Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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 (GAPDH), 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 (PKM), Pyruvate kinase (PKLR), 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei33 – 331NAD1 Publication
Binding sitei78 – 781NAD; via carbonyl oxygen1 Publication
Binding sitei120 – 1201NADBy similarity
Active sitei150 – 1501Nucleophile
Sitei177 – 1771Activates thiol group during catalysis
Binding sitei180 – 1801Glyceraldehyde 3-phosphateBy similarity
Binding sitei232 – 2321Glyceraldehyde 3-phosphateBy similarity
Binding sitei314 – 3141NAD1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi11 – 122NAD1 Publication

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

ChEMBLiCHEMBL1075199.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 333332Glyceraldehyde-3-phosphate dehydrogenasePRO_0000145493Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei3 – 31N6,N6-dimethyllysineBy similarity
Modified residuei7 – 71Deamidated asparagineBy similarity
Modified residuei40 – 401PhosphotyrosineBy similarity
Modified residuei59 – 591N6-acetyllysineBy similarity
Modified residuei62 – 621Deamidated asparagineBy similarity
Modified residuei64 – 641N6,N6-dimethyllysineBy similarity
Modified residuei68 – 681Deamidated asparagineBy similarity
Modified residuei73 – 731PhosphothreonineBy similarity
Modified residuei120 – 1201PhosphoserineBy similarity
Modified residuei146 – 1461PhosphoserineBy similarity
Modified residuei147 – 1471Deamidated asparagineBy similarity
Modified residuei149 – 1491PhosphoserineBy similarity
Modified residuei150 – 1501ADP-ribosylcysteine; by autocatalysis; in irreversibly inhibited formBy similarity
Modified residuei150 – 1501Cysteine persulfideBy similarity
Modified residuei150 – 1501S-nitrosocysteine; in reversibly inhibited formBy similarity
Modified residuei153 – 1531Deamidated asparagineBy similarity
Modified residuei175 – 1751PhosphothreonineBy similarity
Modified residuei180 – 1801PhosphothreonineBy similarity
Modified residuei182 – 1821PhosphothreonineBy similarity
Modified residuei192 – 1921N6,N6-dimethyllysine; alternateBy similarity
Modified residuei192 – 1921N6-acetyllysine; alternateBy similarity
Modified residuei192 – 1921N6-malonyllysine; alternateBy similarity
Modified residuei209 – 2091PhosphothreonineBy similarity
Modified residuei213 – 2131N6,N6-dimethyllysine; alternateBy similarity
Modified residuei213 – 2131N6-malonyllysine; alternateBy similarity
Modified residuei217 – 2171N6-acetyllysineBy similarity
Modified residuei223 – 2231Deamidated asparagineBy similarity
Modified residuei225 – 2251N6,N6-dimethyllysine; alternateBy similarity
Modified residuei225 – 2251N6-acetyllysine; alternateBy similarity
Modified residuei227 – 2271PhosphothreonineBy similarity
Modified residuei235 – 2351PhosphothreonineBy similarity
Modified residuei239 – 2391PhosphoserineBy similarity
Modified residuei245 – 2451S-nitrosocysteineBy similarity
Modified residuei252 – 2521N6-acetyllysineBy similarity
Modified residuei258 – 2581N6,N6-dimethyllysineBy similarity
Modified residuei261 – 2611N6,N6-dimethyllysineBy similarity
Modified residuei310 – 3101PhosphoserineBy similarity
Modified residuei314 – 3141Deamidated asparagineBy similarity
Modified residuei332 – 3321N6,N6-dimethyllysineBy similarity

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 interaction.
DIPiDIP-6005N.
IntActiP46406. 3 interactions.
MINTiMINT-1515666.
STRINGi9986.ENSOCUP00000017094.

Chemistry

BindingDBiP46406.

Structurei

Secondary structure

1
333
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi3 – 75Combined sources
Helixi11 – 2313Combined sources
Beta strandi25 – 328Combined sources
Beta strandi34 – 363Combined sources
Helixi38 – 469Combined sources
Turni49 – 513Combined sources
Beta strandi58 – 614Combined sources
Beta strandi64 – 674Combined sources
Beta strandi70 – 756Combined sources
Helixi80 – 823Combined sources
Helixi85 – 884Combined sources
Beta strandi91 – 955Combined sources
Beta strandi97 – 993Combined sources
Helixi103 – 1075Combined sources
Helixi108 – 1125Combined sources
Beta strandi115 – 1217Combined sources
Beta strandi124 – 1263Combined sources
Turni131 – 1333Combined sources
Helixi135 – 1373Combined sources
Beta strandi143 – 1464Combined sources
Helixi150 – 16617Combined sources
Beta strandi168 – 17811Combined sources
Beta strandi183 – 1875Combined sources
Helixi194 – 1974Combined sources
Turni200 – 2023Combined sources
Beta strandi205 – 2084Combined sources
Helixi211 – 2188Combined sources
Helixi220 – 2223Combined sources
Beta strandi225 – 23410Combined sources
Beta strandi239 – 24911Combined sources
Helixi253 – 26513Combined sources
Turni266 – 2716Combined sources
Beta strandi272 – 2754Combined sources
Helixi281 – 2844Combined sources
Beta strandi290 – 2945Combined sources
Turni295 – 2973Combined sources
Beta strandi299 – 3024Combined sources
Beta strandi305 – 3128Combined sources
Helixi316 – 33015Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1J0XX-ray2.40O/P/Q/R2-333[»]
ProteinModelPortaliP46406.
SMRiP46406. Positions 2-333.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP46406.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 146145Interaction with WARSBy similarityAdd
BLAST
Regioni149 – 1513Glyceraldehyde 3-phosphate bindingBy similarity
Regioni209 – 2102Glyceraldehyde 3-phosphate bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi243 – 2486[IL]-x-C-x-x-[DE] motifBy similarity

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
EntryMethodResolution (Å)ChainPositionsPDBsum
1J0XX-ray2.40O/P/Q/R2-333[»]
ProteinModelPortaliP46406.
SMRiP46406. Positions 2-333.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi1172097. 1 interaction.
DIPiDIP-6005N.
IntActiP46406. 3 interactions.
MINTiMINT-1515666.
STRINGi9986.ENSOCUP00000017094.

Chemistry

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.

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...

Publicationsi

  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.

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: February 17, 2016
This is version 133 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.