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Protein

Glyceraldehyde-3-phosphate dehydrogenase

Gene

Gapdh

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. 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. Also 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. 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 (By similarity).By similarity4 Publications

Catalytic activityi

D-glyceraldehyde 3-phosphate + phosphate + NAD+ = 3-phospho-D-glyceroyl phosphate + NADH.PROSITE-ProRule annotation

Pathwayi: glycolysis

This protein is involved in step 1 of the subpathway that synthesizes pyruvate from D-glyceraldehyde 3-phosphate.
Proteins known to be involved in the 5 steps of the subpathway in this organism are:
  1. Glyceraldehyde-3-phosphate dehydrogenase (Gapdh), Glyceraldehyde-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase, testis-specific (Gapdhs), Glyceraldehyde-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase (LOC108351137), Glyceraldehyde-3-phosphate dehydrogenase (Gapdh-ps2), Glyceraldehyde-3-phosphate dehydrogenase (Gapdhs), Glyceraldehyde-3-phosphate dehydrogenase (RGD1562758)
  2. Phosphoglycerate kinase 1 (Pgk1)
  3. no protein annotated in this organism
  4. Alpha-enolase (Eno1), Beta-enolase (Eno3), Gamma-enolase (Eno2)
  5. Pyruvate kinase PKLR (Pklr), Pyruvate kinase PKM (Pkm), Pyruvate kinase (Pklr), Pyruvate kinase (LOC100362738), Pyruvate kinase (Pkm), Pyruvate kinase (Pklr), Pyruvate kinase (Pkm)
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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei33NADBy similarity1
Binding sitei78NAD; via carbonyl oxygenBy similarity1
Binding sitei120NADBy similarity1
Active sitei150NucleophilePROSITE-ProRule annotation1 Publication1
Sitei177Activates thiol group during catalysisBy similarity1
Binding sitei180Glyceraldehyde 3-phosphateBy similarity1
Binding sitei232Glyceraldehyde 3-phosphateBy similarity1
Binding sitei314NADBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi11 – 12NADBy similarity2

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

  • apoptotic process Source: RGD
  • carbohydrate metabolic process Source: RGD
  • gluconeogenesis Source: RGD
  • glycolytic process Source: RGD
  • microtubule cytoskeleton organization Source: UniProtKB
  • neuron apoptotic process Source: UniProtKB
  • peptidyl-cysteine S-trans-nitrosylation Source: UniProtKB
  • protein stabilization Source: UniProtKB
  • regulation of translation Source: UniProtKB-KW
  • response to ammonium ion Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase, Transferase

Keywords - Biological processi

Apoptosis, Glycolysis, Translation regulation

Keywords - Ligandi

NAD

Enzyme and pathway databases

BRENDAi1.2.1.12. 5301.
SABIO-RKP04797.
UniPathwayiUPA00109; UER00184.

Names & Taxonomyi

Protein namesi
Recommended name:
Glyceraldehyde-3-phosphate dehydrogenase (EC:1.2.1.12)
Short name:
GAPDH
Alternative name(s):
38 kDa BFA-dependent ADP-ribosylation substrate
BARS-38
Peptidyl-cysteine S-nitrosylase GAPDH (EC:2.6.99.-)
Gene namesi
Name:Gapdh
Synonyms:Gapd
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi2661. Gapdh.

Subcellular locationi

  • Cytoplasmcytosol
  • Cytoplasmcytoskeleton
  • Nucleus

  • 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.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • GAIT complex Source: UniProtKB
  • microtubule cytoskeleton Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi149S → A: Does not affect interaction with SIRT1. 1 Publication1
Mutagenesisi150C → S: Abolishes S-nitrosylation and subsequent nuclear translocation. 2 Publications1
Mutagenesisi151T → A: Does not affect interaction with SIRT1. 1 Publication1
Mutagenesisi152T → A: Abolishes interaction and subsequent nitrosylation of SIRT1. 1 Publication1
Mutagenesisi225K → A: Abolishes interaction with SIAH1. 1 Publication1
Mutagenesisi234P → A: Does not affect interaction with SIAH1. 1 Publication1
Mutagenesisi235T → A: Does not affect interaction with SIAH1. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2176832.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001454942 – 333Glyceraldehyde-3-phosphate dehydrogenaseAdd BLAST332

