G3P_JACOR
ID G3P_JACOR Reviewed; 363 AA.
AC P80534; P80447; Q64418;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Glyceraldehyde-3-phosphate dehydrogenase, muscle;
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 Contains:
DE RecName: Full=Glyceraldehyde-3-phosphate dehydrogenase, muscle, N-terminally processed;
OS Jaculus orientalis (Greater Egyptian jerboa).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Dipodoidea;
OC Dipodidae; Dipodinae; Jaculus.
OX NCBI_TaxID=48868;
RN [1]
RP PROTEIN SEQUENCE OF 1-54, AND NUCLEOTIDE SEQUENCE [MRNA] OF 25-363.
RC TISSUE=Skeletal muscle;
RX PubMed=8973322; DOI=10.1016/s0378-1119(96)00494-5;
RA Soukri A., Valverde F., Hafid N., Elkebbaj M.S., Serrano A.;
RT "Occurrence of a differential expression of the glyceraldehyde-3-phosphate
RT dehydrogenase gene in muscle and liver from euthermic and induced
RT hibernating jerboa (Jaculus orientalis).";
RL Gene 181:139-145(1996).
RN [2]
RP PROTEIN SEQUENCE OF 2-25.
RC TISSUE=Liver;
RX PubMed=8547342; DOI=10.1016/0167-4838(95)00200-6;
RA Soukri A., Hafid N., Valverde F., Elkebbaj M.S., Serrano A.;
RT "Evidence for a posttranslational covalent modification of liver
RT glyceraldehyde-3-phosphate dehydrogenase in hibernating jerboa (Jaculus
RT orientalis).";
RL Biochim. Biophys. Acta 1292:177-187(1996).
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 -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P04406}.
CC -!- PTM: S-nitrosylation of Cys-180 leads to interaction with SIAH1,
CC followed by translocation to the nucleus S-nitrosylation of Cys-275 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-180 increases catalytic activity.
CC {ECO:0000250|UniProtKB:P16858}.
CC -!- SIMILARITY: Belongs to the glyceraldehyde-3-phosphate dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; X87226; CAA60678.1; -; mRNA.
DR PIR; JC5370; JC5370.
DR AlphaFoldDB; P80534; -.
DR SMR; P80534; -.
DR PRIDE; P80534; -.
DR SABIO-RK; P80534; -.
DR UniPathway; UPA00109; UER00184.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0097452; C:GAIT complex; 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; 2.
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; 2.
DR TIGRFAMs; TIGR01534; GAPDH-I; 1.
DR PROSITE; PS00071; GAPDH; 1.
PE 1: Evidence at protein level;
KW Acetylation; ADP-ribosylation; Apoptosis; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Glycolysis; Immunity; Innate immunity;
KW Isopeptide bond; Methylation; NAD; Nucleus; Oxidoreductase; Phosphoprotein;
KW S-nitrosylation; Transferase; Translation regulation; Ubl conjugation.
FT CHAIN 1..363
FT /note="Glyceraldehyde-3-phosphate dehydrogenase, muscle"
FT /id="PRO_0000145487"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000250|UniProtKB:P10096"
FT CHAIN 2..363
FT /note="Glyceraldehyde-3-phosphate dehydrogenase, muscle, N-
FT terminally processed"
FT /id="PRO_0000421780"
FT REGION 1..176
FT /note="Interaction with WARS"
FT /evidence="ECO:0000250"
FT ACT_SITE 180
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10009"
FT BINDING 11..12
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 33
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 108
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 150
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT BINDING 179..181
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 210
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 239..240
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 262
FT /ligand="D-glyceraldehyde 3-phosphate"
FT /ligand_id="ChEBI:CHEBI:59776"
FT /evidence="ECO:0000250|UniProtKB:P22513"
FT BINDING 344
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT SITE 207
FT /note="Activates thiol group during catalysis"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 3
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 7
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 70
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 89
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 92
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 94
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 98
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 103
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 177
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 179
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 180
FT /note="ADP-ribosylcysteine; by autocatalysis; in
FT irreversibly inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 180
FT /note="Cysteine persulfide"
FT /evidence="ECO:0000250|UniProtKB:P16858"
FT MOD_RES 180
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 180
FT /note="S-nitrosocysteine; in reversibly inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 181
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 183
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 205
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 210
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 212
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 222
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 222
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 222
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 239
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 243
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 243
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 247
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 253
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 255
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 255
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 257
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 265
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 275
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:P04797"
FT MOD_RES 275
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 282
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 291
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 344
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT MOD_RES 362
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT CROSSLNK 214
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P04406"
FT VARIANT 7
FT /note="N -> D (in hibernating adult liver isoform)"
SQ SEQUENCE 363 AA; 39413 MW; 6CB549D9A1163C3F CRC64;
MVKVGVNGFG RIGRLVTRAA FNSGKVDIVA INDPFIDLNY MVYMFKYDST HGKFKVDIVA
INDPFIDLNY MVYMFKYDST HGKFKGTVKA ENGKLVINGH AITIFQERDP SKIKWGDAGA
EYVVESTGVF TTMEKAGAHL KGGAKRVIIS APSRDAPMFV MGVNHEKYDK SLKIVSNASC
TTNCLAPLAK VIHDNFGIVE GLMTTVHAIT ATQKTVDGPS AKLWRDGAGA AQNIIPASTG
AAKAVGKVIP ELNGKLTGMA FRVPTANVSV VDLTCRLEKP AKYDDIKRVV KQACDGPLKG
MLGYTEHQVV SSDFNGDSHS STFDAGAGIA LNDHFVKLVS WYDNEFGYSN RVVDLMVHMA
SKE
