GAPDH
entrez
2597
canonical
uniprot
P04406
canonical
ensembl
ENSG00000111640
resolver
ensp
ENSP00000229239
resolver
ensp
ENSP00000380067
resolver
ensp
ENSP00000380068
resolver
ensp
ENSP00000380070
resolver
ensp
ENSP00000590850
resolver
genesymbol
GAPDH
resolver
genesymbol
HEL-S-162eP
resolver
genesymbol_syn
GAPD
resolver
hgnc
HGNC:4141
resolver
uniprot
E7EUT4
resolver
uniprot
P00354
resolver
uniprot
Q53X65
resolver
uniprot
V9HVZ4
resolver
uniprot_entry
G3P_HUMAN
resolver
uniprot_entry
V9HVZ4_HUMAN
resolver
uniprot_sec
E7EUT4
resolver
uniprot_sec
P00354
resolver
uniprot_sec
Q53X65
resolver
activity_regulation
ACTIVITY REGULATION: Glyceraldehyde-3-phosphate dehydrogenase activity is inhibited by fumarate, via the formation of S-(2-succinyl)cysteine residues. {ECO:0000250|UniProtKB:P04797}.
uniprot
proteins
amino_acid_sequence
MGKVKVGVNGFGRIGRLVTRAAFNSGKVDIVAINDPFIDLNYMVYMFQYDSTHGKFHGTVKAENGKLVINGNPITIFQERDPSKIKWGDAGAEYVVESTGVFTTMEKAGAHLQGGAKRVIISAPSADAPMFVMGVNHEKYDNSLKIISNASCTTNCLAPLAKVIHDNFGIVEGLMTTVHAITATQKTVDGPSGKLWRDGRGALQNIIPASTGAAKAVGKVIPELNGKLTGMAFRVPTANVSVVDLTCRLEKPAKYDDIKKVVKQASEGPLKGILGYTEHQVVSSDFNSDTHSSTFDAGAGIALNDHFVKLISWYDNEFGYSNRVVDLMAHMASKE
uniprot
proteins
ec_number
1.2.1.12
uniprot
proteins
ec_number
2.6.99.-
uniprot
proteins
function
FUNCTION: Catalyzes the conversion of D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate in glycolysis and the reverse reaction in gluconeogenesis (PubMed:11724794, PubMed:3170585). Also shows nitrosylase activity, thereby playing a role in nuclear functions (PubMed:11724794, PubMed:3170585). 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 cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}.
uniprot
proteins
mass_dalton
36053
uniprot
proteins
mutagenesis
MUTAGEN 46; /note="M->L: Drastic reduction of the extent and significant prolongation of the lag phase of free radical-induced aggregation."; /evidence="ECO:0000269|PubMed:25086035"; MUTAGEN 105; /note="M->L: Increased resistance to free radical-induced aggregation."; /evidence="ECO:0000269|PubMed:25086035"; MUTAGEN 152; /note="C->S: Markedly reduced glycolytic activity; when associated with S-156 and S-247. Forms free radical-induced aggregates, but to a lesser extent than wild-type protein; when associated with S-156 and S-247. Abolished interaction with TRAF2 and TRAF3."; /evidence="ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:25086035, ECO:0000269|PubMed:27387501"; MUTAGEN 156; /note="C->S: Markedly reduced glycolytic activity; when associated with S-152 and S-247. Forms free radical-induced aggregates, but to a lesser extent than wild-type protein; when associated with S-156 and S-247."; /evidence="ECO:0000269|PubMed:25086035"; MUTAGEN 196; /note="W->F: Increased free radical-induced aggregation."; /evidence="ECO:0000269|PubMed:25086035"; MUTAGEN 211; /note="T->A: Does not affect glycosylation by C.rodentium protein NleB."; /evidence="ECO:0000269|PubMed:23332158"; MUTAGEN 229; /note="T->A: Does not affect glycosylation by C.rodentium protein NleB."; /evidence="ECO:0000269|PubMed:23332158"; MUTAGEN 241; /note="S->A: Does not affect glycosylation by C.rodentium protein NleB."; /evidence="ECO:0000269|PubMed:23332158"; MUTAGEN 245; /note="L->M: Inhibits S-nitrosylation of Cys-247; when associated with M-250."; /evidence="ECO:0000269|PubMed:25417112"; MUTAGEN 246; /note="T->A: Does not affect glycosylation by C.rodentium protein NleB."; /evidence="ECO:0000269|PubMed:23332158"; MUTAGEN 247; /note="C->S: Markedly reduced glycolytic activity; when associated with S-152 and S-156. Forms free radical-induced aggregates, but to a lesser extent than wild-type protein; when associated with S-156 and S-247."; /evidence="ECO:0000269|PubMed:25086035"; MUTAGEN 250; /note="E->M: Inhibits S-nitrosylation of Cys-247; when associated with M-245."; /evidence="ECO:0000269|PubMed:25417112"; MUTAGEN 277; /note="T->A: Does not affect glycosylation by C.rodentium protein NleB."; /evidence="ECO:0000269|PubMed:23332158"; MUTAGEN 320; /note="Y->F: No effect on free radical-induced aggregation."; /evidence="ECO:0000269|PubMed:25086035
uniprot
proteins
pathway_participation
PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5.
