Glyceraldehyde-3-phosphate dehydrogenase

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P04797 (G3P_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 141. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Glyceraldehyde-3-phosphate dehydrogenase
Short name=GAPDH
EC=1.2.1.12

Alternative name(s):
38 kDa BFA-dependent ADP-ribosylation substrate
BARS-38
Peptidyl-cysteine S-nitrosylase GAPDH
EC=2.6.99.-

Gene names

Name:	Gapdh
Synonyms:	Gapd

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	333 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.3 Ref.13 Ref.14 Ref.16
Catalytic activity	D-glyceraldehyde 3-phosphate + phosphate + NAD⁺ = 3-phospho-D-glyceroyl phosphate + NADH.
Pathway	Carbohydrate degradation; glycolysis; pyruvate from D-glyceraldehyde 3-phosphate: step 1/5.
Subunit structure	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. Associates with microtubules. Component of the GAIT complex By similarity. Ref.13 Ref.14 Ref.15 Ref.16
Subcellular location	Cytoplasm › cytosol. Cytoplasm › cytoskeleton. 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. Ref.13 Ref.14 Ref.15 Ref.16
Tissue specificity	High levels in skeletal muscle and heart, low levels in liver, brain, and kidney. Ref.9
Post-translational modification	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 (Ref.12). According to others, it does not affect glycolysis (Ref.14). ADP-ribosylation is likely to be a pathophysiological event associated with inhibition of gluconeogenesis. ISGylated By similarity. Sulfhydration at Cys-150 increases catalytic activity By similarity.
Sequence similarities	Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.

Ontologies

Keywords
Biological process	Apoptosis Glycolysis Translation regulation
Cellular component	Cytoplasm Cytoskeleton Nucleus
Ligand	NAD
Molecular function	Oxidoreductase Transferase
PTM	ADP-ribosylation Acetylation Methylation Phosphoprotein S-nitrosylation Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	gluconeogenesis Inferred from direct assay PubMed 15720133. Source: RGD glycolysis Inferred from direct assay PubMed 8255543. Source: RGD microtubule cytoskeleton organization Inferred from direct assay Ref.13. Source: UniProtKB neuron apoptotic process Inferred from direct assay Ref.15. Source: UniProtKB peptidyl-cysteine S-trans-nitrosylation Inferred from direct assay Ref.16. Source: UniProtKB protein stabilization Inferred from direct assay Ref.14. Source: UniProtKB regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW response to ammonium ion Inferred from direct assay PubMed 8255543. Source: RGD
Cellular_component	cytosol Inferred from direct assay Ref.14 Ref.15. Source: UniProtKB microtubule cytoskeleton Inferred from direct assay Ref.13. Source: UniProtKB nucleus Inferred from direct assay Ref.14 Ref.15 Ref.16. Source: UniProtKB
Molecular_function	NAD binding Inferred from electronic annotation. Source: InterPro NADP binding Inferred from electronic annotation. Source: InterPro glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity Inferred from direct assay Ref.14. Source: UniProtKB microtubule binding Inferred from direct assay Ref.13. Source: UniProtKB peptidyl-cysteine S-nitrosylase activity Inferred from direct assay Ref.16. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Chp1	P61023	3	EBI-349219,EBI-917838
Slc2a4	P19357	2	EBI-349219,EBI-915426

