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Protein

Glyceraldehyde-3-phosphate dehydrogenase

Gene

GAPDH

Organism
Sus scrofa (Pig)
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 (GAPDH), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Glyceraldehyde-3-phosphate dehydrogenase (GAPDHS)
  2. Phosphoglycerate kinase 1 (PGK1), Phosphoglycerate kinase 2 (PGK2)
  3. no protein annotated in this organism
  4. Beta-enolase (ENO3)
  5. Pyruvate kinase (PKM), Pyruvate kinase, Pyruvate kinase
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
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

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

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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00001454912 – 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

PeptideAtlasiP00355.
PRIDEiP00355.

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

GO - Molecular functioni

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 strandi24 – 32Combined sources9
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 strandi92 – 95Combined sources4
Beta strandi97 – 99Combined sources3
Helixi103 – 106Combined sources4
Helixi107 – 112Combined sources6
Beta strandi115 – 121Combined sources7
Beta strandi124 – 126Combined sources3
Turni131 – 133Combined sources3
Helixi135 – 137Combined sources3
Beta strandi143 – 146Combined sources4
Helixi150 – 165Combined sources16
Beta strandi168 – 177Combined sources10
Beta strandi185 – 187Combined sources3
Helixi195 – 197Combined sources3
Turni200 – 202Combined sources3
Beta strandi205 – 207Combined sources3
Turni211 – 214Combined sources4
Helixi215 – 218Combined sources4
Helixi220 – 222Combined sources3
Beta strandi225 – 232Combined sources8
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
5DDIX-ray2.40P/R/S2-333[»]
ProteinModelPortaliP00355.
SMRiP00355.
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

HOVERGENiHBG000227.
InParanoidiP00355.
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.

P00355-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVKVGVNGFG RIGRLVTRAA FNSGKVDIVA INDPFIDLHY MVYMFQYDST
60 70 80 90 100
HGKFHGTVKA ENGKLVINGK AITIFQERDP ANIKWGDAGA TYVVESTGVF
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 VDLTCRLEKP
260 270 280 290 300
AKYDDIKKVV KQASEGPLKG ILGYTEDQVV SCDFNSDTHS STFDAGAGIA
310 320 330
LNDHFVKLIS WYDNEFGYSN RVVDLMVHMA SKE
Length:333
Mass (Da):35,836
Last modified:January 23, 2007 - v4
Checksum:i5F29175285D897BB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7N → D AA sequence (PubMed:4299800).Curated1
Sequence conflicti62N → D AA sequence (PubMed:4299800).Curated1
Sequence conflicti68N → D AA sequence (PubMed:4299800).Curated1
Sequence conflicti70 – 71KA → NP in AAB94053 (Ref. 1) Curated2
Sequence conflicti82N → K in AAB94053 (Ref. 1) Curated1
Sequence conflicti90 – 91AT → TA AA sequence (PubMed:4299800).Curated2
Sequence conflicti91T → E in AAB94053 (Ref. 1) Curated1
Sequence conflicti133V → M in AAB94053 (Ref. 1) Curated1
Sequence conflicti145V → I in AAB94053 (Ref. 1) Curated1
Sequence conflicti165H → N in AAB94053 (Ref. 1) Curated1
Sequence conflicti201A → L in AAB94053 (Ref. 1) Curated1
Sequence conflicti223N → D AA sequence (PubMed:4299800).Curated1
Sequence conflicti236P → A in AAB94053 (Ref. 1) Curated1
Sequence conflicti277D → H in AAB94053 (Ref. 1) Curated1
Sequence conflicti282C → S in AAB94053 (Ref. 1) Curated1
Sequence conflicti286 – 287SD → DS AA sequence (PubMed:4299800).Curated2
Sequence conflicti311W → S in AAB94053 (Ref. 1) Curated1
Sequence conflicti321R → W in AAB40155 (PubMed:9241041).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017079 mRNA. Translation: AAB94053.1.
Z84063 mRNA. Translation: CAB06323.1.
U48832 mRNA. Translation: AAA91804.1.
U82261 mRNA. Translation: AAB40155.1.
X94251 mRNA. Translation: CAA63935.1.
PIRiB12055.
RefSeqiNP_001193288.1. NM_001206359.1.
UniGeneiSsc.16135.

Genome annotation databases

GeneIDi396823.
KEGGissc:396823.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF017079 mRNA. Translation: AAB94053.1.
Z84063 mRNA. Translation: CAB06323.1.
U48832 mRNA. Translation: AAA91804.1.
U82261 mRNA. Translation: AAB40155.1.
X94251 mRNA. Translation: CAA63935.1.
PIRiB12055.
RefSeqiNP_001193288.1. NM_001206359.1.
UniGeneiSsc.16135.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DDIX-ray2.40P/R/S2-333[»]
ProteinModelPortaliP00355.
SMRiP00355.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PeptideAtlasiP00355.
PRIDEiP00355.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi396823.
KEGGissc:396823.

Organism-specific databases

CTDi2597.

Phylogenomic databases

HOVERGENiHBG000227.
InParanoidiP00355.
KOiK00134.

Enzyme and pathway databases

UniPathwayiUPA00109; UER00184.

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_PIG
AccessioniPrimary (citable) accession number: P00355
Secondary accession number(s): O18816
, P79299, P79317, Q29546
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 137 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, 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.