uniprot
proteins
post_translational_modification
PTM: S-nitrosylation of Cys-152 leads to interaction with SIAH1, followed by translocation to the nucleus (By similarity). S-nitrosylation of Cys-247 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 (PubMed:22771119, PubMed:25417112). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:22771119, ECO:0000269|PubMed:25417112}.; PTM: ISGylated. {ECO:0000305|PubMed:16815975}.; PTM: Sulfhydration at Cys-152 increases catalytic activity. {ECO:0000250|UniProtKB:P16858}.; PTM: Oxidative stress can promote the formation of high molecular weight disulfide-linked GAPDH aggregates, through a process called nucleocytoplasmic coagulation. Such aggregates can be observed in vivo in the affected tissues of patients with Alzheimer disease or alcoholic liver cirrhosis, or in cell cultures during necrosis. Oxidation at Met-46 may play a pivotal role in the formation of these insoluble structures. This modification has been detected in vitro following treatment with free radical donor (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide. It has been proposed to destabilize nearby residues, increasing the likelihood of secondary oxidative damages, including oxidation of Tyr-45 and Met-105. This cascade of oxidations may augment GAPDH misfolding, leading to intermolecular disulfide cross-linking and aggregation. {ECO:0000305|PubMed:25086035}.; PTM: Succination of Cys-152 and Cys-247 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits glyceraldehyde-3-phosphate dehydrogenase activity. Fumarate concentration as well as succination of cysteine residues in GAPDH is significantly increased in muscle of diabetic mammals. It was proposed that the S-(2-succinyl)cysteine chemical modification may be a useful biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins by fumarate may contribute to the metabolic changes underlying the development of diabetes complications. {ECO:0000250|UniProtKB:P04797}.; PTM: (Microbial infection) Glycosylated by C.rodentium protein NleB, enteropathogenic E.coli protein NleB1 and S.typhimurium protein Ssek1: arginine GlcNAcylation prevents the interaction with TRAF2 and TRAF3 (PubMed:23332158, PubMed:27387501, PubMed:28522607). This leads to reduced ubiquitination of TRAF2 and TRAF3, and subsequent inhibition of NF-kappa-B signaling and type I interferon production, respectively (PubMed:23332158, PubMed:27387501). {ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:28522607}.
uniprot
proteins
protein_family
Glyceraldehyde-3-phosphate dehydrogenase family
uniprot
proteins
pubmed
10944468
uniprot
proteins
pubmed
11724794
uniprot
proteins
pubmed
1193541
uniprot
proteins
pubmed
12665801
uniprot
proteins
pubmed
12829261
uniprot
proteins
pubmed
14654843
uniprot
proteins
pubmed
15479637
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
15628863
uniprot
proteins
pubmed
16239728
uniprot
proteins
pubmed
16501887
uniprot
proteins
pubmed
16510976
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
16815975
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18183946
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19001379
uniprot
proteins
pubmed
1924305
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20644585
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21908771
uniprot
proteins
pubmed
22771119
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
22905912
uniprot
proteins
pubmed
23071094
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23332158
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25086035
uniprot
proteins
pubmed
25417112
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27387501
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28522607
uniprot
proteins
pubmed
2987855
uniprot
proteins
pubmed
3027061
uniprot
proteins
pubmed
3170585
uniprot
proteins
pubmed
3664468
uniprot
proteins
pubmed
6096136
uniprot
proteins
pubmed
6096821
uniprot
proteins
pubmed
7030790
uniprot
proteins
pubmed
7498159
uniprot
proteins
pubmed
957435
uniprot
proteins
sequence_length
335
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12829261}. Nucleus {ECO:0000250|UniProtKB:P04797}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:12829261}. Membrane {ECO:0000269|PubMed:12829261}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P04797}. Note=Translocates to the nucleus following S-nitrosylation and interaction with SIAH1, which contains a nuclear localization signal (By similarity). Postnuclear and Perinuclear regions (PubMed:12829261). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:12829261}.
uniprot
proteins