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed By similarity

Chain

2 – 333

332

Glyceraldehyde-3-phosphate dehydrogenase

PRO_0000145494

Regions

Nucleotide binding

11 – 12

NAD By similarity

Region

2 – 146

145

Interaction with WARS By similarity

Region

149 – 151

Glyceraldehyde 3-phosphate binding By similarity

Region

209 – 210

Glyceraldehyde 3-phosphate binding By similarity

Sites

Active site

150

Nucleophile Ref.12

Binding site

NAD By similarity

Binding site

NAD; via carbonyl oxygen By similarity

Binding site

120

NAD By similarity

Binding site

180

Glyceraldehyde 3-phosphate By similarity

Binding site

232

Glyceraldehyde 3-phosphate By similarity

Binding site

314

NAD By similarity

Site

154

Not nitrosylated

Site

177

Activates thiol group during catalysis By similarity

Amino acid modifications

Modified residue

N6,N6-dimethyllysine By similarity

Modified residue

Deamidated asparagine By similarity

Modified residue

Phosphotyrosine By similarity

Modified residue

N6-acetyllysine By similarity

Modified residue

Deamidated asparagine By similarity

Modified residue

N6,N6-dimethyllysine By similarity

Modified residue

Deamidated asparagine By similarity

Modified residue

Phosphothreonine By similarity

Modified residue

120

Phosphoserine By similarity

Modified residue

146

Phosphoserine By similarity

Modified residue

147

Deamidated asparagine By similarity

Modified residue

149

Phosphoserine By similarity

Modified residue

150

ADP-ribosylcysteine; by autocatalysis; in irreversibly inhibited form

Modified residue

150

Cysteine persulfide By similarity

Modified residue

150

S-nitrosocysteine; in reversibly inhibited form Ref.7 Ref.12 Ref.14 Ref.16

Modified residue

153

Deamidated asparagine By similarity

Modified residue

182

Phosphothreonine By similarity

Modified residue

192

N6,N6-dimethyllysine; alternate By similarity

Modified residue

192

N6-acetyllysine By similarity

Modified residue

192

N6-malonyllysine; alternate By similarity

Modified residue

209

Phosphothreonine By similarity

Modified residue

213

N6,N6-dimethyllysine; alternate By similarity

Modified residue

213

N6-malonyllysine; alternate By similarity

Modified residue

217

N6-acetyllysine By similarity

Modified residue

223

Deamidated asparagine By similarity

Modified residue

225

N6,N6-dimethyllysine; alternate By similarity

Modified residue

225

N6-acetyllysine; alternate By similarity

Modified residue

227

Phosphothreonine By similarity

Modified residue

235

Phosphothreonine By similarity

Modified residue

252

N6-acetyllysine By similarity

Modified residue

258

N6,N6-dimethyllysine By similarity

Modified residue

261

N6,N6-dimethyllysine By similarity

Modified residue

310

Phosphoserine By similarity

Modified residue

312

Phosphotyrosine By similarity

Modified residue

314

Deamidated asparagine By similarity

Modified residue

316

Phosphotyrosine By similarity

Modified residue

318

Phosphotyrosine By similarity

Modified residue

328

Phosphotyrosine By similarity

Modified residue

332

N6,N6-dimethyllysine By similarity

Experimental info

Mutagenesis

149

S → A: Does not affect interaction with SIRT1. Ref.16

Mutagenesis

150

C → S: Abolishes S-nitrosylation and subsequent nuclear translocation. Ref.14 Ref.16

Mutagenesis

151

T → A: Does not affect interaction with SIRT1. Ref.16

Mutagenesis

152

T → A: Abolishes interaction and subsequent nitrosylation of SIRT1. Ref.16

Mutagenesis

225

K → A: Abolishes interaction with SIAH1. Ref.14

Mutagenesis

234

P → A: Does not affect interaction with SIAH1. Ref.14

Mutagenesis

235

T → A: Does not affect interaction with SIAH1. Ref.14

Sequence conflict

81 – 82

AN → VK in AAA41193. Ref.1

Sequence conflict

129

F → L in AAH87743. Ref.5

Sequence conflict

305

F → I in AAA41193. Ref.1

Sequence conflict

305

F → I in CAA26150. Ref.9

Sequences

Sequence

Length

Mass (Da)

Tools

P04797 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: D9E5ED4F38544C77
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FASTA

333

35,828

        10         20         30         40         50         60 
MVKVGVNGFG RIGRLVTRAA FSCDKVDIVA INDPFIDLNY MVYMFQYDST HGKFNGTVKA 

        70         80         90        100        110        120 
ENGKLVINGK PITIFQERDP ANIKWGDAGA EYVVESTGVF TTMEKAGAHL KGGAKRVIIS 

