ID G3P_MESAU Reviewed; 312 AA.
AC P51640;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 24-JAN-2024, entry version 125.
DE RecName: Full=Glyceraldehyde-3-phosphate dehydrogenase;
DE Short=GAPDH;
DE EC=1.2.1.12 {ECO:0000250|UniProtKB:P04406};
DE AltName: Full=Peptidyl-cysteine S-nitrosylase GAPDH {ECO:0000305};
DE EC=2.6.99.- {ECO:0000250|UniProtKB:P04797};
DE Flags: Fragment;
GN Name=GAPDH; Synonyms=G3PDH, GAPD;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pancreas;
RX PubMed=7780969;
RA Chang K.W., Laconi S., Mangold K.A., Hubchak S., Scarpelli D.G.;
RT "Multiple genetic alterations in hamster pancreatic ductal
RT adenocarcinomas.";
RL Cancer Res. 55:2560-2568(1995).
CC -!- FUNCTION: Has both glyceraldehyde-3-phosphate dehydrogenase and
CC nitrosylase activities, thereby playing a role in glycolysis and
CC nuclear functions, respectively. Glyceraldehyde-3-phosphate
CC dehydrogenase is a key enzyme in glycolysis that catalyzes the first
CC step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P)
CC into 3-phospho-D-glyceroyl phosphate (By similarity). Modulates the
CC organization and assembly of the cytoskeleton. Facilitates the CHP1-
CC dependent microtubule and membrane associations through its ability to
CC stimulate the binding of CHP1 to microtubules (By similarity).
CC Component of the GAIT (gamma interferon-activated inhibitor of
CC translation) complex which mediates interferon-gamma-induced
CC transcript-selective translation inhibition in inflammation processes.
CC Upon interferon-gamma treatment assembles into the GAIT complex which
CC binds to stem loop-containing GAIT elements in the 3'-UTR of diverse
CC inflammatory mRNAs (such as ceruplasmin) and suppresses their
CC translation. Also plays a role in innate immunity by promoting TNF-
CC induced NF-kappa-B activation and type I interferon production, via
CC interaction with TRAF2 and TRAF3, respectively (By similarity).
CC Participates in nuclear events including transcription, RNA transport,
CC DNA replication and apoptosis. Nuclear functions are probably due to
CC the nitrosylase activity that mediates cysteine S-nitrosylation of
CC nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity).
CC {ECO:0000250|UniProtKB:P04406, ECO:0000250|UniProtKB:P04797}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glyceraldehyde 3-phosphate + NAD(+) + phosphate = (2R)-3-
CC phospho-glyceroyl phosphate + H(+) + NADH; Xref=Rhea:RHEA:10300,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57604, ChEBI:CHEBI:57945, ChEBI:CHEBI:59776; EC=1.2.1.12;
CC Evidence={ECO:0000250|UniProtKB:P04406, ECO:0000255|PROSITE-
CC ProRule:PRU10009};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-cysteinyl-[protein] + S-nitroso-L-cysteinyl-[GAPDH] = L-
CC cysteinyl-[GAPDH] + S-nitroso-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:66684, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:17089,
CC Rhea:RHEA-COMP:17090, Rhea:RHEA-COMP:17091, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:149494; Evidence={ECO:0000250|UniProtKB:P04797};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66685;
CC Evidence={ECO:0000250|UniProtKB:P04797};
CC -!- ACTIVITY REGULATION: Glyceraldehyde-3-phosphate dehydrogenase activity
CC is inhibited by fumarate, via the formation of S-(2-succinyl)cysteine
CC residues. {ECO:0000250|UniProtKB:P04797}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D-
CC glyceraldehyde 3-phosphate: step 1/5.
CC -!- SUBUNIT: Homotetramer (By similarity). Interacts with TPPP; the
CC interaction is direct (By similarity). Interacts (when S-nitrosylated)
CC with SIAH1; leading to nuclear translocation. Interacts with
CC RILPL1/GOSPEL, leading to prevent the interaction between GAPDH and
CC SIAH1 and prevent nuclear translocation. Interacts with CHP1; the
CC interaction increases the binding of CHP1 with microtubules. Associates
CC with microtubules (By similarity). Interacts with EIF1AD, USP25, PRKCI
CC and WARS1. Interacts with phosphorylated RPL13A; inhibited by
CC oxidatively-modified low-densitity lipoprotein (LDL(ox)). Component of
CC the GAIT complex. Interacts with FKBP6; leading to inhibit GAPDH
CC catalytic activity. Interacts with TRAF2, promoting TRAF2
CC ubiquitination. Interacts with TRAF3, promoting TRAF3 ubiquitination
CC (By similarity). {ECO:0000250|UniProtKB:P04406,
CC ECO:0000250|UniProtKB:P04797, ECO:0000250|UniProtKB:P10096}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P04797}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P04797}. Nucleus {ECO:0000250|UniProtKB:P04797}.
CC Note=Translocates to the nucleus following S-nitrosylation and
CC interaction with SIAH1, which contains a nuclear localization signal.
CC Colocalizes with CHP1 to small punctate structures along the
CC microtubules tracks. {ECO:0000250|UniProtKB:P04797}.
