G3P_PONAB
ID G3P_PONAB Reviewed; 335 AA.
AC Q5RAB4;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 112.
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};
GN Name=GAPDH; Synonyms=GAPD;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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-152 leads to interaction with SIAH1,
CC followed by translocation to the nucleus S-nitrosylation of Cys-247 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-152 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; CR859104; CAH91296.1; -; mRNA.
DR RefSeq; NP_001125767.1; NM_001132295.2.
DR AlphaFoldDB; Q5RAB4; -.
DR SMR; Q5RAB4; -.
DR STRING; 9601.ENSPPYP00000004774; -.
DR PRIDE; Q5RAB4; -.
DR GeneID; 100172694; -.
DR KEGG; pon:100172694; -.
DR CTD; 2597; -.
DR eggNOG; KOG0657; Eukaryota.
DR InParanoid; Q5RAB4; -.
DR OrthoDB; 945145at2759; -.
DR UniPathway; UPA00109; UER00184.
DR Proteomes; UP000001595; 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 I-kappaB kinase/NF-kappaB signaling; 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 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 PANTHER; PTHR10836; PTHR10836; 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; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01534; GAPDH-I; 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..335
FT /note="Glyceraldehyde-3-phosphate dehydrogenase"
FT /id="PRO_0000145492"
FT REGION 1..148
FT /note="Interaction with WARS1"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOTIF 245..250
FT /note="[IL]-x-C-x-x-[DE] motif"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT ACT_SITE 152
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10009"
FT BINDING 13..14
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 35
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 80
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 122
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 151..153
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 182
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 211..212
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 234
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 316
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT SITE 179
FT /note="Activates thiol group during catalysis"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 5
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 9
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 42
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 61
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 64
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 66
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 70
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 75
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 148
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 149
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 152
FT /note="ADP-ribosylcysteine; by autocatalysis; in
FT irreversibly inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 152
FT /note="Cysteine persulfide"
FT /evidence="ECO:0000250|UniProtKB:P16858"
FT MOD_RES 152
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 152
FT /note="S-nitrosocysteine; in reversibly inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 153
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 155
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 177
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 182
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 184
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 194
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 194
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 194
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 211
FT /note="Phosphothreonine"
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-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 219
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 225
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 227
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 227
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 229
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 237
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 247
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 247
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 254
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 260
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 263
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 316
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 334
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT CROSSLNK 186
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P04406"
SQ SEQUENCE 335 AA; 35993 MW; 966EF7D1843D3873 CRC64;
MGKVKVGING FGRIGRLVTR AAFNSGKVDI VAINDPFIDL NYMVYMFQYD STHGKFHGTV
KAENGKLVIN GNPITIFQER DPSKIKWGDA GAEYVVESTG VFTTMEKAGA HLQGGAKRVI
ISAPSADAPM FVMGVNHEKY DNSLKIVSNA SCTTNCLAPL AKVIHDNFGI VEGLMTTVHA
ITATQKTVDG PSGKLWRDGR GALQNIIPAS TGAAKAVGKV IPELNGKLTG MAFRVPTANV
SVVDLTCRLE KAAKYDDIKK VVKQASEGPL KGILGYTEHQ VVSSDLNSDT HSSTFDAGAG
IALNDHFVKL ISWYDNEFGY SNRVVDLMAH MASKE