       130        140        150        160        170        180 
APSADAPMFV MGVNHEKYDN SLKIVSNASC TTNCLAPLAK VIHDNFGIVE GLMTTVHAIT 

       190        200        210        220        230        240 
ATQKTVDGPS GKLWRDGRGA AQNIIPASTG AAKAVGKVIP ELNGKLTGMA FRVPTPNVSV 

       250        260        270        280        290        300 
VDLTCRLEKP AKYDDIKKVV KQAAEGPLKG ILGYTEDQVV SCDFNSNSHS STFDAGAGIA 

       310        320        330 
LNDNFVKLIS WYDNEYGYSN RVVDLMAYMA SKE

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family." Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J.-M. Nucleic Acids Res. 13:1431-1442(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar. Tissue: Muscle.
[2]	"Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene." Tso J.Y., Sun X.-H., Kao T.-H., Reece K.S., Wu R. Nucleic Acids Res. 13:2485-2502(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Over-expression of GAPDH induces apoptosis in COS-7 cells transfected with cloned GAPDH cDNAs." Tajima H., Tsuchiya K., Yamada M., Kondo K., Katsube N., Ishitani R. NeuroReport 10:2029-2033(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Strain: Sprague-Dawley. Tissue: Cerebellum.
[4]	"Isolation of a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) cDNA isoform from rat brain by a rapid PCR-based cloning method and its expression by RT-PCR." Zheng J., Ramirez V.D. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Brain.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Pituitary anterior lobe.
[6]	Lubec G., Afjehi-Sadat L., Chen W.-Q. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 65-105; 116-137; 144-184; 233-246 AND 308-321, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Hippocampus and Spinal cord.
[7]	"SNOSID, a proteomic method for identification of cysteine S-nitrosylation sites in complex protein mixtures." Hao G., Derakhshan B., Shi L., Campagne F., Gross S.S. Proc. Natl. Acad. Sci. U.S.A. 103:1012-1017(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 144-160, S-NITROSYLATION [LARGE SCALE ANALYSIS] AT CYS-150, MASS SPECTROMETRY. Tissue: Cerebellum.
[8]	"Trifluoperazine activates and releases latent ATP-generating enzymes associated with the synaptic plasma membrane." Leung T.K.C., Hall C., Monfries C., Lim L. J. Neurochem. 49:232-238(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 235-333. Tissue: Brain.
[9]	"Post-transcriptional regulation of glyceraldehyde-3-phosphate-dehydrogenase gene expression in rat tissues." Piechaczyk M., Blanchard J.-M., Marty L., Dani C., Panabieres F., el Sabrouty S., Fort P., Jeanteur P. Nucleic Acids Res. 12:6951-6963(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 261-323, TISSUE SPECIFICITY. Tissue: Glial tumor.
[10]	"1.5 kb mRNA abundantly expressed in rat tumors encodes a 37 kilodalton protein in vitro." Maehara Y., Fujiyoshi T., Takahashi K., Yamamoto M., Endo H. Biochem. Biophys. Res. Commun. 131:800-805(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 267-333.
[11]	"Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation." Molina y Vedia L., McDonald B., Reep B., Brune B., Di Silvio M., Billiar T.R., Lapetina E.G. J. Biol. Chem. 267:24929-24932(1992) [PubMed] [Europe PMC] [Abstract] Cited for: S-NITROSYLATION.
[12]	"Posttranslational modification of glyceraldehyde-3-phosphate dehydrogenase by S-nitrosylation and subsequent NADH attachment." Mohr S., Stamler J.S., Brune B. J. Biol. Chem. 271:4209-4214(1996) [PubMed] [Europe PMC] [Abstract] Cited for: S-NITROSYLATION AT CYS-150, ADP-RIBOSYLATION AT CYS-150, ABSENCE OF NITROSYLATION AT CYS-154, ACTIVE SITE.