CC -!- DOMAIN: The [IL]-x-C-x-x-[DE] motif is a proposed target motif for
CC cysteine S-nitrosylation mediated by the iNOS-S100A8/A9
CC transnitrosylase complex. {ECO:0000250|UniProtKB:P04406}.
CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P04406}.
CC -!- PTM: S-nitrosylation of Cys-140 leads to interaction with SIAH1,
CC followed by translocation to the nucleus S-nitrosylation of Cys-235 is
CC induced by interferon-gamma and LDL(ox) implicating the iNOS-S100A8/9
CC transnitrosylase complex and seems to prevent interaction with
CC phosphorylated RPL13A and to interfere with GAIT complex activity (By
CC similarity). {ECO:0000250|UniProtKB:P04406,
CC ECO:0000250|UniProtKB:P04797}.
CC -!- PTM: Sulfhydration at Cys-150 increases catalytic activity.
CC {ECO:0000250|UniProtKB:P16858}.
CC -!- PTM: Oxidative stress can promote the formation of high molecular
CC weight disulfide-linked GAPDH aggregates, through a process called
CC nucleocytoplasmic coagulation. {ECO:0000250|UniProtKB:P04406}.
CC -!- SIMILARITY: Belongs to the glyceraldehyde-3-phosphate dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; U10983; AAA88860.1; -; mRNA.
DR AlphaFoldDB; P51640; -.
DR SMR; P51640; -.
DR STRING; 10036.ENSMAUP00000014693; -.
DR UniPathway; UPA00109; UER00184.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0097452; C:GAIT complex; ISS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004365; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0035605; F:peptidyl-cysteine S-nitrosylase activity; ISS:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; IEA:InterPro.
DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0035606; P:peptidyl-cysteine S-trans-nitrosylation; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISS:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR InterPro; IPR020831; GlycerAld/Erythrose_P_DH.
DR InterPro; IPR020830; GlycerAld_3-P_DH_AS.
DR InterPro; IPR020829; GlycerAld_3-P_DH_cat.
DR InterPro; IPR020828; GlycerAld_3-P_DH_NAD(P)-bd.
DR InterPro; IPR006424; Glyceraldehyde-3-P_DH_1.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR NCBIfam; TIGR01534; GAPDH-I; 1.
DR PANTHER; PTHR10836; GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE; 1.
DR PANTHER; PTHR10836:SF111; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; 1.
DR Pfam; PF02800; Gp_dh_C; 1.
DR Pfam; PF00044; Gp_dh_N; 1.
DR PIRSF; PIRSF000149; GAP_DH; 1.
DR PRINTS; PR00078; G3PDHDRGNASE.
DR SMART; SM00846; Gp_dh_N; 1.
DR SUPFAM; SSF55347; Glyceraldehyde-3-phosphate dehydrogenase-like, C-terminal domain; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR PROSITE; PS00071; GAPDH; 1.
PE 2: Evidence at transcript level;
KW Acetylation; ADP-ribosylation; Apoptosis; Cytoplasm; Cytoskeleton;
KW Glycolysis; Immunity; Innate immunity; Isopeptide bond; Methylation; NAD;
KW Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome;
KW S-nitrosylation; Transferase; Translation regulation; Ubl conjugation.
FT CHAIN <1..>312
FT /note="Glyceraldehyde-3-phosphate dehydrogenase"
FT /id="PRO_0000145489"
FT MOTIF 233..238
FT /note="[IL]-x-C-x-x-[DE] motif"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT ACT_SITE 140
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10009"
FT BINDING 1..2
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 23
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 68
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 110
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 139..141
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 170
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 199..200
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 222
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 304
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT SITE 167
FT /note="Activates thiol group during catalysis"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 30
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 49
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 52
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 54
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 58
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 63
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 137
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 140
FT /note="ADP-ribosylcysteine; by autocatalysis; in
FT irreversibly inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 140
FT /note="Cysteine persulfide"
FT /evidence="ECO:0000250|UniProtKB:P16858"
FT MOD_RES 140
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 140
FT /note="S-nitrosocysteine; in reversibly inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 141
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 165
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 170
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 172
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 182
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 182
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 182
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 199
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 203
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 203
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 207
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 213
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 215
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 215
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 217
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 225
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 235
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 235
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 242
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 248
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 251
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 304
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT CROSSLNK 174
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT NON_TER 1
FT NON_TER 312
SQ SEQUENCE 312 AA; 33532 MW; 4E1D4D9A2E772101 CRC64;
RIGRLVTRAA FTSGKVDIVA INDPFIDLNY MVYMFQYDST HGKFKGTVKA ENGKLVINGK
AITIFQERDP TNIKWGDAGA EYVVESTGVF TTMEKAGAHL KGGAKRVIIS APSADAPMFV
MGVNHDKYDN SLKIVSNASC TTTCLAPLAK VIHDNFGIVK GLMTTVHAIT ATQKTVDGPS
GKLWRDGRGA AQNIIPASTG AAKAVGKVIP ELNGKLTGMA FRVPTPNVSV VDLTCRLEKA
AKYEDIKKVV KQASEGPLKG ILGYTEDQVV SCDFKSDSHS STFDAGAGIA LNDNFVKLIS
WYDNEFGYSN RV
//
