P46406 (G3P_RABIT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Peptidyl-cysteine S-nitrosylase GAPDH
EC=2.6.99.-

Gene names

Name:	GAPDH
Synonyms:	GAPD

Organism

Oryctolagus cuniculus (Rabbit) [Reference proteome]

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

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.
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. 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.4
Subcellular location	Cytoplasm › cytosol By similarity. Nucleus By similarity. Cytoplasm › cytoskeleton By similarity. Note: Translocates to the nucleus following S-nitrosylation and interaction with SIAH1, which contains a nuclear localization signal By similarity.
Post-translational modification	ISGylated By similarity. S-nitrosylation of Cys-150 leads to interaction with SIAH1, followed by translocation to the nucleus 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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glycolysis Inferred from electronic annotation. Source: UniProtKB-UniPathway microtubule cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB neuron apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-cysteine S-trans-nitrosylation Inferred from sequence or structural similarity. Source: UniProtKB protein stabilization Inferred from sequence or structural similarity. Source: UniProtKB regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB microtubule cytoskeleton Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. 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 sequence or structural similarity. Source: UniProtKB microtubule binding Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-cysteine S-nitrosylase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Chp1	P61023	2	EBI-2750726,EBI-917838	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 333

332

Glyceraldehyde-3-phosphate dehydrogenase

PRO_0000145493

Regions

Nucleotide binding

11 – 12

2

NAD

Region

2 – 146

145

Interaction with WARS By similarity

Region

149 – 151

3

Glyceraldehyde 3-phosphate binding By similarity

Region

209 – 210

2

Glyceraldehyde 3-phosphate binding By similarity

Sites

Active site

150

1

Nucleophile

Binding site

33

1

NAD

Binding site

78

1

NAD; via carbonyl oxygen

Binding site

120

1

NAD By similarity

Binding site

180

1

Glyceraldehyde 3-phosphate By similarity

Binding site

232

1

Glyceraldehyde 3-phosphate By similarity

Binding site

314

1

NAD

Site

177

1

Activates thiol group during catalysis

Amino acid modifications

Modified residue

3

1

N6,N6-dimethyllysine By similarity

Modified residue

7

1

Deamidated asparagine By similarity

Modified residue

40

1

Phosphotyrosine By similarity

Modified residue

59

1

N6-acetyllysine By similarity

Modified residue

62

1

Deamidated asparagine By similarity

Modified residue

64

1

N6,N6-dimethyllysine By similarity

Modified residue

68

1

Deamidated asparagine By similarity

Modified residue

73

1

Phosphothreonine By similarity

Modified residue

120

1

Phosphoserine By similarity

Modified residue

146

1

Phosphoserine By similarity

Modified residue

147

1

Deamidated asparagine By similarity

Modified residue

149

1

Phosphoserine By similarity

Modified residue

150

1

ADP-ribosylcysteine; by autocatalysis; in irreversibly inhibited form By similarity

Modified residue

150

1

Cysteine persulfide By similarity

Modified residue

150

1

S-nitrosocysteine; in reversibly inhibited form By similarity

Modified residue

153

1

Deamidated asparagine By similarity

Modified residue

182

1

Phosphothreonine By similarity

Modified residue

192

1

N6,N6-dimethyllysine; alternate By similarity

Modified residue

192

1

N6-acetyllysine By similarity

Modified residue

192

1

N6-malonyllysine; alternate By similarity

Modified residue

209

1

Phosphothreonine By similarity

Modified residue

213

1

N6,N6-dimethyllysine; alternate By similarity

Modified residue

213

1

N6-malonyllysine; alternate By similarity

Modified residue

217

1

N6-acetyllysine By similarity

Modified residue

223

1

Deamidated asparagine By similarity

Modified residue

225

1

N6,N6-dimethyllysine; alternate By similarity

Modified residue

225

1

N6-acetyllysine; alternate By similarity

Modified residue

227

1

Phosphothreonine By similarity

Modified residue

235

1

Phosphothreonine By similarity

Modified residue

252

1

N6-acetyllysine By similarity

Modified residue

258

1

N6,N6-dimethyllysine By similarity

Modified residue

261

1

N6,N6-dimethyllysine By similarity

Modified residue

310

1

Phosphoserine By similarity

Modified residue

312

1

Phosphotyrosine By similarity

Modified residue

314

1

Deamidated asparagine By similarity

Modified residue

318

1

Phosphotyrosine By similarity

Modified residue

332

1

N6,N6-dimethyllysine By similarity

Secondary structure

1

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333

Helix Strand Turn

Details...

