UniProtKB - P46406 (G3P_RABIT)
Glyceraldehyde-3-phosphate dehydrogenase
GAPDH
Functioni
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).
By similarityCatalytic activityi
- D-glyceraldehyde 3-phosphate + NAD+ + phosphate = (2R)-3-phospho-glyceroyl phosphate + H+ + NADHPROSITE-ProRule annotation1 PublicationEC:1.2.1.12PROSITE-ProRule annotation1 Publication
- L-cysteinyl-[protein] + S-nitroso-L-cysteinyl-[GAPDH] = L-cysteinyl-[GAPDH] + S-nitroso-L-cysteinyl-[protein]By similarityThis reaction proceeds in the forwardBy similarity direction.
Activity regulationi
: glycolysis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes pyruvate from D-glyceraldehyde 3-phosphate. This subpathway is part of the pathway glycolysis, which is itself part of Carbohydrate degradation.View all proteins of this organism that are known to be involved in the subpathway that synthesizes pyruvate from D-glyceraldehyde 3-phosphate, the pathway glycolysis and in Carbohydrate degradation.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 33 | NAD1 Publication | 1 | |
Binding sitei | 78 | NAD; via carbonyl oxygen1 Publication | 1 | |
Binding sitei | 120 | NADBy similarity | 1 | |
Active sitei | 150 | Nucleophile | 1 | |
Sitei | 177 | Activates thiol group during catalysis1 Publication | 1 | |
Binding sitei | 180 | Glyceraldehyde 3-phosphateBy similarity | 1 | |
Binding sitei | 232 | Glyceraldehyde 3-phosphateBy similarity | 1 | |
Binding sitei | 314 | NAD1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 11 – 12 | NAD1 Publication | 2 |
GO - Molecular functioni
- glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity Source: UniProtKB
- microtubule binding Source: UniProtKB
- NAD binding Source: InterPro
- NADP binding Source: InterPro
- peptidyl-cysteine S-nitrosylase activity Source: UniProtKB
GO - Biological processi
- glucose metabolic process Source: InterPro
- glycolytic process Source: UniProtKB-UniPathway
- innate immune response Source: UniProtKB-KW
- microtubule cytoskeleton organization Source: UniProtKB
- neuron apoptotic process Source: UniProtKB
- peptidyl-cysteine S-trans-nitrosylation Source: UniProtKB
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- positive regulation of type I interferon production Source: UniProtKB
- protein stabilization Source: UniProtKB
- regulation of translation Source: UniProtKB-KW
Keywordsi
Molecular function | Oxidoreductase, Transferase |
Biological process | Apoptosis, Glycolysis, Immunity, Innate immunity, Translation regulation |
Ligand | NAD |
Enzyme and pathway databases
BRENDAi | 1.2.1.12, 1749 |
SABIO-RKi | P46406 |
UniPathwayi | UPA00109;UER00184 |
Protein family/group databases
MoonProti | P46406 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:GAPDH Synonyms:GAPD |
Organismi | Oryctolagus cuniculus (Rabbit) |
Taxonomic identifieri | 9986 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus |
Proteomesi |
|
Subcellular locationi
Nucleus
- Nucleus By similarity
Cytoplasm and Cytosol
- cytosol By similarity
Cytoskeleton
- cytoskeleton By similarity
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.By similarity
Cytoskeleton
- microtubule cytoskeleton Source: UniProtKB
Cytosol
- cytosol Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- GAIT complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, NucleusPathology & Biotechi
Protein family/group databases
Allergomei | 12131, Ory c GAPDH |
Chemistry databases
ChEMBLi | CHEMBL1075199 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000145493 | 1 – 333 | Glyceraldehyde-3-phosphate dehydrogenaseAdd BLAST | 333 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 3 | N6,N6-dimethyllysineBy similarity | 1 | |
Modified residuei | 7 | Deamidated asparagineBy similarity | 1 | |
Modified residuei | 40 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 59 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 62 | Deamidated asparagineBy similarity | 1 | |