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3N6,N6-dimethyllysineBy similarity1
Modified residuei7Deamidated asparagineBy similarity1
Modified residuei40PhosphotyrosineBy similarity1
Modified residuei59N6-acetyllysineBy similarity1
Modified residuei62Deamidated asparagineBy similarity1
Modified residuei64N6,N6-dimethyllysineBy similarity1
Modified residuei68Deamidated asparagineBy similarity1
Modified residuei73PhosphothreonineBy similarity1
Modified residuei120PhosphoserineBy similarity1
Modified residuei146PhosphoserineBy similarity1
Modified residuei147Deamidated asparagineBy similarity1
Modified residuei149PhosphoserineBy similarity1
Modified residuei150ADP-ribosylcysteine; by autocatalysis; in irreversibly inhibited form1 Publication1
Modified residuei150Cysteine persulfideBy similarity1
Modified residuei150S-nitrosocysteine; in reversibly inhibited form3 Publications1
Modified residuei151PhosphothreonineBy similarity1
Modified residuei153Deamidated asparagineBy similarity1
Modified residuei175PhosphothreonineBy similarity1
Modified residuei180PhosphothreonineBy similarity1
Modified residuei182PhosphothreonineBy similarity1
Modified residuei192N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei192N6-acetyllysine; alternateBy similarity1
Modified residuei192N6-malonyllysine; alternateBy similarity1
Modified residuei209PhosphothreonineBy similarity1
Modified residuei213N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei213N6-malonyllysine; alternateBy similarity1
Modified residuei217N6-acetyllysineBy similarity1
Modified residuei223Deamidated asparagineBy similarity1
Modified residuei225N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei225N6-acetyllysine; alternateBy similarity1
Modified residuei227PhosphothreonineBy similarity1
Modified residuei235PhosphothreonineBy similarity1
Modified residuei239PhosphoserineBy similarity1
Modified residuei245S-nitrosocysteineBy similarity1
Modified residuei252N6-acetyllysineBy similarity1
Modified residuei258N6,N6-dimethyllysineBy similarity1
Modified residuei261N6,N6-dimethyllysineBy similarity1
Modified residuei310PhosphoserineBy similarity1
Modified residuei314Deamidated asparagineBy similarity1
Modified residuei331PhosphoserineBy similarity1
Modified residuei332N6,N6-dimethyllysineBy similarity1

Post-translational modificationi

S-nitrosylation of Cys-150 leads to interaction with SIAH1, followed by translocation to the nucleus. The effect of S-nitrosylation on enzymatic activity is unclear: according to some authors, it inhibits enzymatic activity and increases endogenous ADP-ribosylation, inhibiting the enzyme in a non-reversible manner (PubMed:8626764). According to others, it does not affect glycolysis (PubMed:15951807). ADP-ribosylation is likely to be a pathophysiological event associated with inhibition of gluconeogenesis. 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).By similarity4 Publications
ISGylated.By similarity
Sulfhydration at Cys-150 increases catalytic activity.By similarity
Oxidative stress can promote the formation of high molecular weight disulfide-linked GAPDH aggregates, through a process called nucleocytoplasmic coagulation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei154Not nitrosylated1

Keywords - PTMi

Acetylation, ADP-ribosylation, Methylation, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

PaxDbiP04797.
PRIDEiP04797.

2D gel databases

World-2DPAGE0004:P04797.

PTM databases

iPTMnetiP04797.
PhosphoSitePlusiP04797.

Expressioni

Tissue specificityi

High levels in skeletal muscle and heart, low levels in liver, brain, and kidney.1 Publication

Gene expression databases

BgeeiENSRNOG00000018630.
GenevisibleiP04797. RN.

Interactioni

Subunit structurei

Homotetramer. Interacts with EIF1AD, USP25, PRKCI and WARS. 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. Interacts with phosphorylated RPL13A (By similarity). Associates with microtubules. Component of the GAIT complex. Interacts with FKBP6; leading to inhibit GAPDH catalytic activity (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Akt1P471963EBI-349219,EBI-7204362
Chp1P610233EBI-349219,EBI-917838
Ppm1eQ80Z305EBI-349219,EBI-7473061
Slc2a4P193572EBI-349219,EBI-915426

GO - Molecular functioni

  • microtubule binding Source: UniProtKB

Protein-protein interaction databases

BioGridi246554. 6 interactors.
IntActiP04797. 8 interactors.
MINTiMINT-1775142.
STRINGi10116.ENSRNOP00000040878.

Structurei

3D structure databases

ProteinModelPortaliP04797.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 146Interaction with WARSBy similarityAdd BLAST145
Regioni149 – 151Glyceraldehyde 3-phosphate bindingBy similarity3
Regioni209 – 210Glyceraldehyde 3-phosphate bindingBy similarity2

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi243 – 248[IL]-x-C-x-x-[DE] motifBy similarity6