Beta strand

3 – 7

5

Helix

11 – 23

13

Beta strand

25 – 32

8

Beta strand

34 – 36

3

Helix

38 – 46

9

Turn

49 – 51

3

Beta strand

58 – 61

4

Beta strand

64 – 67

4

Beta strand

70 – 75

6

Helix

80 – 82

3

Helix

85 – 88

4

Beta strand

91 – 95

5

Beta strand

97 – 99

3

Helix

103 – 107

5

Helix

108 – 112

5

Beta strand

115 – 121

7

Beta strand

124 – 126

3

Turn

131 – 133

3

Helix

135 – 137

3

Beta strand

143 – 146

4

Helix

150 – 166

17

Beta strand

168 – 178

11

Beta strand

183 – 187

5

Helix

194 – 197

4

Turn

200 – 202

3

Beta strand

205 – 208

4

Helix

211 – 218

8

Helix

220 – 222

3

Beta strand

225 – 234

10

Beta strand

239 – 249

11

Helix

253 – 265

13

Turn

266 – 271

6

Beta strand

272 – 275

4

Helix

281 – 284

4

Beta strand

290 – 294

5

Turn

295 – 297

3

Beta strand

299 – 302

4

Beta strand

305 – 312

8

Helix

316 – 330

15

Sequences

	Sequence		Length	Mass (Da)
	P46406 [UniParc]. Last modified November 13, 2007. Version 3. Checksum: 346DB9B59DF3C1DF	FASTA	333	35,780
	10 20 30 40 50 60 MVKVGVNGFG RIGRLVTRAA FNSGKVDVVA INDPFIDLHY MVYMFQYDST HGKFHGTVKA 70 80 90 100 110 120 ENGKLVINGK AITIFQERDP ANIKWGDAGA EYVVESTGVF TTMEKAGAHL KGGAKRVIIS 130 140 150 160 170 180 APSADAPMFV MGVNHEKYDN SLKIVSNASC TTNCLAPLAK VIHDHFGIVE GLMTTVHAIT 190 200 210 220 230 240 ATQKTVDGPS GKLWRDGRGA AQNIIPASTG AAKAVGKVIP ELNGKLTGMA FRVPTPNVSV 250 260 270 280 290 300 VDLTCRLEKA AKYDDIKKVV KQASEGPLKG ILGYTEDQVV SCDFNSATHS STFDAGAGIA 310 320 330 LNDHFVKLIS WYDNEFGYSN RVVDLMVHMA SKE

References

[1]	"Sequence of the rabbit glyceraldehyde-3-phosphate dehydrogenase-encoding cDNA." Applequist S.E., Keyna U., Calvin M.R., Beck-Engeser G.B., Raman C., Jaeck H.-M. Gene 163:325-326(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Spleen.
[2]	"A new troponin T and cDNA clones for 13 different muscle proteins, found by shotgun sequencing." Putney S.D., Herlihy W.C., Schimmel P.R. Nature 302:718-721(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 33-79.
[3]	"Limbal epithelial side-population cells have stem cell-like properties, including quiescent state." Umemoto T., Yamato M., Nishida K., Yang J., Tano Y., Okano T. Stem Cells 24:86-94(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 107-267.
[4]	"Structure of rabbit-muscle glyceraldehyde-3-phosphate dehydrogenase." Cowan-Jacob S.W., Kaufmann M., Anselmo A.N., Stark W., Gruetter M.G. Acta Crystallogr. D 59:2218-2227(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH NAD, SUBUNIT.
+	Additional computationally mapped references.

Web resources

Worthington enzyme manual

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L23961 mRNA. Translation: AAA85218.1.
V00884 mRNA. Translation: CAA24253.1.
AB231852 mRNA. Translation: BAE19661.1.

PIR

JC4309.

RefSeq

NP_001075722.1. NM_001082253.1.

UniGene

Ocu.87.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J0X	X-ray	2.40	O/P/Q/R	2-333	[»]

ProteinModelPortal

P46406.

SMR

P46406. Positions 2-333.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6005N.

IntAct

P46406. 1 interaction.

MINT

MINT-1515666.

STRING

9986.ENSOCUP00000017094.

Proteomic databases

PRIDE

P46406.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

100009074.

Organism-specific databases

CTD

2597.

Phylogenomic databases

eggNOG

COG0057.

HOGENOM

HOG000071678.

HOVERGEN

HBG000227.

OrthoDB

EOG4Q84XS.

Enzyme and pathway databases

SABIO-RK

P46406.

UniPathway

UPA00109; UER00184.

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

BindingDB

P46406.

ChEMBL

CHEMBL1075199.

EvolutionaryTrace

P46406.

Entry information

Entry name

G3P_RABIT

Accession

Primary (citable) accession number: P46406
Secondary accession number(s): Q4AC92

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 13, 2007
Last modified:	April 3, 2013
This is version 113 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program