Modified residuei | 64 | N6,N6-dimethyllysineBy similarity | 1 | |
Modified residuei | 68 | Deamidated asparagineBy similarity | 1 | |
Modified residuei | 73 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 120 | PhosphoserineBy similarity | 1 | |
Modified residuei | 146 | PhosphoserineBy similarity | 1 | |
Modified residuei | 147 | Deamidated asparagineBy similarity | 1 | |
Modified residuei | 149 | PhosphoserineBy similarity | 1 | |
Modified residuei | 150 | ADP-ribosylcysteine; by autocatalysis; in irreversibly inhibited formBy similarity | 1 | |
Modified residuei | 150 | Cysteine persulfideBy similarity | 1 | |
Modified residuei | 150 | S-(2-succinyl)cysteine1 Publication | 1 | |
Modified residuei | 150 | S-nitrosocysteine; in reversibly inhibited formBy similarity | 1 | |
Modified residuei | 151 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 153 | Deamidated asparagineBy similarity | 1 | |
Modified residuei | 175 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 180 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 182 | PhosphothreonineBy similarity | 1 | |
Cross-linki | 184 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 192 | N6,N6-dimethyllysine; alternateBy similarity | 1 | |
Modified residuei | 192 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 192 | N6-malonyllysine; alternateBy similarity | 1 | |
Modified residuei | 209 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 213 | N6,N6-dimethyllysine; alternateBy similarity | 1 | |
Modified residuei | 213 | N6-malonyllysine; alternateBy similarity | 1 | |
Modified residuei | 217 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 223 | Deamidated asparagineBy similarity | 1 | |
Modified residuei | 225 | N6,N6-dimethyllysine; alternateBy similarity | 1 | |
Modified residuei | 225 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 227 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 235 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 239 | PhosphoserineBy similarity | 1 | |
Modified residuei | 245 | S-(2-succinyl)cysteine1 Publication | 1 | |
Modified residuei | 245 | S-nitrosocysteineBy similarity | 1 | |
Modified residuei | 252 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 258 | N6,N6-dimethyllysineBy similarity | 1 | |
Modified residuei | 261 | N6,N6-dimethyllysineBy similarity | 1 | |
Modified residuei | 310 | PhosphoserineBy similarity | 1 | |
Modified residuei | 314 | Deamidated asparagineBy similarity | 1 | |
Modified residuei | 331 | PhosphoserineBy similarity | 1 | |
Modified residuei | 332 | N6,N6-dimethyllysineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, ADP-ribosylation, Isopeptide bond, Methylation, Phosphoprotein, S-nitrosylation, Ubl conjugationProteomic databases
PRIDEi | P46406 |
PTM databases
CarbonylDBi | P46406 |
SwissPalmi | P46406 |
Interactioni
Subunit structurei
Homotetramer (By similarity).
Interacts with TPPP; the interaction is direct (By similarity).
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).
By similarityBinary interactionsi
P46406
With | #Exp. | IntAct |
---|---|---|
Chp1 [P61023] from Rattus norvegicus. | 2 | EBI-2750726,EBI-917838 |
SLC4A1 [P02730] from Homo sapiens. | 4 | EBI-2750726,EBI-7576138 |
GO - Molecular functioni
- microtubule binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 1172097, 2 interactors |
DIPi | DIP-6005N |
IntActi | P46406, 4 interactors |
MINTi | P46406 |
Chemistry databases
BindingDBi | P46406 |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P46406 |
SMRi | P46406 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P46406 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 146 | Interaction with WARS1By similarityAdd BLAST | 146 | |
Regioni | 149 – 151 | Glyceraldehyde 3-phosphate bindingBy similarity | 3 | |
