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Protein

Glyceraldehyde-3-phosphate dehydrogenase

Gene

GAPDH

Organism
Oryctolagus cuniculus (Rabbit)
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 similarity

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 (GAPDHS), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Glyceraldehyde-3-phosphate dehydrogenase, Glyceraldehyde-3-phosphate dehydrogenase (GAPDHS)
  2. no protein annotated in this organism
  3. no protein annotated in this organism
  4. Beta-enolase (ENO3)
  5. Pyruvate kinase (PKLR), Pyruvate kinase (PKLR), Pyruvate kinase (PKM), Pyruvate kinase (pklr), Pyruvate kinase PKM (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 sitei33NAD1 Publication1
Binding sitei78NAD; via carbonyl oxygen1 Publication1
Binding sitei120NADBy similarity1
Active sitei150Nucleophile1
Sitei177Activates thiol group during catalysis1
Binding sitei180Glyceraldehyde 3-phosphateBy similarity1
Binding sitei232Glyceraldehyde 3-phosphateBy similarity1
Binding sitei314NAD1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi11 – 12NAD1 Publication2

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase, Transferase

Keywords - Biological processi

Apoptosis, Glycolysis, Translation regulation

Keywords - Ligandi

NAD

Enzyme and pathway databases

SABIO-RKP46406.
UniPathwayiUPA00109; UER00184.

Names & Taxonomyi

Protein namesi
Recommended name:
Glyceraldehyde-3-phosphate dehydrogenase (EC:1.2.1.12)
Short name:
GAPDH
Alternative name(s):
Peptidyl-cysteine S-nitrosylase GAPDH (EC:2.6.99.-)
Gene namesi
Name:GAPDH
Synonyms:GAPD
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

  • Cytoplasmcytosol By similarity
  • Nucleus By similarity
  • Cytoplasmcytoskeleton By similarity

  • Note: Translocates to the nucleus following S-nitrosylation and interaction with SIAH1, which contains a nuclear localization signal.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1075199.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001454932 – 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 formBy similarity1
Modified residuei150Cysteine persulfideBy similarity1
Modified residuei150S-nitrosocysteine; in reversibly inhibited formBy similarity1
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

ISGylated.By similarity
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).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

Keywords - PTMi

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

Proteomic databases

PRIDEiP46406.

PTM databases

SwissPalmiP46406.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
Chp1P610232EBI-2750726,EBI-917838From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi1172097. 1 interactor.
DIPiDIP-6005N.
IntActiP46406. 3 interactors.
MINTiMINT-1515666.
STRINGi9986.ENSOCUP00000017094.

Chemistry databases

BindingDBiP46406.

Structurei

Secondary structure

1333
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 7Combined sources5
Helixi11 – 23Combined sources13
Beta strandi25 – 32Combined sources8
Beta strandi34 – 36Combined sources3
Helixi38 – 46Combined sources9
Turni49 – 51Combined sources3
Beta strandi58 – 61Combined sources4
Beta strandi64 – 67Combined sources4
Beta strandi70 – 75Combined sources6
Helixi80 – 82Combined sources3
Helixi85 – 88Combined sources4
Beta strandi91 – 95Combined sources5
Beta strandi97 – 99Combined sources3
Helixi103 – 107Combined sources5
Helixi108 – 112Combined sources5
Beta strandi115 – 121Combined sources7
Beta strandi124 – 126Combined sources3
Turni131 – 133Combined sources3
Helixi135 – 137Combined sources3
Beta strandi143 – 146Combined sources4
Helixi150 – 166Combined sources17
Beta strandi168 – 178Combined sources11
Beta strandi183 – 187Combined sources5
Helixi194 – 197Combined sources4
Turni200 – 202Combined sources3
Beta strandi205 – 208Combined sources4
Helixi211 – 218Combined sources8
Helixi220 – 222Combined sources3
Beta strandi225 – 234Combined sources10
Beta strandi239 – 249Combined sources11
Helixi253 – 265Combined sources13
Turni266 – 271Combined sources6
Beta strandi272 – 275Combined sources4
Helixi281 – 284Combined sources4
Beta strandi290 – 294Combined sources5
Turni295 – 297Combined sources3
Beta strandi299 – 302Combined sources4
Beta strandi305 – 312Combined sources8
Helixi316 – 330Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J0XX-ray2.40O/P/Q/R2-333[»]
ProteinModelPortaliP46406.
SMRiP46406.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP46406.

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.
HOGENOMiHOG000071678.
HOVERGENiHBG000227.
InParanoidiP46406.
KOiK00134.

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.

P46406-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:333
Mass (Da):35,780
Last modified:November 13, 2007 - v3
Checksum:i346DB9B59DF3C1DF
GO

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.
PIRiJC4309.
RefSeqiNP_001075722.1. NM_001082253.1.
UniGeneiOcu.87.

Genome annotation databases

GeneIDi100009074.
KEGGiocu:100009074.

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.
PIRiJC4309.
RefSeqiNP_001075722.1. NM_001082253.1.
UniGeneiOcu.87.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J0XX-ray2.40O/P/Q/R2-333[»]
ProteinModelPortaliP46406.
SMRiP46406.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi1172097. 1 interactor.
DIPiDIP-6005N.
IntActiP46406. 3 interactors.
MINTiMINT-1515666.
STRINGi9986.ENSOCUP00000017094.

Chemistry databases

BindingDBiP46406.
ChEMBLiCHEMBL1075199.

PTM databases

SwissPalmiP46406.

Proteomic databases

PRIDEiP46406.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100009074.
KEGGiocu:100009074.

Organism-specific databases

CTDi2597.

Phylogenomic databases

eggNOGiKOG0657. Eukaryota.
COG0057. LUCA.
HOGENOMiHOG000071678.
HOVERGENiHBG000227.
InParanoidiP46406.
KOiK00134.

Enzyme and pathway databases

UniPathwayiUPA00109; UER00184.
SABIO-RKP46406.

Miscellaneous databases

EvolutionaryTraceiP46406.
PROiP46406.

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_RABIT
AccessioniPrimary (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: November 2, 2016
This is version 137 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.