DHE3_PIG
ID DHE3_PIG Reviewed; 558 AA.
AC P42174;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 07-OCT-2020, sequence version 2.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Glutamate dehydrogenase 1, mitochondrial;
DE Short=GDH 1;
DE EC=1.4.1.3 {ECO:0000269|PubMed:8240242};
DE AltName: Full=Membrane protein 50 {ECO:0000303|PubMed:8240242};
DE Short=MP50 {ECO:0000303|PubMed:8240242};
DE Flags: Precursor;
GN Name=GLUD1; Synonyms=GLUD;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 54-73 AND 364-381, CATALYTIC ACTIVITY, FUNCTION, AND
RP TISSUE SPECIFICITY.
RX PubMed=8240242; DOI=10.1042/bj2950447;
RA Rajas F., Rousset B.;
RT "A membrane-bound form of glutamate dehydrogenase possesses an ATP-
RT dependent high-affinity microtubule-binding activity.";
RL Biochem. J. 295:447-455(1993).
CC -!- FUNCTION: Mitochondrial glutamate dehydrogenase that converts L-
CC glutamate into alpha-ketoglutarate. Plays a key role in glutamine
CC anaplerosis by producing alpha-ketoglutarate, an important intermediate
CC in the tricarboxylic acid cycle (PubMed:8240242). Plays a role in
CC insulin homeostasis (By similarity). May be involved in learning and
CC memory reactions by increasing the turnover of the excitatory
CC neurotransmitter glutamate (By similarity).
CC {ECO:0000250|UniProtKB:P10860, ECO:0000250|UniProtKB:P26443,
CC ECO:0000269|PubMed:8240242}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutamate + NAD(+) = 2-oxoglutarate + H(+) + NADH +
CC NH4(+); Xref=Rhea:RHEA:15133, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.4.1.3;
CC Evidence={ECO:0000269|PubMed:8240242};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutamate + NADP(+) = 2-oxoglutarate + H(+) + NADPH +
CC NH4(+); Xref=Rhea:RHEA:11612, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.4.1.3;
CC Evidence={ECO:0000250|UniProtKB:P00367};
CC -!- ACTIVITY REGULATION: Subject to allosteric regulation. Activated by
CC ADP. Inhibited by GTP and ATP. ADP can occupy the NADH binding site and
CC activate the enzyme. Inhibited by SIRT4 (By similarity). Inhibited by
CC HADH (By similarity). {ECO:0000250|UniProtKB:P00367,
CC ECO:0000250|UniProtKB:P26443}.
CC -!- SUBUNIT: Homohexamer (By similarity). Interacts with HADH; this
CC interaction inhibits the activation of GLUD1 (By similarity).
CC {ECO:0000250|UniProtKB:P00366, ECO:0000250|UniProtKB:P26443}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P00367}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:P00367}. Note=Mostly
CC translocates into the mitochondria, only a small amount of the protein
CC localizes to the endoplasmic reticulum. {ECO:0000250|UniProtKB:P00367}.
CC -!- TISSUE SPECIFICITY: Liver, brain and thyroid.
CC {ECO:0000269|PubMed:8240242}.
CC -!- PTM: ADP-ribosylated by SIRT4, leading to inactivate glutamate
CC dehydrogenase activity. Stoichiometry shows that ADP-ribosylation
CC occurs in one subunit per catalytically active homohexamer.
CC {ECO:0000250|UniProtKB:P00367}.
CC -!- SIMILARITY: Belongs to the Glu/Leu/Phe/Val dehydrogenases family.
CC {ECO:0000305}.
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DR EMBL; AEMK02000096; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; S39010; S39010.
DR RefSeq; NP_001231430.1; NM_001244501.1.
DR AlphaFoldDB; P42174; -.
DR SMR; P42174; -.
DR PaxDb; P42174; -.
DR PeptideAtlas; P42174; -.
DR PRIDE; P42174; -.
DR Ensembl; ENSSSCT00000011350; ENSSSCP00000011056; ENSSSCG00000010368.
DR Ensembl; ENSSSCT00025034039; ENSSSCP00025014172; ENSSSCG00025025117.
DR Ensembl; ENSSSCT00030091528; ENSSSCP00030042102; ENSSSCG00030065447.
DR Ensembl; ENSSSCT00035079984; ENSSSCP00035032921; ENSSSCG00035059666.
DR Ensembl; ENSSSCT00045058193; ENSSSCP00045040681; ENSSSCG00045033938.
DR Ensembl; ENSSSCT00050091367; ENSSSCP00050039305; ENSSSCG00050067038.
DR Ensembl; ENSSSCT00055054205; ENSSSCP00055043253; ENSSSCG00055027367.
DR Ensembl; ENSSSCT00060082867; ENSSSCP00060035914; ENSSSCG00060060739.
DR Ensembl; ENSSSCT00065050932; ENSSSCP00065022079; ENSSSCG00065037327.
