 | Glyceraldehyde-3-phosphate dehydrogenase | |||
Sequence: VKVGVNGFGRIGRLVTRAAFNSGKVDIVAINDPFIDLHYMVYMFQYDSTHGKFNGTVKAENGKLVINGKAITIFQERDPANIKWGDAGAEYVVESTGVFTTMEKAGAHLKGGAKRVIISAPSADAPMFVMGVNHEKYNNTLKIVSNASCTTNCLAPLAKVIHDHFGIVEGLMTTVHAITATQKTVDGPSGKLWRDGRGAAQNIIPASTGAAKAVGKVIPELNGKLTGMAFRVPTPNVSVVDLTCRLEKPAKYDEIKKVVKQASEGPLKGILGYTEDQVVSCDFNSDTHSSTFDAGAGIALNDHFVKLISWYDNEFGYSNRVVDLMVHMASKE | ||||||
Modified residue | 3 | N6,N6-dimethyllysine | ||||
Sequence: K | ||||||
Modified residue | 7 | Deamidated asparagine | ||||
Sequence: N | ||||||
Modified residue | 40 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 59 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 62 | Deamidated asparagine | ||||
Sequence: N | ||||||
Modified residue | 64 | N6,N6-dimethyllysine | ||||
Sequence: K | ||||||
Modified residue | 68 | Deamidated asparagine | ||||
Sequence: N | ||||||
Modified residue | 73 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 120 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 146 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 147 | Deamidated asparagine | ||||
Sequence: N | ||||||
Modified residue | 149 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 150 | ADP-ribosylcysteine; by autocatalysis; in irreversibly inhibited form | ||||
Sequence: C | ||||||
Modified residue | 150 | Cysteine persulfide | ||||
Sequence: C | ||||||
Modified residue | 150 | S-(2-succinyl)cysteine | ||||
Sequence: C | ||||||
Modified residue | 150 | S-nitrosocysteine; in reversibly inhibited form | ||||
Sequence: C | ||||||
Modified residue | 151 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 153 | Deamidated asparagine | ||||
Sequence: N | ||||||
Modified residue | 175 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 180 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 182 | Phosphothreonine | ||||
Sequence: T | ||||||
Cross-link | 184 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 192 | N6,N6-dimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 192 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 192 | N6-malonyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 209 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 213 | N6,N6-dimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 213 | N6-malonyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 217 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 223 | Deamidated asparagine | ||||
Sequence: N | ||||||
Modified residue | 225 | N6,N6-dimethyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 225 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 227 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 235 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 239 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 245 | S-(2-succinyl)cysteine | ||||
Sequence: C | ||||||
Modified residue | 245 | S-nitrosocysteine | ||||
Sequence: C | ||||||
Modified residue | 252 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 258 | N6,N6-dimethyllysine | ||||
Sequence: K | ||||||
Modified residue | 261 | N6,N6-dimethyllysine | ||||
Sequence: K | ||||||
Modified residue | 310 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 314 | Deamidated asparagine | ||||
Sequence: N | ||||||
Modified residue | 331 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 332 | N6,N6-dimethyllysine | ||||
Sequence: K |
Post-translational modification
ISGylated.
S-nitrosylation of Cys-150 leads to interaction with SIAH1, followed by translocation to the nucleus S-nitrosylation of Cys-245 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 (By similarity).
Sulfhydration at Cys-150 increases catalytic activity.
Oxidative stress can promote the formation of high molecular weight disulfide-linked GAPDH aggregates, through a process called nucleocytoplasmic coagulation.
Keywords
- PTM
Proteomic databases
Expression
Gene expression databases
Interaction
Subunit
Homotetramer (By similarity).
Interacts with TPPP; the interaction is direct (PubMed:17027006).
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 WARS1. Interacts with phosphorylated RPL13A; inhibited by oxidatively-modified low-densitity lipoprotein (LDL(ox)). Component of the GAIT complex. Interacts with FKBP6; leading to inhibit GAPDH catalytic activity. Interacts with TRAF2, promoting TRAF2 ubiquitination. Interacts with TRAF3, promoting TRAF3 ubiquitination (By similarity).
Interacts with TPPP; the interaction is direct (PubMed:17027006).
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 WARS1. Interacts with phosphorylated RPL13A; inhibited by oxidatively-modified low-densitity lipoprotein (LDL(ox)). Component of the GAIT complex. Interacts with FKBP6; leading to inhibit GAPDH catalytic activity. Interacts with TRAF2, promoting TRAF2 ubiquitination. Interacts with TRAF3, promoting TRAF3 ubiquitination (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P10096 | TPPP Q27957 | 2 | EBI-7025562, EBI-7025612 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-146 | Interaction with WARS1 | ||||
Sequence: VKVGVNGFGRIGRLVTRAAFNSGKVDIVAINDPFIDLHYMVYMFQYDSTHGKFNGTVKAENGKLVINGKAITIFQERDPANIKWGDAGAEYVVESTGVFTTMEKAGAHLKGGAKRVIISAPSADAPMFVMGVNHEKYNNTLKIVS | ||||||
Motif | 243-248 | [IL]-x-C-x-x-[DE] motif | ||||
Sequence: LTCRLE |
Domain
The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.
Sequence similarities
Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length333
- Mass (Da)35,868
- Last updated2007-01-23 v4
- Checksum17E17FE4289099FB
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A3Q1M8J9 | A0A3Q1M8J9_BOVIN | GAPDH | 330 |
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 30 | in Ref. 2; AA sequence | ||||
Sequence: A → F |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BC102589 EMBL· GenBank· DDBJ | AAI02590.1 EMBL· GenBank· DDBJ | mRNA | ||
U85042 EMBL· GenBank· DDBJ | AAB47507.1 EMBL· GenBank· DDBJ | mRNA | Frameshift |