Domaini

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.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0657. Eukaryota.
COG0057. LUCA.
GeneTreeiENSGT00760000119172.
HOGENOMiHOG000071678.
HOVERGENiHBG000227.
InParanoidiP04797.
KOiK00134.
OMAiWEWDDVE.
OrthoDBiEOG091G0B1Y.
PhylomeDBiP04797.
TreeFamiTF300533.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR020831. 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.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERiPTHR10836. PTHR10836. 1 hit.
PfamiPF02800. Gp_dh_C. 1 hit.
PF00044. Gp_dh_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000149. GAP_DH. 1 hit.
PRINTSiPR00078. G3PDHDRGNASE.
SMARTiSM00846. Gp_dh_N. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR01534. GAPDH-I. 1 hit.
PROSITEiPS00071. GAPDH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P04797-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVKVGVNGFG RIGRLVTRAA FSCDKVDIVA INDPFIDLNY MVYMFQYDST
60 70 80 90 100
HGKFNGTVKA ENGKLVINGK PITIFQERDP ANIKWGDAGA EYVVESTGVF
110 120 130 140 150
TTMEKAGAHL KGGAKRVIIS APSADAPMFV MGVNHEKYDN SLKIVSNASC
160 170 180 190 200
TTNCLAPLAK VIHDNFGIVE GLMTTVHAIT ATQKTVDGPS GKLWRDGRGA
210 220 230 240 250
AQNIIPASTG AAKAVGKVIP ELNGKLTGMA FRVPTPNVSV VDLTCRLEKP
260 270 280 290 300
AKYDDIKKVV KQAAEGPLKG ILGYTEDQVV SCDFNSNSHS STFDAGAGIA
310 320 330
LNDNFVKLIS WYDNEYGYSN RVVDLMAYMA SKE
Length:333
Mass (Da):35,828
Last modified:January 23, 2007 - v3
Checksum:iD9E5ED4F38544C77
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti81 – 82AN → VK in AAA41193 (PubMed:2987824).Curated2
Sequence conflicti129F → L in AAH87743 (PubMed:15489334).Curated1
Sequence conflicti305F → I in AAA41193 (PubMed:2987824).Curated1
Sequence conflicti305F → I in CAA26150 (PubMed:6548307).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02231 mRNA. Translation: CAA26150.1.
M17701 mRNA. Translation: AAA41193.1.
AB017801 mRNA. Translation: BAB11748.1.
AF106860 mRNA. Translation: AAD08929.2.
BC059110 mRNA. Translation: AAH59110.1.
BC087743 mRNA. Translation: AAH87743.1.
M29341 mRNA. Translation: AAA40814.1.
M11561 mRNA. Translation: AAA41795.1.
PIRiA23013. DERTG.
RefSeqiNP_058704.1. NM_017008.4.
XP_017447924.1. XM_017592435.1.
XP_017458425.1. XM_017602936.1.
UniGeneiRn.129558.
Rn.91450.

Genome annotation databases

EnsembliENSRNOT00000050443; ENSRNOP00000040878; ENSRNOG00000018630.
GeneIDi108351137.
24383.
KEGGirno:24383.
UCSCiRGD:2661. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02231 mRNA. Translation: CAA26150.1.
M17701 mRNA. Translation: AAA41193.1.
AB017801 mRNA. Translation: BAB11748.1.
AF106860 mRNA. Translation: AAD08929.2.
BC059110 mRNA. Translation: AAH59110.1.
BC087743 mRNA. Translation: AAH87743.1.
M29341 mRNA. Translation: AAA40814.1.
M11561 mRNA. Translation: AAA41795.1.
PIRiA23013. DERTG.
RefSeqiNP_058704.1. NM_017008.4.
XP_017447924.1. XM_017592435.1.
XP_017458425.1. XM_017602936.1.
UniGeneiRn.129558.
Rn.91450.

3D structure databases

ProteinModelPortaliP04797.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246554. 6 interactors.
IntActiP04797. 8 interactors.
MINTiMINT-1775142.
STRINGi10116.ENSRNOP00000040878.

Chemistry databases

ChEMBLiCHEMBL2176832.

PTM databases

iPTMnetiP04797.
PhosphoSitePlusiP04797.

2D gel databases

World-2DPAGE0004:P04797.

Proteomic databases

PaxDbiP04797.
PRIDEiP04797.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000050443; ENSRNOP00000040878; ENSRNOG00000018630.
GeneIDi108351137.
24383.
KEGGirno:24383.
UCSCiRGD:2661. rat.

Organism-specific databases

CTDi2597.
RGDi2661. Gapdh.

Phylogenomic databases

eggNOGiKOG0657. Eukaryota.
COG0057. LUCA.
GeneTreeiENSGT00760000119172.
HOGENOMiHOG000071678.
HOVERGENiHBG000227.
InParanoidiP04797.
KOiK00134.
OMAiWEWDDVE.
OrthoDBiEOG091G0B1Y.
PhylomeDBiP04797.
TreeFamiTF300533.

Enzyme and pathway databases

UniPathwayiUPA00109; UER00184.
BRENDAi1.2.1.12. 5301.
SABIO-RKP04797.

Miscellaneous databases

PROiP04797.

Gene expression databases

BgeeiENSRNOG00000018630.
GenevisibleiP04797. RN.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR020831. 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.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERiPTHR10836. PTHR10836. 1 hit.
PfamiPF02800. Gp_dh_C. 1 hit.
PF00044. Gp_dh_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000149. GAP_DH. 1 hit.
PRINTSiPR00078. G3PDHDRGNASE.
SMARTiSM00846. Gp_dh_N. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
TIGRFAMsiTIGR01534. GAPDH-I. 1 hit.
PROSITEiPS00071. GAPDH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiG3P_RAT
AccessioniPrimary (citable) accession number: P04797
Secondary accession number(s): P09328, Q5M916, Q9QWU4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 172 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.