DR Ensembl; ENSSSCT00070048400; ENSSSCP00070040872; ENSSSCG00070024230.
DR GeneID; 100157162; -.
DR KEGG; ssc:100157162; -.
DR CTD; 2746; -.
DR eggNOG; KOG2250; Eukaryota.
DR GeneTree; ENSGT00390000000854; -.
DR Proteomes; UP000008227; Chromosome 14.
DR Proteomes; UP000314985; Chromosome 14.
DR Bgee; ENSSSCG00000010368; Expressed in Ammon's horn and 43 other tissues.
DR ExpressionAtlas; P42174; baseline.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004352; F:glutamate dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0004354; F:glutamate dehydrogenase (NADP+) activity; IEA:RHEA.
DR GO; GO:0004353; F:glutamate dehydrogenase [NAD(P)+] activity; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0006541; P:glutamine metabolic process; ISS:UniProtKB.
DR GO; GO:0072350; P:tricarboxylic acid metabolic process; ISS:UniProtKB.
DR CDD; cd01076; NAD_bind_1_Glu_DH; 1.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR006095; Glu/Leu/Phe/Val_DH.
DR InterPro; IPR033524; Glu/Leu/Phe/Val_DH_AS.
DR InterPro; IPR006096; Glu/Leu/Phe/Val_DH_C.
DR InterPro; IPR006097; Glu/Leu/Phe/Val_DH_dimer_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR033922; NAD_bind_Glu_DH.
DR Pfam; PF00208; ELFV_dehydrog; 1.
DR Pfam; PF02812; ELFV_dehydrog_N; 1.
DR PRINTS; PR00082; GLFDHDRGNASE.
DR SMART; SM00839; ELFV_dehydrog; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53223; SSF53223; 1.
PE 1: Evidence at protein level;
KW Acetylation; ADP-ribosylation; ATP-binding; Direct protein sequencing;
KW Endoplasmic reticulum; GTP-binding; Hydroxylation; Mitochondrion; NAD;
KW NADP; Nucleotide-binding; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..53
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P00367"
FT CHAIN 54..558
FT /note="Glutamate dehydrogenase 1, mitochondrial"
FT /id="PRO_0000182741"
FT REGION 34..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 183
FT /evidence="ECO:0000250|UniProtKB:P10860"
FT BINDING 141..143
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 147
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 171
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 176
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 252
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 266
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 270
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 319
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 322
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 438
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 444
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 450
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 516
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 68
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10860"
FT MOD_RES 84
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 84
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 90
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 110
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 110
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10860"
FT MOD_RES 135
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 147
FT /note="N6-(2-hydroxyisobutyryl)lysine"
FT /evidence="ECO:0000250|UniProtKB:P00367"
FT MOD_RES 162
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 162
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 171
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 172
FT /note="ADP-ribosylcysteine"
FT /evidence="ECO:0000250|UniProtKB:P00367"
FT MOD_RES 183
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 183
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 187
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 191
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 191
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 200
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 211
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 227
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00367"
FT MOD_RES 326
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 346
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 346
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 352
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 352
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 363
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 363
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 365
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 365
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00367"
FT MOD_RES 386
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 390
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 390
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 399
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 410
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10860"
FT MOD_RES 415
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 415
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 457
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 457
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250"
FT MOD_RES 457
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 477
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 477
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 480
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 480
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 503
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 503
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250"
FT MOD_RES 503
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 512
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P00367"
FT MOD_RES 527
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 527
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250"
FT MOD_RES 527
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 545
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 545
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 548
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
SQ SEQUENCE 558 AA; 61308 MW; B0096993A9A7F225 CRC64;
MYRCLGEALL LSRAGPAALG SAAADSAALL GRTRGQPATA PQPGLAPPAR RHYSEAAADR
EDDPNFFKMV EGFFDRGASI VEDKLVEDLK TRESEEQKRN RVRGILRIIK PCNHVLSLSF
PIRRDDGSWE VIEGYRAQHS QHRTPCKGGI RYSTDVSVDE VKALASLMTY KCAVVDVPFG
GAKAGVKINP KNYTDNELEK ITRRFTMELA KKGFIGPGID VPAPDMSTGE REMSWIADTY
ASTIGHYDIN AHACVTGKPI SQGGIHGRIS ATGRGVFHGI ENFINEASYM SILGMTPGFG
DKTFVVQGFG NVGLHSMRYL HRFGAKCVGV GESDGSIWNP DGIDPKELED FKLQHGTILG
FPKAKIYEGS ILEADCDILI PAASEKQLTK SNAPRVKAKI IAEGANGPTT PEADKIFLER
NIMVIPDLYL NAGGVTVSYF EWLKNLNHVS YGRLTFKYER DSNYHLLMSV QESLERKFGK
HGGTIPIVPT AEFQDRISGA SEKDIVHSGL AYTMERSARQ IMRTAMKYNL GLDLRTAAYV
NAIEKVFKVY NEAGVTFT