Regioni | 209 – 210 | Glyceraldehyde 3-phosphate bindingBy similarity | 2 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 243 – 248 | [IL]-x-C-x-x-[DE] motifBy similarity | 6 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0657, Eukaryota |
InParanoidi | P46406 |
OrthoDBi | 945145at2759 |
Family and domain databases
InterProi | View protein in InterPro IPR020831, GlycerAld/Erythrose_P_DH IPR020830, GlycerAld_3-P_DH_AS IPR020829, GlycerAld_3-P_DH_cat IPR020828, GlycerAld_3-P_DH_NAD(P)-bd IPR006424, Glyceraldehyde-3-P_DH_1 IPR036291, NAD(P)-bd_dom_sf |
PANTHERi | PTHR10836, PTHR10836, 1 hit |
Pfami | View protein in Pfam PF02800, Gp_dh_C, 1 hit PF00044, Gp_dh_N, 1 hit |
PIRSFi | PIRSF000149, GAP_DH, 1 hit |
PRINTSi | PR00078, G3PDHDRGNASE |
SMARTi | View protein in SMART SM00846, Gp_dh_N, 1 hit |
SUPFAMi | SSF51735, SSF51735, 1 hit |
TIGRFAMsi | TIGR01534, GAPDH-I, 1 hit |
PROSITEi | View protein in PROSITE PS00071, GAPDH, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MVKVGVNGFG RIGRLVTRAA FNSGKVDVVA INDPFIDLHY MVYMFQYDST
60 70 80 90 100
HGKFHGTVKA ENGKLVINGK AITIFQERDP ANIKWGDAGA EYVVESTGVF
110 120 130 140 150
TTMEKAGAHL KGGAKRVIIS APSADAPMFV MGVNHEKYDN SLKIVSNASC
160 170 180 190 200
TTNCLAPLAK VIHDHFGIVE GLMTTVHAIT ATQKTVDGPS GKLWRDGRGA
210 220 230 240 250
AQNIIPASTG AAKAVGKVIP ELNGKLTGMA FRVPTPNVSV VDLTCRLEKA
260 270 280 290 300
AKYDDIKKVV KQASEGPLKG ILGYTEDQVV SCDFNSATHS STFDAGAGIA
310 320 330
LNDHFVKLIS WYDNEFGYSN RVVDLMVHMA SKE
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L23961 mRNA Translation: AAA85218.1 V00884 mRNA Translation: CAA24253.1 AB231852 mRNA Translation: BAE19661.1 |
PIRi | JC4309 |
RefSeqi | NP_001075722.1, NM_001082253.1 |
Genome annotation databases
GeneIDi | 100009074 |
KEGGi | ocu:100009074 |
Similar proteinsi
Cross-referencesi
Web resourcesi
Worthington enzyme manual |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L23961 mRNA Translation: AAA85218.1 V00884 mRNA Translation: CAA24253.1 AB231852 mRNA Translation: BAE19661.1 |
PIRi | JC4309 |
RefSeqi | NP_001075722.1, NM_001082253.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1J0X | X-ray | 2.40 | O/P/Q/R | 2-333 | [»] | |
AlphaFoldDBi | P46406 | |||||
SMRi | P46406 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 1172097, 2 interactors |
DIPi | DIP-6005N |
IntActi | P46406, 4 interactors |
MINTi | P46406 |
Chemistry databases
BindingDBi | P46406 |
ChEMBLi | CHEMBL1075199 |
Protein family/group databases
Allergomei | 12131, Ory c GAPDH |
MoonProti | P46406 |
PTM databases
CarbonylDBi | P46406 |
SwissPalmi | P46406 |
Proteomic databases
PRIDEi | P46406 |
Genome annotation databases
GeneIDi | 100009074 |
KEGGi | ocu:100009074 |
Organism-specific databases
CTDi | 2597 |
Phylogenomic databases
eggNOGi | KOG0657, Eukaryota |
InParanoidi | P46406 |
OrthoDBi | 945145at2759 |
Enzyme and pathway databases
UniPathwayi | UPA00109;UER00184 |
BRENDAi | 1.2.1.12, 1749 |
SABIO-RKi | P46406 |
Miscellaneous databases
EvolutionaryTracei | P46406 |
PROi | PR:P46406 |
Family and domain databases
InterProi | View protein in InterPro IPR020831, GlycerAld/Erythrose_P_DH IPR020830, GlycerAld_3-P_DH_AS IPR020829, GlycerAld_3-P_DH_cat IPR020828, GlycerAld_3-P_DH_NAD(P)-bd IPR006424, Glyceraldehyde-3-P_DH_1 IPR036291, NAD(P)-bd_dom_sf |
PANTHERi | PTHR10836, PTHR10836, 1 hit |
Pfami | View protein in Pfam PF02800, Gp_dh_C, 1 hit PF00044, Gp_dh_N, 1 hit |
PIRSFi | PIRSF000149, GAP_DH, 1 hit |
PRINTSi | PR00078, G3PDHDRGNASE |
SMARTi | View protein in SMART SM00846, Gp_dh_N, 1 hit |
SUPFAMi | SSF51735, SSF51735, 1 hit |
TIGRFAMsi | TIGR01534, GAPDH-I, 1 hit |
PROSITEi | View protein in PROSITE PS00071, GAPDH, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | G3P_RABIT | |
Accessioni | P46406Primary (citable) accession number: P46406 Secondary accession number(s): Q4AC92 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1995 |
Last sequence update: | November 13, 2007 | |
Last modified: | May 25, 2022 | |
This is version 159 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families