[13]	"Interactions among p22, glyceraldehyde-3-phosphate dehydrogenase and microtubules." Andrade J., Pearce S.T., Zhao H., Barroso M. Biochem. J. 384:327-336(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CHP1, ASSOCIATION WITH MICROTUBULES, SUBCELLULAR LOCATION.
[14]	"S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding." Hara M.R., Agrawal N., Kim S.F., Cascio M.B., Fujimuro M., Ozeki Y., Takahashi M., Cheah J.H., Tankou S.K., Hester L.D., Ferris C.D., Hayward S.D., Snyder S.H., Sawa A. Nat. Cell Biol. 7:665-674(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SIAH1, S-NITROSYLATION AT CYS-150, MUTAGENESIS OF CYS-150; LYS-225; PRO-234 AND THR-235.
[15]	"GOSPEL: a neuroprotective protein that binds to GAPDH upon S-nitrosylation." Sen N., Hara M.R., Ahmad A.S., Cascio M.B., Kamiya A., Ehmsen J.T., Agrawal N., Hester L., Dore S., Snyder S.H., Sawa A. Neuron 63:81-91(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH RILPL1 AND SIAH1.
[16]	"GAPDH mediates nitrosylation of nuclear proteins." Kornberg M.D., Sen N., Hara M.R., Juluri K.R., Nguyen J.V., Snowman A.M., Law L., Hester L.D., Snyder S.H. Nat. Cell Biol. 12:1094-1100(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS NITROSYLASE, SUBCELLULAR LOCATION, INTERACTION WITH SIRT1, S-NITROSYLATION AT CYS-150, MUTAGENESIS OF SER-149; CYS-150; THR-151 AND THR-152.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00555252.
PIR	DERTG. A23013.
RefSeq	NP_058704.1. NM_017008.4. XP_002726600.1. XM_002726554.2.
UniGene	Rn.129558. Rn.91450.
3D structure databases
ProteinModelPortal	P04797.
SMR	P04797. Positions 2-333.
ModBase	Search...
Protein-protein interaction databases
IntAct	P04797. 4 interactions.
MINT	MINT-1775142.
STRING	10116.ENSRNOP00000040878.
PTM databases
PhosphoSite	P04797.
2D gel databases
World-2DPAGE	0004:P04797.
Proteomic databases
PaxDb	P04797.
PRIDE	P04797.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000050443; ENSRNOP00000040878; ENSRNOG00000018630.
GeneID	24383. 685186.
KEGG	rno:24383. rno:685186.
UCSC	RGD:2661. rat.
Organism-specific databases
CTD	2597.
RGD	2661. Gapdh.
Phylogenomic databases
eggNOG	COG0057.
GeneTree	ENSGT00690000101860.
HOGENOM	HOG000071678.
HOVERGEN	HBG000227.
InParanoid	P04797.
KO	K00134.
OrthoDB	EOG4Q84XS.
Enzyme and pathway databases
SABIO-RK	P04797.
UniPathway	UPA00109; UER00184.
Gene expression databases
ArrayExpress	P04797.
Genevestigator	P04797.
GermOnline	ENSRNOG00000033057. Rattus norvegicus.
Family and domain databases
Gene3D	3.40.50.720. 1 hit.
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. IPR016040. NAD(P)-bd_dom. [Graphical view]
PANTHER	PTHR10836. PTHR10836. 1 hit.
Pfam	PF02800. Gp_dh_C. 1 hit. PF00044. Gp_dh_N. 1 hit. [Graphical view]
PIRSF	PIRSF000149. GAP_DH. 1 hit.
PRINTS	PR00078. G3PDHDRGNASE.
SMART	SM00846. Gp_dh_N. 1 hit. [Graphical view]
TIGRFAMs	TIGR01534. GAPDH-I. 1 hit.
PROSITE	PS00071. GAPDH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	603149.

Entry information

Entry name

G3P_RAT

Accession

Primary (citable) accession number: P04797
Secondary accession number(s): P09328, Q5M916, Q9QWU4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 141 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

2D gel databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents