G3P_SHEEP
ID G3P_SHEEP Reviewed; 322 AA.
AC Q28554; O02701; O02760; O18908; O46400;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 4.
DT 03-AUG-2022, entry version 137.
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 Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-205.
RC STRAIN=Suffolk Dorset; TISSUE=Brain;
RA Tai T.C., Lye S.J., Adamson S.L.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 34-311.
RC TISSUE=Adrenal cortex;
RX PubMed=9408883; DOI=10.1177/107155769700400604;
RA Cale J.M., Millican D.S., Itoh H., Magness R.R., Bird I.M.;
RT "Pregnancy induces an increase in the expression of glyceraldehyde-3-
RT phosphate dehydrogenase in uterine artery endothelial cells.";
RL J. Soc. Gynecol. Invest. 4:284-292(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 62-127.
RA Ing N.H., Bhattacharyya S.;
RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 109-230.
RC STRAIN=New Zealand Wiltshire; TISSUE=Skin;
RA Nixon A.J., Wildermoth J.E., Ford C.A., Pearson A.J.;
RT "Ovine glyceraldehyde-3-phosphate dehydrogenase (GAPDH) sequence.";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 139-322.
RA Lee G.H.Y., Thonney M.L.;
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 205-318.
RA Leroux C.;
RL Submitted (NOV-1995) 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-139 leads to interaction with SIAH1,
CC followed by translocation to the nucleus S-nitrosylation of Cys-234 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-139 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; AF035421; AAB88484.1; -; mRNA.
DR EMBL; AF030943; AAB86435.1; -; mRNA.
DR EMBL; U94718; AAB57838.1; -; mRNA.
DR EMBL; AF022183; AAB71712.1; -; mRNA.
DR EMBL; U94889; AAC16069.1; -; mRNA.
DR EMBL; U39091; AAA81516.1; -; mRNA.
DR AlphaFoldDB; Q28554; -.
DR SMR; Q28554; -.
DR STRING; 9940.ENSOARP00000008476; -.
DR Allergome; 12130; Ovi a GAPDH.
DR eggNOG; KOG0657; Eukaryota.
DR UniPathway; UPA00109; UER00184.
DR Proteomes; UP000002356; 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..322
FT /note="Glyceraldehyde-3-phosphate dehydrogenase"
FT /id="PRO_0000145495"
FT MOTIF 232..237
FT /note="[IL]-x-C-x-x-[DE] motif"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT ACT_SITE 139
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10009"
FT BINDING 22
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 67
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 109
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 138..140
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 169
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 198..199
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 221
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 303
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT SITE 166
FT /note="Activates thiol group during catalysis"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 29
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 48
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 51
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 53
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 57
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 62
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 109
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 136
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 139
FT /note="ADP-ribosylcysteine; by autocatalysis; in
FT irreversibly inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 139
FT /note="Cysteine persulfide"
FT /evidence="ECO:0000250|UniProtKB:P16858"
FT MOD_RES 139
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 139
FT /note="S-nitrosocysteine; in reversibly inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 140
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 142
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 164
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 169
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 171
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 181
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 181
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 181
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 198
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 202
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 202
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 206
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 212
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 214
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 214
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 216
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 224
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 234
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 234
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 241
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 247
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 250
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 303
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 321
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT CROSSLNK 173
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT CONFLICT 105..106
FT /note="KV -> II (in Ref. 3; AAB57838)"
FT /evidence="ECO:0000305"
FT CONFLICT 105
FT /note="K -> R (in Ref. 2; AAB86435)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="A -> L (in Ref. 3; AAB57838)"
FT /evidence="ECO:0000305"
FT CONFLICT 178..179
FT /note="PS -> LP (in Ref. 1; AAB88484)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="V -> A (in Ref. 6; AAA81516)"
FT /evidence="ECO:0000305"
FT NON_TER 1
SQ SEQUENCE 322 AA; 34732 MW; DFDA9C84FE4F862E CRC64;
IGRLVTRAAF NTGKVDIVAI NDPFIDLHYM VYMFQYDSTH GKFHGTVKAE NGKLVINGKA
ITIFQERDPA NIKWGDAGAE YVVESTGVFT TMEKAGAHLK GGAKKVIISA PSADAPMFVM
GVNHEKYNNT LKIVSNASCT TNCLAPLAKV IHDHFGIVEG LMTTVHAITA TQKTVDGPSG
KLWRDGRGAA QNIIPASTGA AKAVGKVIPE LNGKLTGMAF RVPTPNVSVV DLTCRLEKPA
KYDEIKKVVK QASEGPLKGI LGYTEDQVVS CDFNSDTHSS TFDAGAGIAL NDHFVKLISW
YDNEFGYSNR VVDLMVHMAS KE
