G3P_CAVPO
ID G3P_CAVPO Reviewed; 123 AA.
AC P70685;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 113.
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=GAPD;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Hartley; TISSUE=Cartilage;
RX PubMed=9588741;
RX DOI=10.1002/1529-0131(199805)41:5<877::aid-art16>3.0.co;2-#;
RA Huebner J.L., Otterness I.G., Freund E.M., Caterson B., Kraus V.B.;
RT "Collagenase 1 and collagenase 3 expression in a guinea pig model of
RT osteoarthritis.";
RL Arthritis Rheum. 41:877-890(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 37-111.
RA Aguan K., Weiner C.P.;
RL Submitted (NOV-1996) 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 leads to interaction with SIAH1, followed by
CC translocation to the nucleus. S-nitrosylation is induced by interferon-
CC gamma and LDL(ox) implicating the iNOS-S100A8/9 transnitrosylase
CC complex and seems to prevent interaction with phosphorylated RPL13A and
CC to interfere with GAIT complex activity (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P04406}.
CC -!- PTM: Sulfhydration 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; U51572; AAC32447.1; -; mRNA.
DR EMBL; U76741; AAB18821.1; -; mRNA.
DR AlphaFoldDB; P70685; -.
DR SMR; P70685; -.
DR STRING; 10141.ENSCPOP00000017692; -.
DR eggNOG; KOG0657; Eukaryota.
DR InParanoid; P70685; -.
DR UniPathway; UPA00109; UER00184.
DR Proteomes; UP000005447; Unassembled WGS sequence.
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:0035605; F:peptidyl-cysteine S-nitrosylase activity; ISS:UniProtKB.
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; IPR020829; GlycerAld_3-P_DH_cat.
DR PANTHER; PTHR10836; PTHR10836; 1.
DR Pfam; PF02800; Gp_dh_C; 1.
DR PRINTS; PR00078; G3PDHDRGNASE.
PE 2: Evidence at transcript level;
KW Acetylation; Apoptosis; Cytoplasm; Cytoskeleton; Glycolysis; Immunity;
KW Innate immunity; Isopeptide bond; Methylation; NAD; Nucleus;
KW Oxidoreductase; Phosphoprotein; Reference proteome; S-nitrosylation;
KW Transferase; Translation regulation; Ubl conjugation.
FT CHAIN <1..>123
FT /note="Glyceraldehyde-3-phosphate dehydrogenase"
FT /id="PRO_0000145483"
FT MOTIF 77..82
FT /note="[IL]-x-C-x-x-[DE] motif"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 14
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 43..44
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 66
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT SITE 11
FT /note="Activates thiol group during catalysis"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 9
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 14
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 16
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 26
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 26
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 26
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 43
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 47
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 47
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 51
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 57
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 59
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 59
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 61
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 69
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 79
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 79
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 86
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 92
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 95
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT CROSSLNK 18
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 123
SQ SEQUENCE 123 AA; 12966 MW; C13BDB277FE1E8B3 CRC64;
GIVEGLMTTV HAITATQKTV DGPSGKLWRD GRAAAQNIIP ASTGAAKAVG KVIPELNGKL
TGMAFRVPTP NVSVVDLTCR LEKPAKYDDI KKVVKQASEG SLKGILGYTE DQVVSCDFNS
DTH
